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A  MANUAL  OF  PHYSIOLOGY 


THE  'UNIVERSITY'  SERIES  OF 

MANUALS 

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(Jawul  Blood  o/ 


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after  addition  o/\oattT 


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1.  Red  blood-corpuBcles. 


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afVtr  additicrn  of  tali 


Sccturtu.    N\tel»us 
en :  nueteir  emd 
eorpuKular  tnvtloper 
ruptured. 


2.  The  colourless  corposcles  of  human  blood,  x  1000.  a,  eosinophile  cells  ; 
b,  finely  granular  oxyphile  cells  ;  c,  hyaline  cells  :  d,  lymphocyte ; 
e,  polymorphonuclear  nentrophile  cells  (Kanthack  and  Hardy).  The 
magnification  is  much  greater  than  in  1 . 


3.   Cover-glass  preparation  of  spinal  cord  of  ox, 
{Stained  vjiih  methylene  blue). 
Dendritic  jtrnce*$t* 


250. 


Bipoiar  nerve  c- 


«•  /j.JJar» 


4.  Potassium  in  a,  frog's  erythrocyte  (black) ; 
/>,  nerve  (black) ;  c,  striped  muscle  (black) : 
d,  cartilage  cells  (yellow)  (Macalluni). 


Fronhspieee 


A 


MANUAL  OF  PHYSIOLOGY 

HlHitb  practical  lEvcrcisce 


BY 

G.  N.  STEWART,  M.A  ,  D.Sc,  M.D.  Edin.,  D.P.H.  Camb. 

PKOPESSOR   OF    EXPERIMENTAL    MEDICINE   IN    WESTERN    RESERVE   UNIVERSITY,    CLINICAL 

'I'HVSIOLOGIST   TO    LAKFSIDE    HOSPITAL,    CLEVELAND  ;    FORMERLV   PROFESSOR   OK 

l-HVSIOLOOV  IN  THE  UNIVEKSITV  OF  CHICAGO  ;    PROFESSOR  OF  PHVSIOI.nnY  IN 

THR  Wl-STEKN  RESERVE  UNIVERSITY;   GEORGE  HEN'RY  LEWES  STUDENT; 

EXAMINER    IN    PHYSIOLOGY    IN    THE    UNIVERSITY   OF   ABERDI  KN  ; 

SENIOR    DEMONSTRATOR    OF    PHYSIOLOGY   IN   THE   OWENS 

COLLEGE,    VICTORIA    UNIVERSITY,    ETC. 


WITH  COLOURED  PLATE  AND  492  OTHER  ILLUSTRATIONS 


EIGHTH    EDITION 


UNIVERSITY  SERIES 


NEW    YORK 

WILLIAM     WOOD    AND    COMPANY 

MDCCCCXVIII 
All  rights  reserved 


// 


Printed  in  Great  Britain 


PREFACE  TO    THE   EIGHTH   EDITION 


In  tlio  midst  of  arms  the  laboratories  are  silent,  and  if  the  book  has 
not  been  quite  so  extensively  revised  in  this  as  in  the  previous 
edition  tliere  is  only  too  valid  an  excuse  in  the  withering  influence 
of  the  war  upon  the  output  of  new  work.  Nevertheless,  consider- 
able changes  and  additions  have  been  made,  especially  in  the 
portions  dealing  with  the  chemical  phenomena  of  respiration,  the 
functions  of  the  endocrine  organs  and  metabolism.  Some  of  the 
newer  calorimetric  work  has  been  more  adequately  taken  account 
of.  The  tiltration-reabsorption  theory  of  urine  formation,  as 
recently  formulated  by  Professor  Cushny,  is  discussed,  although 
necessarily  in  less  detail  than  its  importance  merits.  Some  of  the 
more  recent  results  of  the  examination  of  the  mechanics  of  the 
circulation  by  optical  methods  of  recording  have  been  noticed. 
Several  of  the  old  illustrations  have  been  omitted  and  a  considerable 
number  of  new  ones  added.  In  deference  to  the  opinion  of  a 
number  of  teachers  a  bibliography  has  been  inserted  in  the  form  of 
an  appendix.  Most  of  the  references  are  to  papers  written  in 
English,  as  these  will  necessarily  be  of  the  most  general  use,  and  in 
an}'  case  will  usually  contain  references  to  the  most  important  paper;-, 
in  other  languages.  An  exception  is  made  in  favour  of  monographs 
which  are  themselves  provided  with  extensive  bibliographies. 
Recent  communications  are  often  cited  in  preference  to  older  ones 
on  the  same  subject,  not  because  the  new  work  is  necessarily 
better  or  more  important  than  the  old,  but  because  recent  papers 
will,  as  a  matter  of  course,  refer  to  previous  publications. 

Despite  suggestions  made  from  time  to  time  by  critical  friends 
and  friendly  critics  (it  is  curious  how  little  there  is  of  cross  division 
here),  the  Practical  Exercises  have  been  retained  in  their  original 
place  at  the  end  of  the  related  chapters.  The  author  has  been 
asked  more  than  once  whether  it  would  not  be  better  to  collect 
them  into  a  separate  small  volume,  for  greater  convenience  of  use 
in  the  laboratory.  Apart  from  the  fact  that  this  would  entail  a  not 
inconsiderable  duplication  of  material,  including  illustrations,  the 
exercises  in  their  present  form  and  position  being  supplemented  freely 
by  cress-references  to  the  text,  the  suggested  change  would  run 
counter  to  all  the  ideas  of  the  author  as  to  the  relation  between  text- 
book and  practical  work  in  the  study  of  a  science  like  physiology. 
But  for  the  exigencies  of  curricula,  which  necessarily,  having  to  reckon 

V  l> 


vi  PREFACE  TO  THE  EIGHTH  EDITIOS 

v\"ith  the  brcxity  of  life,  tend  to  sunder  thin|<s  which  should  be  joined, 
and  in  the  stuh-  measure,  the  law  of  action  and  reaction  holding^ 
own  in  scheduK-s  and  time  tables,  to  join  tiling's  whicli  were  better 
apart,  it  would  have  seemed  to  the  author  even  more  appropriate 
to  place  the  exercises  at  the  beginning  of  the  chapters,  or  best  of 
all  to  interweave  them  with  the  text  till  the  '  phase  boundaries  ' 
between  the  two  disappeared  as  far  as  might  be — a  process  which 
might  perhaps  often  be  applied  with  adxaiitage  to  the  phase 
boundaries  (of  lath  and  plaster,  still  more  of  mental  attitude) 
between  lecture  -  room  and  laboratory.  The  book  would  then 
become,  if  the  design  could  be  adequately  carried  out,  a  text-book 
of  physiology,  in  the  perusal  of  which  the  student  was  not  permitted 
to  forget  for  a  moment  that  the  value  of  the  so  -  called  '  facts  ' 
described  was  in  the  last  analysis  dependent  wholly  upon  the 
accuracy  of  innumerable  observations  carried  out  in  the  laborator\' 
by  methods  and  apparatus  with  which  he  had  gained,  or  was  gaining, 
some  first-hand  acquaintance  in  his  practical  work.  When  a 
statement  in  the  text  is  followed  by  a  page  reference  to  the  Practical 
Exercises  this  is  for  the  precise  purpose  of  reminding  the  student 
that  the  laboratory  is  the  seed-bed  of  the  whole  science.  Lest  he 
forget  this  the  exercises  are  not  even  placed  all  at  the  end  of  the 
book,  still  less  in  a  separate  volume. 

The  question  has  been  sometimes  asked  whether  the  methods, 
and  especiallv  the  apparatus  described  in  the  exercises,  will  exactly 
suit  most  laboratories.  They  will  not,  and  they  ought  not  to  be 
expected  to  do  so.  This  is  also  necessarily  true  of  all  laboratory- 
guides.  All  must  be  adapted  in  some  measure  not  only  to  the 
material  equipment  of  any  particular  laboratory  in  which  they  are 
being  used,  but  quite  as  much  to  the  ideas  and,  what  is  by  no  means 
unimportant,  to  the  habits  of  the  teacher.  To  a  certain  extent  in 
America  a  standardization  of  physiological  apparatus  for  students^ 
has  been  realized,  and  this  has  Ix^en  of  considerable  benefit  to  the 
teaching  of  physiology.  Individual  teachers  and  laboratories  have 
nevertheless  gone  on  developing  their  own  ideas  with  marked 
advantage,  and  nothing  would  be  less  desirable  than  the  unifomiity 
of  machine-made  physiological  teaching,  could  this  be  achieved, 
which  luckilv.  in  the  nature  of  things,  it  cannot  be. 


Cleveland, 

April,  191S. 


EXTRACT  FROM  THE   PREFACE  TO 
THE  FIRST  EDITION 

In  this  book  an  attempt  has  been  made  to  iutenveave  formal  ex- 
position with  practical  work,  according  to  a  programme  which  I 
have  followed  for  some  time  past  in  teaching  Physiology  to  medical 
students  on  the  other  side  of  the  Atlantic,  and  which  has,  it  is 
believed,  proved  to  be  well  adapted  to  their  needs  and  opportunities. 
It  ought,  however,  to  be  explained  that,  for  various  reasons,  a 
somewhat  wider  range  of  experiment  is  open  to  the  student  in 
America  than  in  this  countr}-.  But  as  nobody  will  use  this  book 
except  in  a  regular  laboratory  and  under  responsible  guidance,  it 
has  not  been  thought  necessary'  to  mark  in  any  special  manner  the 
parts  of  the  exercises  which  the  English  student  must  do  by  proxy 
(that  is,  learn  from  demonstrations),  and  the  parts  he  ought  to 
perform  for  himself. 

An  arrangement  of  the  exercises  with  reference  to  the  systematic 
course  has  this  advantage — that  by  a  little  care  it  is  possible  to 
secure  that  practical  work  on  a  given  subject  shall  actually  be  going 
on  at  the  time  it  is  being  expounded  in  the  lectures.  Cross-refer- 
ence from  lecture-room  to  laboratory,  and  from  laboratory  to 
iecture-room,  from  the  detailed  discussion  of  the  relations  of  a 
phenomenon  to  the  living  fact  itself,  is  thus  rendered  easy,  natural, 
and  fruitful. 

As  some  teachers  may  wish  to  know  how  a  course  such  as  that 
described  in  the  Practical  Exercises  maj-  be  conducted  for  a  fairly 
large  class,  a  few  words  on  the  method  we  have  followed  may  not 
be  out  of  place.  It  is  obvious  that  many  of  the  exercises  require 
more  than  one  person  for  their  performance;  and  it  may  be  said 


viii     EXTRACT  FROM  THE  PREFACE  TO  THE  FIRST  EDITION 

that,  except  in  the  case  of  the  simpler  experiments  and  the  chemical 
work  as  a  whole,  which  each  student  does  for  himself,  it  has  been 
found  convenient  to  divide  the  class  into  groups  of  four,  each  group 
remaining  together  throughout  the  session.  It  is  possible  that  some 
may  find  a  group  of  four  too  large  a  unit,  and  it  is  certain  that  three, 
or  perhaps  even  two,  would  be  better;  but  in  a  large  school  so 
minute  a  subdivision  is  hardly  possible,  without  entailing  excessive 
labour  on  the  teachers. 

The  systematic  portion  of  the  book  is  so  arranged  that  it  can 
equally  well  be  used  independently  of  the  practical  work,  and  aims 
at  being  in  itself  a  complete  exposition  of  the  subject,  adapted  to 
the  requirements  of  the  student  of  medicine. 

As  to  the  matter  of  the  text,  it  is  hardly  necessary  to  say  that 
this  book  does  not  aspire  to  the  dubious  distinction  of  originality; 
and  it  is  literally  impossible  to  acknowledge  all  the  sources  from 
which  information  has  been  derived.  In  many  cases  names  have 
been  quoted,  but  names  no  less  worthy  of  mention  have  often  been 
of  necessity  omitted. 

G.  N.  STEWART. 

Cambridge, 

September,  1895. 


ERRATA 

On  p.  G17,  line  5  from  bottom,  for  '  McCollom  '  read  '  McCollum  ' 

,,  p.  C32,  line  28.  for  '  McGollom  '  read  '  McCollum.' 

,,  p.  647,  line  13.  for  '  are'  rend  '  is.' 

,,  p.  648.  line  II,  for  '  and  '  rend  '  the.' 

,,  pp.  667  and  669  (headline),  /(>/■  '  adrenals  '  read  '  pituitary.' 

,,  p.  671  (headline), /o/-  'adrenals'  read  '  pineal  gland.' 

•  •  P-  f'73  (headline), /oy  '  adreii-ils'  read  'spleen,' 


CONTENTS 

CHAPTER  I. 
INTRODUCTION. 

PAca 

Chemical  composition  of  living  matter      -  -  -  -         i 

Proteins      --------i 

Carbo-hydrates       .-..-.-         3 
Fats  ....  ^  ...         3 

Structure  of  living  matter  ------         4 

l-unctions  of  living  matter  -  -  -  -  -         6 

CHAPTER  II. 

THE    CIRCULATING  LIQUIDS  OF  THE  BODY. 

Section  I. — Morphology  of  the  Blood  -  -  *       '4 

Blood-corpuscles  -  -  -  .  .  _       le 

Life-history  of  the  corpuscles  -  -  -  -       20 

Section  II. — General  Physical  and  Chemical  Properties  of 

THE  Blood               -             -             -  -  .  -       23 

Viscosity  of  blood        -             -             -  .  -  -23 

Reaction  of  blood        -             -             -  -  .  -       24 

Specific  gravity  of  blood          -             -  -  -  -       26 

Electrical  conductivity  of  blood          -  -  -  -       26 

Relative  volume  of  corpuscles  and  plasma  -  -  -       27 

Haemolysis       -             -             -             -  -  .  -       28 

Agglutination  -             -             -             -  -  .  -       30 

Precipitins        -              -              -              -  -  -  -31 

Anaphylaxis    -              -              •              -  -  .  -       32 

Coagulation  of  blood  -             -             -  -  -  -       33 

Vaso-constrictor  property  of  shed  blood  -  -  -45 

Section  III. — The  Chemical  Composition  of  Blood  -  -      47 

Haemoglobin  and  its  derivatives         -  -  -  -       50 

Section  IV. — Quantity  and  Distribution  of  the  Bi  god     -       55 
Quantity  of  blood        -  -  -  -  -  -cc 

Distribution  of  blood  ------         ^ 


X  CONTENTS 

PACK 

Section  V. — J  '^mph  and  Chyle              -             -            -             -  57 

Lymph              -------  57 

Chyle -  58 

Section  VI. — Functions  of  Blood  and  Lymph           -             -  59 

Phagocytosis  -             -             -             -             -             -             -  59 

Diapedesis       --  -  -  -  -  -61 

CHAPTER   III. 

THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH. 

Section  I. — Preliminary  Anatomical  and  Physical  Data   -  80 

Physiological  anatomy  of  the  vascular  system             -             -  81 

Flow  of  a  liquid  through  tubes            -             -             -             -  83 

Section   II. — The   Beat  of  the  Heart  in   its  Physical  or 

Mechanical  Relations     -             -             -             -             -  85 

Events  in  the  cardiac  cycle    -             -             -             -             -  85 

The  sounds  of  the  heart         -             -             -             -             -  88 

The  cardiac  impulse    -             -             -             -             -             -  90 

Endocardiac  pressure               -             -             -             -             -  92 

The  ventricular  pressure-curve            -             -             -             -  94 

The  auricular  and  venous  pressure-curve        -             -             -  98 

Section  III. — Physical  or  Mechanical  Phenomena  of  the 

Circulation  in  the  Bloodvessels          .            -             .  loi 

The  arterial  pulse        ..----  loi 

Arterial  blood -pressure             .             .              .             .              _  109 

Measurement  of  the  blood-pressure  in  man     -             -             -  113 
Velocity  of  the  blood  -             -             -             -             -             -117 

Measurement  of  velocity  of  blood       -             -             -             -  120 

The  volume-pulse        -  -  -  -  -  -127 

The  circulation  in  the  capillaries        -             -             -             -  129 

The  circulation  in  the  veins  -             -             -             -             -  132 

The  circulation -time    -             -             -             -             -             -  ^35 

Work  and  output  of  heart      -             -             -             -             -  ^39 

Section  IV. — The  Heart-Beat  in  its  Physiological  Rela- 
tions ..-.---  140 
Intrinsic  nerves  of  the  heart  -  -  -  -  -141 
Cause  of  the  heart-beat  .....  141 
Conduction  and  co-ordination  in  heart  ...  146 
Auriculo- ventricular  bundle  -  -  -  -  -  ^47 
Fibrillary  contractions  -  -  -  -  -151 
Chemical  conditions  of  heart-beat  ...  -  152 
Resuscitation  of  the  heart  -  -  -  -  -  ^53 
Refractory  period  of  heart     -             -             -             -             -  '55 


coxTi:yTS  xi 

PACK 

Section  V. — The  Nervous  Regulation  of  the  Heart  (Ex- 
trinsic Nervous  Mechanism  of  the  Heart)        -             -  156 
Action  of  poisons  on  the  heart             -             -             -             -  166 
Normal  excitation  of  cardiac  nervous  mechanism       -             -  168 

Section  VI. — The  Nervous  Regulation  of  the  Bloodvessels 

(Vaso-Motor  Nerves)        -            -            -            -            -  173 

The  chief  vaso-motor  nerves  -             -             -             -             -  175 

Vaso-dilator  fibres        -             -             -             -             -             -  179 

Course  of  the  vaso-motor  nerves          -             -             -             -  181 

Vaso-motor  centres      -             -             -             -             -             -  1S2 

Vaso-motor  reflexes     -             -             -             -             -             -  185 

Influence  of  gravity  on  the  circulation             -             -             -  iqo 

Section  VII. — The  Lymphatic  Circulation        -             -             -  192 

CH.\PTER    TV. 

RESPIRATION. 

Section  I. — Pret.iminarv  Anatomical  Data       ...  22> 

Physiological  anatomy  of  the  respiratory  apparatus  -             -  223 

Blood-supply  of  the  lungs        -----  223 

Section  II. — Mechanical  Phenomena  or  External  Respira- 
tion              --..--.  225 
Types  of  respiration     -              -              -              -              -              -229 

.Artificial  respiration    -              -              -              -              -              -  230 

Respiratory  sovmds      -  -  -  -  -  -231 

Frequency  of  respiration          -              -              -              -              -  2  3.f 

Vital  capacity  -------  236 

The  dead  space             -             -             -             -             -             -  236 

Intrathoracic  pressure              .             -             -             -             .  236 

Respiratory  pressure    -.----  238 

Section  III. — The  Chemistry  of  External  Respiration          -  239 

Inspired  and  expired  air           -             -             -             -             -  239 

.\lveolar  air      -             -             -             -             -             -             -  -41 

Respiratory  quotient  -              -              -              -              -              -  -41 

Ventilation       -------  242 

The  quantity   of  carbon   dioxide   given   off   and   of  oxygen 

absorbed       -------  243 

Section  IV. — The  Gases  of  the  Blood  .             -             -             -  245 

Physical  introduction  ------  245 

Quantity  of  the  blood -gases     -             -             -             -             -  ^50 

Distribution  and  condition  of  oxygen  in  the  blood     -             -  252 

Distribution  and  condition  of  carbon  dioxide  in  the  blood     -  255 

The  tension  of  the  blood-gases             ...             -  2^8 

Mechanism  of  the  gaseous  exchar.ge  in  the  lungs        -             -  263 


xii  CONTEXTS 

lACB 

Section  \'. — Intiunai.  or  Tissuf.  Rt-spiration  -             -             -  265 

Seats  of  oxidation         ---...  265 

Passage  of  oxy<^en  fioTu  the  blood  into  the  tissues      -              -  266 

Respiration  of  muscle                 -              -              -              .              .  269 

Nature  of  the  oxidati\e  process            -             -             -             -  271 

Passage  of  carbon  dioxide  from  the  tissues  intn  the  blood      -  2jz 

SfXTION     VI.  —  RliLATIOX     OI-      RESPIRATION      TO      THE      N'ERVOIS 

System          ---....  274 

The  respiratory  centre  and  its  connections      -             -             -  274 

Regulation  of  respiration  through  the  vagus  -             -             -  276 

Action  of  other  afferent  fibres  on  the  respiration         •             -  280 

The  chemical  regulation  of  the  respiration      -             -             -  281 

Apnoea               .......  283. 

Automaticity  of  the  respiratory  centre            ...  284 

Special  moditications  of  the  respiratory  movements  -              -  287 

Section  \'II. — The  Influence  of  Respiration  on  the  Blood- 
Pressure      ---.-..  2St> 

Section  VIII. — The  Effects  of  breathing  CondensI'D  and 

Rarefied  .\ir          ---...  295 

Section  IX. — Cutaneous  Respiration    -             .             .             .  299 

CHAPTER  V. 

VOICE  AND  SPEECH. 

Voice            --.-....  307 

Speech  -  -  -  -  -  -  -  -312 

CHAPTER  VI. 

DIGESTION. 

Section  I. — Preliminary  Anatomical  and  Chemical  Data      -  318 

Anatomy  of  alimentary  canal               -             -             -             -  319 

Section  II. — Mechanical  Phenomena  of  Digestion      -             -  321 

Mastication      ...              ....  321 

Deglntition       ----...  ^^22 

Movements  of  stomach             -             -             -             -             -  326 

Movements  of  intestines           -             -             -             -             .  t;28 

Influence    of   central    nervous    system    on  gastro-intestina! 
movements  -      "     \  -  -  -  -  -  -331 

Defeecation       -             -             -             -             -             -             -  33-2 

Vomiting          .......  ^^^ 

Section  III. — Chemistry  of  the  Digestive  Juices — Ferments  336 

Saliva ..-----.  ^.^^ 

Gastric  juice    -------  ^^c^ 

Antiseptic  functions  of  gastric  jiiice    ...              -  ^.^5 


co.vrt.vrs  xiu 

Sr.cTiON  III.   {continued) —  pa<* 

Pancreatic  juice           ......  358 

Bile      -             -             -             -             -             -             -             -  :^^'3 

Succus  entericus           -..-.-  370 

Section  IV. — Secretion  of  the  Digestive  Juices — Micro- 
scopical Ch.\xges  in  the  Glan'd  Cells  -  -  -  374 
Changes  in  pancreas  and  parotid  during  secretion  -  -  375 
Changes  in  gastric  glands  during  secretion  ...  377 
Changes  in  mucous  glands  during  secretion  -  -  -  381 
Mode  of  formation  of  the  digestive  juices  -  -  -  383 
Why  are  the  tissues  of  digestion  not  affected  by  the  digestive 
ferments  ?-             -             -             -             -             -             -  38S 

Section    V. — Influence    of    the    Xervous    System    on    the 

Digestive  Glands  -             -             -             -             -             -  39' 

Influence  of  nervous  system  on  salivary  glands  -  -391 

Influence  of  nervous  system  on  gastric  glands             -             -  40 

Influence  of  nervous  5\-stem  on  the  pancreas               -             -  405 

Secretin             .-....-  407 

Influence  of  nervous  system  on  secretion  of  bile          -             -  411 
Influence  of  nervous  system  on  the  secretion  of  intestinal 

juice               .......  ^i^ 

Secretion  of  the  digestive  juices  (summary)    .             -             -  415 

Section  VI. — Survey  of  Digestion  as  a  Whole             -             -  416 

Reaction  of  intestinal  contents             -             .             -             -  419 

Bacterial  digestion       ..,..-  422 

Faeces  .---.---  423 


CHAPTER  VII. 

ABSORPTION. 

Section  I. — Preliminary  Physico-Chemical  Data        •             -  426 

Imbibition,  diffusion,  and  osmosis       ....  426 

Electrolytes      -              -              -              -              -              -              -  428 

Surface  tension             -             -             -             .             .             -  429 

Adsorption      -             -             -             -             -             ■             -  430 

Section  II. — Mechanism  of  Absorption  -  •  -431 

Theories  of  absorption              .             .             .             .             .  ^33 

Permeability  of  intestinal  epithelium               -             -             -  437 

Absorption  from  the  peritoneal  cavity             -             -             -  439 

Section  III. — Absorption  of  the  Various  Food  Substances  -  441 

.\bsorption  of  fat         -             -             -             .             -             -  44  • 

Absorption  of  carbo-hydrates               -             .             .             -  4^3 

Absorption  of  water  and  salts               ....  ^^u 

Ab-orption  of  proteins              ....              -  4^7 


CONTESTS 

CHAPTER  VIII. 
FORMATION  OF  LYMPH. 


PAGK 


Difieren    kinds  of  lymph    -----.  466 

Fa  :tors  concerned  in  lymph  formation       -  .  .  .  ^57 

The  contribution  of  the  tissue-cells  to  the  lymph  -  -  -  472 

CHATTER  IX. 

EXCRETION. 

Section  I. — Excretion  by  ihe  Kionevs — The  Chemistry  of 

THE  Urine  -  -  -  -  -  -  -4  76 

The  urine  in  disease     .---..  ^83 

Section  II. — The  Secretion  of  the  Urine         ...  ^g^ 

Bloodvessels  and  tubules  of  the  kidney  -  .  -  489 

Theories  of  renal  secretion       -  -  -  -  .  ^gj 

Excretion  of  pigments  by  the  Icidney  .  -  .  _  ^g^ 

Influence  of  the  circulation  on  the  secretion  of  urine  -  506 

Section  III. — Expulsion  of  the  Urine  -  -  -  -  510 

Section  IV. — Excretion  by  tmf.  Skin     -  .  -  -  511 

CHAPTER  X. 
METABOLISM,  NUTRITION  AND  DIETETICS. 

Section  I. — Met.^bolism  of  Carbo-Hvdr.'vtes — Glycogen         -  533 

Glycogen-formsrs         .-..-.  3^5 

Function  and  fate  of  the  glycogen      -  -  .  .  339 

Fate  of  the  sugar — glycob'sis  ....  ^^q 

Intermediary  metabolism  of  carbo-hydrates  .  -  -  5-}- 

The  experimental  glycosurias  ....  3^5 

Diabetes  m?llitus         -  -  -  -  -  -  552 

Section  II. — Metabolism  of  Fat  ....  ^^^ 

Form  ition  of  fat  from  carbo-hydrates  -  -  -  500 

Formation  of  fat  from  protein  ....  3^2 

Intermediary  metabohsm  of  fat  ....  ^(j^ 

Non-nutritive  functions  of  fat  -  -  -  -  50b 

Obesity  ..-..-.  308 

Metabolism  of  sterins  -  '  -  -  -  -570 

Metabolism  of  phosphatides    ...  -  -  371 

Section  HI. — Metabolism  of  Proteins  -  -  -  .  372 

Living  and  dead  proteins         -  -  -  -  '57^ 

Formition  of  amino-acids  from  tissue-proteins  .  .  378 

Formation  of  hippuric  acid      .  -  -  .  .  380 

Fate  of  amino-aci'.ls  in  the  boJy  ....  382 


CONTENTS  XV 

Section   III.   (continued) —  pace 

Formation  of  urea        .---.-  583 

Formation  of  uric  acid              .....  590 

Metabolism  of  nucleic  acids  and  purin  bases  -             -             -  592 

Creatin  and  creatinin  ------  597 

Autolysis           -------  599 

Section  IV. — Statistics  of  Nutrition — Income  and  Expendi- 
ture OF  the  Body  in  Terms  of  Matter  -            -            -  601 
The  nitrogen  balance-sheet — nitrogenous  equilibrium              -  602 
Relation  of  nitrogenous  metabolism  to  muscular  work            -  610 
Relative  value  of  different  proteins  in  nutrition          -             -  612 
The  carbon  balance-sheet        -             -             -             -             -  618 

The  oxygen  deficit       ------  620 

Inorganic  salts  in  nutrition     -  ...  -  620 

Section  V. — Dietetics     ------  622 

Stimulants       -  -  -  -  -  -  -  630 

Vitamines        -..-.--  632 

CHAPTER  XL 

INTERNAL  SECRETION— ENDOCRINE  GLANDS. 

Pancreas     --------  C3O 

Sexual  organs  ..----.  5^0 

Thymus      .-.--.--  643 

Thyroid  and  parathyroid   ------  645 

Adrenals      --------  5^3 

Pituitary    ---.----  666 

Spleen         --------  672 

CHAPTER    XTI. 
ANIMAL  HEAT. 

Section  I. — Thermometry  and  Calorimktry    -  -  .    674 

Body-temperature       .--...     580 

Section  II. — Income  and  Expenditure  of  the  Body  in  Terms 

OF  Energy  -  -  -  -  -  -  -681 

Heat-loss  -  -  -  -  -  -  -     681 

Heat-production  --....     5S3 

Basal  metabolism        -.-...     5S6 
Seats  of  heat-production  .  .  -  .  .     585 

Section  III. — Thermotaxis          .             -             -             .             .  5qo 

Relations  between  heat-production,  surface  and  blood -flow  -  696 

The  nervous  system  and  thermotaxis               ...  yoo 

Fever  --------  703 

Section  IV. — Temperature  Topography  -  -  -     709 

Normal  variations  in  body  temperature  -  -  -     712 


XVI  COSTLXTS   '■ 

CHAPTER  XIII. 
THE  PHYSIOLOGY  OF  THE  CONTRACTILE   TISSUES. 

I'ACB 

Section  I. — Prf.limin.\ry  OBsiiRVATioxs — Phv.sical  and  Tkch- 

NiCAL  Data               ......  723 

Cilia     --.-.-.-  733 

Section     II. — Physical     Properties     and     Stimulation     of 

Muscle         .--....  735 

Elasticity  of  muscle     --..--  735 

Stimulation  of  muscle               .....  737 

Direct  excitability  of  muscle  -             ...             -  738 

SrxTiON  III. — Physical  and  Mechanical  Phenomena  of  the 

Muscular  Contraction     ....             -  742 

Optical  phenomena — structure  of  muscle        -             -             -  742 

Mechanical  phenomena             .....  745 

Mu.scular  fatigue           ......  749 

Electrical  tetanus         ......  756 

Voluntary  contraction               .....  760 

Thermal  phenfimena  and  transformation  of  energy  irt  mus- 
cular contraction      ......  762 

Relation  between  mechanical  energy  and  heat-production  in 

active  muscle             ......  76^ 

Section  IV. — Chemical  Phenomena  of  Muscular  Contraction  767 

Formation  of  lactic  acid           .....  759 

The  substances  metabolized  in  muscular  contraction               -  771 

Rigor   -----...  774 

CHAPTER  XIV. 

NERVE. 

Section  I. — The  Nerve-Impulse  or  Propagated  Disturb- 
ance: its  Initiation  and  Conduction  -  -  .  7S1 
Stimulation  of  nerve  ----..  783 
Excitability  of  nerve  ---...  784 
Electrotonus  .---.-.  785 
Conduction  in  nerve  ----..  790 
Velocity  of  the  nerve-impulse               ....  79^ 

Section  II. — Chemistry,  Degeneration,  and  Regeneration 

OF  Nerve     .----..  794 

Chemistry  of  nerve      ......  794 

Degeneration  of  nerve              .....  79^ 

Regeneration  of  nerve              .....  798 

Trophic  nerves             ......  805 

Classification  of  nerves             .....  807 


CONTENTS  xvji 

CHATTER  XV. 
ELECTRO-PHYSIOLOGY. 

PACI 

Currents  of  rest  and  action              .....  82^ 

Relation  between  action  current  and  functional  activity  -             -  ^-^7 

Polarization  of  muscle  and  nerve  ....             -  829 

F.lectrotonic  currents          .-...-  830 

Heart-currents         _.---•-  833 

Human  electro-cardiogram              .....  835 

Glandular  currents               ......  838 

Eye-currents            .......  839 

Electric  fishes         ....                          .             .  840 

CH.\PTER  XVT. 
THE  CENTRAL  NERVOUS  SYSTEM. 

Section  I. — Structure — Histological  Elements         -            -  847 

Development  -              ......  849 

Histological  elements  ------  850 

Nutrition  of  the  neuron           -             -             -             -             -  858 

Section  II. — Gener.\l  Arr.'^ngement  of  the  Grey  and  White 

Matter  in  the  Central  Nervous  System            -            -  861 

Section  III. — Arrangement  of  Grey  and  White  Matter  in 

Spinal  Cord             ......  863 

Tracts  of  the  cord        ......  866 

Section  IV. — .\rrangement   of  Grey  and  White  Matter  in 

THE  Upper  Portion  of  the  Cerebro-Spinal  Axis            -  869 

Section  V. — Connections  of  the  Long  Paths  of  the  Cord      -  870 

Section  VI. — Paths  from  and  to  the  Cortex  -             -             -  878 

Section    VII. — Connections    of    Brain    Ste.m    with    Cord — 

Connections  of  Cerebellum         .             .             .             .  S84 

Section  VIII. — Functions  of  the  Central  Nervous  System 

— the  Spinal  Cord              .....  887 

Decussation  of  the  sensory  paths         ....  gg^ 

Refle.x  action    -  -  -  -  -  -  -897 

Principle  of  the  common  path              ....  899 

Role  of  the  receptor  in  reflex  action    -             .              -             -  900 

Characteristic  properties  of  the  reflex  arc        -             -              -  902 

Irradiation  of  refle.x  action      ...                           .  905 

Co-ordination  of  refle.xes           -              .              .              .              .  908 

Influence  of  the  brain  on  spinal  reflexes          ...  qi© 

Automatism  of  the  spinal  cord              ....  916 

Muscular  tonus — postural  reflexes       -             -             -             -  917 


xviii  CONTENTS 

I'ACC 

Section  IX. — The  Cranial  Xf.rvhs  ....     920 

Section  X. — Functions  of  thi.  Uhain     .  -  -  -  931 

Functions  of  the  cerebellum    -----  933 

Equilibration  and  orientation  ....  936 

Forced  movements       .-..-.  944 

Functions  of  the  cerebral  c(;rte.\  ...  -  947 

Motor  areas      -  -  -  -  -  •  -  951 

Histological  differentiation  of  the  cortex         -  -  -  958 

Sensory  areas  .-.----  965 

Aphasia  ....--.  969 

Localization  of  function  in  central  nervous  sj'stem     -  -  975 

Influence  of  anastomosis  of  nerves  on  function  •  -  976 

Co-ordmation  of  voluntary  movements  -  -  -  981 

Reaction  time  ...---  982 

Section  XL—  Fatigue  and  Sleep— Hypnosis    -  -  -     983 

Section  XI f. — Size  of  Brain  and  Intelligence — Cerebral 
Circulation — Chemistry  of  Nervous  Activity — Cere- 
BRo-spiNAL  Fluid    ------     988 

(•iiapti:r  xvil 
the  autonomic  nervous  systeim      -  -  1003 

chapter  xvi il 
the  senses. 

The  Senses  in  General  ------  1006 

Section  I. — Vision  .-..--  1008 

Physical  introduction  .  .  -  .  -  1008 

Structure  of  the  eye    -  -  -  -  -  -   10 14 

Chemistry  of  the  refractive  media       -  -  -  -  ioi(» 

Refraction  in  the  eye  ------  10x7 

Accommodation  ..----  1020 

Functions  of  the  iris    ------  1026 

Defects  of  the  eye        ..----   1027 

Ophthalmoscope  -  -  -  -  -  -  1031 

Skiascopy         -------   1034 

Diplopia  .--..--  1037 

Steroscopic  vision         ------   1039 

Visual  judgments  and  illusions  ...  -  1040 

Purkinje's  figures         ------   1042 

Blind  spot        -------  1044 

Rods  and  cones  in  vision  -  -  .  -  -   1045 

Talbot "s  law    -  -  -  -  -  -  -  1050 

Colour  vision  -  -  -  -  -  -  -   1051 

Contrast  -  -  -  -  -  -  -  1056 

Perimetrv         -  -  -  •  -   '  '  "   '°58 


COM  i:nts  xt% 

Section   I.   [contiinwd) —  ta-.b 

Culoiir-blindncss  -...--   1059 

Movements  of  the  eyes  .....   loUi 

Section  II. — Hearing       -...--  10O4 
Section  III. — Smell  and  Taste  -----  loj^ 

Section  IV. — Cutaneous  and  Inter.val  Sensations      -  -  1078 

Tactile  senses  -------  1078 

Sensations  of  warmth  and  cold  .  .  -  -   1081 

Pain      --------  1083 

Phenomena  after  section  of  cutaneous  nerves  -  -  1085 

Muscular  sense  ...-.-   1094 

Sensations  of  hunger  and  thirst  -  .  .  -  109O 

CHAPTER    -XIX. 
REPRODUCTION. 
Regeneration  of  tissues       -  -  -  . 

Reproduction  in  the  higher  animals 
Menstruation  -  -  - 

Development  of  the  ovum  ... 

Parthenogenesis      -  -  -  .  - 

Formation  of  the  embryo  - 

Development  of  the  connections    -  -  - 

Exchange  of  materials  in  the  placenta 
MetaboUsm  of  the  embryo  .      - 

Par?urition  -  .  -  -  . 

Milk  ------ 

Cultivation  of  tissues  outside  of  the  body  - 
Transplantation  of  tissues  .  -  - 

Parabiosis   ------ 

Appendix    A.  —  Comparison     of    Metrical     with 
Measures     -  .  -  -  . 

Appendix  B. — Bibliography        -  -  - 

Index         ------ 

PRACTICAL  EXERCISES. 

CHAPTER   I. 

General  reactions  of  proteins           -             -             -  -  -         7 

Colour  reactions  of  proteins             -             -             -  -  -         8 

Precipitation  reactions  of  proteins               -             -  -  -         8 

Special  reactions  of  groups  of  proteir.s        -             -  .  -         g 

ReaTtions  of  I'erivalives  of  pr.-teins            -             -  .  .         ^ 

Carbo-hydrates        -             -             -             -             -  -  -i» 

Fats              -             -             -             -             -             --  -II 

Scheme  for  testing  for  proteins  and  carbo-hydratas  -  -       13 


• 

- 

III7 

- 

- 

II18 

- 

- 

1 1  20 

- 

- 

II22 

- 

- 

1 123 

- 

- 

II24 

- 

- 

II26 

- 

- 

II 29 

- 

- 

I  133 

- 

- 

II37 

- 

- 

II39 

- 

- 

II42 

- 

- 

II42 

- 

- 

II46 

Engli; 

H 

- 

- 

II5I 

- 

- 

II5-J 

. 

. 

1216 

2X  C0^  TENTS 

CHAPTER  II. 

1.  Reaction  of  blood          -             -             -             -             -  -  02 

2.  Sjjecific  gravity  of  blood            -              -              -              -  -  62 

3.  Coagulation  of  blood    -              -              -              -              -  -  62 

4.  Preparation  of  fibrin-ferment   -             -             -             -  -  '^5 

5.  Preparation  of  extracts  containing  thrombokinase      -  -  05 

6.  Serum    -             -             -             -             -             -             -  -  '\5 

7.  Action  of  serum  on  artery  rings            ...  -  00 

8.  Comparison  of  action  of  serum  and  epinephrin  on  artery  rings  66 

9.  Comparison  of  action  of  serum  and  plasma  on  artery  rings  -  66 
10.  Enumeration  of  the  blood-corpuscles  -  -  -  -  ''7 
\  I .  Hacmatocrite  ....  .-.08 
\2.  Electrical  conductivity  of  blood            -             -             -  -  68 

13.  Opacity  of  blood            -              -              -              -              -  -  70 

14.  Laking  of  blood             -             -             -             •             -  -  70 

15.  Hitmolysis  and  agglutination  -             -              -              -  •71 

16.  Osmotic  resistance  of  coloured  corpuscles        -             -  -  73 

17.  Blood-pigment               -             -             -             -             -  -  73 

(i)   Preparation  of  haemoglobin  crystals  -              -  -  73 
{2)  Spectroscopic   examination   of  haemoglobin   and  its 

derivatives               -              -              -              -  "74 

(3)  Guaiacum  test  for  blood         -             -             -  -  7^ 

(4)  Quantitative  estimation  of  haemoglobin         -  -  76 

(5)  Haemin  test  for  blood -pigment            -             -  •  7^ 

CHAPTER  HI. 

1.  Microscopic  examination  of  the  circulating  blood        -  -  193 

2.  Anatomy  of  the  frog's  heart    -             -             -             -  -  i94 

3.  Beat  of  the  heart          -             -             -             -             -  -  194 

4.  Apex  of  the  heart         -             -             -             -             -  -  194 

5.  Heart  tracings                -              -              -              -              -  -  194 

6.  Dissection  of  vagus  and  cardiac  sympathetic  in  frog  -  -  1 96 

7.  Stimulation  of  the  vagus  in  the  frog    -             -             -  -  198 

8.  Stimulation  of  the  junction  of  the  sinus  and  auricles  -  -  198 

9.  Action  of  muscarine  and  atropine  on  the  heart            -  -  199 

10.  Stannius'  experiment    -             -             -             -             -  -  i99 

11.  Stimulation  of  cardiac  sympathetic  in  frog      -             -  -  i99 

12.  Action  of  inorganic  salts  on  heart-muscle         -             -  -  200 

13.  Action  of  the  mammalian  heart            -             -             -  -  201 

14.  Perfusion  of  the  isolated  mammalian  heart      -             -  -  205 

15.  Action  of  the  valves  of  the  heart          ....  206 

16.  Sounds  of  the  heart      .-----  207 

17.  Cardiogram       -.---•-  207 


CONTENTS 


xxi 


PACK 

1 8.  Sphygmographic  tracings          .....  208 

19.  Venous  pulse  tracing  from  jugular       ....  209 

20.  Polygraph  tracings       --....  209 

21.  Plethysmographic  tracings       -             -             -             -             -  210 

22.  Pulse-rate  -  -  -  -  -  -  -210 

23.  Blood-pressure  tracing               .             .             _             .             -  210 

24.  Estimation  of  arterial  pressure  in  man              ...  213 

25.  Influence  of  position  of  the  body  oti  blood-pressure    -             -  213 

26.  Effects  of  haemorrhage  and  transfusion  on  blood-pressure       -  214 

27.  Influence  of  proteoses  on  blood-pressure           -             -             -  215 

28.  Effect  of  suprarenal  extract  on  blood-pressure             -             -  216 

29.  Action  of  epinephrin  on  artery  rings    -             .             -             -  216 

30.  Determination  of  the  circulation-time               ...  217 

31.  Measurement  of  the  blood-flow  in  the  hands  .             .             -  219 

32.  Vaso-motor  reflexes      -  -  -  -  •  -221 


I. 
2. 
3- 
4- 
5- 
6. 

7- 
8. 

9- 
10. 
II. 


CHAPTER  IV. 

Tracing  of  the  respiratory  movements  in  man 
Production  of  apnoea  and  periodic  breathing  in  man  - 
Tracing  of  the  respiratory  movements  in  animals 
Heat  dyspnoea  -----.- 
Measurement  of  volume  of  air  inspired  and  expired    - 
Cardio-pneumatic  movements  -  -  -  .  - 

Auscultation  of  the  lungs  .  _  -  .  . 

Measurement  of  the  respiratory  pressure  -  .  - 

Estimation  of  carbon  dioxide  and  water  given  off  by  an  animal 
Muscular  contraction  in  the  absence  of  free  oxygen    - 
Oxidizinsr  ferments       ------ 


300 
300 
300 
302 
303 
303 
304 
304 
305 
306 
306 


CHAPTERS  VI.  AND  VII. 

1.  Contraction  of  isolated  intestines  in  Ringer's  solution  -  452 

2.  Effect  of  serum,  on  the  contractions  of  intestinal  segments      -  453 

3.  Action  of  epinephrin  on  intestinal  segments    -  -  -  433 

4.  Quantitative  estimation  of  ferment  action       -  -  -  433 

5.  Chemistry  and  digestive  action  of  saliva  -  .  .  ^^^ 

6.  Stimulation  of  the  chorda  tympani      -  -  -  .  436 

7.  Effect  of  drugs  on  the  secretion  of  saliva  ...  437 

8.  Digestive  action  of  gastric  juice  ....  438 

9.  To  obtain  chyme  and  gastric  juice       ....  439 

10.  Digestive  action  of  pancreatic  juice     -  -  -  -  460 

11.  Chemistry  of  bile  .--...  462 

12.  Microscopical  examination  of  fa?ces      -  -  -  -  463 


CONTENTS 


rAGR 


13.  Absorption  of  fat          -.----  463 

14.  Time   required    for   digestion   and   absorption   of   food   sub- 

stances         -------  464 

15.  Quantity  of  cane-sugar  inverted   and  absorbed  in  a  given 

time              -------  464 

16.  Auto-digestion  of  the  stomach              ....  465 

CHAPTER  IX. 

1.  Specific  gravity  of  urine  -  -  -  -  -515 

2.  Reaction  of  urine  -  -  -  -  -  -515 

3.  Chlorides  in  urine         -  -  •  -  -  -     515 

4.  Phosphates  in  urine      -  -  -  -  -  -516 

5.  Sulphates  in  urine         ------     517 

6.  Indoxyl  in  urine  -  -  -  -  -  -517 

7.  Urea      -.---.--     518 

8.  Ammonia  in  urine        -  -  -  -  -  -521 

9.  Total  nitrogen  in  urine  -  -  -  -  -521 

10.  Uric  acid  -------     523 

11.  Creatinin  -------     323 

12.  Hippuric  acid   -------     524 

13.  Proteins  in  urine  ------     524 

14.  Sugar  in  urine  ......     325 

15.  Pentoses  in  urine  ------     528 

16.  Acetone  in  urine  ------     529 

17.  Determination  of  the  freezing-point  of  urine  -  -  -     529 

18.  Examination  of  urine  -  -  -  -  -  "531 

19.  Urinary  sediments        -  -  -  -  -  -531 

CHAPTERS  X.,  XL,  AND  XII. 

1.  Glycogen  -  -  -  -  -  -  -     715 

2.  Catheterism      -------     716 

J.  Experimental  glycosuria  -  -  -  -  -     716 

(i)  Injection  of  sugar  into  the  blood  -  -  -  716 

(2)  Phlorhizin  glycosuria               -  -  -  *  717 

(3)  Alimentary  glycosuria             -  -  -  -  717 

(4)  Estimation  of  the  sugar  in  blood  -  -  -  717 

4.  Milk      --------  718 

5.  Cheese  --------  719 

6.  Flour     --------  719 

7.  Bread    --------  720 

8.  Excretion  of  urea  (and  total  nitrogen)  and  proteins  in  food       -  720 

9.  Action  of  epinephrin     ------  720 

10.  Measurement  of  the  heat  given  off  in  respiration         -  -  721 


CONTENTS 


CHAPTERS  XIII.   AND  XIV. 

Difference  of  make  and  break  induction  shocks 

Stimulation  by  the  voltaic  current       -  -  -  - 

CiHary  motion  ...--- 

Direct  excitability  of  muscle — curara  -  -  -  - 

Graphic  record  of  '  twitch  '      - 

Influence  of  temperature  on  the  muscle-curve 

Influence  of  load  on  the  muscle-curve  .  -  - 

Influence  of  fatigue  on  the  muscle-curve  .  .  - 

Seat  of  exhaustion  in  fatigue  of  the  muscle-nerve  preparation 

Influence  of  veratrine  on  muscular  contraction 

Measurement  of  the  latent  period  of  muscular  contraction 

Summation  of  stimuli   ------ 

Superposition  of  contractions  -  -  -  -  - 

Composition  of  tetanus  _  .  -  -  - 

Contraction  of  smooth  muscles  .  .  -  - 

Velocity  of  the  nerve-impulse  -  -  -  -  - 

Chemistry  of  muscle      ------ 

Reaction  of  muscle  in  rest,  activity,  and  rigor 

CHAPTER  XV. 

Galvani's  experiment    ------ 

Contraction  without  metals      -  -  -  -  - 

Secondary  contraction  .  -  -  -  - 

Demarcation  and  action  currents  with  capillary  electrometer 
Action  current  of  the  heart      -  -  -  -  - 

Electrotonus     ------- 

Paradoxical  contraction  .  .  .  -  - 

Alterations  in  excitability  and  conductivity  produced  in  nerve 
by  a  voltaic  current  .  .  -  -  - 

9.  Formula  of  contraction  .  -  -  -  - 

10.  Formula  of  contraction  for  (human)  nerves  in  situ 

11.  Ritter's  tetanus  ------ 


I. 
2. 
3- 

4- 
5- 
o. 

7- 
8. 

9- 
10. 
II. 

12. 

13- 
14. 

15- 
16. 

17- 

18. 


PAGE 
807 
810 
811 
811 
811 
813 

813 
813 
8I4 

815 
81O 
816 
816 
817 
818 
819 
820 


842 
842 
842 
842 
844 
844 
844 

844 

845 
846 
846 


CHAPTER  XVI. 

1 .  Section  and  stimulation  of  nerve-roots 

2.  Reflex  action  in  the  '  spinal  '  frog 

3.  Reflex  time       -  -  -  - 

4.  Inhibition  of  the  reflexes 

5.  Spinal  cord  and  muscular  tonus 

6.  Spinal  cord  and  tonus  of  the  bloodvesseh 

7.  Action  of  strychnine     -  -  - 

8.  Mammalian  spinal  preparation 

9.  Decerebrate  cat  preparation     - 

10.  Swallowing  reflex  _  -  - 


-  994 

-  995 

-  995 

-  996 

-  996 

-  996 

-  996 

-  996 

-  998 

-  1000 


CONTENTS 


PACP 


11.  Reflex  postural  tonus  .....  ioo( 

12.  Reflexes  in  man  ......  looo 

13.  Excision  of  cerebral  hemispheres  in  the  frog  -  -  -  1000 

14.  Excision  of  cerebral  hemispheres  in  the  pigeon  -  looi 

15.  Stimulation  of  the  motor  areas  in  the  dog       -  -  -  looi 

CHAPTER   XVIII. 

T.  Dissection  of  the  eye    ------  iioi 

2.  I'ormation  of  inverted  image  on  the  retina  -  -   1102 

3.  Helmholtz's  phakoscope  .....  1102 

4.  Scheiner's  experiment  -  -  -  -  -  1103 

5.  Kiihne's  artificial  eye   ------  1104 

6.  Astigmatism  (ophthalmometer)  -  -  -  -  1105 

7.  Spherical  aberration      ------  1106 

8.  Chromatic  aberration    -  -  -  -  -  -11 06 

9.  Measurement  of  the  field  of  vision  -  -  -  -  iioo 
;o.  Mapping  the  blind  spot  -  .  .  .  .  noy 
[I.  The  yellow  spot             --....  1107 

12.  Ophthalmoscope            -  -  -  -  -  -11 08 

13.  Retinoscopy      ---.._.  nog 

14.  Pupillo-dilator  and  constrictor  fibres   -  -  -  -mo 
13.  Colour-mixing  -             -  -  -  -  -  -iiii 

16.  After-images      -             -  -  -  -  -  -mi 

17.  Retinal  fatigue-             -  -  -  -  -  -im 

18.  Visual  acuity     -              -  -  -  -  -  -iiii 

19.  Colour-blindness             -  -  -  -  -  -1112 

20.  Talbot's  law      -             -  -  -  -  -  -1113 

21.  Purkinje's  figures           -  -  -  -  -  -  1113 

22.  Relation  of  pitch  and  vibration  frequency  -  -  -   1113 

23.  Beats     -              -              -  -  -  -  -  -III  3 

24.  Sympathetic  vibration  -  -  -  -  -  m  ^ 

25.  Galton's  whistle             -  -  -  -  -  -iii^ 

26.  Cranial  conduction  of  sound  -  -  -  -  -1113 

27.  Taste     -             -             -  -  -  -  -  -1113 

28.  Smell     -             -             -  -  -  -  -  -1114 

29.  Touch  and  pressure       -  -  -  -  -  -1114 

30.  Temperature  sensations  -  -  -  -  -1115 

31.  Pciin      -            -             -  -  -  -  -  -mo 

CHAPTER  XIX. 

1.  Contractions  of  isolated  uterine  rings  -  -  -  .  1147 

2.  Comparison  of  changes  of  tone  produced  in  uterus  segments  by 

ditlerent  concentrations  of  adrenalin  -  -  -  1149 

3.  Partition  of  adrenalin  between  serum  and  corpuscles  -  11 49 


A    MANUAL   OF    PHYSIOLOGY 


CHAPTER  I 
INTRODUCTION 

Living  matter,  whether  it  is  studied  in  plants  or  in  animals,  has 
certain  peculiarities  of  chemical  composition  and  structure,  but 
especially  certain  peculiarities  of  action  or  function,  which  mark  it 
off  from  the  unorganized  material  of  the  dead  world  around  it. 

Chemical  Composition  of  Living  Matter. — ^Although  we  cannot 
analyze  the  living  substance  as  such,  we  can  to  a  certain,  but 
limited,  extent  reconstruct  it,  so  to  speak,  from  its  ruins.  When 
subjected  to  anal)i:ical  processes,  which  necessarily  kill  it,  living 
matter  in\'ariably  yields  bodies  of  the  class  of  proteins,  exceeding^ 
complex  substances,  which  have  approximately  the  following  com- 
position: Carbon,  51-5  to  54-5  per  cent.;  oxygen,  20-9  to  23-5  per 
cent.;  nitrogen,  15-2  to  17  per  cent.;  hydrogen,  6-9  to  7-3  per  cent., 
with  small  quantities  of  sulphur.  Nucleo-proteins ,  which  are  com- 
pounds of  ordinar}^  proteins  with  nucleic  acids,  a  series  of  sulphur- 
free  organic  acids  rich  in  phosphorus,  are  constantly  met  with. 
Certain  carbo-hydrates,  composed  of  carbon,  hydrogen,  and  oxygen 
(the  last  two  in  the  proportions  necessary  to  form  water),  of  which 
glycogen  (CgHioOjln  may  be  taken  as  a  type,  appear  to  be  always 
present.  Fats,  which  consist  of  carbon,  hydrogen,  and  oxygen,  and 
of  which  tristeaiin,  a  compound  of  stearic  acid  with  glycerin,  of 
the  formula  C3H5,3(Ci8H3502),  may  be  given  as  an  example,  are 
often,  and  certain  lipoids,  e.g.,  lecithin  (p.  4),  are  always,  found. 
Finally,  water  and  certain  inorganic  salts,  such  as  the  chlorides  and 
phosphates  of  sodium,  potassium,  and  calcium,  are  constantly  present. 

The  Proteins. — The  constitution  of  the  protein  molecule  is  still  un- 
known ;  but  when  proteins  are  broken  down  by  the  action  of  ferments, 
such  as  exist  in  gastric  and  in  pancreatic  juice,  or  by  chemical  methods 
— for  example,  by  boiling  with  dilute  acids — the  most  important  of 
the  cleavage  products  are  various  amino-acids  (p.  360).  It  has  there- 
fore been  suggested  that  proteins  arc  built  up  by  the  linking  together  of 
amino-acids,  the  different  proteins  ditfering  quantitatively  or  quali- 
tatively as  regards  the  amino-acids  present  (E.  Fischer).  Thus  serum- 
albumin  and  egg-albumin  yield  no  glycin  or  glycocoll  (amino-acetic 
acid,  CH2.NH2.COOH),  while  glycin  is  constantly  found  among  the 
cleavage    products    of    serum-globulin.     And    while    leucin    («-amino- 

I 


2  INTRODUCTION 

isobutylacL-tic  acid)  is  present  to  the  extent  of  about  205  per  cent,  in 
the  cleavage  products  of  (horse's)  serum-albumin,  (hen's)  egg-albumin 
yields  only  j' i  per  cent. 

On  the  other  hand,  egg-albumin  yields  8'i  per  cent,  of  alanin  (amino- 
propionic  acid,  C2H4.NH2.COOH),  while  serum-albumin  yields  only 
2'  7  per  cent.  Of  the  aromatic  amino-acids — that  is,  amino-acids  united 
to  the  benzene  ring — phenyl-alanin  (amino-propionic  acid  in  which  one 
atom  of  H  is  replaced  by  phenyl,  CeHg)  is  obtained  to  the  extent  of 
44  per  cent,  from  egg-albumin,  and  a  little  over  3  per  cent,  from  .serum- 
albumin.  Tj'rosin  or  oxyphenyl-alanin  (amino-propionic  acid  in  which 
a  H  atom  is  replaced  by  oxyplienyl,  QH4.OH)  appears  to  the  amount 
of  I' 5  per  cent,  among  the  cleavage  products  of  egg-albumin,  and  to 
the  amount  of  2"i  per  cent,  among  tho.se  of  serum-albumin.  It  is  an 
interesting  point  in  this  connection  that  gelatin,  which  jdelds  165  per 
cent,  of  glycin,  yields  no  tyrosin  at  all;  tryptophane,  an  aromatic 
amino-acid  still  more  complex  than  tj-rosin,  is  also  absent.  These  facts 
afford  an  explanation  of  certain  colour  reactions  of  proteins  long  known 
empirically,  but  only  recently  understood  (p.  8).  The  process  by  which 
the  protein  molecule  is  thus  decomposed  is  called  hydrolysis — that  is, 
the  molecule  takes  up  water,  and  then  splits  into  smaller  molecules. 
The  hydrolysis  occurs  in  various  stages,  bodies  like  acid-  or  alkali- 
albumin  (meta-  or  infra-proteins)  being  first  formed,  then  proteoses, 
then  peptones.  The  peptones  are  further  split  into  bodies  containing 
a  relatively  small  number  of  amino-acids  linked  together.  These  bodies 
are  called  polypeptides,  which  finally  are  decomposed  so  as  to  yield  the 
individual  amino-acids,  also  called  in  this  connection  the  peptides  or 
monopeptides,  the  "  building-stones  "  out  of  which  the  protein  molecule 
is  constructed.  The  inverse  process  can  al.so  be  carried  on  to  a  certain 
extent,  and  Fischer  has  taken  an  important  step  towards  the  eventual 
synthesis  of  proteins  by  showing  how  polypeptides  of  increasing  com- 
plexity can  be  built  up  by  linking  amino-acids  together.  When  two 
amino-acids  are  so  united,  the  resulting  compound  is  called  a  dipeptide ; 
with  three  amino-acids  we  get  tripeptidcs,  etc.  Still  more  complicated 
polypeptides  may  thus  be  formed  in  the  laborator\',  which  give  some  of 
the  characteristic  reactions  of  peptones. 

The  numerous  substances  included  in  the  group  of  proteins  may  be 
classified  as  follows,  beginning  with  the  simplest: 

1.  Protamins,  such  as  the  bodies  called  salmin  and  sturin  present  in 
fish-sperm. 

2.  Histones,  bodies  separated  from  blood-corpuscles.  Globin,  the 
protein  constituent  of  haemoglobin,  is  one  of  them.  Unlike  the  other 
groups  of  proteins,  they  arc  precipitated  by  ammonia. 

3.  Albumins. 

4.  Globulins. 

5.  Sclcro-proteins  or  albuminoids,  such  as  gelatin  and  keratin. 

6.  Phospho-protcins,  including  such  substances  as  vitellin,  a  body 
obtainable  from  egg-yolk,  and  caseinogen,  the  chief  protein  of  milk. 
They  are  rich  in  phosphorus,  but  are  to  be  distinguished  from  nucleo- 
proteins,  which  also  contain  a  relatively  large  amount  of  phosphorus, 
by  the  fact  that  they  do  not  yield  tho  purin  bases,  the  characteristic 
products  of  the  decomposition  of  nucleo-proteins. 

7.  Conjugated  proteins,  substances  in  which  the  protein  molecule  is 
united  to  another  constituent,  usually  spoken  of  as  a  '  prosthetic  '  group. 
Thus  the  nucleo-proteins  consist  of  protein  united  with  nucleic  acid, 
the  chromo-proteins  {e.g.,  hremoglobin)  of  protein  united  with  a  pig- 
ment, and  the  gluco-protcins  {e.g  ,  mucin)  of  protein  united  with  a 
carbo-hydrate  group. 


CHEMICAL  COMPOSITION  OF  LIVING  MATTER  3 

Among  the  derivatives  of  proteins,  the  most  important  are  those 
already  mentioned  as  being  produced  in  protein-hydrolysis,  viz.: 

(a)  Meta-protcins. 

(6)  Proteoses,  including  albumose,  the  proteose  derived  from  albu- 
min; globulose,  that  derived  from  globulin;  gclatose,  thiit  derived  from 
gelatin,  etc.  The  proteoses  may  be  further  subdivided,  according  to 
the  order  in  which  they  are  formed  in  digestion  into  proto-proteoses, 
hetero-protcoses,  and  deutero-proteoses. 

(c)  Peptones. 

(d)  Polypeptides.  The  majority  of  these  are  artificial  products, 
formed  by  the  synthesis  of  amino-acids,  although  some  can  be  obtained 
from  proteins  by  hydrolysis.  Only  a  few  of  those  hitherto  prepared 
give  the  biuret  test. 

However  formidable  the  above  list  may  appear  to  the  student,  it 
gives  an  inadequate  idea  of  the  extreme  complexity  of  the  protein  class 
and  its  richness  in  individuals.  For,  apart  from  the  fact  that  the  list 
has  been  purposely  left  incomplete,  especially  as  regards  the  numerous 
vegetable  proteins,  there  is  the  best  evidence  that  proteins  of  the  same 
name  from  different  animal  species  have  certain  properties  which  dis- 
tinguish them  from  each  other.  The  serum-albumins  can  be  crystal- 
lized much  more  easily  in  some  animals  than  in  others.  The  same  is 
conspicuously  true  of  the  haemoglobins,  which  differ  also  in  certain 
animals  in  the  relative  proportion  of  sulphur  and  iron  in  the  molecule, 
as  well  as  in  the  crystalline  form.  Even  when  no  chemical  or  physical 
differences  have  as  yet  been  made  out,  proteins  of  the  same  name  from 
the  blood  or  organs  of  different  species  show  notable  '  specific  '  differ- 
ences when  subjected  to  certain  biological  tests  (see,  e.g.,  the  paragraph 
on  Precipitins,  p.  31 ;  and  that  on  Anaphylaxis,  p.  32). 

Carbo-Hydrates. — The  most  important  carbo-hydrates  in  their  physio- 
logical relations  are   dextrose,    levulose,    galactose,   lactose,    maltose, 
sucrose  (cane-sugar),  starch,  and  glycogen.     As  regards  their  chemical 
constitution,  the  simplest  carbo-hydrates  are  aldehydes  or  ketones — 
that  is,  the  first  oxidation  products  of  primary  and  secondary  alcohols 
respectively.     Thus  dextrose  is  the  aldehyde  of  sorbite,  a  hexatomic 
alcohol  (an  alcohol  containing  six  OH  groups),  while  levulose  is  the 
ketone  of  the  isomeric  alcohol  called  mannite,  and  galactose  the  alde- 
hyde of  the  isomeric  alcohol  called  dulcite.     The  sugars  containing  six 
carbon  atoms  are  termed  hexoses.     They  include  dextrose,  levulose, 
and  galactose.     The  empirical  formula  of  these  three  simple  sugars  (or 
monosaccharides)  is  the  same   (CgHj^Og),  but,  owing  to  the  different 
arrangement  of  the  atoms  or  groups  of  atoms,  they  have  each  their 
characteristic  properties  by  which  they  can  be  easily  distinguished. 
For  example,  dextrose  rotates  the  plane  of  polarization  to  the  right, 
levulose  to  the  left.     By  the  union  or  '  condensation  '  of  two  molecules 
of  a  monosaccharide,  with  loss  of  a  molecule  of  water,  a  disaccharide  is 
formed.     Cane-sugar,  maltose,  and  lactose,  all  with  the  same  empirical 
formula,  (CJ2H22O11),  are  disaccharides.     Cane-sugar  yields  on  hydro- 
lysis a  mixture  of  equal  parts  of  dextrose  and  levulose;  lactose,  a  mix- 
ture of  dextrose  and  galactose ;  while  maltose  is  converted  into  dextrose. 
By  the  condensation  of  more  than  two  molecules  of  monosaccharide 
polysaccharides  are  formed,  such  as  starch,  dextrin,  and  glycogen.     The 
exact   molecular  weights   of  these    substances   are    unknown.     Their 
general  formula  can  be  written   (CgHjoOs)*,   where  n  represents  the 
number  of  monosaccharide   molecules  condensed   to  form  the   poly- 
saccharide, in  the  case  of  starch  probably  some  hundreds. 

Fats  and  Lipoids. — The  fats  are  compounds  of  higher  fatty  acids 
with  glycerin  (glycerin  esters).     The  ordinary  body-fat  consists  of  a 


4  INTRODUCTION 

mixture  of  three  neutral  fats  (palmitin,  stearin,  and  olein)  which  differ 
both  chemically  and  physically  from  each  other — e.g..  in  melting-point 
and  in  the  so-called  iodine  value,  the  number  which  represents  the 
amount  of  iodine  taken  up  from  a  standard  solution.  Olein  melts  at 
-5°  C,  palmitin  at  45°  C,  and  stearin  at  a  still  higher  temperature. 
It  is,  therefore,  the  presence  of  olein  which  keeps  the  body-fat  liquid 
at  the  temperature  of  the  body.  The  fats  are  soluble  in  ether,  in  hot 
alcohol,  and  in  many  other  liquids,  but  insoluble  in  water.  Besides 
the  ordinary  fats,  the  tissues  and  liquids  of  the  bod}-  contain  phospha- 
tides, a  group  of  compounds  wliich  stand  in  close  relation  to  the  fats, 
but  differ  in  containing  phosphoric  acid  and  nitrogenous  bases.  The 
most  important  representative  of  this  group  is  lecithin  (C42Hg4NP09), 
a  fat-like  compound  which  yields  on  decomposition,  in  addition  to 
gljxerin  and  a  fatty  acid,  phosphoric  acid  and  a  nitrogen-containing 
substance  called  cholin  (p.  366).  Lecithin,  though  foimd  in  all  cells,  is 
especially  abundant  in  nervous  tissues.  It  is  associated  with  choles- 
terin  and  with  other  substances  which,  like  lecithin  and  cholesterin, 
are  soluble  in  ether  and  similar  solvents  of  fat.  For  this  reason  these 
substances  are  often  grouped  together  as  lipoids,  although  some  of 
them  are  chemically  different  from  fat.  Cholesterin,  for  instance,  is  an 
alcohol.  Although  usually  present  only  in  small  amount,  the  lipoids 
play  a  very  important  part  in  the  structure  and  in  the  economy  of  the 
cell. 

Structure  of  Living  Matter — The  Cell.* — Bioplasm  is  the  name 
given  to  the  living  matter  of  cells.  The  portion  of  the  bioplasm 
differentiated  as  the  nucleus  is  distinguished  by  the  term  karyo- 
plasm,  and  the  portion  outside  the  nucleus  bv  the  term  protoplasm 
or  cytoplasm.  Protoplasm,  when  examined  in  its  most  primitive 
undifferentiated  condition  in  such  cells  as  the  amoeba  or  the  white 
blood-corpuscles,  appears  on  tirst  view  a  homogeneous,  structureless 
mass,  except  for  certain  granules  embedded  in  it,  and  consisting 
either  of  products  formed  by  its  activity  or  of  food  materials.  But 
even  here  more  careful  study  reveals  a  certain  complexity  of  struc- 
ture. At  the  very  least,  an  external  layer,  or  ectoplasm,  can  be  dis- 
tinguished from  the  interior  mass,  or  endoplasm.  There  is  reason 
to  believe  that  even  where  no  histological  demonstration  of  an 
ectoplasmic  layer  or  a  definite  envelope  is  possible,  the  surface  of 
the  cell  is  physiologically  different  from  its  interior.  In  many  cells 
the  protoplasm  presents  the  appearance  of  a  honeycomb  or  net- 
work, with  granules  usually  situated  at  the  nodes,  and  holding  in 
its  vesicles  or  meshes  a  fluid,  perhaps  containing  pabulum,  from 
which  the  waste  of  the  living  framework  is  made  good,  or  material 
upon  which  it  works,  and  which  it  is  its  business  to  transform. 
Some  observers,  however,  maintain  that  the  network  is  an  artificial 
appearance  produced  by  the  precipitation  of  the  colloid  constituents 
of  the  protoplasm  by  the  fixing  reagent,  or  even  by  the  coagulative 
processes  associated  with  the  act  of  dying,  and  that  the  unaltered 
living  substance  is  a  homogeneous  fluid  or  jelly.     It  is  known  that 

*  Space  permits  only  the  slightest  sketch  of  this  subject  here.  For  de- 
tailed information  the  student  is  referred  to  textbooks  of  histology. 


STRUCTURE  OF  LIVING   MATTER  5 

changes  of  reaction  occur  when  the  living  substance  dies,  and  slight 
chanpes  of  reaction,  i.e.,  changes  in  the  relative  concentration  of 
hydrogen  ions  (H  +  )  and  hydroxyl  ions  (0H-),  can  bring  about 
similar  precipitates  in  colloid  solutions.  Nevertheless  in  some  cells 
a  certain  differentiation  in  the  structure  of  the  protoplasm  can  be 
seen  during  life  and  before  the  addition  of  any  reagent,  and  in  such 
cases  there  can  be  no  doubt  that  the  structural  details  pre-exist 
and  arc  not  arte-facts.  In  certain  respects  protoplasm  behaves 
like  a  liquid,  and  in  others  like  a  solid,  a  peculiarity  which  is  un- 
doubtedly associated  with  the  fact  that  its  chief  constituents  exist 
in  the  colloid  state,  as  experiments  with  such  substances  as  gelatin 
and  agar  have  shown.  In  building  up  our  typical  cell  we  start  with 
a  piece  of  protoplasm.  Somewhere  in  the  midst  of  this  we  find  a 
body  which,  if  not  absolutely  different  in  kind  from  the  protoplasm 
of  the  rest  of  the  cell  or  cytoplasm,  is  yet  marked  off  from  it  by  very 
definite  morphological  and  chemical  characters. 

This  is  the  nucleus,  generally  of  round  or  oval  shape,  and  bounded 
by  an  envelope.  Within  the  envelope  lies  a  second  network  of 
fine  threads,  which  do  not  themselves  stain  with  nuclear  dyes  such 
as  hematoxylin.  But  in  or  on  these  '  achromatic  '  filaments  lie 
small,  highly  refractive  particles,  staining  readily  and  deeply  with 
dyes,  and  therefore  described  as  consisting  of  chromatin.  This  chro- 
matin is  either  made  up  of  nucleins  (conjugated  proteins  particu- 
larly rich  in  nucleic  acid,  and  therefore  in  phosphorus),  or  yields 
nucleins  by  its  decomposition;  and  it  seems  to  owe  its  affinity  for 
certain  staining  substances  to  the  presence  of  nucleic  acid.  The 
meshes  of  the  nuclear  reticulum  contain  a  semi-fluid  material, 
which  does  not  readily  stain.  The  nucleus  is  distinguished  from 
the  cytoplasm,  even  as  regards  its  inorganic  constituents,  by  the 
absence  of  potassium.*  Besides  the  nucleus,  another  much  smaller 
structure,  the  centrosome,  is  differentiated  from  the  protoplasm 
of  many  cells.  This  is  a  minute  dot  staining  deeply  with  such  dyes 
as  hematoxylin,  and  generally  situated  near  the  nucleus.  Sur- 
rounding it  is  a  clear  area,  the  attraction  sphere,  in  and  beyond 
which  fine  fibrils  radiate  out  into  the  cytoplasm.  Both  the  attrac  • 
tion  sphere  and  the  nucleus  play  an  important  part  in  division  of 
the  cell  by  the  process  known  as  karyokinesis,  or  mitosis,  or  in- 
direct division,  which  is  by  far  the  most  common  mode. 

When  the  nucleus  is  about  to  divide,  the  chromatin  granules 
arrange  themselves  into  one  or  more  coiled  filaments  or  skeins, 
which  then  break  up  into  a  number  of  separate  portions  called 

*  This  has  been  shown  microchemically.  The  potassium  is  precipitated 
by  a  solution  of  hexanitrite  of  sodium  and  cobalt  as  orange-yellow  crystals  of 
the  triple  salt,  hexanitrite  of  potassium,  sodium,  and  cobalt.  Where  very 
minute  traces  of  potassium  are  present,  ammonium  sulphide  must  be  added, 
after  washing  out  the  excess  of  the  cobalt  reagent.  Black  cobalt  sulphide  is 
thus  formed  from  the  triple  salt  (Macallum,  Frontispiece). 


6  INTRODUCTION 

chromosomes.  These  undergo  a  remarkable  series  of  transforma- 
tions, leading  eventually  to  the  segregation  of  the  nuclear  chromatin 
in  two  separate  daughter  nuclei,  each  surrounded  by  a  portion  of 
the  original  cytoplasm.  Apart  from  its  role  in  the  division,  and 
therefore  in  the  multiplication,  of  the  cell,  the  nucleus  is  now  known 
to  exert  an  influence  perhaps  not  less  important  upon  those  chemical 
changes  in  the  cytoplasm  which  are  necessary  for  its  normal  nutri- 
tion and  function.*  It  is  doubtful  whether  any  portion  of  proto- 
plasm can  permanently  survive  the  loss  of  its  nuclear  material.  It 
must  be  remembered,  however,  that  nuclear  material  may  some- 
times be  present  in  diffuse  form  in  cells  which  do  not  show  a  nucleus 
in  the  histological  sense. 

When  we  carry  back  the  analysis  of  an  organized  body  as  far  as 
we  can,  we  find  that  every  organ  of  it  is  made  up  of  cells,  which 
upon  the  whole  conform  to  the  type  we  have  been  describing, 
although  there  are  many  differences  in  details.  Some  organisms 
there  are,  low  down  in  the  scale,  w^ose  whole  activity  is  confined 
within  the  narrow  limits  of  a  single  cell.  The  amceba  sets  up  in  life 
as  a  cell  split  off  from  its  parent.  It  divides  in  its  turn,  and  each 
half  is  a  complete  amoeba.  When  we  come  a  little  higher  than  the 
amoeba,  we  find  organisms  which  consist  of  several  cells,  and 
'  specialization  of  function  '  begins  to  appear.  Thus  the  hydra,  the 
'  common  fresh-water  polyp '  of  our  ponds  and  marshes,  has  an  outer 
set  of  cells,  the  ectoderm,  and  an  inner  set,  the  endoderm.  Through 
the  superficial  portions  of  the  former  it  learns  what  is  going  on  in 
the- world;  by  the  contraction  of  their  deeply  placed  processes  it 
shapes  its  life  to  its  environment.  As  we  mount  in  the  animal 
scale,  specialization  of  structure  and  of  function  are  found  con- 
tinually advancing,  and  the  various  kinds  of  cells  are  grouped 
together  into  colonies  or  organs.  In  some  organs  and  tissues  the 
bond  of  union  is  simple  juxtaposition  and  similarity  of  function  of 
the  constituent  cells.  But  in  others  the  union  is  protoplasmic,  pro- 
cesses of  the  cytoplasm  actually  passing  from  cell  to  cell.  This  is 
seen  in  certain  epithelial  tissues,  and  conspicuously  in  the  cardiac 
muscle. 

The  Functions  of  Living  Matter. — The  pecnUnv  functions  of  living 
matter  as  exhibited  in  the  animal  body  will  form  the  subject  of  the 
main  portion  of  this  book ;  and  we  need  only  say  here:  (i)  That  in  all 
living  organisms  certain  chemical  changes  go  on,  the  sum  total  of 
which  constitutes  the  metabolism  of  the  body.  These  may  be 
divided  into  {a)  integrative  or  anabolic  changes,  by  which  complex 
substances  (including  the  living  matter  itself)  are  built  up  from 

♦  According  to  Hertwig,  a  precursor  of  chromatin,  '  prochromatin,'  a  sub- 
stance without  characteristic  staining  reaction,  is  formed  in  the  cytoplasm, 
taken  up  by  the  nucleus,  and  there  elaborated  into  chromatin.  From  the 
nucleus  chromatin  and  its  derivatives  return  to  the  cytoplasm  to  be  used  in 
its  function. 


FUNCTIONS  Of  LIVING   MATTER  7 

simpler  materials;  and  (b)  disintegrative  or  kataholic  changes,  in 
which  complex  bodies  (including  the  living  substance)  are  broken 
down  into  comparatively  simple  products.  In  plants,  upon  the 
whole,  it  is  integration  which  predominates;  from  substances  so 
simple  as  the  carbon  dioxide  of  the  air  and  the  nitrates  of  the  soil 
the  plant  builds  up  its  carbo-hydrates  and  its  proteins.  In  animals 
the  main  drift  of  the  metabolic  current  is  from  the  complex  to  the 
simple;  no  animal  can  construct  its  own  protoplasm  from  the 
inorganic  materials  that  lie  around  it;  it  must  have  ready-made 
f >rotcin  in  its  food.  But  in  all  plants  there  is  some  disintegration ; 
in  all  animals  there  is  some  synthesis.  The  progress  of  biochemistry 
in  recent  years  has  indeed  shown  that  the  synthetic  powers  of 
animal  cells  have  been  greatly  underestimated.  (2)  The  living  sub- 
stance is  excitable — that  is,  it  responds  to  certain  external  im- 
pressions, or  stimuli,  by  actions  peculiar  to  each  kind  of  cell. 
(3)  The  living  substance  reproduces  itself.  All  the  manifold  activities 
included  under  these  three  heads  have  but  one  source,  the  trans- 
formation of  the  energy  of  the  food.  It  is  not,  however,  upon  the 
whole,  peculiarities  in  food,  but  in  molecular  structure,  that  underlie 
the  peculiarities  of  function  of  different  living  cells.  A  locomotive 
is  fed  with  coal;  a  steam-pump  is  fed  with  coal.  The  one  carries 
the  mail,  and  the  other  keeps  a  mine  from  being  flooded.  Wherein 
lies  the  difference  of  action  ?  Clearly  in  the  build,  the  structure  of 
the  mechanism,  which  determines  the  manner  in  which  energy  shall 
be  transformed  within  it,  not  in  any  difference  in  the  source  of  the 
energy.  So  one  animal  cell,  wh(  a  it  is  stimulated,  shortens  or  con- 
tracts; another,  fed  perhaps  with  the  same  food,  selects  certain 
constituents  from  the  blood  or  lymph,  and  passes  them  through  its 
substance,  changing  them,  it  may  be,  on  the  way;  and  a  third  sets 
up  impulses  which,  when  transmitted  to  the  other  two,  initiate  the 
contraction  or  secretion.  In  the  living  body  the  cell  is  the  machine; 
the  transformation  of  the  energy  of  the  food  is  the  process  which 
'  runs  '  it.  The  structure  and  arrangement  of  cells  and  the  steps 
by  which  energy  is  transformed  within  them  sum  up  the  whole  of 
biology. 

PRACTICAL  EXERCISES  ON  CHAPTER  I. 

Reactions  of  Proteins. 

I.  General  Reactions  of  Proteins. — Egg-alburain  may  be  taken  as  a 
type.  Prepare  a  sohition  of  it  by  adding  water  to  white  of  egg,  which 
consists  mainly  of  egg-albumin  with  a  little  globulin.  In  breaking  the 
egg,  take  care  that  none  of  the  yolk  gets  mixed  with  the  white.  Snip 
the  white  up  witli  scissors  in  a  large  capsule,  then  add  ten  or  fifteen 
times  its  volume  of  distilled  water.  The  solution  becomes  turbid  from 
the  precipitation  of  traces  of  globulin,  since  globulins  a,re  insoluble  in 
distilled  water.  Stir  thoroughly,  strain  through  several  layers  of  muslin, 
and  then  filter  through  paper. 


8  INTRODUCTION 

Colour  Reactions. 

(i)  Add  to  a  little  of  the  solution  in  a  test-tube  a  few  drops  of  strong 
nitric  acid.  A  precipitate  is  tlirown  down,  wliich  becomes  yellow  on 
boiling.  Cool,  and  add  strong  ammonia;  the  colour  changes  to  orange 
[xantho-proteic  reaction).  The  reaction  depends  upon  tlic  presence  of 
aromatic  groups  in  the  protein  (in  phenylalanin,  tyrosin,  tryptophane, 
oxj-tryptophane),  which  are  converted  into  nitro-compounds. 

(2)  To  a  third  portion  add  a  drop  or  two  of  very  dilute  cupric  sulphate 
and  excess  of  sodium  or  potassium  hydroxide;  a  violet  colour  appears 
{Piotrow ski's  test).  Peptones  and  proteoses  (albumoses)  give  a  pink 
[biuret  reaction).*     See  p.  458. 

(3)  To  another  portion  add  Millon's  reagent  ;t  a  white  precipitate 
comes  down,  which  is  turned  reddish  on  boiling.  If  only  traces  of 
protein  are  present,  no  precipitate  is  caused,  but  the  liquid  takes  on  a 
red  tinge.  The  reaction  is  due  to  tyrosin.  It  is  given  by  all  aromatic 
substances  which  contain  tiie  group  CgHg  with  at  least  one  H  replaced 
by  OH,  i.e.,  the  hydroxyphenyl  group  CaH40H. 

(4)  Adamkiewicz's  Reaction  {Hopkins's  modification). — To  a  small 
quantity  of  the  albumin  solution  add  the  same  bulk  of  dilute  glyoxylic 
acid. J  Mix,  and  to  the  mixture  add  an  equal  volume  of  strong  pure 
sulphuric  acid.  A  purple  colour  is  obtained.  The  substance  in  the 
protein  molecule  which  gives  tlie  reaction  is  tryptophane  (p.  360). 

(5)  The  Formaldehyde  Reaction. — Add  to  the  albumin  solution  a  few- 
drops  of  a  very  dilute  solution  of  formaldehyde  (i  :  2,500),  and  then 
allow  some  strong  (commercial)  sulphuric  acid  to  run  from  a  pipette 
into  the  bottom  of  the  test-tube.  A  purple  ring  appears  at  the  surface 
of  contact.  This  reaction  depends  on  the  presence  of  tryptophane  in 
the  protein. 

Precipitation  Reactions, 

(6)  Acidify  another  portion  strongly  with  acetic  acid,  and  add  a  few 
drops  of  a  solution  of  potassium  ferrocyanide.  A  white  precipitate  is 
obtained.     Peptones  do  not  give  this  reaction. 

(7)  Heat  a  portion  to  30°  C.  on  a  water-bath.  Saturate  with  crystals 
of  ammonium  sulphate;  the  albumin  is  precipitated.  Filter,  and  test 
the  filtrate  for  proteins  by  (2).  None,  or  only  slight  traces,  wUl  be 
found.  The  sodium  hydroxide  must  be  added  in  more  than  sufficient 
quantity  to  decompose  all  the  ammonium  sulphate.  It  will  be  best  to 
add  a  piece  of  the  solid  hydroxide.  Peptones  are  not  precipitated  by 
ammonium  sulphate,  but  all  other  proteins  are. 

(8)  Add  alcohol  to  a  small  quantity  of  the  solution.     The  protein  is 

•  The  reaction  is  also  given,  although  more  faintly,  with  the  hydroxides  of 
lithium,  strontium,  and  barium.  It  is  given  by  all  substances  containing  at 
lea^t  two  CONH2  groups  attached  to  one  another  (as  in  oxamide),  or  to  the 
nitrogen  atom  (as  in  biuret) ,  or  to  the  same  carbon  atom. 

f  Millon's  reagent  consists  of  a  mixture  of  the  nitrates  of  mercury  with 
nitric  acid  in  excess,  and  some  nitrous  acid.  To  make  it.  dissolve  mercury  in 
its  own  weight  of  strong  nitric  acid,  and  add  to  the  solution  thus  obtained 
twice  its  volume  of  water.  Let  it  stand  for  a  short  time,  and  then  decant  the 
clear  liquid,  which  is  the  reagent. 

X  A  solution  containing  glyoxylic  acid  in  the  requisite  strength  can  be 
prepared  by  treating  half  a  litre  of  a  saturated  solution  of  oxalic  acid  with 
40  grammes  of  2  per  cent,  sodium  amalgam  in  a  tall  cylinder.  When  all  the 
hydrogen  has  been  evolved,  the  solution  is  filtered,  and  diluted  with  twice  its 
volume  of  water.  Oxalic  acid  and  sodium  binoxalate  are  also  present  in  the 
solution. 


PRACTICAL  EXERCISES  g 

precipitated.     It  can  be  redissolvcd  at  first,  but  rapidly  becomes  in- 
soluble. 

.;.  Special  Reactions  of  Certain  Proteins — (i)  Heat-Coagulable  Pro- 
teins :  (u)  Albumins. — (a)  Heat  a  little  ot  the  solution  of  egg-albumin  in 
a  Ust-tubc;  it  coagulates.  With  another  sample  determine  the  tem- 
perature of  coagulation,  first  very  slightly  acidulating  with  a  2  per  cent, 
solution  of  acetic  acid. 

To  determine  the  Temperature  of  Coagulation. — Support  a  beaker  by 
a  ring  which  just  grips  it  at  the  rim.  Nearly  fill  the  beaker  with  water, 
and  slide  the  ring  on  the  stand  till  the  lower  part  of  the  beaker  is  im- 
mersed in  a  small  water-bath  (a  tin  can  will  do  quite  well).  In  this 
beaker  place  a  test-tube,  and  in  the  test-tube  a  thermometer,  both  sup- 
ported by  rings  or  clamps  attached  to  the  same  stand.  Put  into  the 
test-tube  at  least  enough  of  the  albumin  solution  to  completely  cover 
the  bulb  of  the  thermometer,  and  heat  the  bath,  stirring  the  water  in 
the  beaker  occasionally  with  a  feather  or  a  splinter  of  wood,  or  a  glass 
rod,  the  end  of  which  is  guarded  with  a  piece  of  indiarubber  tubing. 
Note  the  temperature  at  which  the  solution  becomes  turbid,  and  then 
the  temperature  at  which  a  distinct  coagulum  or  precipitate  is  formed. 
Repeat  with  the  unacidulated  albumin  solution. 

(/3)  A  similar  experiment  may  be  performed  with  serum-albumin 
obtained  as  on  p.  65. 

{b)  Globulins. — Use  serum-globulin  (p.  65),  or  myosinogen  (p.  819). 
Fibrinogen  is  also  a  globulin,  but  cannot  easily  be  obtained  in  quantity. 
Verify  the  following  properties  of  globulins: 
(a)  They  coagulate  on  heating. 
0)  They  are  insoluble  in  distilled  water  (p.  65). 
(7)  They  are  precipitated  by  saturation  with  magnesium  sulphate  or 
sodium  chloride  (p.  65). 

They  give  the  general  protein  tests  (i)  to  (8). 

Both  the  heat-coagulated  proteins  and  such  protein-s  as  the  solid 
fibrin  which  is  formed  from  fibrinogen  in  the  clotting  of  blood  give  such 
of  the  general  protein  tests,  (i),  (2),  (3)  (p.  8),  as  with  suitable  modifica- 
tions can  be  instituted  on  solid  substances.  Thus,  in  performing  (2),  a 
flake  of  fibrin  or  a  small  piece  of  the  boiled  egg-white  should  be  soaked 
for  a  few  minutes  in  a  dilute  solution  of  cupric  sulphate.  Then  the 
excess  of  the  cupric  sulphate  should  be  poured  off,  and  sodium  hydroxide 
added,  when  the  coagulated  protein  will  become  violet.  Heat-coagu- 
lated proteins  are  insoluble  in  water,  weak  acids  and  alkalies,  and  salxne 
solutions ;  fibrin  is  slightly  soluble  in  the  latter. 

(2)  Gelatin. — Add  some  pieces  of  gelatin  to  cold  water  in  a  test-tube. 
It  does  not  dissolve.  Immerse  the  tube  in  a  boiling  water-bath  till  the 
gelatin  goes  into  solution.  Then  cool  the  test-tube  under  the  tap;  the 
solution  sets  into  a  jelly.     On  heating  it  redissolves. 

Try  the  general  protein  reactions  (p.  8)  on  a  dilute  solution.  In 
Piotrowski's  test  a  violet  colour  is  obtained.  The  tests  which  depend 
on  the  presence  of  tyrosin  or  tryptophane  are  not  given  by  a  solution 
of  pure  gelatin,  since  these  amino-acids  are  absent  from  the  gelatin 
molecule.  Commercial  gelatin  may  give  a  slight  reaction  due  to 
traces  of  other  proteins. 

3.  Reactions  of  Certain  Derivatives  of  Native  Proteins — (i)  Meta- 
Proteins :  {a)  Acid- Albumin.— 'Yo  a  solution  of  egg-albumin  add  a  little 
04  per  cent,  hydrochloric  acid,  and  heat  to  about  body  temperature — 
say  40°  C. — for  a  few  minutes.  Acid-albumin  is  formed.  It  can  be 
produced  from  all  albumins  and  globulins  by  the  action  of  dilute  acid. 
Make  the  following  tests : 

(a)  Add  to  a  portion  of  the  solution  in  a  test-tube  a  few  drops  of  a 


lo  INTRODUCTION 

solution  of  litmus;  the  colour  becomes  red.  Now  add  drop  by  drop 
sodium  carbonate  or  dilute  sodium  hydroxide  solution  till  the  tint  just 
begins  to  change  to  blue.  A  precipitate  of  acid-albumin  is  thrown 
down .  Add  a  little  more  of  the  alkali,  and  the  precipitate  is  redissolved. 
It  can  be  again  brought  down  by  neutralizing  with  acid. 

(fi)  Heat  a  portion  of  the  solution  to  boiling;  no  precipitate  is  formed. 
(y)  Add  strong  nitric  acid;  a  precipitate  appears,  which  dissolves  on 
heating,  and  the  liquid  becomes  yellow. 

(6)  Alkali-albumin. — To  a  solution  of  egg-albumin  add  a  little  sodium 
hydroxide,  and  heat  gently  for  a  few  minutes.  Alkali-albumin  is 
produced.  It  can  be  derived  by  similar  treatment  from  any  albumin 
or  globulin. 

(a)  Neutralize,  after  colouring  with  litmus  solution,  by  the  addition 
of  dilute  hydrochloric  or  acetic  acid.  Alkali-albumin  is  precipitated 
when  neutralization  has  been  reached.  It  is  redissolved  in  excess  of 
the  acid. 

(3)  To  another  portion  of  the  solution  of  alkali-albumin  add  a  few 
drops  of  sodium  phosphate  solution,  then  litmus,  and  then  dilute  acid 
till  the  alkali-albumin  is  precipitated.  More  of  the,  dilute  acid  should 
now  be  required  to  precipitate  the  alkali-albumin,  since  the  sodium 
phosphate  must  first  be  changed  into  acid  sodium  phosphate. 

(y)  On  heating  the  solution  of  alkali-albumin  there  is  no  coagulation. 
(2)  Proteoses. — For  preparation  and  reactions,  see  p.  458.  They 
differ  from  albumins  and  globulins  in  not  being  coagulated  by  heat,  and 
from  meta-proteins  in  not  being  precipitated  by  neutralization.  They 
are  soluble  (with  the  exception  of  hetero-albumose)  in  distilled  water, 
and  are  not  precipitated  by  saturation  of  their  solutions  with  mag- 
nesium sulphate  or  sodium  chloride.  Saturation  with  ammonium  sul- 
phate precipitates  them.  With  a  solution  of  '  commercial  peptone,' 
which  consists  chiefly  of  albumoses,  and  contains  only  a  little  true 
peptone,  perform  the  following  tests: 

(a)  Boil  the  slightly  acidulated  solution;  there  is  no  coagulation. 
()9)  Biuret  reaction,  p.  8. 

(y)  To  a  portion  oif  the  solution  add  its  own  volume  of  saturated 
ammonium  sulphate  solution.  The  primary  albumoses  (proto-  and 
hetero-albumose)  are  precipitated.  Filter.  Add  a  drop  of  sulphuric 
acid  to  the  filtrate  and  saturate  it  with  ammonium  sulphate  crystals. 
The  secondary'  or  deutero-albumoses  are  precipitated.  Filter.  The 
filtrate  still  contains  peptones.     Use  it  for  (3). 

(3)  Peptones. — For  preparation  and  tests,  see  p.  459.  They  differ 
from  heat-coagulable  proteins  and  meta-proteins  in  the  same  way  as 
proteoses,  and  they  differ  from  proteoses  in  not  being  precipitated  by 
ammonium  sulphate.  On  the  filtrate  from  (2)  perform  the  biuret  test, 
as  described  in  (7),  p.  8;  and  note  that  the  pink  colour  is  the  same  as 
that  given  by  proteoses. 

Carbo-Hydrates. 

1.  Glucose  or  Dextrose. — Make  a  solution  of  dextrose  in  water,  and 
applv  to  it  Trommer  's  test  for  reducing  sugar.  Put  some  of  the  dextrose 
solution  in  a  test-tube,  tlicn  a  few  drops  of  cupric  sulphate,  and  then 
excess  of  sodium  or  potassium  hydroxide.  The  blue  precipitate  of 
cupric  hydroxide  which  is  first  thrown  down  is  immediately  dissolved 
in  the  presence  of  dextrose  and  many  other  organic  substances.  Now 
boil  the  blue  liquid,  and  a  yellow  or  red  precipitate  (cuprous  hydroxide 
or  oxide)  is  formed. 


PRACTICAL  EXERCISES  ii 

2.  Cane-Sugar. — Perform  Truium'^r's  test  witli  a  .sample  of  a  solution. 
A  blue  liquid  is  obtained,  which  is  not  changed  on  boiling.  Now  put 
the  rest  of  the  .solution  in  a  flask.  Add  s'^th  of  its  bulk  of  strong  hydro- 
chloric acid,  and  boil  for  a  quarter  of  an  hour.  Again  perform  Trom- 
mer's  test.  Remember  that  excess  of  alkali  must  be  present  after  the 
acid  is  neutralized.  The  test  now  shows  much  reducing  sugar.  The 
cane-sugar  has  been  '  inverted  ' — i.e.,  changed  into  a  mixture  of 
dextrose  and  levulose. 

3.  Starch. — (i)  Cut  a  slice  from  a  well-washed  potato  ;  take  a  scraping 
from  it  with  a  knife,  and  examine  with  the  microscope.  Note  the  starcii 
granules  with  their  concentric  markings,  using  a  small  diaphragm. 
Run  a  drop  of  dilute  iodine  solution  under  the  cover-slip,  and  observe 
that  the  granules  become  bluish.  Examine  also  with  a  polarization 
microscope.  (2)  Rub  up  a  little  starch  in  a  mortar  with  cold  water, 
then  add  boiling  water  and  stir  thoroughly.  Decant  into  a  capsule  or 
beaker,  and  boil  for  a  few  minutes.  After  the  liquid  has  cooled,  perform 
the  following  experiments: 

(a)  Add  a  few  drops  of  iodine  solution  to  a  little  of  the  thin  starch 
mucilage  in  a  test-tube.  A  blue  colour  is  produced,  which  disappears 
on  heating,  returns  on  cooling,  is  bleached  by  the  addition  of  a  little 
sodium  hydroxide,  and  restored  by  dilute  acid. 

(6)  Test  the  starch  solution  for  reducing  sugar  by  Trammer's  test. 
If  none  is  found,  boil  some  of  the  mucilage  with  a  little  dilute  sulphuric 
acid  in  a  flask  for  twenty  minutes,  and  again  perform  Trommer's  test. 
Abundance  of  reducing  sugar  will  now  be  present. 

4.  Dextrin. — Dissolve  some  dextrin  in  boiling  water.  Cool.  Add 
iodine  solution  to  a  portion;  a  reddish-brown  (port-wine)  colour  results, 
which  disappears  on  heating.  As  a  control,  the  same  amount  of  iodine 
should  be  added  to  an  equal  quantity  of  water  in  another  test-tube. 
The  colour  returns  on  cooling.  The  colour  is  also  bleached  by  alkali, 
restored  by  acid.  Excess  of  iodine  should  be  added  for  the  bleaching 
experiment  {i.e.,  more  than  enough  to  give  the  maximum  depth  of  tint). 
If  too  little  iodine  has  been  added,  there  may  be  no  restoration  of  the 
colour  by  the  acid.  The  addition  of  a  little  more  iodine  to  the  acid 
solution  will  then  cause  the  port- wine  colour  to  return,  and  this  may 
be  again  bleached  by  alkali,  and  will  now  be  restored  by  acid. 

5.  Glycogen. — See  p.  715. 

6.  Molisch  's  Test  for  Carbo-Hydrates. — This  is  a  general  test  for  carbo- 
hydrates. It  is  also  given  by  proteins  which  contain  a  carbo-hydrate 
group.  Put  a  drop  of  dextrose  solution  in  a  test-tube.  Add  a  drop 
of  a  10  per  cent,  solution  of  a-naphthol  in  methyl  alcohol,  and  then 
o'5  c.c.  of  water.  Then  cautiously  allow  i  c.c.  of  pure  concentrated 
sulphuric  acid  to  run  under  the  mixture,  and  shake  gently.  A  violet  or 
reddish  colour  appears. 

Fats. 

1.  Take  a  little  lard  or  olive-oil,  and  observe  that  fat  is  soluble  in 
ether  or  warm  alcohol,  but  not  in  water.  Put  a  drop  of  the  ethereal 
solution  of  fat  on  a  piece  of  paper,  and  note  that  it  leaves  a  greasy  stain. 

2.  Put  a  little  alcohol  in  a  test-tube,  and  then  a  drop  of  phenol- 
phthalein  solution  and  a  drop  or  two  of  dilute  sodium  hydroxide  to  give 
the  solution  a  red  colour.  Add  a  few  drops  of  an  ethereal  solution  of 
the  lard  or  olive-oil.  If  the  red  colour  persists,  the  fat  is  neutral;  if  it 
disappears,  the  fat  contains  free  fatty  acids. 

3.  Saponification. — Melt  some  lard  in  a  porcelain  dish,  and  pour  it 


12  INTRODUCTION 

into  an  alcoholic  solution  of  potassium  hydroxide  previously  heated  on 
a  water-bath  nearly  to  boiling.  Mix  well,  and  keep  the  mixture  gently 
boiling  on  the  bath  till  saponification  is  complete.  This  only  takes  a 
short  time.  Remove  a  little  of  the  soap  solution,  and  drop  it  into  dis- 
tilled water  in  a  test-tube.  If  unsaponificd  fat  is  present,  it  will  rise  to 
the  top  as  drops  of  oil.  In  this  case  boiling  should  be  continued.  If 
all  the  fat  has  been  saponified,  the  soap  solution  will  mix  with  the 
water  and  no  oil-drops  will  separate. 

4.  Fatty  Acids. — Heat  some  20  per  cent,  sulphuric  acid  in  a  small 
flask  nearly  to  boiling,  and  drop  into  it  some  of  the  soap  obtained  in  3. 
The  fatty  acids  separate  out  and  rise  to  the  top  as  an  oily  layer.  Cool, 
skim  off  the  fatty  acid,  and  wash  it  with  distilled  water  till  the  wash- 
water  is  no  longer  acid. 

(a)  Dissolve  a  little  of  the  washed  fatty  acid  in  ether.  Add  a  few 
drops  of  an  alkaline  solution  of  phenolphthalein  to  a  few  c.c.  of  water 
in  a  test-tube .  Drop  into  this  the  ethereal  solution  of  fatty  acid.  The 
red  colour  is  discharged. 

(b)  Put  a  small  portion  of  the  fatty  acid  on  a  glass  slide  resting  on  a 
piece  of  white  paper.  Place  on  it  a  drop  or  two  of  a  i  per  cent,  solution 
of  osmic  acid  (osmium  tetroxide).  The  osmic  acid  is  reduced  to  a  lower 
oxide  (which  is  black)  by  the  action  of  oleic  acid  present  in  the  fatty 
acid  raixture,  which  abstracts  some  of  the  oxygen.  Any  fat  which 
contains  olein  or  oleic  acid,  as  body-fat  does,  is  therefore  blackened  by 
osmic  acid. 

(c)  Add  to  a  portion  of  the  fatty  acid  some  sodium  hydroxide  solution, 
and  warm.  Sodium  soap  is  formed.  Add  warm  water  and  shake  up. 
A  lather  is  produced.  Keep  the  soap  solution  for  6.  Keep  a  little  of 
the  fatty  acid  for  5  (b)  and  6  (b). 

5.  Glycerin. — (a)  Add  to  a  little  glycerin  in  a  dry  test-tube  a  few 
crystals  of  potassium  bisulphate  (KHSO4),  and  heat  over  the  free  flame. 
Acrolein  is  given  off,  which  is  recognized  by  its  pungent  odour,  and  by 
blackening  a  piece  of  filter-paper  moistened  with  ammoniacal  silver 
nitrate  solution,  and  held  over  the  mouth  of  the  test-tube.  The  paper 
is  blackened  owing  to  the  reducing  action  of  the  vapour  on  the  silver 
nitrate. 

(6)  Repeat  this  test  with  lard,  and  with  a  portion  of  the  fatty  acid 
from  4.  Acrolein  will  be  given  off  by  the  lard  because  glycerin  is  con- 
tained in  neutral  fat,  but  not  by  the  fatty  acid  if  it  has  been  properly 
separated  from  the  glycerin. 

6.  Emulsification. — (a)  Take  three  test-tubes  and  label  them  A,  B, 
and  C.  Put  a  few  c.c.  of  water  in  A,  a  solution  of  soap  in  B,  and  a 
dilute  solution  of  sodium  carbonate  or  sodium  hydroxide  in  C.  To  each 
add  a  few  drops  of  fresh  olive-oil  and  shake .  An  emulsion  will  be  formed 
in  B,  but  not  in  A.  Probably  there  will  be  some  emulsification  in  C  also, 
owing  to  the  presence  in  the  oil  of  some  fatty  acid,  which  forms  soap 
with  the  alkali.  But  if  the  oil  is  free  from  fatty  acid,  no  emulsion  will 
be  formed. 

(6)  Repeat  (a)  with  rancid  olive-oil,  which  contains  much  fatty  acid, 
or  with  fresh  olive-oil  to  which  some  of  the  fatty  acid  obtained  in  4  has 
been  added.     A  good  emulsion  will  be  produced  in  C  as  well  as  in  B. 

7.  MeUing-Point  of  Fat. — Put  into  a  very  narrow  test-tube  or  a  short 
piece  of  narrow  glass  tubing  some  finely  divided  mutton  fat,  freed,  as 
far  as  possible,  from  connective  tissue.  Fasten  the  test-tube  on  to  the 
bulb  of  a  thermometer  with  a  rubber  band,  and  immerse  the  ther- 
mometer and  tube  in  a  beaker  filled  with  water  and  standing  on  a  water- 
bath,  which  is  gradually  heated.  Observe  the  temperature  at  which 
the  fat  melts.     Repeat  the  experiment  with  hog's  lard  and  dog's  fat. 


PRACTICAL  EXERCISES  13 

SCHEME  FOR  TESTING  A  SOLUTION  FOR  THE  MORE  COMMON 
PROTEINS  AND  PROTEIN-DERIVATIVES,  AND  FOR  CARBO- 
HYDRATES 

1.  Note  the  reaction,  and  whether  the  Hquid  is  coloured  or  colourless,  clear 
or  opalescent.  A  reddish  c  olour  suggests  blood  ;  opalescence  suggests  glyco- 
gen or  starch.  Try  one  or  more  of  the  general  protein  tests  {e.g.,  the  xantho- 
proteic or  biuret).  If  the  result  is  positive,  proceed  as  in  2;  if  negative,  pass 
to  3. 

2.  Test  for  Proteins. — (i)  If  the  reaction  is  acid  or  alkaline,  neutralize  with 
very  dilute  sodium  carbonate  or  sulphuric  acid.  A  precipitate =acid-  or 
alkali-albumin,  according  as  the  original  reaction  is  acid  or  alkaline.  If  the 
original  reaction  is  neutral,  no  acid-  or  alkali-albumin  can  be  present  in 
solution.     Filter  off  the  precipitate,  if  any. 

(2)  Boil  some  of  the  filtrate  from  (i)  (or  some  of  the  original  solution  if 
it  is  neutral),  acidulating  slightly  with  dilute  acetic  acid.  A  precipitate  = 
albumin  or  globulin.     Filter,  and  keep  the  filtrate. 

(3)  If  a  precipitate  has  been  obtained  in  (2),  [a)  saturate  some  of  the  original 
solution  with  magnesium  sulphate,  or  half  saturate  it  with  ammonium  sulphate 
{i.e.,  add  to  it  an  equal  volume  of  saturated  ammonium  sulphate  solution). 
If  there  is  no  precipitate,  globulin  is  absent,  and  therefore  the  precipitate 
obtained  in  (2)  must  be  albumin.  A  precipitate  ^globulin.  But  albumin 
may  also  be  present  in  the  solution.  To  see  whether  this  is  so,  filter  off  the 
globulin  and  boil  the  filtrate  after  acidulation  with  acetic  acid.  A  precipitate 
=  albumin. 

{b)  Half  saturate  the  filtrate  from  (2)  with  ammonium  sulphate  {i.e.,  add  its 
own  volume  of  a  saturated  solution  of  the  salt).  A  precipitate = primary 
proteoses.     Filter. 

(c)  Satura^-e  the  filtrate  from  {b)  with  ammonium  sulphate  crystals.  A 
precipitate  =  secondary  proteoses.     Filter. 

{d)  To  the  filtrate  from  (c)  add  excess  of  solid  sodium  hydroxide  in  small 
pieces  at  a  time.  Much  ammonia  is  given  off.  Allow  the  test-tube  to  stand 
fifteen  minutes,  shaking  it  at  intervals.  Then  add  dilute  cupric  sulphate, 
and  if  much  of  the  sodium  sulphate  formed  remains  undissolved,  add  water 
to  dissolve  it.     A  well-marked  rose  colour  =  peptone. 

(4)  If  no  precipitate  has  been  obtained  in  (2),  the  solution  contains  neither 
albumin  nor  globulin.  To  test  whether  primary  or  secondary  proteose  or 
peptone  is  present,  apply  (3)  {b),  (c),  and  {d). 

3.  Test  for  Carbo-Hydrates. — Use  the  original  solution,  freed  from  coagu- 
lable  proteins,  if  such  have  been  found,  by  acidulation  and  boiling. 

(i)  Add  iodine.  If  the  solution  is  alkaline  neutralize  it  before  adding  the 
iodine.  A  blue  colour  =  starch.  Confirm  by  boiling  with  dilute  sulphuric 
acid  and  testing  for  reducing  sugar.  A  reddish-brown  colour  with  iodine  = 
glycogen  or  dextrin. 

Glycogen  gives  an  opalescent,  dextrin  a  clear,  solution.  Glycogen  is  pre- 
cipitated by  basic  lead  acetate,  dextrin  is  not  (p.  715).  Both  are  changed 
into  reducing  sugar  by  boiling  with  dilute  acid. 

(2)  Add  to  some  of  the  original  solution  cupric  sulphate  and  excess  of 
sodium  hydroxide,  and  boil.     Yellow  or  red  precipitate  =  reducing  sugar. 

(3)  If  (i)  and  (2)  are  negative,  boil  some  of  the  liquid  with  one-twentieth 
of  its  volume  of  strong  hydrochloric  acid  for  fifteen  minutes,  and  test  as  in  (2). 
A  red  or  yellow  precipitate  indicates  that  a  disaccharide  like  cane-sugar  was 
originally  present,  and  has  been  inverted. 


CHAPTER  II 
THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

In  the  living  cells  of  the  animal  body  chemical  changes  are  con- 
stantly going  on;  energy,  on  the  whole,  is  running  down;  complex 
substances  are  being  broken  up  into  simpler  combinations.  So  long 
as  life  lasts,  food  must  be  brought  to  the  tissues,  and  waste  products 
carried  away  from  them.  In  lowly  forms  like  the  amoeba  these 
functions  are  performed  by  interchange  at  the  surface  of  the 
animal  without  any  special  mechanism;  but  in  all  complex  organ- 
isms they  are  the  business  of  special  liquids,  which  circulate  in 
finely  branching  channels,  and  are  brought  into  close  relation  at 
various  parts  of  their  course  with  absorbing  organs,  with  eliminating 
organs,  and  with  the  tissue  elements  in  general. 

In  the  higher  animals  three  circulating  liquids  have  been  dis- 
tinguished: blood,  lymph,  and  chyle.  But  it  is  to  be  remarked 
that  chyle  is  only  lymph  derived  from  the  walls  of  the  alimentar\- 
canal,  and  therefore,  during  digestion,  containing  certain  freshly- 
absorbed  constituents  of  the  food ;  while  both  ordinary  lymph  and 
chyle  ultimately  find  their  way  into  the  blood,  and  are  in  their  turn 
recruited  from  it.  The  blood  contains  at  one  time  or  another 
everything  which  is  about  to  become  part  of  the  tissues,  and  every- 
thing which  has  ceased  to  belong  to  them.  It  is  at  once  the 
scavenger  and  the  food-provider  of  the  cell.  But  no  bloodvessel 
enters  any  cell;*  and  if  we  could  unravel  the  complex  mass  of 
tissue  elements  which  essentially  constitute  what  we  call  an  organ, 
we  should  see  a  sheet  of  cells,  with  capillaries  in  very  close  relation 
to  them,  but  everywhere  separated  from  them  by  a  thin  layer  of 
Ivmph.  And  to  describe  in  a  word  the  circulation  of  the  food 
substances  we  may  say  that  the  blood  feeds  the  lymph,  and  the  lymph 
feeds  the  cell. 

Section  I. — Morphology  of  the  Blood. 

The  blood  consists  essentially  of  a  Hquid  part,  the  plasma,  in 
which  are  suspended  cellular  elements,  the  corpuscles.  When  the 
circulation  in  a  frog's  web  or  lung  or  in  the  tail  of  a  tadpole  is 

*  Fine  intracellular  canaliculi,  communicating  with  the  blood-capillaiits, 
and  probably  performing  a  nutritive  function,  since  they  seem  to  contain 
bloocl-plasma   have  been  described  by  Schafer  and  others  in  the  liver  cells. 

14 


THE  BLOOD-CORPUSCLES 


15 


examined  under  tlie  microscope,  the  bloodvessels  are  seen  to  be 
crowded  with  oval  bodies — of  a  yellowish  tinge  in  a  thin  layer,  but 
in  thick  layers  crimson — which  move  with  varying  velocity,  now 
in  single  file,  now  jostling  each  other  two  or  three  abreast,  as  they 
are  borne  along  in  the  axis  of  an  apparently  scanty  stream  of 
transparent  liquid.  Nearer  the  walls  of  the  vessels,  sometimes 
clinging  to  them  for  a  little  and  then  being  washed  away  again, 
may  be  seen,  especially  as  the  blood-flow  slackens,  a  few  com- 
paratively small,  round,  colourless  cells.  The  oval  bodies  are  the 
red  or  coloured  corpuscles,  or  erythrocytes;  the  colourless  elements 
are  the  white  blood-corpuscles,  or  leucocytes;  the  liquid  in  which 
they  float  is  the  plasma  (Practical  Exercises,  p.  193). 

The  Red  Blood-Corpuscles,  or  Erythrocytes,  differ  in  shape  and 
size  and  in  other  respects  in  different  animal  groups.  In  amphib- 
ians, such  as  the  frog  and  the  newt,  they  are  flattened  ellipsoids 
containing  a  nucleus,  and  the  same 

is  true  of  nearly  all  the  other  ver-  Elephant       00^4. 

tebrates,     except     mammals.      In        /'^l^^^^zHr  -^'^  ""V 

mammals  they  are  discs,  hollowed      f  f//<^^:^\^..Sheep.         -ooso 
out  on  both  the   flat  surfaces,  or        [([{C)mTT-'%°''^i  j        T*' 
biconcave,  and  possess  no  nucleus.      \  \S>=^^/ 
But  the  red  corpuscles  of  the  llama       ^-^^Zll^^^^ 
and    the     camel,     although    non- 

1,1  IT  J    1   •        u  Fig-   I- — Diagram  showing  Relative 

nucleated,  are  ellipsoidal  in  shape,  %^^^  ^f  r/^  Corpuscles  of  Various 

like  those  of  the  lower  vertebrates.        Animals. 

As  to  size,  the  average  diameter 

in  man  is  between  7  and  8  /u*     In  the  frog  the  long  diameter  is 

about  22  f^,  while  in  Proteus  it  is  as  much  as  60  ju,  and  in  Amphiuma, 

the  corpuscles  of  which  can  be  seen  with  the  naked  eye,  nearly 

80  /J,  [Frontispiece) . 

As  regards  the  structure  of  the  red  corpuscles,  the  most  prob- 
able view  is  that  they  are  solid  bodies,  with  a  spongy  and  elastic 
structureless  framework,  denser  at  the  surface  of  the  corpuscle  than 
in  its  centre,  but  continuous  throughout  its  whole  mass  (Rollett). 
The  denser  peripheral  layer  constitutes  a  physiological  envelope 
which  permits  the  passage  of  certain  substances  into  or  out  of  the 
corpuscles,  and  hinders  the  passage  of  others.  In  the  large  oval 
corpuscles  of  Necturus  (see  Frontispiece)  the  envelope  can  be  clearly 
demonstrated  as  a  detachable  membrane  comparable  to  the  mem- 
brane surrounding  the  nucleus. 

Envelope  and  spongework  are  sometimes  spoken  of  as  the  stroma 
of  the  corpuscle,  in  contradistinction  to  its  most  important  con- 
stituent, a  highly  complex  pigment,  the  haemoglobin.  This  pigment 
is  not  in  solution  as  such,  for  its  solubility  is  not  nearly  great 
enough  to  permit  this,  but  either  in  solution  as  a  compound  with 
*  A  micro-millimetre,  represented  by  symbol  fi,  is  ttjVtt  millimetre. 


i6  77//:  CIRCULATING  LIQUIDS  OF  THE  BODY 

some  otluT  nnUnown  substance,  or  more  probably  bound  in  some 
solid  or  semi-solid  combination  to  the  stroma,  and  filling  up  the 
space  within  the  enxelope  in  the  interstices  of  the  spongework. 
Since  there  is  good  reason  to  believe  that  the  haemoglobin  as 
obtained  artificiall}^  from  the  corpuscles  is  not  quite  the  same  sub- 
stance as  the  native  blood-pigment  within  them,  the  latter  is  some- 
times distinguished  by  a  separate  name — haemochrome.  To  the 
physical  properties  of  the  stroma  it  is  usual  to  attribute  the  great 
elasticity  of  the  corpuscles  -that  is,  the  power  of  recovering  their 
original  shape  after  distortion — for  their  elasticity  is  in  no  wise 
impaired  by  the  removal  of  the  haemoglobin. 

Rouleaux  Formation. — When  blood  with  disc-shaped  corpuscles  is 
shed,  there  is  a  great  tendency  for  the  corpuscles  to  run  together  into 
groups  resembling  rouleaux,  or  piles  of  coin.  No  satisfactory  explana- 
tion of  this  curious  fact  has  yet  been  given. 

Crenation  of  the  corpuscles,  a  condition  in  which  they  become 
studded  with  fine  projections,  is  caused  by  the  addition  of  moderately 
strong  salt  solution,  by  the  passage  of  shocks  of  electricity  at  high 
potential,  as  from  a  Leyden  jar,  or  by  simple  exposure  to  the  air.  Con- 
centrated saline  solutions,  which  abstract  water  from  the  corpuscles 
and  cause  them  to  shrink,  make  the  colour  of  blood  a  brighter  red, 
because  more  light  is  now  reflected  from  the  crumpled  surfaces.  On 
the  other  hand,  the  addition  of  water  renders  the  corpuscles  spherical; 
more  of  the  light  passes  through  them,  less  is  reflected,  and  the  colour 
becomes  dark  crimson  [Frontispiece). 

The  White  Blood-Corpuscles,  or  Leucocytes. — The  red  corpuscles 
are  peculiar  to  blood.  The  white  corpuscles  may  be  looked  upon 
as  peripatetic  portions  of  the  mesoderm  (see  Chap.  XIX.),  and  some 
of  them  ought  not  in  strictness  to  be  called  blood-corpuscles.  They 
are  more  truly  body  corpuscles.     Similar  cells  are  found  in  many 

situations,  and  wan- 
der everywhere  in  the 
spaces  of  the  connec- 
tive tissue.  They  pass 
into  the  bloodvessels 
with  the  lymph,  and 
may  pass  out  of  them 
again  in  virtue  of 
their  amoeboid  power. 
They  consist  of  proto- 

Fig.  3.— Amoeboid  Movement.     A,  B,  C.  D.  succes-        P^''^sm,       lesS       differ- 
sive  changes  in  the  form  of  an  amoeba.  entiated      than      that 

of  any  other  cells  in 
the  body,  and  under  the  microscope  appear  as  granular,  colour- 
less, transparent  bodies,  spherical  in  form  when  at  rest,  and 
containing  a  nucleus,  often  tri-  or  multi-lobed.  Many  of  the  leuco 
cytes  of  frog's  blood  at  the  ordinary  temperature,  and  of  mam- 
malian blood  when  artificially  heated  on  the  warm  stage,  may  be 


THE  BLOOD-CORPUSCLES 


n 


seen  to  undergo  slow  changes  of  form.  Processes  called  pseudo- 
podia  are  pushed  out  at  one  portion  of  the  surface,  retracted  at 
another,  and  thus  the  corpuscle  gradually  moves  or  '  flows  '  from 
place  to  place,  and  envelopes  or  cats  up  substances,  such  as  grains 
of  carmine,  which  come  in  its  way.  This  kind  of  motion  was  first 
observed  in  the  amoeba,  and  is  therefore  called  amcjeboid.  It  is 
perhaps  due  to  local  alterations  of  surface  tension;  at  any  rate, 
similar  phenomena  can  be  thus  produced  artificially.  The  leuco- 
cytes of  human  blood  are  not  all  of  the  same  size,  and  differ  also  in 
other  respects.  They  may  be  classified  according  to  the  presence 
or  absence  of  granules  in  their  protoplasm,  and  the  fineness  or 
coarseness  of  the  granules ;  according  to  the  chemical  nature  of  the 
dyes  with  which  the  granules  most  readily  stain,  and  according  to 
the  form  of  the  nucleus.  Five  or  six  varieties  of  leucocytes  may 
-thus  be  distinguished  in  normal  blood  [Frontispiece) : 

1.  Polymoyphonudear  Neutrophile  Cells. — The  nucleus  assumes  a 
great  variety  of  forms,  often  contorted  or  deeply  lobed,  the  lobes  being 
united  by  fine  strands  of  chromatin.  The  cytoplasm  contains  numerous 
fine  refractive  granules,  which  stain  best  neither  with  simple  acid  dyes 
like  eosin  nor  with  simple  basic  dyes  like  methylene  blue,  but  with 
mixtures  which  must  be  assumed  to  contain  '  neutral  '  stains,  like 
Ehrlich's  so-called  triacid  stain.*  These  cells  make  up  65  to  75  per 
cent,  of  the  total  number  of  leucocytes.  Their  diameter  is  10  to 
12  /i. 

2.  Eosinophile  Cells  (12  to  15  ^  in  diameter),  much  less  numerous  in 
normal  blood  than  the  neutrophiles  (less  than  5  per  cent,  of  the  whole), 
but  found  in  considerable  numbers  in  the  serous  cavities,  the  connec- 
tive tissue,  and  the  bone-marrow.  The  granules  in  the  cytoplasm  are 
coarser  than  the  neutrophile  granules,  and  stain  much  more  deeply 
with  eosin.  The  nucleus  may  be  simple,  lobed,  or  even  divided  into 
fragments  between  which  no  connection  can  be  traced.  It  is  less  rich 
in  chromatin,  and  stains  less  easily  with  basic  dyes,  like  methylene  blue, 
than  the  nucleus  of  the  first  variety. 

3.  Large  Mononuclear  (also  called  Transitional)  Leucocytes,  with  a 
diameter  of  12  to  15  /x.  They  possess  a  large  simple  or  slightly  lobed 
nucleus,  poor  in  chromatin,  surrounded  by  a  relatively  great  amount 
of  cytoplasm,  with  faint  neutrophile  granules — i.e.,  granules  which  stain 
with  neutral  dyes.  They  constitute  3  to  5  per  cent,  of  the  total  number 
of  leucocytes. 

4.  Lymphocytes  of  Two  Varieties — {a)  Small  Lymphocytes. — Smaller 
cells  than  any  of  the  preceding  (diameter  6  fi),  possessing  a  single  large 
nucleus,  surrounded  by  a  comparatively  small  amount  of  non-granular 
cytoplasm;  20  to  25  per  cent,  of  the  leucocytes  of  the  blood  belong  to 
this  group.  The  lymphocytes  are  markedly  deficient  in  the  power  of 
amoeboid  motion  in  comparison  with  the  other  varieties  of  colourless 
corpuscles. 

(b)  Large  Lymphocytes. — The  largest  of  all  the  white  cells  of  the  blood, 
and  at  least  twice  as  large  as  the  small  lymphocytes.  They  possess 
a  relatively  great  proportion  of  cytoplasm,  which  is  devoid  of  (;ranules. 
They  constitute  no  more  than  i  per  cent,  of  the  total  number  of  the 
colourless  corpuscles. 

*  A  mixture  of  orange  G.,  acid  fuchsin,  and  methyl  green. 

2 


l8  THE  CIRCULATING  LIQUIDS  OF  THE  bOD\ 

5.  '  Mast  Cells,'  or  '  Basophiles,'  the  least  numerous  variety  (05  per 
cent,  of  the  total  number).  Wry  few  arc  to  be  found  in  the  normal 
blood  of  adults,  but  more  in  cliildren.  They  are  somewhat  smaller 
than  the  neutrophils  (average  diameter  about  10  fi).  The  nucleus  is 
irregularly  trilobed.  The  protoplasm  shows  coarse  granules,  which  do 
not  glitter  like  the  granules  of  the  eosinophile  cells,  and  are  therefore 
less  conspicuous  in  the  unstained  condition.  Unlike  the  eosinophile 
granules,  they  stain  with  basic  dyes,  such  as  methylene  blue. 

Blood-Plates,  or  Thromboqrtes. — When  blood  is  examined  im- 
mediately after  being  shed,  small  colourless  bodies  (i  to  3  //  in 
diameter)  of  various  shapes,  but  usually  round  or  oval,  may  be  seen. 
These  are  the  blood-plates  or  platelets,  also  called  thrombocytes, 
on  account  of  their  function  in  the  coagulation  of  blood.  If  the 
blood  is  not  at  once  subjected  to  some  procedure  which  prevents 
clotting,  the  platelets  swell  and  then  break  up.  There  is  reason  to 
believe  that  in  most  of  the  methods  of  preventing  coagulation  the 
essential  action  is  to  hinder  the  break-up  of  the  platelets  (p.  37). 
They  can  be  isolated  by  receiving  a  drop  of  blood  from  the  finger 
upon  a  well-cleaned  cover-slip,  which  is  then  laid,  supported  by  two 
thin  glass  fibres,  on  a  carefully  cleaned  slide.  The  plasma  with  the 
coloured  corpuscles  and  leucocytes  are  washed  away  by  irrigating 
the  space  between  slide  and  sUp  with  a  suitable  solution,  e.g.,  a 
salt  solution  containing  a  certain  proportion  of  manganese  sulphate, 
which  prevents  disintegration  of  the  platelets.  The  platelets  stick 
to  the  cover-shp  (Deetjen).  They  can  then  be  fixed  and  stained. 
The  blood-plates  can  even,  like  leucocytes,  be  kept  alive  on 
the  warm  stage  in  an  appropriate  medium  (agar,  to  which  certain 
salts  have  been  added),  and  then  show  lively  amoeboid  movements 
(Deetjen).  They  have  been  described  as  nucleated  cells,  although 
the  nucleus  is  not  easy  to  stain,  and  with  the  ultra-microscope,  a 
delicate  mesins  of  testing  whether  such  an  object  as  a  platelet  is 
optically  homogeneous,  no  evidence  of  the  presence  of  a  nucleus 
has  been  obtained.  The  origin  of  the  platelets  has  been  a  matter  of 
lively  controversy.  They  are  not  produced  by  the  breaking  up  of 
other  elements  of  the  shed  blood,  for  they  have  been  observed 
within  the  freshly  excised,  and  therefore  still  living,  capillaries — 
in  the  mesentery  of  the  guinea-pig  and  rat  (Osier).  According  to 
the  best  evidence,  they  are  derivatives  neither  of  the  erythro- 
C5rtes  nor  of  the  leucocytes  of  the  blood,  but  are  de\eloped  from 
special  elements  (so-called  megakar\'ocytes)  of  the  blood-forming 
organs  (bone-marrow)  (J.  H.  Wright). 

Enumeration  of  the  Blood-Corpuscles.— This  is  done  by  taking  a 
measured  quantitv  of  l)l()od.  diluting  it  to  a  knowTi  extent  with  a 
liquid  which  does  not  destroy  the  corpuscles,  and  counting  the 
number  in  a  given  volume  of  the  diluted  blood  (p.  67). 

The  average  number  of  red  corpuscles  in  a  cubic  millimetre  of 
blood  is  about  5,000,000  in  a  healthy  man,  and  about  4,500,000  in 


THE  BLOOD-CORPUSCLES 


19 


a  healthy  vvuiiian,  but  a  variation  of  1,000,000  up  or  down  can  hardly 
he  considered  abnormal.  In  persons  suffering  from  profound  anaemia 
the  number  may  sink  to  1,000,000  per  cubic  millimetre,  or  even 
less.     In  one  case  of  pernicious  anaemia,  only  143,000  corpuscles 

per  cubic  millimetre  were  present,  the 
lowest  number  recorded.    In  new-born 
children  the  average  is  over  6,000,000, 
and  in  the  inhabitants  of  high  plateaus 
or  mountnins  it  may  rise  to  7,000,000  or 
Fig.s-CurveshowingtheNumber  ^ven  more.     In  the  latter  instance  a 
of  Red  Corpuscles  at  Different  residence  of  a  fortnight  m  the  rarefied 
Ages  (after  Sorensen's  Estima-  ^ir  is  Sufficient  to  bring  about  the  in- 
tions).    The  figures  along  the  ^     Subsequent  residence  of  a 

horizontal  axis  are  vears  ot  age,  ^'^^'^  ^'  ""'^  a.     kj^u     ^  1  •,  * 

those  along  the  vertical  axis  fortnight  m  the  lowlands  to  annul  it.'^ 
millions  of  corpuscles  per  cubic  In  certain  pathological  conditions  a 
millimetre  of  blood.  ^^^^^  increase  in  the  relative  number  of 

corpuscles  (polycythemia)  is  found.  Over  13,000,000  erythrocyte*^ 
to  the  cubic  millimetre  have  been  counted  in  a  case  of  cyanosis  (im- 
perfect oxygenation  of  the  blood,  with  blueness  of  the  lips,  etc.),  due 
to  congenital  disease  of  the  heart.  An  interesting  form  of  experi- 
mental polycythaemia  is  caused  by  injection  of  adrenahn. 

The  nimiber  of  white  blood-corpuscles  is  on  the  average  about 
10,000  per  cubic  millimetre  of  blood,  or 
one  leucocyte  for  every  500  red  blood- 
corpuscles.  But  if  the  count  is  made 
when  digestion  is  relatively  inactive, 
four  to  five  hours  after  a  meal,  it  gives 
no  more  than  7,000  to  the  cubic  milli- 
metre. In  new-born  children  the 
average  number  is  over  18,000  per 
cubic  millimetre.  The  total  leucocyte 
count,  and  still  more  the  so-called  dif- 
ferential count,  i.e.,  the  determination 
of  the  relative  number  of  the  different 
kinds  of  leucocytes,  is  often  resorted  to 
in  the  study  of  pathological  conditions. 
A  distinct  increase  in  the  number  is 
designated  leucocytosis.  In  leukaemia 
the  number  of  white  corpuscles  is 
enormously  increased — on  the  average 
to  about  300,000,  but  in  extreme  cases 
to  600,000  per  cubic  miUimetre — while  at  the  same  time  the  number 

*  In  113  apparently  healthy  students  (male)  the  average  number  of  red 
corpuscles  was  5,190,000  per  cubic  millimetre.  In  104  of  these,  the  number 
ranged  from  4,000,000  to  6,400,000;  in  71  (or  63  per  cent,  of  the  whole), from 
4.400,000  to  5,500,000;  in  3,  from  3,500,000  to  3,900,000;  in  5,  from  6,500,000 
to  7,000,000.     In  one  observation  the  number  reached  7,300,000. 


i:m 


I 


K        m 

Fig.  4. — Curve  showing  Propor 
tion  of  White  Corpuscles  to  Red 
at  Different  Times  of  the  Day 
(after  the  Results  of  Hirt).  At 
I  the  morning  meal  was  taken ; 
at  II  the  midday  meal;  at  III 
the  evening  meal.  During 
active  digestion  the  number  of 
lymphocytes  in  the  blood  is 
greatly  increased,  both  abso- 
lutely and  relatively  to  the 
number  of  the  other  leucocytes. 


20  THE  CIRCULATING  LIQUIDS  OP  THE  BODl 

of  the  red  corpuscles  is  diminished;  and  the  ratio  of  white  to  red 
may  approach  1:4.  As  the  anaemia  rapidly  advances  towards  the 
fatal  termination  of  an  acute  case,  and  the  erytlirocyte  count  falls  to 
1,000,000,  or  even  less,  the  ratio  may  come  still  nearer  to  unity.  An 
increase  in  the  number  of  leucocytes  has  also  been  observed  in  cer 
tain  infective  diseases  as  part  of  the  inflammatory'  reaction.  There 
are  also  physiological  variations,  even  within  short  periods  of  time; 
for  example,  the  number  of  lymphocytes  is  increased  when  digestion 
is  going  on  (digestive  lymphocytosis).  The  normal  number  of 
blood-plates  varies  from  a  quarter  to  half  a  million  to  the  cubic 
millimetre,  but  may  be  greater  in  disease  and  at  high  levels 
(Kemp). 

Life-History  of  the  Corpuscles. — The  corpuscles  of  the  blood,  like 
the  body  itself,  fulhl  the  allotted  round  of  life,  and  then  die.  They 
arise,  perform  their  functions  for  a  time,  and  disappear.  But 
although  the  place  and  mode  of  their  origin,  the  seat  of  their  destruc- 
tion or  decay,  and  the  average  length  of  their  life,  have  been  the 
subject  of  active  research  and  still  more  active  discussion  for  many 
years,  much  yet  remains  unsettled. 

Origin  of  the  Erythrocytes. — In  the  embryo  the  red  corpuscles,  even 
of  those  forms  (mammals)  whicli  have  non-nucleated  corpuscles  in 
adult  life,  are  at  first  possessed  of  nuclei,  and  approximately  spherical 
in  form.  In  the  human  foetus,  at  the  fourth  week  all  the  red  corpuscles 
are  nucleated.  Later  on  the  nucleated  corpuscles  gradually  diminish 
in  number,  and  at  birth  they  have  almost  or  altogether  disappeared, 
some  of  them,  at  least,  having  been  converted  by  a  shrivelling  of  the 
nucleus  into  the  ordinary  non-nucleated  form.  In  the  newly  bom  rat, 
which  comes  into  the  world  in  a  comparatively  immature  state,  many 
of  the  red  corpuscles  may  be  seen  to  be  still  nucleated.  The  first  cor- 
puscles formed  in  embryonic  life  are  developed  outside  of  the  embryo 
altogether.  Even  before  the  heart  has  as  yet  begun  to  beat,  certain 
cells  of  the  mesoderm  (see  Chapter  XIX.)  in  a  zone  ('  vascular  area  ') 
around  the  growing  embryo  begin  to  sprout  into  long,  anastomosing 
processes,  which  afterwards  become  hollowed  out  to  form  capillary 
bloodvessels.  At  the  same  time  clumps  of  nuclei,  formed  by  division 
of  the  original  nuclei  of  the  cells,  gather  at  the  nodes  of  the  network. 
Around  each  nucleus  clings  a  little  lump  of  protoplasm,  which  soon 
develops  haemoglobin  in  its  substance ;  and  the  new-made  corpuscles 
float  away  within  the  new-made  vessels,  where  they  rapidly  multiply 
by  mitosis.  In  later  cmbrj'onic  life  the  nucleated  corpuscles  continue 
in  part  to  be  developed  within  the  bloodvessels  in  the  liver,  allantois, 
spleen,  and  red  bone-marrow,  and  in  certain  localities  in  the  connective 
tissue,  by  mitotic  division  of  previously  existing  nucleated  corpuscles, 
in  part  to  be  formed  endogenously  within  special  cells  in  the  liver  and 
perhaps  other  organs.  Still  later  the  nucleated  corpuscles  give  place  in 
the  blood  of  the  mammal  to  non-nucleated  erythrocytes.  Many  of 
these  are  doubtless  derived  from  the  nucleated  corpuscles,  but  some 
appear  to  be  produced  in  the  interior  of  certain  cells  of  the  connective 
tissue,  and  are  non-nucleated  from  the  start. 

In  the  mammal  in  extra-uterine  life  the  chief  seat  of  formation 
of  the  red  blood-corpuscles,  or  haematopoiesis,  is  the  red  marrow  of 


THE  BLOOD-CORPUSCLES  ai 

the  bones  of  the  skull  and  trunk,  and  of  the  ends  of  the  long  bones 
of  tile  limbs.  Special  nucleated  cells  in  the  marrow,  originally 
colourless,  multiply  by  karyokinesis,  take  up  hsemoglobin  or,  what 
is  much  more  likely,  form  it  within  their  j)rotoplasm,  and  are 
transformed  by  various  stages  into  the  ordinary  non-nucleated  red 
corpuscles,  which  then  pass  into  the  blood-stream.  These  blood- 
fomiing  cells  have  received  the  name  of  erythroblasts  or  h.'emato- 
blasts.  According  to  their  size,  erythroblasts  have  been  distinguished 
as  normoblasts,  megaloblasts,  and  microblasts.  The  normo- 
blasts are  most  numerous,  and  have  about  the  same  diameter  as 
the  full-formed  erythrocytes,  into  which  they  are  believed  to 
develop.  The  megaloblasts  are  larger,  and  the  microblasts  smaller, 
and  they  are  thought  to  be  the  precursors  of  those  aberrant  forms 
of  erythrocytes  sometimes  found  in  the  blood  in  certain  diseases. 
After  haemorrhage  rapid  regeneration  of  the  blood  takes  place,  so 
that  in  a  few  weeks  the  loss  of  even  as  much  as  a  third  of  the  total 
blood  is  made  good.  The  plasma  is  much  sooner  restored  to  its 
normal  amount  than  the  corpuscles.  Microscopical  examination 
shows  in  the  red  marrow  the  tokens  of  increased  production  of 
coloured  corpuscles,  and  nucleated  erythrocytes  appear  in  the 
blood,  the  normoblasts  being,  as  it  were,  hurried  into  the  circula- 
tion before  the  transformation  which  normally  results  in  the  dis- 
appearance of  the  nucleus  is  complete.  The  same  is  true  in 
severe  pathological  ansemias,  e.g.,  pernicious  ansemia.  It  is  a 
matter  of  interest  that  other  organs  also,  which  in  embr^'onic 
life  perform  a  haematopoietic  function,  particularly  the  spleen, 
may,  in  such  emergencies,  again  take  on  the  office  of  forming 
blood-corpuscles. 

A  constant  destruction  of  red  blood-corpuscles  must  go  on,  for 
the  bile-pigment  and  the  pigments  of  the  urine  are  derived  from 
blood-pigment.  The  bile-pigment  is  formed  in  the  liver.  It  con- 
tains no  iron ;  but  the  liver  cells  are  rich  in  iron,  and  on  treatment 
with  hydrochloric  acid  and  potassium  ferrocyanide,  a  section  of 
liver  is  coloured  by  Prussian  blue.  Iron  must  therefore  be 
removed  by  the  liver  from  the  blood-pigment  or  from  one  of  its 
derivatives;  and  there  is  other  evidence  that  the  liver  is  either  one 
of  the  places  in  which  red  corpuscles  are  actually  destroyed,  or 
receives  blood  charged  with  the  products  of  their  destruction. 
Although  it  cannot  be  doubted  that  in  all  animals  whose  blood 
contains  haemoglobin  the  iron  found  in  the  liver  bears  an  important 
relation  to  the  building  up  or  breaking  down  of  the  blood-pigment, 
the  injection  of  haemoglobin  or  haemin,  indeed,  increasing  markedly 
the  amount  of  iron  in  the  liver,  as  well  as  in  the  spleen,  bone-marrow 
and  other  tissues,  this  does  not  seem  to  be  the  only  function  of  the 
hepatic  iron,  for  the  liver  of  the  crayfish  and  the  lobster,  which 
have  no  haemoglobin  in  their  blood,  is  rich  in  iron.     Destruction  of 


22  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

erythrocytes  may  also  take  place  in  the  spleen  and  bone-marrow. 
Although  the  statement  that  free  blood-pigment  exists  in  demon- 
strable amount  in  the  plasma  of  the  splenic  \ein  is  incorrect,  red 
corpuscles  have  been  seen  in  various  stages  of  decomposition  within 
large  amceboid  cells  in  the  splenic  pulp;  and  deposits  containing 
iron  ha\e  been  found  there  and  in  tlie  red  l:)one-marrow  in  certain 
pathological  conditions.  But  there  is  no  good  foundation  for  the 
statement  sometimes  rather  fancifully  made  that  the  spleen  is  in 
any  special  sense  the  '  graveyard  of  the  red  corpuscles.'  Some  of 
the  coloured  corpuscles  may  break  up  in  the  blood  itself,  forming 
granules  of  pigment,  which  may  then  be  taken  up  by  the  liver, spleen, 
and  lymph  glands.  Indeed,  it  is  probable  that  a  large  proportion 
of  the  woni-out  erythrocytes  are  finally  destroyed  in  the  blood- 
stream. The  portal  circulation  may  be  more  than  other  vascular 
tracts  a  seat  of  this  natural  decay,  perhaps  in  virtue  of  the  presence 
of  substances  with  a  hemolytic  action  (p.  28)  absorbed  from  the 
alimentary-  canal. 

It  has  been  argued  that  the  erythrocytes  must  be  short-lived, 
since  they  are  devoid  of  nuclei  (p.  6).  and  attempts  have  been 
made  to  calculate  the  average  time  for  which  they  survive  in  the 
circulation  from  the  amount  of  haemoglobin  (or  of  its  derivative, 
haematin)  required  to  furnish  the  daily  excretion  of  bile-pigment. 
The  results  arrived  at,  however,  are  not  sufficiently  trustworthv  to 
warrant  their  citation. 

Origin  and  Fate  of  the  Leucocytes. — There  has  been  much  dis- 
cussion as  to  the  origin  of  the  white  blood-corpuscles.  The 
numerous  theories  fall  into  two  groups,  which  have  been  designated 
somewhat  pompously  the  monistic  and  the  dualistic.  According 
to  the  first,  all  the  colourless  corpuscles  arise  from  a  single  type 
of  parent  cell,  namely,  the  lymphocyte  type,  in  its  small  or  large 
variety.  According  to  the  dualistic  school,  a  fundamental  distinc- 
tion exists  between  the  lymphocytes,  or  cells  peculiar  to  lymphoid 
tissues,  and  to  the  blood  on  the  one  hand,  and  the  remaining  varieties 
of  leucocytes  on  the  other.  The  former  are  supposed  to  be  derived 
from  the  lymphoUasts  of  lymphoid  tissue,  and  the  latter  from  the 
myeloblasts,  the  forerunners  of  the  myelocytes  of  bone-marrow. 
The  question  has  recently  been  studied  by  Foot  by  a  new  method, 
namely,  by  cultivating  chicken  marrow  outside  of  the  body,  and 
watching  the  transformation  of  certain  of  its  cells.  He  concludes 
in  favour  of  the  development  of  the  polymorphonuclear  leucocyte 
from  a  lymphoid  type  of  cell  existing  in  the  marrow,  a  conclusion 
in  harmonv  with  the  monistic  view.  As  regards  their  immediate 
source,  the  small  lymphocytes  of  the  blood  are  undoubtedly  derived 
from  the  lymph,  and  are  identical  with  the  lymph-corpuscles. 
That  they  are  formed  largely  in  the  l^nnphatic  glands  is  shown 
by  the  fact  that  the  lymph  coming  to  the  glands  is  much  poorer 


THE  BLOOD-CORPUSCLES  23 

in  corpuscles  than  that  which  leaves  them.  The  lymphatic  glands, 
however,  although  the  principal,  are  not  the  only  seat  of  formation 
of  lymphocytes,  for  lymph  contains  some  corpuscles  before  it  has 
passed  through  any  gland;  and  although  a  certain  number  of  these 
may  have  found  their  way  by  diapedesis  from  the  blood,  others  are 
developed  in  the  diffuse  adenoid  tissue,  or  in  special  collections  of  it, 
such  as  the  thymus,  the  tonsils,  the  Payer's  patches  and  solitary 
follicles  of  the  intestine,  and  the  splenic  corpuscles.  To  a  very 
small  extent  white  blood-corpuscles  may  multiply  by  karyokinesis 
or  indirect  division  in  the  blood. 

The  fate  of  the  leucoc5rtes  is  even  less  known  than  that  of  the 
red  corpuscles,  for  they  contain  no  characteristic  substance,  like 
the  blood-pigment,  by  which  their  destruction  may  be  traced.  That 
they  are  constantly  disappearing  is  certain,  for  they  are  constantly 
being  produced.  Not  a  few  of  them  actually  escape  from  the 
mucous  membranes  of  the  respiratory,  digestive,  and  urinary 
tracts.  The  remnants  of  broken-down  leucocytes  have  been  found 
in  the  spleen  and  lymph  glands.  It  must  be  assumed  that  many 
break  up  in  the  blood-plasma  itself. 


Section  II. — General  Physical  and  Chemical  Properties  of 

THE  Blood. 

Fresh  blood  varies  in  colour,  from  scarlet  in  the  arteries  to 
purple-red  in  the  veins.  It  is  a  somewhat  viscid  liquid,  with  a 
saline  taste  and  a  peculiar  odour. 

Viscosity  of  Blood. — The  viscosity  of  normal  dog's  blood  is  about 
six  times  greater  than  that  of  distilled  water  at  body  temperature. 
It  can  be  determined  by  allowing  the  blood  to  flow  through  a  capil- 
lary tube  of  known  dimensions  under  a  definite  pressure,  and 
measuring  the  amount  which  escapes  in  a  given  time.  In  general 
the  viscosity  and  specific  gravity  of  the  blood  vary  in  the  same 
direction,  although  there  is  not  an  exact  proportionality^  between 
them.  Thus,  sweating,  which  causes  a  diminution  of  the  water  of 
the  blood,  causes  also  an  increase  in  its  viscosity.  With  increasing 
temperature  the  viscosity  of  the  blood  diminishes,  as  is  the  case 
with  other  liquids  (Burton-Opitz). 

In  polycythasmia,  where  the  number  of  ervthrocytes  in  propor- 
tion to  plasma  is  greatly  increased,  the  viscosity  of  the  blood  in- 
creases in  an  equal  degree.  In  one  case  of  polj^cythsemia,  with  a 
blood-count  of  8,300,000,  the  viscosit}''  was  9-4  times  that  of  water; 
in  a  case  of  marked  chlorosis  it  was  only  2-14.  But  the  importance 
of  this  factor  in  causing  an  abnormal  blood-pressure  by  increasing 
or  diminishing  the  resistance  to  the  blood-flow  has  been  exaggerated. 
Although  it  has  been  shown  that  in  the  living  vessels,  so  long  as 


24  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

their  calibre  remains  constant,  the  flow  is  affected  by  changes  in 
the  viscosity  of  the  blood,  just  as  in  ghiss  tubes,  compensation  by 
adjustment  of  the  vascular  calibre  is  so  ample  and  so  easy  tha: 
even  the  greatest  alterations  of  viscosity  produce  little  effect  on 
the  mean  blood-pressure. 

Reaction  of  Blood. — In  the  sense  in  which  the  term  is  used  in 
physical  chemistry,  the  reaction  of  a  solution  depends  on  the  pro- 
portion between  its  content  of  hydrogen  (H  + )  and  hvdroxyl 
(OH  — )  ions,  an  excess  of  hydrogen  ions  corresponding  to  an  acid 
and  an  excess  of  hydroxyl  ions  to  an  alkaline  reaction.  It  has  been 
sho\Mi  by  a  physical  method  (the  determination  of  the  electro- 
motive force  of  a  cell  containing  blood  or  serum  as  one  liquid)  that 
hydroxyl  ions  are  present  only  in  small  excess,  and  that  blood  is 
really  but  a  little  more  alkaline  than  distilled  water.  Practically, 
it  may  be  regarded  as  a  neutral  liquid.  Under  a  great  variety  of 
conditions,  physiological  and  pathological,  its  reaction  remains 
almost  unchanged.  Yet  it  is  known  that  acids  (carbon  dioxide, 
lactic,  phosphoric,  and  sulphuric  acids)  are  constantly  being  pro- 
duced in  the  normal  metabolism  of  the  tissues.  The  administra- 
tion of  large  quantities  of  acid  or  alkali  causes  a  surprisingly  small 
effect.  In  diabetes,  even  when  it  can  be  proved  that  an  abnormal 
production  of  acid  substances  is  taking  place,  the  blood  shows  little, 
if  any,  diminution  in  the  proportion  of  hydroxyl  ions;  it  remains 
to  all  intents  and  purposes  a  neutral  liquid.  In  diabetic  coma, 
where  the  blood  may  in  extreme  cases  turn  blue  litmus  red,  the 
true  reaction  is  only  slightly  altered. 

The  manner  in  which  the  reaction  of  the  blood,  the  tissue  liquids, 
and  probably  the  protoplasm  itself,  is  regulated  within  sucli  narrow 
limits  is  a  subject  of  great  interest.  For  there  is  reason  to  believe 
that  it  is  of  the  utmost  moment  that  the  equilibrium  should  be 
maintained  not  only  in  order  that  the  functions  of  the  tissues  may 
be  properly  perfonned,  but  that  danger  to  life  may  be  averted. 
To  be  sure,  the  excretor\'  organs,  the  lungs  and  the  kidneys,  provide 
the  means  by  which  the  excess  of  acid  (or  of  alkali)  is  finallv,  under 
normal  circumstances,  eliminated.  Other  regulative  mechanisms 
also  exist.  For  example,  it  has  been  shown  that  when  an  excessive 
production  of  acids  (acidosis)  occurs  in  conditions  of  disordered 
metabolism,  or  when  acids  are  purposely  administered  in  large 
amount,  a  greater  quantity  of  ammonia,  split  off  from  the  pro- 
teins, is  mobilized  to  aid  in  neutralizing  the  acids.  But  very 
simple  experiments  on  blood  in  vitro  are  sufficient  to  show  that 
the  blood  itself  has  a  great  capacity,  as  compared  with  water,  to 
resist  a  change  in  its  reaction  even  when  large  amounts  of  acid  or 
alkali  are  added  to  it.  The  secret  of  the  reaction-regulating  power 
lies,  therefore,  to  a  large  extent  in  the  blood  itself.  Two  factors 
have  been  shown  to  be  of  importance:  (i)  The  power  of  the  proteins^ 


GENERAL  PHYSICAL  A SD  CHEMICAL  PROPERTIES         25 

in  virtue  of  their  amphoteric  character,  to  combine  either  with 
acids  or  with  bases,  so  that,  when  excess  of  base  is  added  to  blood, 
the  proteins  act  as  acids,  and  neutraHze  the  base;  when  excess  of 
acid  is  added,  the  proteins  act  as  bases,  and  neutralize  the  acid. 
(2)  The  equilibrium  of  certain  of  the  inorganic  constituents  of  the 
blood  (carbon  dioxide,  the  carbonates,  and  the  phosphates)  is  such 
that  even  great  variations  in  the  concentration  of  any  of  these, 
such  as  may  nomially  occur,  produce  scarcely  any  effect  upon  the 
concentrations  of  the  hydrogen  and  hydroxyl  ions. 

Thus,  when  phosphoric  acid  and  sodiuin  hydroxide  are  added  to 
water  in  certain  proportions,  and  the  sohition  placed  under  a  certain 
tension  of  carbon  dioxide  (which  is  kept  constant),  we  get  a  more  or 
less  accurate  imitation  of  blood  as  regiirds  tlie  inorganic  substances 
concerned  in  the  regulation  of  its  reaction,  sodium  bicarbonate 
(NaHCOg)  and  disodium  phosphate  (Na2HP04)  being  present  in  the 
solution  as  in  blood.  It  is  found  that  when  the  quantities  are  so  chosen 
that  the  H  +  concentration  lies  within  the  limits  of  variation  of  the 
normal  blood  reaction,  relatively  large  quantities  of  alkalies  can  be 
added  or  withdrawn  without  causing  much  change  in  the  H  +  concen- 
tration. It  can  be  shown  both  theoretical!}'  and  experimentally  that 
precisely  those  weak  acids  present  in  blood  (CO2,  XaH2P04)  require  the 
largest  addition  of  alkali  to  alter  the  reaction  to  a  given  extent,  and 
are  therefore  particularly  suited  to  give  stability  to  the  reaction. 
Thus  carbon  dioxide  requires  twenty-four  times,  and  monosodium 
phosphate  thirty-tliree  times,  as  much  alkali  as  an  equivalent  solution 
of  acetic  acid  to  cause  a  g^ven  alteration  of  colour  in  rosolic  acid 
(E.  Henderson). 

The  so-called  '  titratable  '  alkalinity  of  blood  or  serum,  measured  by 
the  amount  of  standard  acid  which  must  be  added  before  the  colour  of 
the  indicator  used  changes  from  alkaline  to  acid,  bears  no  necessary  or 
fixed  proportion  to  the  actual  alkalinity.  When  blood,  for  instance, 
is  titrated  with  hydrochloric  acid,  with  methyl  orange  as  indicator,  at 
the  point  where  the  red  colour  appears  all  the  disodium  phosphate  and 
sodium  bicarbonate  will  have  been  changed  into  monosodium  phos- 
phate and  carbon  dioxide,  all  the  alkali  removed  from  combination 
with  proteins,  a  certain  amount  of  acid-protein  compounds  formed, 
and  other  minor  reactions  produced  (Henderson).  It  is  difficult  to 
correlate  the  quantity  deduced  from  such  a  titration  with  any  physio- 
logical condition,  although  undoubtedly  it  bears  some  relation  to  the 
acid-neutralizing  power  of  the  blood,  and  some  relation  to  its  real 
reaction.  Still,  by  titration  information  of  value  can  be  obtained 
which  is  not  j-ielded  by  the  physico-chemical  method  in  regard  to  the 
potential '  acid  capacity  '  of  the  blood  and  its  power  of  resistance  against 
acid-poisoning. 

What  is  estimated  here  is  the  quantity  of  acid  required  to  satisfy  the 
proteins  and  to  react  with  the  carbonates  and  phosphates  before  that 
concentration  of  hydrogen  and  hydroxyl  ions  just  necessary  to  cause 
the  change  of  colour  is  established.  This  is  not  the  same  for  different 
indicators,  since  there  is  a  certain  minimum  ratio  in  the  concentration 
of  these  ions  at  which  each  indicator  turns  in  one  or  the  other  direction, 
none  turning  precisely  at  the  neutral  point.  Thus  sermn  appears  to  be 
acid  when  tested  with  phenolphthalein,  and  alkali  must  be  added  to 
the  serum  before  the  pink  colour  indicating  alkalinity  is  produced. 
On  the  other  hand,  with  litmus  or  methyl  orange  it  gives  the  alkaline 


26  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

reaction,  and  a  considerable  amount  of  acid  must  be  added  before  the 
colour  of  the  indicator  which  denotes  acidity  appears.  The  true  re- 
action of  the  serum  is  not,  of  course,  at  one  and  tlic  same  time  both 
alkaline  and  acid ;  but  it  is  so  near  neutrality  that  it  falls  just  below  the 
degree  of  alkalinity  necessary  to  give  the  pink  colour  with  phenol- 
phthalcin,  and  just  below  tlie  degree  of  acidity  wliich  gives  the  pink 
colour  corresponding  to  an  acid  reaction  with  metliyl  orange.  Certain 
indicators — for  example,  rosolic  acid — turn  so  as  to  give  sharp  cok)ur 
reactions  at  about  the  concentration  of  hydrogen  and  hydroxyl  ions 
in  the  blood,  and  these  may  possibly  be  of  use  in  determining  the 
changes  in  the  true  reaction  for  clinical  purposes  (Adler). 

More  closely  related  to  the  true  alkalinity  of  the  blood  than  the 
titratable  alkalinity  is  the  carbon  dioxide  content.  The  estimation 
of  the  total  carbon  dioxide  in  a  sample  of  blood  throws  light  upon 
the  capacity  of  the  blood  to  perform  one  of  its  most  important 
functions — the  transportation  of  carbon  dioxide — and  to  preserve 
one  of  its  essential  properties— an  almost  neutral  reaction — in  the 
presence  of  an  excessive  intake  or  production  of  acid  substances. 
In  herbivorous  animals  the  carbon  dioxide  content  of  the  blood  is 
easily  lessened  by  the  administration  of  acids,  but  in  carnivora 
and  in  man  it  is  much  more  difficult  to  bring  about  such  a  decided 
effect,  for  the  reason  already  mentioned,  the  acid  being  neutralized 
by  ammonia.  In  many  diseases,  however,  and  particularly  in  those 
accompanied  by  fever,  this  protective  mechanism  breaks  down. 

Specific  Gravity  of  Blood. — ^The  average  specific  gravity  of  blood 
is  about  1066  at  birth.  It  falls  during  infancy  to  about  1050  in 
the  third  year,  then  rises  till  puberty  is  reached  to  about  1058  in 
males  (at  the  seventeenth  year),  and  1055  in  females  (at  the  four- 
teenth year).  It  remains  at  this  level  during  middle  life  in  males, 
but  falls  somewhat  in  females.  In  chlorotic  anaemia  of  young 
women  it  may  be  as  low  as  1030  or  1035.  It  rises  in  starvation. 
Sleep  and  regular  exercise  increase  it  (Lloyd  Jones).*  The  specific 
gravity  of  the  serum  or  plasma  varies  from  1026  to  1032. 

The  Electrical  Conductivity  of  Blood.— The  liquid  portion  of  the 
blood  conducts  the  current  entirely  by  means  of  the  electrolytes 
dissolved  in  it,  the  most  important  of  these  being  the  inorganic 
salts;  and  the  conductivity  of  the  serum  varies,  in  different  speci- 
mens of  blood,  within  a  comparatively  narrow  range.  The  con- 
ductivity of  entire  (defibrinated)  blood,  on  the  contrary,  varies 
within  wide  limits.  For  instance,  in  a  case  of  pernicious  anaemia 
the  conductivity  of  the  blood  was  found  to  be  almost  double  that 
of  normal  human  blood,  while  the  conductivity  of  the  serum  was 
normal.     The  most  influential  factor  which  governs  this  variation 

*  In  165  students  (male)  the  average  specific  gravity  of  the  blood,  as  deter- 
mined by  Hammerschlag's  method  (p.  02)  was  1054-4.  In  149  of  these  the 
variation  was  from  1050  to  1065;  in  94  (or  57  per  cent,  of  the  whole),  from 
1054  to  1060;  in  4,  from  1046  to  1049;  in  9,  from  1066  to  1070.  In  3  the 
specific  gravity  was  only  1040  to  1042. 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         27 

is  the  relative  volume  of  the  corpuscles  and  serum.  When  the 
blood  is  relatively  rich  in  corpuscles  and  poor  in  serum,  its  con- 
ductivity is  low;  when  it  is  poor  in  corpuscles  and  rich  in  serum, 
its  conductivity  is  high.  The  explanation  is  that  the  corpuscle 
refuses  passage  to  the  ions  of  the  dissociated  molecules,  which,  in 
virtue  of  their  electrical  charges,  render  a  liquid  like  blood  a  con- 
ductor (p.  428),  or  permits  them  only  to  pass  very  slowly,  so  that 
the  intact  red  corpuscles  have  an  electrical  conductivity  so  man}- 
times  less  than  that  of  serum,  that  they  may,  in  comparison,  be 
looked  upon  as  non-conductors  (Practical  Exercises,  p.  69). 

The  Relative  Volume  of  Corpuscles  and  Plasma  in  Unclotted 
Blood,  or,  what  can  be  converted  into  this  by  a  small  correction, 
the  relative  volume  of  corpuscles  and  serum  in  defibrinated  blood, 
can  be  easily  determined,  with  approximate  accuracy,  by  com- 
paring the  electrical  conductivity  of  entire  blood  with  that  of  its 
serum.*  Another  method,  more  suitable  for  clinical  work,  though 
not  so  accurate,  is  the  so-called  hgematocrite  method.  A  small 
quantity  of  blood  is  centrifugalized  in  a  graduated  glass  tube  of 
narrow  bore  until  the  corpuscles  have  been  collected  into  a  solid 
'  thread  '  at  the  outer  extremity  of  the  tube.  Their  volume  and 
that  of  the  clear  plasma  which  has  been  separated  from  them  are 
then  read  off  on  the  scale.  The  hsematocrite  must  rotate  at  such  a 
high  speed  (10,000  turns  a  minute)  that  separation  of  the  corpuscles 
from  the  plasma  is  accomplished  before  clotting  has  occurred. 
Dilution  of  the  blood  with  liquids  which  prevent  clotting  is  not 
permissible  for  exact  work  (Practical  Exercises,  p.  68).  By  these 
and  other  methods  too  elaborate  for  description  here,  it  has  been 
shown  that  the  plasma  or  serum  usually  makes  up  rather  less  than 
two-thirds,  and  the  corpuscles  rather  more  than  one-third,  of  the 
blood.  But  this  proportion  is,  of  course,  liable  to  the  same  varia- 
tions as  the  number  of  corpuscles  in  a  cubic  millimetre  of  blood. 
It  depends,  further,  the  number  of  corpuscles  being  given,  on  the 
average  volume  of  each  corpuscle.  For  instance,  when  the  mole- 
cular concentration,  and  therefore  the  osmotic  pressure  (p.  427), 
of  the  plasma  is  reduced,  as  by  the  addition  of  water  or  the  abstrac- 
tion of  salts,  water  passes  into  the  corpuscles  and  they  swell ;  when 
the  molecular  concentration  of  the  plasma  is  increased,  by  the 
abstraction  of  water  or  the  addition  of  salts,  water  passes  out  of 
the  corpuscles,  and  they  shrink.     In  human  serum  the  average 

♦  The  formula  p  =  jr  -^  (174  -  K(b)),  where  p  is  the  number  of  c.c.  of  serum 

in  100  c.c.  of  blood;  K{b),  K{s),  the  specific  conductivities  respectively  of  the 
blood  and  serum  (both  measured  at  or  reduced  to  5°  C,  and,  to  obtain  whole 
numbers,  multipHed  by  10*),  may  be  used  in  the  calculation.  K  is  the  specific 
conductivity  of  the  liquid — i.e.,  the  conductivity  of  a  cube  of  the  liquid  of 
I  centimetre  side.     The  conductivity  of  a  similar  cube  of  mercury  is  10,630. 


28  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

depression  of  tlie  freezing-point  below  that  of  distilled  water,  which 
is  a  measure  of  the  molecular  concentration  and  of  the  osmotic 
pressure,  is  about  o-^fr  C.  (Practical  Exercises,  p.  73).  For  clinical 
purposes,  the  determination  of  the  relative  volume  of  corpuscles  and 
plasma  is  most  useful  in  cases  where  the  average  size  of  the  erythro- 
cytes departs  from  the  normal,  and  where,  accordingly,  the  enumera- 
tion of  the  corpuscles  would  give  an  erroneous  idea  of  thf^ir  total  mass. 

Laking  of  Blood,  or  Haemolysis.- — Even  in  thin  layers  blood  is 
opaque,  owing  to  reflection  of  tlie  light  by  the  red  corpuscles.  It 
becomes  transparent  or  '  laky  '  when  by  any  means  the  pigment 
is  brought  out  of  the  corpuscles  and  goes  into  true  solution.  Re- 
peated freezing  and  thawing  of  the  blood,  the  addition  of  water, 
the  passage  of  electricaJ  currents,  constant  and  induced,*  putre- 
faction, heating  the  blood  to  60°  C.,  and  many  chemical  agents  (as 
bile-salts,  ether,  saponin),  cause  this  change.  Certain  complex 
poisons  of  animal  origin,  such  as  snake- venoms,  bee-poison,  spider- 
poison  or  arachnolysin,  and  certain  toxins  produced  by  pathogenic 
bacteria — -for  instance,  tetanolysin,  formed  by  the  tetanus  bacillus 
— also  possess  decided  hsemol\i;ic  power.  The  blood-serum  of 
certain  animals  acts  on  the  coloured  corpuscles  of  others,  and  sets 
free  their  pigment — for  example,  the  serum  of  the  dog  or  ox  causes 
haemolysis  of  rabbit's  corpuscles;  the  serum  of  the  ox,  goat,  dog, 
or  rabbit  lakes  guinea-pig's  corpuscles.  But  rabbit's  serum  does 
not  lake  dog's  corpuscles,  and  guinea-pig's  serum  is  inactive  towards 
the  corpuscles  both  of  the  rabbit  and  the  dog.  It  has  been  shown 
that  in  haemoh^sis  bv  foreign  serum  two  bodies  are  concerned:  one, 
which  is  easilv  destroyed  by  heating  to  about  56°  C,  the  so-called 
complement,  and  another,  the  intermediary  body  or  amboceptor, 
which  is  not  affected  by  being  heated  to  this  temperature.  Thus 
if  dog's  serum  be  heated  to  56°  C.  for  twenty  minutes,  no  amount 
of  it  will  lake  rabbit's  washed  corpuscles— that  is,  rabbit's  corpuscles 
freed  from  their  own  serum  by  repeated  washing  with  salt  solution 
and  centrifugalization.  If,  however,  serum  which  is  not  itself 
haemol^-tic  for  rabbit's  blood  {e.g.,  rabbit's  or  guinea-pig's  serum) 
be  added  to  the  washed  rabbit's  corpuscles,  they  will  be  laked  by 
the  heated  dog's  serum.  Unheated  dog's  serum  will  lake  rabbit's 
corpuscles,  whether  they  have  been  washed  free  from  their  own 
serum  or  not  (Practical  Exercises,  p.  71). 

The  hypothesis  which  best  explains  these  facts  and  many  similar 
ones  is  that  dog's  serum  contains  both  of  the  bodies  necessary  for 
haemolysis  of  rabbit's  corpuscles.  When  the  complement  has  been 
rendered  inactive  by  heating,  the  amboceptor  cannot  cause  laking 

•  The  laking  action  of  induced  currents  is  due  simply  to  the  heating  of  the 
blood.  Condenser  discharges,  which  cause  liberation  of  the  haemoglobin 
without  raising  the  temperature  of  the  blood  as  a  whole  to  the  point  at  which 
heat-laking  occurs,  possibly  act  in  the  same  way  by  causing  local  heating  of 
the  corpuscles  owing  to  their  high  resistance. 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         29 

by  itself.  Rabbit's  serum  contains  complement,  but  not  the 
specific  amboceptor  necessary  for  the  laking  of  rabbit's  corpuscles. 
Accordingly,  the  addition  of  fresh  rabbit's  serum  to  heated  dog's 
scrum  restores  complement  to  the  latter,  and  thus  it  is  again  ren- 
dered active  for  rabbit's  corpuscles.  The  amboceptor  is  supposed 
to  unite  on  the  one  hand  with  certain  groups  in  the  corpuscle  and 
on  the  other  with  the  complement,  which  is  thus  enabled  to  develop 
its  hi€mol}d;ic  action  upon  the  envelope  or  the  stroma.  The  com- 
plement is  incapable  of  acting,  even  in  the  presence  of  amboceptor, 
if  the  temperature  is  reduced  to  0°  C.  Nevertheless,  the  corpuscles 
take  up  amboceptor  at  this  temperature,  and  on  this  fact  is  based 
a  method  of  freeing  serum  from  amboceptor.  For  example,  if 
dog's  serum  and  excess  of  rabbit's  washed  corpuscles,  both  pre- 
viously cooled  to  0°  C,  be  mixed  and  placed  at  0°  C  for  some  hours, 
and  the  serum  then  removed,  it  will  be  found  that  it  has  lost  the 
power  of  laking  rabbit's  corpuscles,  washed  or  unwashed,  at  air  or 
body  temperature,  although  it  will  still  do  so  on  the  addition  of 
dog's  serum  in  which  the  complement  has  been  destroyed  by 
heating  it  to  56°  C  The  real  nature  and  mode  of  action  of  com- 
plements and  amboceptors  are  not  yet  satisfactorily  determined. 
The  laws  of  chemical  equivalents  and  definite  proportions  do  not 
seem  to  be  observed  in  the  reactions  into  which  they  enter.  It  has 
therefore  been  suspected  that  the  bodies  in  question  belong  to  the 
group  of  ferments,  or  are  closely  related  thereto,  and  there  is  some 
evidence  that  a  fat-splitting  enzyme,  or  lipase,  is  concerned  in  the 
complement  action  (Jobling). 

As  to  the  manner  in  which  hasmolytic  agents  cause  the  hberation  of 
the  blood-pigment,  the  fact  that  in  so  many  forms  of  laking  the  cor- 
puscles swell  up  before  the  heemoglobin  escapes  indicates  that  the 
entrance  of  water  is  an  important  step.  The  entrance  of  water  is 
favoured  by  changes  produced  in  the  chemical  and  physical  condition 
of  certain  constituents  of  the  superficial  layer  (envelope)  of  the  cor- 
puscle, as  well  as  by  changes  in  its  interior.  Saponin  and  ether,  for 
example,  are  known  to  be  solvents  of  cholesterin  and  lecithin,  and 
cholesterin  and  lecithin  are  important  constituents  of  the  stroma  and 
envelope  of  the  erjirhrocyte.  It  is  easy  to  understand  that  if  a  portion 
of  one  or  both  of  these  substances  is  dissolved,  or  altered  without  being 
actually  dissolved,  profound  changes  may  be  produced  in  the  permea- 
bility of  the  corpuscle  to  water  and  to  the  salts  dissolved  in  the  liquid 
in  which  the  erythrocytes  are  suspended.  In  addition  to  this  change 
of  permeability,  many  laking  agents,  perhaps  all,  exert  also  a  more  direct 
influence  on  the  normal  relations  of  the  native  blood-pigment  to  tlu 
stroma.  Ether  and  saponin,  for  instance,  seem  to  act  in  two  ways — 
bv  disorganizing  the  envelope  through  solution  of  its  lipoids,  and  thus 
increasing  its  permeability  to  water;  and  by  helping  to  dissociate  the 
blood-pigment-stroma  complex  by  exerting  a  pull  on  the  lipoids  of  the 
stroma,  while  the  water  simultaneously  exerts  a  pull  on  the  pigment. 

The  conclusion  follows  from  this  view  of  haemolysis,  that  the  erythro- 
cytes, normally  so  perfectly  adapted  to  the  plasma  in  which  they  float, 
may.  when  the  conditions  on  which  their  equihbrivun  with  it  depends 


30  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

are  altered,  be  rapidly  and  inevitably  destroyed  by  that  very  plasma 
itself.  It  is,  indeed,  the  very  fact  of  the  exquisite  adaptation  of  liquid 
and  cell  for  a  strictly  regulated  exchange  of  material  which  constitutes 
the  danger  when  the  regulation  is  upset.  A  liquid  like  mercury,  which 
is  not  adapted  either  to  give  anything  to  erythrocytes  in  contact  with 
it  or  to  take  anything  from  them,  would  not  cause  hajmolysis,  even  if 
the  permeability  of  the  corpuscles  for  water  or  sodium  chloride  were 
increased  to  any  extent.  The  continued  survival  of  the  erythrocytes  in 
an  aqueous  solution  of  salts  and  proteins  like  the  plasma — nay,  more, 
the  protection  of  the  corpuscles  up  to  a  certain  point  by  the  plasma 
against  the  attack  of  extraneous  haemolytic  agents — are  facts  we  are 
prone  to  take  so  much  for  granted  as  to  forget  that  they  depend  entirely 
upon  a  most  delicate  adjustment  of  the  permeability  of  the  corpuscles 
for  essential  constituents  of  the  plasma.  Disturb  these  relations  to  a 
sufficient  degree,  and  the  plasma  becomes  a  poison  to  tlie  erythrocytes 
not  much  less  deadly  than  distilled  water. 

When  we  add  to  blood  a  hemolytic  substance,  and  see  that  presently 
the  blood-pigment  has  left  the  corpuscles,  we  are  apt  to  attribute  the 
whole  effect  to  the  foreign  material  added,  and  to  say  that  the  saponin, 
the  ether,  the  alien  serum,  has  laked  the  blood.  In  a  certain  sense  this 
is  true,  but  it  is  not  the  whole  truth.  In  reality  the  h^emolytic  agent 
has  acted  in  an  essential  degree,  although  not  exclusively,  by  overthrow- 
ing the  equilibrium  between  the  corpuscles  and  the  aqueous  solution 
of  certain  substances  in  which  they  are  suspended.  To  say  that  the 
foreign  substance  alone  causes  the  hemolysis  is  no  more  accurate  than 
it  would  be  to  say  that  a  man  swimming  strongly  in  a  rough  sea,  who 
sinks  when  hit  and  stunned  by  a  piece  of  wreckage,  was  drowned  by 
the  blow,  and  not  by  the  sea.  No  doubt  it  is  true  that,  but  for  the 
blow,  he  would  have  continued  to  swim;  yet,  in  reality,  he  loses  his  life 
because  he  is  environed  by  a  medium  deadly  to  him  as  soon  as  his  power 
of  adjustment  to  it  has  been  too  much  diminished.  On  land,  the  blow 
would  have  stunned,  but  would  not  have  killed  him.  In  like  manner, 
to  glance  at  one  phase  of  the  natural  decay  of  the  corpuscles  within  the 
body,  an  erythrocyte  may  float  secure  in  its  watery  environment 
through  many  rounds  of  the  circulation.  But  its  security  is  not  static, 
like  that  of  a  log  floating  on  the  water.  It  is  dynamic,  a  triumph  of 
perfect  physico-chemical  poise,  as  the  security  of  the  swimmer,  still 
more  of  the  tight-rope  dancer,  is  dynamic,  a  triumph  of  perfect  neuro- 
muscular poise.  The  time,  however,  arrives  when,  either  through 
changes  in  the  corpuscle  itself  (the  changes  of  cellular  senility,  as  we 
may  call  them),  or  through  changes  in  the  environing  medium,  or 
through  a  combination  of  the  two,  the  adjustment  is  upset,  and  the 
erythrocyte  is  now  destroyed  by  the  plasma  in  which  it  has  so  long 
lived . 

In  general  haemolysis  by  foreign  serum  is  preceded  by  agglutina- 
tion or  aggregation  of  the  corpuscles  into  groups.  Agglutination 
may  be  obtained  without  haemolysis  by  heating  the  haimolytic 
serum  to  the  temperature  at  which  the  complement  is  destroyed, 
since  the  agglutinating  agents,  or  agglulinins,  are  relatively  resistant 
to  heat.  Besides  the  amboceptors  naturally  present  in  the  blood 
of  certain  animals,  and  capable,  in  conjunction  with  complement,  of 
hsemolyzing  the  corpuscles  of  certain  other  animals,  amboceptors 
may  be  produced  in  much  greater  strength  by  artificial  means. 


CEXERAL   PHYSICAL  AMD  CHhMlCAL  PROPERIII-.S         31 

When  the  corpuscles  of  one  animal  are  injected  intraperitoneally 
or  subcutaneously  into  an  animal  of  a  different  kind,  the  serum  of 
the  latter  acquires  the  property  of  agglutinating  and  laking  the 
corpuscles  of  an  animal  of  the  same  kind  as  that  whose  corpuscles 
have  been  injected.  This  is  especiall}'  marked  if  the  injection  is 
several  times  repeated  at  intervals  of  a  few  days.  If,  for  instance, 
dog's  corpuscles  are  injected  into  a  rabbit,  the  rabbit's  serum  after 
a  time  becomes  strongly  hgemolytic  for  dog's  corpuscles.  It  also 
agglutinates  them.  This  is  due  to  the  appearance  in  the  rabbit's 
serum  of  an  amboceptor  and  an  agglutinin  which  have  a  specific 
action  on  dog's  corpuscles.  Such  a  serum  is  often  termed  an 
immune  serum,  and  the  animal  which  has  received  the  injections 
is  spoken  of  as  immunized  in  regard  to  this  particular  kind  of 
corpuscles.  For  the  reaction  involved  in  the  production  of  the 
amboceptor  and  agglutinin  is  a  particular  case  of  the  peculiar  and 
specific  response  which  the  body  makes  to  the  presence  of  foreign 
juices  or  cells,  including  bacteria,  and  which  constitutes  an  attempt 
to  render  itself  '  immune  '  to  them. 

Many  other  animal  cells  besides  the  coloured  blood- corpuscles  give 
rise,  when  injected,  to  similar  specific  substances  (cytolysins),  which 
cause  destruction  of  cells  of  the  same  kind — e.g.,  leucocytes  and 
spermatozoa.*  The  process  of  haemolysis  is  more  easily  followed 
than  the  cytol3^sis  of  ordinary  cells.  Yet  in  its  main  features  it  is 
essentially  similar. 

In  each  case  the  specific  antibody  seems  to  be  produced  in  response 
to  the  presence  of  some  particular  constituent  of  the  foreign  cell.  The 
substances  which  on  injection  give  rise  to  antibodies  are  spoken  of  as 
antigens.  In  tlie  case  of  the  ery-throcj^tes  there  is  evidence  that  the 
antigens  (both  the  haemolj-sinogen,  which  causes  the  production  of 
specific  amboceptor,  and  the  agglutininogen,  the  substance  which  gives 
rise  to  specific  agglutinin)  are  lipoids,  or  are  so  closely  associated  with 
the  lipoids  of  the  corpuscles  that  they  are  extracted  by  the  same  solvents. 
Thus  ethereal  extracts  of  erythrocytes  cause  the  production  of  hasmol- 
ysin  and  agglutinin,  just  as  the  entire  corpuscles  do.  The  group  of 
antibodies  known  as  precipitins  is  of  special  interest. 

Precipitins.- — When  the  serum  of  one  animal  is  injected  into 
another  of  a  different  group,  the  serum  of  the  latter  acquires  the 
property  of  causing  a  precipitate  in  the  normal  serum  of  animals 
of  the  same  group  as  that  whose  serum  was  injected,  but  not 

*  Recent  studies  have  tended  to  modify  the  view  that  the  cytotoxins 
formed  after  the  introduction  of  different  foreign  tissues  into  animals  are 
quite  specific  for  each  tissue.  Thus  Lambert,  using  tissues  cultivated  on 
media  outside  of  the  body  for  testing  the  toxic  action,  finds  that  the  plasma 
of  guinea-pigs  which  have  received  injections  of  either  chick  embryo  heart  or 
intestine  becomes  toxic  for  both  of  these  tissues.  In  like  manner  the  plasma 
of  guinea-pigs  treated  by  injection  of  rat  sarcoma,  a  tumour  which  can  be 
propagated  by  inoculation  in  rats,  acquires  a  toxic  action  on  cultures  of  both 
rat  sarcoma  and  the  skin  of  embryo  rats.  And  the  plasma  of  guinea-pigs 
treated  with  rat  embryo  skin  is  also  toxic  for  cells  of  both  types. 


32  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

in  the  serum  of  any  other  kind  of  animal.  Thus,  if  human  blood 
or  serum  is  repeatedly  injected  at  short  intervals  int(j  a  rabbit,  tiie 
serum  of  the  rabbit  will  cause  a  precipitate  in  diluted  human  blood 
or  serum,  but  not  in  the  blood  or  serum  of  other  animals,  except 
that  of  monkeys,  where  a  slight  reaction  may  be  obtained.  The 
specific  bodies  which  cause  the  precipitation  are  termed  precipitins. 
The  phenomenon  has  been  made  the  basis  of  a  method  of  dis- 
tinguishing human  blood  for  forensic  purposes.  Other  animal 
tiuids  and  solutions  containing  tissue  proteins  likewise  give  rise  to 
the  production  of  precipitins.  Thus,  when  cow's  milk  is  injected 
into  a  rabbit,  the  rabbit's  serum  acquires  the  power  of  precipitating 
the  caseinogen  of  cow's  milk.  Indeed,  the  response  of  the  animal 
body  to  the  presence  of  foreign  proteins  is  so  catholic,  and  at  the 
same  time  so  approximately  specific,  that  many  artificially  isolated 
proteins,  even  those  of  vegetable  origin,  after  as  careful  purifica- 
tion as  possible,  occasion,  when  injected,  the  production  of  anti- 
bodies which  will  precipitate  from  a  solution  only  the  variety  of 
protein  injected,  or  sometimes  also,  though  in  slighter  degree,  pro- 
teins nearly  related  to  it. 

Anaphylaxis. — Under  certain  conditions  the  injection  of  a  toxin,  a 
serum,  or  a  protein  solution,  instead  of  chciting  an  immunity  reaction 
which  tends  to  combat  the  eft'ects  of  a  subsequent  injection  of  the  same 
material,  produces  the  opposite  result — namely,  a  sensitization  of  the 
animal  which  renders  the  second  dose  far  more  harmful  than  the  first. 
Thus,  Kichet  found  that  animals  into  which  eel  serum,  or  the  poison 
contained  in  the  tentacles  of  Actinaria,  was  subcutaneously  introduced 
became  much  more  sensitive  to  the  toxic  action  of  a  second  injection. 
This  phenomenon  he  designated  anaphylaxis,  as  being  the  opposite  of 
the  prophylaxis  or  protection  afforded  by  previous  treatment  with  the 
toxins  hitherto  studied.  Later  on  it  was  discovered  that  tlie  sub- 
cutaneous injection  of  a  great  variety  of  proteins  alien  to  the  animal 
into  which  they  are  introduced  causes  anaphylaxis.  Only  very  minute 
amounts  are  necessary  for  the  first  or  sensitizing  dose,  and  an  interval 
considerably  greater  than  that  employed  in  the  production  of  an 
immune  serum  (p.  31)  is  allowed  to  elapse  before  the  second  injection 
is  made.  The  symptoms  induced  in  the  .sensitized  animal  by  a  subse- 
quent dose  of  the  same  material  used  in  sensitization  differ  somewhat 
in  different  animals,  but  may  be  designated  in  general  terms  as  those 
of  collapse  or  shock  (anaphylactic  shock).  They  have  been  especiallv 
studied  in  the  rabbit  and  guinea-pig,  the  heart  being  particularly  affected 
in  the  former,  and  the  lungs  in  the  latter.  Tiie  symptoms  are  very 
severe,  and  manifest  themselves  within  a  very  short  time  (a  few  minutes) 
ol  the  injection.  A  large  proportion  of  the  animals  die.  If  an  animal 
recovers,  it  does  so  suddenly,  and  for  some  time  afterwards  it  is  in- 
sensitive to  the  particular  protein.  While  the  real  nature  of  protein 
sensitization  or  anaphylaxis  is  not  as  yet  understood,  it  affords  a  new 
and  delicate  test  for  the  detection  and  discrimination  of  proteins,  and 
has  already  been  utiHzed  in  a  number  ol  practical  applications.  For 
instance,  the  sophistication  of  sausages  with  other  than  the  orthodox 
ingredients — e.g.,  witli  lionseflcsh — can  be  thus  exposed,  since  an  animal 
sensitized  by  horseflesh  will  exhibit  anaphylaxis  to  horseflesh,  but  not 
to  beef  or  pork.     In  like  manner,  the  anaphylactic  reaction  may  be 


GENERAL  PHYSICAf.  AXD  CHEMICAL  PROPERTIES         33 

iiseJ  lor  the  klciitific.ition  of  human  blood.  It  is  probable  that  an- 
aphylaxis plays  an  important  role  in  certain  pathological  reactions.  It 
is  well  known,  for  example,  that  some  persons  are  so  susceptible  to 
particular  foods  that  the  slightest  indulgence  in  them  brings  on  an 
attack  of  urticaria  or  nettlerash.  it  has  been  suggested  that  these 
persons  have  become  sensitized  to  certain  foreign  proteins — such  as 
those  existing  in  eggs,  veal,  pork,  strawberries,  shellfish,  or  whatever 
the  peccant  article  of  diet  may  be — possibly  by  absorption  at  some 
previous  time,  owing  to  gastro-intestinal  disturbance,  of  small  quan- 
tities of  the  proteins  which  have  escaped  complete  digestion. 

It  is  only  when  proteins  arc  introduced  parenterally  (i.e.,  by  some 
other  route  than  the  alimentary  canal,  such  as  the  subcutaneous  tissue, 
the  blood,  or  the  serous  cavities)  that  the  immunity  reactions  already 
described  and  the  phenomenon  of  anaphylaxis  can  be  experimcntallj'' 
produced.  For  in  digestion  the  protein  molecule  is  decomposed,  and 
although,  as  will  be  seen  later  on,  the  decomposition  products  are  not 
the  same  for  each  kind  of  protein,  the  factor  on  which  the  specificity 
of  the  molecule  depends  does  not  survive  the  hydrolysis. 


Coagulation  of  the  Blood. 

Since  changes  begin  in  the  blood  as  soon  as  it  is  shed,  having 
for  their  outcome  clotting  or  coagulation,  we  have  to  gather  from 
the  composition  of  the  stable  factors  of  clotted  blood,  or  of  blood 
which  has  been  artificially  prevented  from  clotting,  some  notion  of 
the  composition  of  the  unalteied  fluid  as  it  circulates  within  the 
vessels.  The  first  step,  therefore,  in  the  study  of  the  chemistry 
of  blood  is  the  study  of  coagulation. 

When  blood  is  shed,  its  viscidity  soon  begins  to  increase,  and 
after  an  interval,  varying  with  the  kind  of  blood,  the  temperature 
of  the  air,  and  other  conditions,  but  in  man  seldom  exceeding  ten, 
or  falling  below  three,  minutes,  it  sets  into  a  firm  jelly.  This  jelly 
gradually  shrinks  and  squeezes  out  a  straw-coloured  liquid,  the 
serum.  Under  the  microscope  the  serum  is  seen  to  contain  few  or 
no  red  corpuscles;  these  are  nearly  all  in  the  clot,  entangled  in  the 
meshes  of  a  kind  of  network  of  fine  fibrils  composed  of  fibrin.  In 
uncoagulated  blood  no  such  fibrils  are  present ;  they  have  accordingH' 
been  formed  by  a  change  in  some  constituent  or  constituents  of 
the  normal  blood.  Now,  it  has  been  shown  that  there  exists  in  the 
plasma — nhe  liquid  portion  of  unclotted  blood — -a  substance  from 
which  fibrin  can  be  derived,  while  no  such  substance  is  present  in 
the  corpuscles.  In  various  ways  coagulation  can  be  prevented  or 
delayed,  and  the  plasma  separated  from  the  corpuscles.  For 
example,  the  blood  of  the  horse  clots  very  slowly,  and  a  low  tem- 
perature lessens  the  rapidity  of  coagulation  of  every  kind  of  blood. 
If  horse's  blood  is  run  into  a  vessel  surrounded  by  ice  and  allowed 
to  stand,  the  corpuscles,  being  of  greater  specific  gravity  than  the 
plasma,  gradually  sink  to  the  bottom,  and  the  clear  straw-yellow 
plasma  can  be  pipetted  off.     Or  the  addition  of  neutral  salts  to 

3 


34  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

blood  may  be  used  to  delay  coagulation,  the  blood  being  run  direct 
from  the  animal  into,  say,  a  third  of  its  volume  of  saturated  mag- 
nesium sulphate  solution.  The  plasma  may  then  be  conveniently 
separated  from  the  corpuscles  by  means  of  a  centrifugal  machine. 
Again,  two  ligatures  may  be  placed  on  a  large  bloodvessel,  so  that 
a  portion  of  it  can  be  excised  full  of  blood  and  suspended  vertically 
(the  so-called  experiment  of  the  '  living  test-tube  ') ;  coagulation 
is  long  delayed,  and  the  corpuscles  sink  to  the  lower  end.  In  these 
and  man}-  other  ways  plasma  free  from  corpuscles  can  be  got ;  and 
it  is  found  that  when  the  conditions  which  restrain  coagulation  are 
removed— when,  for  instance,  the  temperature  of  the  horse's  plasma 
is  allowed  to  rise  or  the  magnesium  sulphate  plasma  is  diluted  with 
several  times  its  bulk  of  water— clotting  takes  place,  with  forma- 
tion of  fibrin  in  all  respects  similar  to  that  of  ordinary  blood-clot. 
The  corpuscles  themselves  cannot  form  a  clot.*  From  this  we  con- 
clude that  the  essential  process  in  coagulation  of  the  blood  is  the 
formation  of  fibrin  from  some  constituent  of  the  plasma,  and  that 
the  presence  of  corpuscles  in  ordinary  blood-clot  is  accidental. 
In  accordance  with  this  conclusion,  we  find  that  l>-mph  entirely 
free  from  red  corpuscles  clots  spontaneously,  with  formation  of 
fibrin ;  and  when  fibrin  is  removed  from  newly  shed  blood  by  whip- 
ping it  with  a  bundle  of  twigs  or  a  piece  of  wood,  it  will  no  longer 
coagulate,  although  all  the  corpuscles  are  still  there. 

What,  now,  is  the  substance  in  the  plasma  which  is  changed  into 
fibrin  when  blood  coagulates  ?  If  plasma,  obtained  in  any  of  the 
ways  described,  be  saturated  with  sodium  chloride,  a  precipitate  is 
thrown  down.  The  filtrate  separated  from  this  precipitate  does  not 
coagulate  on  dilution  with  water;  but  the  precipitate  itself — the 
so-called  plasmine  of  Denis — on  being  dissolved  in  a  little  water, 
does  form  a  clot.  Fibrin  is  therefore  derived  from  something  in 
this  precipitate.  Now,  '  plasmine  '  contains  two  protein  bodies — 
fibrinogen,  which  coagulates  by  heat  at  about  56°  C,  and  serum- 
globulin,  which  coagulates  at  about  75°  C,  and  it  was  at  one  time 
believed  that  both  of  these  entered  into  the  formation  of  fibrin 
(Schmidt).  Hammersten,  however,  has  sho\\Ti  that  fibrinogen  alone 
is  a  precursor  of  fibrin;  pure  serum-globulin  neither  helps  nor 
hinders  its  formation.  This  obser\-er  isolated  fibrinogen  from  blood- 
plasma  by  adding  sodium  chloride  till  about  13  per  cent,  was 
present.  With  this  amount  the  fibrinogen  is  precipitated,  while 
serum-globulin  is  not  precipitated  till  20  per  cent,  of  salt  is  reached. 
After  precipitation  of  the  fibrinogen,  the  plasma  no  longer  coagu- 
lates; and  a  solution  of  pure  fibrinogen  can  be  made  to  clot  and 
to  form  fibrin,  while  a  solution  of  serum-globulin  cannot.     Blood- 

*  Bird's  corpuscles,  however,  washed  free  from  plasma,  will  form  a  clot 
when  laked  in  various  ways,  as  by  addition  of  water  or  by  freezing  and 
thawing. 


COAGULATION  35 

serum,  too,  which  contains  abundance  of  serum-globuHn,  but  no 
fibrinogen,  will  not  coagulate. 

So  far,  then,  we  have  reached  the  conclusion  that  fibrin  is  formed 
by  a  change  in  a  subsfance,  fibrinogen,  which  can  be  obtained  by 
certain  methods  from  blood-plasma.  It  may  be  added  that  there 
is  evidence  that  fibrinogen  exists  as  such  in  the  circulating  blood; 
for  if  unclotted  blood  be  suddenly  heated  to  about  56°  C,  the  tem- 
perature of  heat-coagulation  of  fibrinogen,  the  blood  for  ever  loses 
its  power  of  clotting.  The  liver  seems  to  be  an  important  place  of 
origin  of  fibrinogen,  which  may  also  be  formed  in  the  bone-marrow. 
That  the  liver  is  intimatel}'  concerned  in  the  production  of  fibrinogen 
is  indicated  by  a  number  of  facts.  In  phosphoras  poisoning,  and 
notably  in  poisoning  by  chloroform,  which  causes  necrosis,  especially 
of  the  central  portions  of  the  hepatic  lobules,  the  amount  of 
fibrinogen  in  the  blood  is  quickly  diminished.  The  diminution  is 
proportional  to  the  extent  of  the  injury  to  the  liver,  and  the  blood 
loses  more  or  less  completely  its  power  of  clotting.  If  the  injury 
is  repaired,  the  fibrinogen  is  rapidly  regenerated  (Whipple).  If  the 
blood  is  allowed  to  circulate  for  a  time  in  the  head  and  thorax  of 
an  animal  without  passing  into  the  rest  of  the  animal's  body,  it 
becomes  incoagulable,  and  the  fibrinogen  is  found  to  be  markedly 
deficient  in  amount.  When  the  blood  of  an  animal  is  defibrinated 
by  whipping,  and  reinjected,  regeneration  of  the  fibrinogen  does 
not  occur  if  the  liver  has  been  eliminated,  whereas  it  takes  place 
rapidly  if  the  liver  is  intact  (Meek) . 

Since  fibrinogen  is  readily  soluble  in  dilute  saline  solutions,  and 
fibrin  only  soluble  with  great  diflficult^^  we  may  say  that  in  coagu- 
lation of  the  blood  a  substance  soluble  in  the  plasma  passes  into  an 
insoluble  form.  How  is  this  change  determined  when  blood  is 
shed  ?  We  have  said  that  a  solution  of  pure  fibrinogen  can  be 
made  to  coagulate,  but  it  does  not  coagulate  of  itself.  The  addition 
of  another  substance  in  minute  quantity  is  necessary.  This  sub- 
stance, to  which  the  name  thrombin  has  been  applied,  can  be 
obtained  in  various  ways,  although  not  in  a  state  of  purity;  for 
example,  by  precipitating  blood-serum,  or  defibrinated  blood,  with 
fifteen  to  twenty  times  its  bulk  of  alcohol,  letting  the  whole  stand 
for  a  month  or  more,  and  then  extracting  the  precipitate  with 
water.  All  the  ordinary  proteins  of  the  blood  having  been  ren- 
dered insoluble  by  the  alcohol,  the  thrombin  passes  into  solution 
in  the  water,  and  the  addition  of  a  trace  of  the  extract  to  a  solution 
of  fibrinogen  causes  coagulation.  When  purified  as  well  as  possible, 
thrombin  still  gives  protein  reactions,  but  it  is  not  known  whether 
it  is  really  a  protein. 

The  action  of  thrombin  on  fibrinogen  helps  to  explain  many 
experiments  in  coagulation.  Thus,  transudations  like  hydrocele 
fluid  do  not  clot  spontaneously,  although  they  contain  fibrinogen, 


36  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

which  can  be  precipitated  from  them  by  a  stream  of  carbon  dioxide 
or  by  sodium  chloride.  But  the  addition  of  a  httle  thrombin 
causes  hydrocele  fluid  to  coagulate.  So  does  the  addition  of  serum, 
not  because  of  the  serum-globulin  which  it  contains,  as  was  once 
believed,  but  because  of  the  thrombin  in  it.  The  addition  of  blood- 
clot,  either  before  or  after  the  corpuscles  have  been  washed  away, 
or  of  serum-globuUn  obtained  from  serum,  also  causes  coagulation 
of  hydrocele  fluid,  and  for  a  similar  reason,  the  thrombin  having  a 
tendency  to  cling  to  everything  derived  from  a  liquid  containing 
it.  On  the  other  hand,  serum  which,  although  thrombin  is  present 
in  it,  does  not  of  itself  clot,  because  the  fibrinogen  has  all  been 
changed  into  fibrin  during  coagulation  of  the  blood,  can  be  made 
to  coagulate  by  the  addition  of  hydrocele  fluid,  which  contains 
fibrinogen.  We  have  thus  arrived  a  step  farther  in  our  attempt  to  ex- 
plain the  coagulation  of  the  blood :  it  is  essentially  due  to  the  formation 
of  fibrin  front  the  fibrinogen  of  the  plasma  under  the  infitience  of 
thrombin.  Up  to  this  point  there  is  agreement  between  physiologists. 
Some  difference  of  opinion  exists,  however,  as  to  the  manner  in 
which  thrombin  is  formed  or  activated  when  blood  is  shed,  aud  a? 
to  the  nature  of  its  action  upon  fibrinogen  once  it  is  fully  formed. 

The  Formation  of  Thrombin  from  its  Precursors. — There  is  good 
reason  to  believe  that  thrombin  is  formed  by  the  interaction  of  three 
factors:  (i)  A  substance  which,  since  it  is  a  precursor  of  thrombin, 
is  called  thrombogen,  or  prothrombin.  It  is  already  present  in  the 
circulating  plasma.  (2)  A  substance  liberated  from  the  formed  ele- 
ments of  the  shed  blood,  but  which  can  be  obtained  also  from  the 
cells  of  all  tissues.  Since  it  has  been  supposed  to  act  upon  throm- 
bogen, changing  it  into  fully  formed  thrombin,  much  in  the  same 
way  as  enterokinase  (p.  37c)  acts  upon  trypsinogen,  changing  it 
into  fully  formed  trypsin,  it  is  called  thrombokinase  (Morawitz). 
(3)  Calcium  ions.  The  following  experiments  illustrate  the  role  of 
these  three  factors: 

The  plasma  obtained  by  drawing  off  bird's  blood — e.g.,  the  blood  of  a 
fowl  or  goose — through  a  perfectly  clean  cannula  into  a  perfectly  clean 
vessel,  without  contact  with  the  tissues,  and  tlicn  rapidlj'  centrifugal- 
izing  off  the  formed  elements,  can  be  kept  unclotted  for  days  and  even 
weeks.  The  addition  of  a  small  amount  of  tissue  extract  (procured  by 
rubbing  up  blood-free  liver,  thymus,  muscle,  or  other  organs  with  sand, 
and  extracting  for  several  hours  with  salt  solution)  to  the  bird's  plasma 
causes  rapid  coagulation.  The  plasma  contains  thrombogen  and 
calcium  salts,  but  is  lacking  in  thrombokinase,  which  is  supplied  by  the 
tissue  extract.  A  solution  of  fibrinogen  containing  calcium  will  clot 
if  serum,  in  which  fibrin-ferment  is  always  present,  be  added.  It  will 
not  clot  on  addition  of  tissue-extract  alone,  nor  on  addition  of  bird's 
plasma  alone  (obtained  as  above),  but  will  readily  coagulate  if  both 
tissue  extract  and  bird's  plasma  be  added.  Therefore,  something  in 
the  bird's  plasma  (thrombogen),  plus  something  in  the  tissue  extract 
(thrombokinase),  produce  in  the  presence  of  calcium  the  same  effect  as 
the  thrombin  of  serum.     It  can  be  shown  that  calcium  is  only  necessary 


COAGULATION  37 

for  the  formation  of  the  tlirombin,  but  not  for  its  action  on  fibrinogen. 
For  instance,  a  calcium-free  sohition  of  fibrinogen  can  be  made  to  clot 
by  serum  from  which  the  calcium  has  been  removed. 

If  a  soluble  oxalate  (potassium  or  ammonium  oxalate)  is  mixed  with 
freshly  drawn  dog's  blood  to  the  amount  of  o"2  or  03  percent.,  the  blood 
remains  unclotted.  The  plasma  separated  from  this  oxalatcd  blood 
contains  both  thrombogen  and  thrombokinasc,  but  it  docs  not  coagu- 
late, because  the  calcium  has  been  precipitated  out  in  the  form  of  in- 
soluble calcium  oxalate.  In  the  absence  of  calcium  the  reaction  of  the 
thrombogen  and  thrombokinase  which  leads  to  the  formation  of 
thrombin  does  not  take  place.  All  that  is  necessary  to  bring  about 
coagulation  is  to  add  calcium  chloride  in  somewhat  greater  quantity 
than  is  required  to  combine  with  any  excess  of  oxalate  present.  If  more 
than  a  certain  amount  of  calcium  be  added,  clotting  is  hindered  instead 
of  being  helped,  so  that  it  is  only  within  certain  limits  of  concentration 
that  calcium  favours  coagulation.  From  oxalate  plasma  a  nucleo- 
protein  or  a  mixture  of  nucleo-proteins  can  be  separated  which  contains 
thrombogen  and  thrombokinase,  but  little  or  no  calcium,  and  does  not 
cause  clotting,  but  which  on  treatment  with  a  calcium  salt  acquires  the 
properties  of  thrombin. 

When  sodium  fluoride  is  added  to  freshly  drawn  blood  to  the  amount 
of  o'3  per  cent.,  coagulation  is  also  prevented.  But  there  is  this  differ- 
ence between  oxalate  and  fluoride  plasma — that,  although  the  calcium 
has  been  precipitated  in  both,  the  addition  of  calcium  chloride  to  fluoride 
plasma  is  not  sufficient  to  induce  clotting.  Tissue  extract  containing 
thrombokinase  must  be  supplied  as  well.  In  some  way  or  other  sodium 
fluoride  interferes  with  the  liberation  of  thrombokinase  from  the  formed 
elements  of  the  blood,  although  in  the  concentration  mentioned  it  does 
not  hinder  the  action  of  fully  formed  thrombin,  as  is  shown  by  the  fact 
that  fluoride  plasma  coagulates  on  the  addition  of  a  little  serum,  which 
supplies  thrombin.  The  fluoride  blood  clots  readily  if  it  is  diluted  with 
water,  and  at  the  same  time  mixed  with  calcium  chloride  solution,  for 
the  water  damages  the  formed  elements,  and  thus  favours  the  liberation 
of  thrombokinase. 

Sodium  citrate  solution  prevents  the  coagulation  of  blood  run  into 
it,  although  there  is  no  precipitation  of  the  calcium.  The  addition  of 
calcium  chloride  to  citrate  plasma  induces  clotting,  and  the  action  of 
the  citrate  is  assumed  to  be  due  to  the  formation  of  a  compound  with 
the  calcium  of  the  blood,  which  does  not  dissociate  so  as  to  yield  calcium 
ions.  It  ought  to  be  remarked,  however,  that  in  all  so-called  decalci- 
fied plasmas,  as  ordinarily  obtained,  blood-platelets  are  present,  and 
that  platelets  disintegrate  under  the  influence  of  calcium  salts.  It 
has  been  shown,  indeed,  that  many  of  the  reagents  and  procedures 
which  hinder  the  clotting  of  shed  blood  also  prevent  the  breaking  up  of 
the  platelets.  Thus,  the  cooling  of  the  blood,  the  addition  of  hirudin, 
sodium  oxalate,  sodium  citrate,  manganese  salts,  etc.,  which  are 
classical  methods  used  in  obtaining  platelets  for  microscopical  study, 
are  also  classical  methods  of  hindering  coagulation.  These  facts  have 
not  hitherto  been  sufficiently  taken  account  of  in  interpreting  experi- 
ments on  decalcified  blood.  They  indicate  that  the  decalcifying  agents 
may  hinder  clotting  by  interfering  with  the  liberation  of  essential  sub- 
stances from  the  platelets,  and  that  this  may  be  the  decisive  factor,  and 
not  merely  the  withdrawal  of  the  calcium  from  the  field  where  the 
already  liberated  thrombokinase  and  thrombogen  would  otherwise 
react  to  form  thrombin. 

When  proteoses  (or  peptones)  are  injected  into  the  circulation  of  a 
dog  or  goose,  the  blood  is  deprived  of  the  power  of  coagulation.     The 


38  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

peptone  plasma  must  be  assumed  to  contain  both  thrombogcn  and 
thronibokinasc,  since  it  can  be  made  to  clot  in  various  ways  {e.g..  by  dilu- 
tion with  water  or  by  slight  acidulation  with  acetic  acid)  without  the 
addition  of  anything  which  could  supply  either  of  these  factors.  Yet 
a  little  tissue  extract  causes  it  to  clot  much  more  rapidly  than  simple 
dilution  or  acidulation,  and  more  rapidly  than  the  addition  of  serum. 
So  that  either  the  thrombokinase  already  present  in  peptone  plasma  is 
present  in  an  unavailable  form,  or  in  some  way  the  formation  of  throm- 
bin from  its  precursors  is  hindered.  .But  this  is  not  the  only  cause  of 
the  incoagulability  of  peptone  plasma.  It  may  be  shown  to  contain 
an  aiitithrombin,  a  body  which  antagonizes  the  action  of  fully  formed 
thrombin,  and  wliich  does  not  seem  to  be  a  ferment,  since  it  acts  quan- 
titatively in  proportion  to  the  amount  present.  This  is  the  reason  why, 
although  peptone  plasma  can  always  be  made  to  clot  by  the  addition 
of  fibrin  ferment,  in  serum,  for  instance,  relatively  large  quantities  of 
it  must  be  supplied  (Practical  Excixises,  pp.  64,  65). 


Fig.  5. — Fibrin  Formation  in  Horse's  Plasma  (Ultramicroscope)  (Stiibel).     Several 
clmnps  of  disintegrated  platelets  from  which  the  fibrin  filaments  radiate. 

An  extract  of  the  head  of  the  medicinal  leech  in  salt  solution  prevents 
the  clotting  of  blood  both  in  the  test-tube  and  when  injected  into  the 
circulation.  The  plasma  obtained  differs  from  peptone  plasma  in 
refusing  to  coagulate  unless  tissue  extract  is  added.  It  is  therefore 
deficient  in  thrombokinase,  or,  rather,  as  has  been  shown,  the  kinase 
present  is  unable  to  act,  because  neutralized  by  antikinase  present  in  the 
leech  extract.  Leech  extract  also  contains  an  antithrombin,  which  can 
be  neutralized  by  a  sufficient  amount  of  thrombin.  In  the  small 
wound  from  which  the  leech  sucks  blood  this  sufficient  amount  is  not 
present,  and  the  blood-remains  unclotted,  as  it  also  docs  in  the  alimen- 
tary canal  of  the  leech.  The  anticoagulant  substance,  hirudin,  has 
been  isolated,  and  gives  the  reactions  of  an  alburaose. 

Sources  of  Thrombogen  and  Thrombokinase.— It  has  already  been 
stated  that  thrombogen  exists  in  the  circulating  plasma.  This  is 
shown  by  the  fact  that  fluoride  plasma  obtained  from  blood  drawn 
directly  through  a  wide  cannula  into  sodium  fluoride  solution,  with 


COAGULATION 


39 


all  precautions  to  prevent  alteration  of  the  blood,  and  immediately 
separated  from  the  formed  elements  by  the  centrifuge,  will  clot 
on  the  addition  of  tissue  extract.  The  source  of  the  thrombogen 
has  been  thought  to  be  the  blood-plates,  but  this  has  not  been 
proved.  Throm])okinase  is  not  present  in  the  circulating  plasma. 
In  shed  and  clotting  blood  which  has  not  been  allowed  to  come  into 
contact  with  cut  tissues,  the  only  possible  sources  of  thrombokinase, 
so  far  as  we  know,  are  the  corpuscles  and  the  blood-plates.  The 
red  corpuscles  we  ma3^  at  once  dismiss,  for  although  the  stromata, 
especiallv  of  nucleated  corpuscles,  contain  thrombokinase,  or  can 
under  artificial  conditions  be  made  to  develop  that  action  on 
coagulation  by  which  we  recognize  its  presence,  not  only  do  they 
remain  intact  under  ordinary  circumstances  during  coagulation, 
but  there  is  strong  evidence,  as 
has  already  been  pointed  out, 
that  they  do  not  make  any  essen- 
tial contribution  to  the  process. 
We  have  left  over  the  leucocytes 
and  the  platelets,  and  it  is  highly 
probable  that  from  the  platelets 
thrombokinase  is  liberated  in  the 
first  moments  after  blood  is 
drawn,  and,  acting  on  the  throm- 
bogen already  present  in  the  plas- 
ma, changes  it  into  actual  throm- 
bin. This  surmise  is  strengthened 
by  the  fact  that  in  freshly  shed 
mammalian  blood  extensive  de- 
struction of  blood-plates  takes 
place.  Viewed  with  the  ultra- 
microscope,  the  blood-platelets, 
in   a  drop  of  clotting  plasma, 

which  are  at  first  homogeneous  in  appearance  (optically  empty), 
become  granular.  Then  the  platelets  begin  to  agglutinate  and 
swell  up,  and  the  agglutinated  platelets  are  transformed  into  clumps 
of  granules,  from  which  needles  of  fibrin  shoot  out.  Other  needles 
and  filaments  of  fibrin  form  in  contact  with  the  glass  or  free  in 
the  plasma,  and  soon  the  field  is  occupied  by  a  felt-work  of 
fibrin.  The  leucocytes  have  not  been  observed  to  be  related  to  the 
process,  at  least,  in  the  blood  of  mammals  (Stiibel).  It  is  true  that 
the  white  layer  or  '  buffy  coat '  which  tops  the  tardily  formed  clot 
of  horse's  blood,  and  consists  of  the  hghter,  and  therefore  more 
slowly  sinking  colourless  cells,  causes  clotting  in  otherwise  in- 
coagulable liquids  like  hydrocele  fluid  much  more  readily  than  the 
red  portion  of  the  clot,  and  yields  far  more  thrombin  on  treatment 
with  alcohol.     It  can  also  be  easily  verified  that  in  mammalian 


Fig .  6. — Fibrin  Formation  in  Plasma  from 
a  Case  of  Haemophilia  (Ultramicro- 
scope)  (Stiibel).  The  needles  of  fibrin 
cire  slowly  formed,  and  very  large. 


|o  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

blood  collected  in  paraffined  vessels,  so  as  to  delay  clotting,  and 
immediately  centrifugalized,  coagulation  begins  in  and  around  the 
layer  of  white  elements,  and  then  spreads  upwards  in  the  stratum 
of  plasma  and  downwards  in  the  stratum  of  erythrocytes.  But  in 
this  white  upper  layer  platelets  are  always  intermingled  with  leuco- 
cytes. It  has  been  shown,  however,  that  the  blood  of  the  cray- 
fish, which  coagulates  with  extreme  rapidity,  contains  certain 
colourless  corpuscles,  which  immediately  it  is  withdrawn,  break 
up  with  explosive  suddenness,  and  that  substances  which  hinder 
the  breaking  up  of  these  corpuscles  restrain  coagulation  (Hardy). 
In  the  blood  of  another  crustacean  Limnlus,  the  kingcrab,  coagula- 
tion is  preceded  by  an  agglutination  of  the  leucocytes  which  exhibit 
amoeboid  movements.  They  become  entangled  by  the  interlacing 
of  the  pseudopodia  which  they  protrude  (L.  Loeb). 

Thedisintegrationof  the  platelets  in  shed  blood  has  been  attributed 
by  Deetjen  to  an  increase  in  the  alkalinity  of  the  blood,  by  escape 
of  carbon  dioxide,  it  may  be.  \\'hen  blood  is  placed  on  a  quartz 
slide  and  covered  with  a  quartz  cover-slip,  the  platelets,  according 
to  this  observer,  do  not  break  up  ;  but  if  they  are  brought  into  con- 
tact with  a  medium  whose  OH  —  concentration  is  raised  ten  times 
or  more  above  that  of  freshly  drawn  blood  (still  only  a  weak  alka- 
line reaction),  disintegration  ensues.  He  supposes  that  the  contact 
of  glass  acts  harmfully  on  account  of  the  alkali  in  it.  It  is  im- 
possible to  say  at  present  whether  this  observation  has  any  bearing 
on  normal  coagulation. 

Thrombokinase  has  been  shown  to  exist  not  only  in  the  leuco- 
cj^tes,  the  platelets,  and  the  stromata  of  the  coloured  corpuscles,  but, 
as  already  stated,  in  all  tissues  hitherto  examined.  Under  ordinary 
circumstances  it  appears  that  a  larger  amount  of  thrombogen  is 
liberated  or  is  already  present  in  shed  blood  than  can  be  changed 
into  thrombin  by  the  thrombokinase  set  free,  since  serum  contains 
a  surplus  of  thrombogen  in  addition  to  the  fully  formed  ferment. 
This  is  shown  by  the  fact  that  the  activity  of  a  given  quantity  of 
serum  in  causing  the  coagulation  of  a  plasma  not  spontaneously 
coagulable  or  of  a  fibrinogen  solution  is  increased  by  the  addition 
of  tissue  extract  (containing  thrombokinase). 

The  thrombin  of  any  particular  kind  of  vertebrate  blood  has  no 
marked  specific  action— that  is,  will  cause  coagulation  in  solutions  of 
fibrinogen  or  plasma  of  very  different  origin.  For  example,  the 
sera  of  all  vertebrates  hitherto  investigated  induce  clotting  in 
goose's  plasma.  On  the  other  hand,  it  appears  that  a  greater  degree 
of  specificity  exists  in  the  case  of  the  thrombokinase  and  throm- 
bogen, the  specificity  being  absolute  in  some  cases,  relative  in  others. 
That  is  to  say,  the  thrombokinase  of  one  animal  may  activate  the 
thrombogen  of  an  animal  of  another  group,  while  it  may  fail  to 
activate  the  thrombogen  of  an  animal  belonging  to  a  third  group. 


COAGULATION  41 

But  it  will  always  activate  the  thrombogen  of  an  animal  of  the 
same  kind. 

To  sum  up,  we  may  say  that  when  blood  is  shed,  thrombin  is  rapidly 
formed  by  the  action  of  thrombokinase,  liberated  from  the  leucocytes, 
the  blood-plates,  and  possibly  to  some  extent  from  the  erythrocytes, 
upon  thrombogen,  already  present  in  the  circulating  plasma.  Further 
—and  this  is  of  great  practical  importance — since  no  vessel  is  opened 
under  ordinary  circumstances  except  through  a  wound  in  the  overly- 
ing structures,  the  cut  tissues  supply  a  store  of  thrombokinase  at 
the  point  tohere  it  is  required  to  aid  in  the  stanching  of  the  wound. 
Calcium  is  essential  to  the  reaction  by  which  thrombogen  and  thrombo- 
kinase form  thrombin,  but  is  not  necessary  for  that  action  of  thrombin 
on  Jlbrinoges  by  which  fibrin  is  produced  (Practical  Exercises, 
pp.  62-65). 

The  Nature  of  the  Action  of  Thrombin  on  Fibrinogen. — The  usual 
view,  first  advanced  by  Schmidt  many  years  ago,  is  that  thrombin 
acts  as  an  enzyme.  Hence  it  is  often  spoken  of  as  hbrin-ferment. 
In  support  of  this  theory  it  has  been  stated  that  the  thrombin 
does  not  itself  seem  to  be  used  up  in  the  process,  nor  to  enter  bodilx' 
into  the  fibrin  formed;  that  a  small  quantity  of  it  can  cause  an 
indefinitely  large  amount  of  fibrinogen  to  clot;  and  that  its  power 
is  abolished  by  boiling  (p.  333).  There  has  been  a  disposition 
among  more  recent  observers  to  question  this  evidence.  Accord- 
ing to  Rettger,  the  quantity  of  fibrin  formed  when  a  small  amount  of 
thrombin  is  added  to  a  fibrinogen  solution  tends  to  a  fixed  maxi- 
mum, which  does  not  increase  with  the  time  of  action.*  Under 
certain  conditions,  also,  it  is  said  that  thrombin  is  not  destroyed  at 
the  temperature  of  boiling  water.  Whatever  the  precise  nature  of 
the  reaction  which  leads  to  the  precipitation  of  the  fibrinogen  in  the 
form  of  fibrils,  thrombin  is  very  loosely  combined  if  combined  at 
all  in  the  fibrin,  since  it  is  readily  extracted  by  an  8  per  cent, 
solution  of  sodium  chloride.  This,  indeed,  is  one  of  the  best  ways 
of  obtaining  an  active  thrombin  solution. 

The  view  which  we  have  followed  above,  in  accordance  with 
Morawitz,  that  the  substances  in  tissue  extracts  which  favour 
coagulation  do  so  by  activating  prothrombin  to  fully  formed 
thrombin,  has  also  been  opposed  by  a  number  of  the  more  recent 
workers.  Some  consider  that  they  exert  a  direct  action  upon 
fibrinogen  similar  to,  although  not  necessarily  identical  with,  that 
of  thrombin,  and  speak  of  them  as  coagulins  (L.  Loeb).  Howell 
holds  that  these  substances,  which  he  prefers  to  term  thromboplastic 
substances,  since  this  makes  no  assumption  as  to  their  mode  of 
action,  play  a  quite  different,  role,  namely,  that  of  neutralizing  anti- 
thrombin.     His  observations  have  led  him  to  the  conclusion  that 

*  The  inquiry  is  complicated  by  the  fact  that  fibrin,  once  formed,  tends  to 
adsorb  the  remaining  thrombin  and  so  to  interfere  with  its  further  action. 


42  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

the  effective  thromboplastic  substance  in  the  tissues  is  a  plios- 
phatide,  probably  kephalin,  united  with  protein. 

Intravascular  Coagulation  Regulation  of  the  Clotting  Process, 
or  Thrombotaxis. — So  far  we  have  been  considering  the  problem 
of  coagulation  as  if  all  the  data  for  its  solution  could  be 
obtained  by  a  study  of  the  blood  itself.  In  other  words,  our  main 
business  up  to  this  point  has  been  the  explanation  of  coagulation 
in  the  shed  blood;  it  has  been  only  incidentally,  and  with  the  object 
of  casting  light  on  the  question  of  extravascular  clotting,  that  we 
have  touched  on  the  coagulation  of  the  blood  within  the  living 
vessels.  It  is  not  possible  here  to  adequately  discuss,  nor  even  to 
define,  the  differences  between  the  two  problems.  All  we  can  do 
is  to  warn  the  student,  and  to  emphasize  the  warning  by  one  or 
two  illustrations,  that  valuable  as  is  the  knowledge  derived  from 
experiments  on  extravascular  coagulation,  it  would  be  totally  mis- 
leading if  applied  without  modification  to  the  circulating  blood. 
For  instance,  we  have  recognized  in  the  blood-plates  an  important 
source  of  the  thrombokinase  which  plays  so  great  a  part  in  the 
clotting  of  shed  blood;  but  wc  may  be  sure  that  blood-plates  are 
constantly  breaking  down  in  the  lymph  and  the  blood,  and  we  have 
to  inquire  how  it  is  that  coagulation  does  not  occur,  except  in 
disease,  within  the  vessels.  Calcium  is  not  wanting  to  the  circu- 
lating plasma,  fibrinogen  is  not  wanting,  and  it  has  already  been 
mentioned  that  thrombogen  exists  in  perfectly  fresh  and,  as  we 
may  say,  still  living  blood.  Why,  then,  docs  it  not  coagulate  ? 
Some  have  said  that  coagulation  is  '  restrained  '  by  the  contact  of 
the  living  walls  of  the  bloodvessels;  but  although  it  is  certain  that 
the  contact  of  foreign  matter — and  all  dead  matter  is  foreign  to 
living  cells — does  hasten  the  destruction  of  blood-plates  or  that 
alteration  in  them  on  which  the  liberation  of  the  precursors  of  the 
ferment  depends,  it  is  evident  that  it  is  just  this  '  restraining  '  in- 
fluence of  the  vessels,  if  it  is  due  to  anything  more  than  the  mere 
smoothness  of  their  endothelial  lining,  which  has  to  be  explained. 
The  best  answer  which  can  be  given  to  the  question  is:  First,  that 
the  quantity  of  thrombokinase  free  in  the  plasma  at  any  given  time 
must  be  small,  since  no  evidence  of  its  presence  in  fluoride  plasma 
can  be  obtained.  If  thrombokinase  is  liberated  in  the  circulating 
blood,  we  may  assume  that  it  is  changed  into  some  inactive  sub- 
stance, or  quickly  eliminated.  And  it  appears  that,  unlike  the  true 
ferments,  thrombokinase  acts  quantitatively — i.e.,  in  proportion  to 
its  amount — upon  thrombogen.  Second,  an  antithrombin  exists 
in  the  circulating  ])lasma,  and  even  if  fully  formed  fibrin-ferment 
were  present,  it  could  not  cause  coagulation  until  the  antithrombin 
had  been  neutralized.  This  antithrombin  is  probably  not  manu- 
factured in  the  blood,  or  at  least  not  exclusively  in  the  blood,  but 
in  the  tissues,  and  there  is  no  reason  to  deny  the  vessels  themselves 


COAGULATION  43 

a  share  in  its  production,  even  if  its  presence  has  not  hitherto  been 
demonstrated  in  the  internal  coat  (L.  Loeb).  So  that  living  blood 
within  the  living  vessels  may  be  said  to  be  acted  upon  by  two  sets 
of  influences,  one  tending  to  favour  coagulation,  the  other  to  oppose 
it.  In  the  clotting  of  extra,vascular  plasma,  free  from  corpuscles, 
we  may  indeed  see  the  continuation,  under  modified  conditions,  of 
a  normal  process  always  going  on  within  the  bloodvessels.  Under 
normal  conditions,  the  processes  that  make  for  coagulation  never 
obtain  the  upper  hand. 

Indeed  the  margin  of  safety  within  which  what  may  be  called 
the  thrombo-regulative  mechanism  works  seems  to  be  surprisingly 
wide,  and  the  equilibrium  in  the  circulating  blood  far  more  stable 
than  observations  on  clotting  outside  of  the  body  might  lead  us  to 
suppose.  Very  considerable  quantities  of  thrombin  or  of  de- 
fibrinated  blood  or  serum  containing  thrombin  can  be  injected  into 
the  blood-stream  without  ill  effect.  According  to  Howell,  the 
presence  of  the  abnoiTnally  great  amount  of  thrombin  causes  the 
formation  of  sufficient  antithrombin  to  neutralize  it,  probably  by  a 
protective  reflex  secretion.  In  like  manner  the  injection  of  tissue 
extracts  or  a  solution  of  thrombo  plastic  substance  (thrombokinase) 
prepared  from  them  by  precipitation  doss  not  necessarily  induce 
coagulation  in  the  vessels.  On  the  contrary,  when  injected  slowly 
or  in  small  amount  into  the  veins  of  an  animal,  it  abolishes  for  a 
time  the  power  of  coagulation  of  the  blood;  and  when  this  '  nega- 
tive phase,'  as  it  is  called,  has  been  once  established,  even  a  very 
large  and  rapid  injection  produces  no  further  effect,  possibly  because 
an  antibody  which  neutralizes  the  action  of  thrombokinase  has 
been  produced.  In  both  cases  the  limits  of  safety  can  be  over- 
stepped, and  intravascular  clotting  induced  by  the  injection  either 
of  thrombin  or  of  thrombokinase.  When  a  considerable  quantity 
of  the  active  substance  in  tissue  extract  is  introduced  at  the  first 
injection,  extensive  coagulation  in  the  vessels  instantly  ensues;  the 
animal  dies  in  a  few  minutes;  and  the  right  side  of  the  heart,  the 
venae  cavse,  the  portal  vein,  and  perhaps  the  pulmonary  arteries, 
may  be  found  choked  with  thrombi.  Here  the  injected  thrombo- 
kinase is  responsible  for  the  clotting,  thrombogen  and  calcium  being 
alreadv  present.  Curiously  enough,  intravascular  coagulation  fails 
to  be  produced  in  a  certain  proportion  of  cases  when  albino  animals 
are  injected  with  material  from  pigmented  animals,  while  there  is 
no  absolute  failure  of  coagulation  when  albinos  are  injected  with 
material  from  albinos,  and  no  failure  when  pigmented  animals  are 
injected  with  material  either  from  other  pigmented  animals  or  from 
albinos.  Intravascular  coagulation  on  injection  of  tissue  extracts 
is  especially  striking  in  birds. 

To  a  certain  extent  the  action  of  tissue  extracts  in  coagulation 
can  be  imitated  by  other  substances  of  animal  origin,  such  as  the 


44  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

venoms  of  some  vipers  (Martin).  It  is  not  known  whether  these 
substances  act  on  the  blood-plates,  leucocytes,  or  other  cells,  and 
thus  cause  an  increased  production  or  an  increased  liberation  of 
one  or  more  of  the  precursors  of  thrombin,  or  whether  they  take 
part  directly  in  its  formation.  But  there  is  some  evidence  that 
the  venoms  which  favour  coagulation  do  so  in  virtue  of  their  con- 
taining a  kinase.  On  tlie  other  hand,  cobra-venom  prevents  coagula- 
tion by  means  of  an  antikinase — that  is,  a  substance  which  antago- 
nizes the  action  of  kinase,  and  so  hinders  the  formation  of  thrombin. 
It  does  not  contain  an  antithrombin — that  is,  a  body  which  will 
prevent  the  action  of  thrombin  already  formed  (Mellanby). 

Relation  of  the  Liver  to  Coagulation.^ — ^It  is  not  known  with  any 
degree  of  certainty  whether  the  thrombo-regulative  processes  are 
especially  associated  with  any  particular  organ.     But  there  are 
facts  which  suggest  that  the  relations  of  the  liver  to  the  coagulation 
of  the  blood  are  peculiarly  close.     Not  only,  as  previously  shown, 
does  it  take  an  important  share  in  the  formation  of  fibrinogen,  but 
there  is  some  evidence  that  it  is  closely  related  to  the  formation 
of  antithrombin.     We  have  already  mentioned  that  the  injection 
of  commercial  peptone,  which  consists  chiefly  of  proteoses,  into 
the  blood  of  dogs  causes  it  to  lose  its  coagulability.     The  effect 
gradually  passes  away,  till  after  some  hours  the  original  power  of 
coagulation  is  restored  (p.  63).     The  liver  is  known  to  be  intimately 
concerned  in  the  production  of  this  remarkable  result,  for  if  the 
circulation  through  it  be  interrupted,  the  injection  of  proteose  is 
ineffective.      Further,    if    a    solution    of    proteose    is    artificially 
circulated  through  an  excised  liver,  a  substance  (perhaps  an  anti- 
thrombin) is  formed  which  is  capable  of  suspending  the  coagula- 
tion of  blood  outside  of  the  body,  a  property  which  proteoses  them- 
selves do  not  possess,  or  possess  only  in  slight  degree.     It  is  not 
believed  that  the  proteose  is  actually  changed  into  this  anticoagu- 
lant substance,   but  rather  that  the  liver  cells  produce  it  as  a 
'  reaction  '  to  the  presence  of  the  foreign  substance,  being  perhaps 
stimulated  in  some  way  by  the  circulating  proteose.     In  part  the 
abnormally  great  alkalinity  of  the  peptone  blood,  due  to  the  excess 
of  alkali  secreted  by  the  liver,  is  responsible  for  its  slow  coagulation. 
Under  certain  conditions,  some  of  which  are  known  and  others  not, 
the  injection  even  of  one  or  other  of  the  purified  proteoses  causes 
not  retardation,  but  hastening,  of  coagulation ;  and  if  this  has  been 
the  result  of  a  first  injection,  a  second  is  equally  unsuccessful.     It 
is  possible  that  by  an  effort  of  the  organism  to  restore  the  normal 
coagulability  of  the  blood,  on  which  its  very  existence  depends, 
substances  which  favour  coagulation  are  produced,  and  that  the 
result  of  an  injection  of  proteose  is  determined  by  the  relative 
amount  of  coagulant  and  anticoagulant  secreted  in  a  given  time. 
Protamins  (products  obtained  from  the  ripe  milt  of  certain  fishes, 


COAGULATION  45 

and  believed  to  be  the  simplest  proteins)  exert,  when  injected 
intravenously,  a  retarding  influence  on  coagulation,  and  lower  the 
blood-pressure,  just  as  albumoses  do  (Thompson).  Even  serum- 
albumin  and  serum-globulin  possess  this  property  in  some  degree. 
All  these  substances  also  cause  a  diminution  in  the  number  of 
leucocytes  in  the  blood  owing,  in  the  case  of  albumose  at  any  rate, 
to  their  accumulation  in  the  abdominal  vessels,  and  not  to  any 
actual  destruction  of  them. 

It  has  been  lately  announced  that  the  adrenal  glands  have  a  relation 
to  the  coagulation  of  the  blood.  Stimulation  of  the  splanchnic  nerve, 
which  supphcs  sccretorj^'  fibres  to  the  adrenal,  greatly  hastens  coagula- 
tion, but  has  no  such  effect  if  the  adrenal  on  the  corresponding  side 
has  been  previously  removed  (Cannon).  It  is  possible  that  this  effect 
is  exerted  through  the  liver,  since  it  is  known  that  one  important 
function  of  the  liver,  the  regulation  of  the  sugar  content  of  the  blood, 
is  intimately  dependent  upon  the  adrenal,  and  is  affected  by  excitation 
of  its  splanchnic  nerve-supply. 

In  certain  pathological  conditions  the  normal  balance  of  the  factors 
that  make  for  clotting  and  prevent  it  may  be  upset,  and  the  scales  may 
tip  in  either  direction.  In  patients  suffering  from  the  formation  of 
spontaneous  clots  in  the  veins  (thrombosis)  it  is  stated  that  the  anti- 
thrombin  in  the  blood  is  diminished,  the  amount  of  prothrombin  being 
normal.  The  mere  slowing  of  the  blood-stream  in  conditions  where 
the  circulatory  mechanism  is  enfeebled  may  favour  thrombosis.  For 
anything  which  cripples  the  circulation,  and  consequently  limits  the 
free  interchange  between  blood  and  tissues,  interferes  with  the  elimina- 
tion or  neutralization  of  the  precursors  of  thrombin,  and  with  the 
entrance  of  the  substances  that  render  the  fully  formed  thrombin  in- 
active. This,  as  well  as  the  injury  caused  by  the  ligature,  which  may 
favour  the  passage  of  thromboplastic  substances  into  the  lumen  of  the 
occluded  vessel,  is  a  possible  factor  in  the  formation  of  the  clot 
on  which  the  surgeon  relies  for  the  permanent  sealing  of  ligated 
vessels. 

In  haemophilia,  a  disease  in  which  the  coagulation  of  the  blood  is 
charactcristicall}^  slow,  and  in  which  even  slight  wounds  may  occasion 
severe  or  fatal  haemorrhage,  the  thrombogen  (prothrombin)  has  been 
found  deficient  in  amount,  and  the  injection  of  normal  serum  or  the 
transfusion  of  normal  blood  has  been  used  with  temporary  advantage 
in  the  treatment  of  the  condition.  In  certain  cases  of  purpura,  how- 
ever, where  haemorrhage  also  occurs  with  abnormal  ease,  no  variation 
from  the  normal  could  be  detected  in  the  content  of  either  antithrombin 
or  prothrombin  (Howell) .  Some  have  supposed  that  in  such  conditions 
the  fault  is  an  unnatural  fragility  of  the  small  vessels  rather  than  a 
deficiency  in  the  power  of  the  blood  to  clot,  but  of  this  also  no  actual 
evidence  has  been  adduced.  Another  factor  on  which  the  promptness 
and  completeness  of  the  sealing  of  wounded  vessels  may  depend  has  been 
recently  brought  into  notice,  namely — 

The  Vaso-Qonstrictor  Property  of  Shed  Blood.— It  has  been  shown 
that  when  blood  is  shed  and  no  precautions  are  taken  to  prevent 
clotting,  it  very  quickly  develops  the  power  of  causing  marked 
constriction  of  bloodvessels.  This  can  be  demonstrated  by  allow- 
ing the  serum  to  act  on  rings  cut  from  arteries  (Practical  Exercises, 


46  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

p.  66),  or  by  perfusing  the  liind-legs  of  frogs  with  a  sahnc  solu- 
tion containing  serum.  Plasma  derived  from  blood  in  which  the 
platelets  have  been  prevented  from  breaking  down,  and  which 
therefore  remains  imclotted,  has  no  such  effect,  or  a  much  slighter 


Pig  y — Sheep  Artery  Rings.  At  14  and  i5  Ringer's  solution  was  replaced  by  citrate 
plasma  (two  different  specimens).  At  15  and  17  the  plasmas  were  replaced  by 
the  corresponding  sera.  At  18  and  19  the  sera  replaced  Ringer's  solution  directly. 
Time-trace,  half-minutes.     Tracings  reduced  to  }. 

effect.  But  when  the  platelets  are  separated  from  the  plasma 
and  then  decomposed,  the  resulting  extracts  of  platelets  are  rich 
in  vaso-constrictor  material.  In  the  sealing  of  wounded  vessels 
the  platelets  would  therefore  appear  to  play  a  double  role,  yielding 


Fig  8. — Frog  Perfusion  Experiment  with  Serum.  The  drops  of  liquid  flowing  through 
the  preparation  are  recorded.  At  11  citrate  plasma  was  injected;  at  13  the 
corresponding  citrate  serum.  The  tracing  is  to  be  read  from  left  to  right. 
Time  is  marked  in  half-minutes 

a  substance  which  causes  constriction  of  the  vessel  in  the  neigh- 
bourhood of  the  wound  while  a  plug  of  clot  is  being  formed,  thanks 
to  other  substances  liberated  from  the  platelets,  whicli  take  an 
essential  part  in  coagulation.     The  vaso-constriction  may  perhaps 


VASO  COXSTJUCTOR  PROPIIRTY  OF  SllIiD  BLOOD 


47 


be  looked  upon  as  a  form  of  '  first  aid  '  to  diminish  the  hiemor- 
rhage,  and  also  to  make  it  less  easy  for  the  beginning  clot  to  be 
washed  away.  It  is  obvious  that  the  two  processes  would  be 
mutually  advantageous  in  dealing  with  those  injuries  of  the  vascular 
system  on  the  prompt  repair  of  which  tlu;  very  existence  of  the 


A    -- 

-\r 

?\/" 

f  1                -,  '^ 

1/ 

V   r 

-v^ 

Jcc  Strum*^ciCraCt 

/cc  P/asma 

/cc  Plasma 

/Ci  SerurrfC Urate 

Fig.  9. — Frog  Perfusion  Experiment  with  Serum.  Curves  showing  the  flow.  The 
number  of  drops  per  half-minute  is  laid  off  along  the  vertical  axis,  and  the  time 
{in  half-minutes)  along  the  horizontal  axis;  38  drops  correspond  to  i  cc. 

organism  at  all  times  depends,  and  it  is  not  without  interest  to 
find  that  special  formed  elements  in  the  blood,  the  platelets,  are 
pre-eminently  associated  with  both  processes. 


Section  III. — ^The  Chemical  Composition  of  Blood. 

The  serum  of  coagulated  blood  represents  the  plasma  minus 
fibrinogen;  the  clot  represents  the  corpuscles  plus  fibrin.     Thus: 

Plasma  -  Fibrin (ogen)  =  Serum. 

Corpuscles  +  Fibrin  =  Clot. 

Plasma  -f  Corpuscles  =  Scrum  -f  Clot  =  Blood. 

Bulky  as  the  clot  is,  the  quantity  of  fibrin  is  trifling  (0-2  to  0-4  per 
cent,  in  human  blood).  The  plasma  contains  about  10  per  cent. 
of  solids,  the  red  corpuscles  about  40  per  cent.,  the  entire  blood 
about  20  per  cent. 

Serum  contains  7  to  8  per  cent,  of  proteins,  about  o-8  per  cent, 
of  inorganic  salts,  and  small  quantities  of  neutral  fats,  soaps, 
cholesterin  esters,  lecithin,  dextrose,  urea,  lactic  acid,  glycuronic 

acid,     amino  -  acids. 


Solids 


\fMV9r 


Corpuscles 
Flasma 


and    other    sub- 


Fig. 


10. — Diagram  showing  Relative  Quantity  of  Solids 
and  Water  in  Red  Corpuscles  and  Plasma. 


stances, 
proteins 
albumin 
globulin. 
bit    the 


The  chief 

are  serum- 

and  serum- 

In  the  rab- 

former,    in 


the  horse  the  latter,  is  the  more  abundant;  in  man  they  exist  in  not 
far  from  equal  amount.  A  small  quantity  of  nucleo-protein  and  of 
fibrino-globulin  (which  some  consider  a  soluble  product  formed  from 


48 


THE  CIRCULATING  LIQUIDS  01'   THE  BODY 


librinogen  in  clotting)  is  also  present.  Ferments  which  cause 
hydrolysis  of  proteins  and  carbohydrates,  a  ferment  (lipase)  which 
acts  upon  fats,  and  certain  oxidizing  ferments  (oxydases),  have  also 
been  demonstrated.  The  chemical  nature  of  the  bodies  which 
confer  on  serum  or  plasma  its  specific  ha^molytic,  agglutinating, 
precipitating,  and  bactericidal  properties  has  not  been  definitely 
determined. 

The  quantitative  composition  of  serum,  especially  as  regards  the 
inorganic  salts,  is  remarkably  con.staut  in  animals  of  the  same  species, 
and  even  in  animals  of  dilfercnt  species  belonging  to  tlie  same,  or  to 
not  very  widely  separated,  natural  groups.  In  cold-blooded  animals 
the  serum-albumin  is  scantier  tlian  in  mammals,  the  globulin  relatively 
more  plentiful. 

Serum-albumin  belongs  to  the  class  of  native  albumins.  It  has 
been  obtained  in  a  crystalline  form  from  the  serum  of  horse's  blood.     It 


Fig.  II. — Perspective  View  of  Vivi-Diflusion  Apparatus  (Abel).  This  form  of  the 
apparatus  contains  sixteen  tubes.  A,  arterial  cannula;  B,  venous  cannula: 
C,  side  tube  for  introduction  of  hirudin;  D,  inflow  tube;  E,  outlet  tube  for  the 
blood ;  F,  G,  supporting  rod  attached  at  H  and  K  to  branched  V-tubes;  L,  burette 
for  hirudin;  M,  N,  tube  for  filling  and  emptying  liquid  in  outer  jacket;  O,  air 
outlet;  P,  dichotomous  branching-point  of  inflow  tube;  Q  and  R,  quadruple 
branching-points  of  the  same  ;  S,  S,  wooden  supports;  T,  thermometer.  At 
each  of  the  points  H  and  K  the  blood  is  collected  from  four  tubes  into  one, 
bending  round  to  the  back,  and  there  redividing  into  four  return  flow  tubes. 
Arrows  show  the  direction  of  the  flow. 

is  soluble  in  distilled  water,  and  is  not  precipitated  by  saturating  its 
solutions  with  certain  neutral  salts.  Heated  in  neutral  or  sliglitly 
acid  solution,  it  coagulates  first  at  73°,  then  at  77°,  then  at  84°  C. 
Altliough  this  is  not  of  itself  sufficient  proof,  there  is  other  evidence 
that  it  consists  of  a  mixture  of  proteins. 

Serum-globulin,  also  called  paraglobulin,  belongs  to  the  globulin 
group  of  proteins.  When  heated,  it  coagulates  at  about  75°  C.  (p.  (j). 
It  is  insoluble  in  distilled  water,  and  is  precipitated  by  saturation  with 
such  neutral  salts  as  magnesium  sulphate,  or  by  half-saturation  with 
ammonium  sulpliatc.  It  appears  tliat,  as  thus  obtained,  it  is  not  a 
single  substance,  but  a  mixture  of  at  least  two  proteins — en-globulin, 


CHEMICAL  COMPOSITION  OF  BLOOD 


49 


which  can  be  precipitated  from  its  saline  solution  by  dialyzing  off  the 
salts,  and  pseudo-globulin,  which  cannot  be  so  precipitated. 

In  addition  to  the  nitrogen  represented  as  protein,  serum  (or  plasma) 
contains  non-protein  nitrogen,  the  amount  of  which  varies  with  the 
nature  of  the  food  and  the  stage  of  digestion.  Part  of  this  fraction  is 
attributal.)le  to  urea  and  other  metabolites  on  their  way  to  be  excreted, 
but  another  portion,  and  an  important  one,  is  due  to  amino-acids 
absorbed  from  the  intestine  during  the  digestion  of  proteins  and  on 
their  way  to  be  utilized  in  the  tissues. 

Of  tlie  inorganic  salts  of  serum,  the  most  important  are  sodium 
chloride  and  sodium  bicarbonate.  Small  amounts  of  potassium, 
calcium,  and  magnesium,  united  with  phosphoric  acid  or  chlorine,  and 
a  trace  of  fluoride,  are  also  present.  A  portion  of  the  salts  is  loosely 
combined  with  the  proteins. 

Our  loiowlcdge  of  the  chemistry  of  the  circulating  plasma  is  likely 
to  be  notably  augmented  by  the  method  of  vivi-diffiision  recently  intro- 
duced by  Abel.  An  arteiy  of  an  anaesthetized  animal  is  connected  by 
a  cannula  to  a  system  of  celloidin  tubes  immersed  in  a  saline  solution. 
Blood  passes  from  the  artery  through  the  tubes,  where  it  exchanges 
diffusible  constituents  with  the  solution,  and  is  then  returned  to  the 
animal's  body  by  another  cannula  attached  to  a  vein.  Coagulation 
of  the  blood  in  the  apparatus  is  prevented  by  hirudin,  and  under 
aseptic  conditions  the  circulation  may  proceed  through  the  tubes  for  a 
long  time.  The  saline  solution  can  then  be  analyzed  for  substances  which 
have  entered  it  from  the  blood — amino-acids,  for  example  (Fig.  ii). 

The  following  tables  give  some  details  of  the  composition  of  blood : 


1,000  Grammes  of  Pig's  Blood  (Corpuscles,  435'09;  Serum,  56491) 

contained 


Corpuscles. 

Serum. 

Corpuscles. 

Serum. 

Water 

272-20 

518-36 

P2O5  as  nuclein 

0-0455 

0-0123 

Solids 

162-89 

46-54 

Na.,b   .. 

* 

2-401 

Haemoglobin 

142-20 

KoO     . . 

2-157 

0-152 

Protein 

8-35 

38-26 

Fe.,03.. 

0-696 

Sugar 

0-684 

CaO     . . 



0-0689 

Cholesterin 

0-213 

0-231 

MgO    .. 

0-0656 

0-0233 

Lecithin 

1-504 

0-805 

CI 

0-642 

2-048 

Fat  . . 

I-I04 

P2O.5    .. 

0-895 

O-III 

Fatty  acids 

0-027 

0-448 

Inorganic  P2O5 

0-719 

0-296 

Proteins  of  Plasma  in  1,000  Grammes. 


Albumin. 

Globulin. 

Fibrinogen. 

Total. 

Man 

40-1 

28.3 

4-2 

72-6 

Dog 

31-7 

22-6 

6-0 

60-3 

Sheep      . . 

38-3 

30-0 

4-6 

72-9 

Horse 

28-0 

47-9 

4-5 

80-4 

Pig          .. 

44-2 

29-8 

6-5 

80-5 

*  The  pig's  erythrocytes  are  peculiar   in  that  the  sodium  appears  to  be 
entirely  confined  to  the  plasma. 


5..  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

The  Coloured  Corpuscles  consist  of  rather  less  than  60  per  cent,  of 
water  and  ratlicr  more  than  40  per  cent,  of  solids.  Of  the  solids  the 
pigment  haemoglobin  makes  up  about  90  per  cent. ;  the  ])roteins  and 
nucleo-protein  of  the  stroma  about  7  percent.;  lecithin  and  choles- 
terin  2  to  3  per  cent.;  inorganic  salts  (which  vary  greatly  in  their 
relative  proportions  in  different  animals,  but  in  man  consist  chiefly 
of  phosphates  and  chloride  of  potassium,  with  a  much  smaller 
amount  of  sodium  chloride)  about  i  per  cent.  Potassium  has  been 
demonstrated  microchemically  in  frog's  erythrocytes  (Macallum) 
{Frontispiece).  There  is  evidence  that  a  portion  of  the  salts  is  more 
firmly  combined  than  the  rest,  so  that,  even  after  the  action  of  the 
most  energetic  laking  agents,  this  fraction  remains  attached  to  the 
stroma.  The  erythrocytes  of  some  animals — e.g.,  the  dog — contain 
dextrose.  When  dextrose  is  added  to  human  blood  it  rapidly  dis- 
tributes itself  over  corpuscles  and  plasma  (Rona),  although  not 
exactly  in  proportion  to  their  respective  volumes  (Masing).  Hither- 
to the  dextrose  in  blood  has  been  reckoned  as  if  it  all  belonged  to  the 
plasma. 

Hcemoglohin. — Of  all  the  solid  constituents  of  the  blood,  haemoglobin 
is  present  in  greatest  amount,  constituting  as  it  does  no  less  than 
13  per  cent.,  by  weight,  of  that  liquid.     It  is  an  exceedingly  complex 

body,  containing  car- 
D  On  bon,  hydrogen,  nitro- 

Wa      gen,     and    oxygen    in 
H  much    the    same  pro- 

portions in  which  they 
exist  in  ordinary  pro- 
teins (p.   i).      Iron  is 
also  present  to  the  ex- 
Fig.  12.— Diagram  of  Spectroscope.     A,  source  of  light ;     *^"*  of  almost  exactly 
B,  lave."  of  bluod;  C.  collimator  for  rendering  rays     one-third  of  I  percent., 
parallel;  D,  prism;  E,  telescope.  ^"'1  there  is alsoahttle 

sxilpliur.  Hai'moglobin 
is  made  up  of  a  protein  element  whicli  contains  all  the  sulphur  and  a 
pigment  which  contains  all  the  iron,  the  protein  constituting  by  far 
the  larger  portion  of  the  gigantic  molecule,  whose  weight  has  been 
estimated  at  more  than  16,000  times  that  of  a  molecule  of  hydrogen. 
Since  its  percentage  composition  is  still  undetermined  with  absolute 
precision,  it  is  impossible  to  give  an  empirical  formula  that  is  more 
than  approximately  correct.  For  dog's  haemoglobin  Jaquet  gives 
^758^^  1203*^  195^:1'"'^^  ^-'iH'  which  would  make  the  molecular  weight  16,669. 
Direct  determinations  of  the  molecular  weight  gave  13,115  for 
oxyhaMUoglobin  of  the  horse,  and  16,321  for  that  of  the  ox  (Hiifner  and 
(iansser).  Whilcthe.se  numbers  need  not  be  taken  as  more  than  a  rough 
approximation,  they  at  least  show  that  the  hsmoglobin  molecule  is  an 
exceedingly  large  one. 

The  most  remarkable  property  of  h.Tmoglobin  is  its  power  of 
combining  loosely  with  oxygen  when  exposed  to  an  atmosphere  con- 
taining it,  and  of  again  giving  it  up  in  the  presence  of  oxidizable 
substances  or  in  an  atmosphere  in  which  the  partial  pressure  of 
oxygen  (pp.  248-253)  has  been  reduced  below  a  certain  limit.     It 


CLEMICAL  C0Ml'06iiiUN  Oh'  CLOOD 


51 


D 


E  b 


BW  630  620  m  600  590  580  570  560  5^0  5¥)  53fll  j2o|  510    500  490\  m 

\i<n\,„X  ■  \i"\.  ..li'lJiMlli.iil.iilr.iJiiiilii.llii 


TO    bOU  iW   beu   6/U  ibU   i)M   OW  JJ(^  Ja/j    oiu    JW   ¥J(/j  '*ot 
I  ,:l,J,..,l„.J|,.il,J,.„l„J,  .1,1.,!.:.!  .i:,.|i,.L.,     I    ■■-.I  iihiiilM,i„'iliii;l;i„li,|;'.i 

7(9  //  I      i2  13   I  74- 

I ■    ■    ■    ■! ,    ,    ,1    ....1 1    ,    ,1    .1,.    I    ,1    I    . ^    I    i    ■    I       ll    M    M    I 


. 

1 

>!?^'" 

1?;^^ 

^ 

1 

» 

Fig.  13.— Table  of  Spectra  of  H.-emoglobin  and  its  Derivatives  (Ziemka  and  Miiller). 
I,  Osyha;moglobin ;  2, reduced  ha:moglobin  3,  met  hemoglobin:  4.  a-  d  l^matin; 
5.  alkaline  ha;matin;  6,  haemochromogen ;  7.  acid  hcxmatoporphyrin ;  S,  alkaliae 
haematoporphyrin ;  9,  cairbon  monoxide  haemoglobin. 


52 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


is  this  property  that  enables  haemoglobin  to  perform  the  part  of  an 
oxygen-carrier  to  the  tissues,  a  function  of  the  first  importance, 
which  will  be  more  minutely  considered  when  we  come  to  deal  with 
respiration. 

The  bright  red  colour  of  blood  drawn  from  an  artery  or  of  venous 
blood  after  free  exposure  to  air  is  due  to  the  fact  that  the  haemo- 
globin is  in  the  oxidized  state 
— in  the  state  of  oxyhaemo- 
globin,  as  it  is  called.  The 
anumnt  of  oxygen  with  which 
haemoglobin  combines  to  form 
oxyliaimoglobin  is  such  that 
one  atom  of  iron  corresponds  to 
two  atoms  of  oxygen.  If  the 
formula  for  haemoglobin  given 
on  p.  50  be  represented  by 
the  sj'^mbol  Hb,  a  molecule  of 
oxy haemoglobin  would  be  re- 
presented as  HbOj.  If  the 
oxygen  is  removed  by  means  of 
reducing  agents,  such  as  am- 
monium sulphide,  or  by  ex- 
posure to  the  vacuum  of  an  air- 
pump,  the  colour  darkens,  the 
blood-pigment  being  now  in  the 
form  of  reduced  haemoglobin. 
In  ordinary  venous  blood  a 
large  proportion  of  the  pigment 
is  in  this  condition,  but  there  is 
always  oxyhaemoglobin  present 
as  well.  In  asphyxia  (p.  281), 
however,  nearly  the  whole  of 
the  oxyhaemoglobin  may  dis- 
appear. 

Crystallization  of  II  aemoglobin. — In  the  circulating  blood  the  haemo- 
globin is  related  in  such  a  way  to  the  .stroma  of  the  corpuscles  that, 
although  the  latter  are  suspended  in  a  liquid  readily  capable  of  dissolv- 
ing the  pigment,  it  yet  remains  under  ordinary  circumstances  strictly 
within  them.  In  a  few  invertebrates,  however,  it  is  normally  in  solution 
in  the  circulating  liquid.  As  a  rare  occurrence  haenioglobin  may  form 
crystals  inside  the  corpuscles  (p.  71).  When  it  is  in  any  way  brought 
into  solution  outside  the  body,  it  shows  in  many  animals,'  but  "not  in  the 
same  degree  in  all,  a  tendency  to  crystallization ;'  and  the  ease  with  which 
crystallization  can  be  induced  is  in  inverse  proportion  to  the  solubility 
of  the  haemoglobin.  Thus,  it  is  far  more  difficult  to  obtain  crystals  of 
haemoglobin  from  human  blood  than  from  the  blood  of  the  rat,  guinea- 
pig,  or  dog,  whose  blood-pigment  is  less  soluble  than  that  of  man,  and 
for  a  like  reason  the  oxyhaemoglobin  of  the  bird,  the  rabbit,  or  the  frog 
crystallizes  still  less  readily  than  that  of  human  blood. 


J'ig.  14. — Oxyharnoglobin  Crystals  (Frey). 
a,h,  from  man;  c,  from  cat;  d,  from  guinea- 
pig;  e,  from  hamster;/,  frotn  squirrel. 


CHEMICAL  COMPOSITION  OF  BLOOD  53 

As  to  the  form  of  the  crystals,  in  the  vast  majority  of  aniiiials  they 
are  rhombic  prisms  or  needles,  but  in  the  guinea-pig  they  are  sphenoids 
belonging  to  the  rhombic  system,  and  in  the  squirrel  six-sided  plates  of 
the  hexagonal  system  (Fig.  14).  Careful  study  of  the  crystallography  of 
'  hemoglobin  from  a  large  number  of  animals  has  established  differences 
and  resemblances  so  constant  and  so  clear-cut  that  they  may  be  used  for 
the  purposes  of  classification  and  for  the  identification  of  the  source  of 
a  specimen  of  blood  (Rcichert  and  Brown). 

Reduced  ha-moglobin  can  also  be  caused  to  crystallize,  though  with 
more  difficulty  than  oxyhaemoglobin,  since  it  is  more  soluble.  Crystals 
of  reduced  haemoglobin  were  first  prepared  from  human  blood  by  Hiifner, 
who  allowed  it  to  putrefy  in  sealed  tubes  for  several  weeks. 

When  a  solution  of  oxyhaemoglobin  of  moderate  strength  is  ex- 
amined with  the  spectroscope,  two  well-marked  absorption  bands 
are  seen,  one  a  little  to  the  right  of  Fraunhofer's  line  D,  and  the  other 
a  little  to  the  left  of  E.  A  third  band  exists  in  the  extreme  violet 
between  G  and  H.  It  cannot  be  detected  with  an  ordinary  spectro- 
scope, but  has  been  studied  by  the  aid  of  a  fluorescent  eyepiece,  by 
projecting  the  spectrum  on  a  fluorescent  screen,  and  by  photograph- 
ing the  spectrum.  The  addition  of  a  reducing  agent,  such  as 
ammonium  sulphide,  causes  the  bands  in  the  visible  spectrum  to 
disappear,  and  they  are  replaced  by  a  less  sharply  defined  band,  of 
which  the  centre  is  about  equidistant  from  D  and  E.  This  is  the 
characteristic  band  of  reduced  haemoglobin.  The  spectrum  of 
ordinary  venous  blood  shows  the  bands  of  oxyhsemoglobin. 

Carbonic  oxide  hcBmoglobin  is  a  representative  of  a  class  of  haemo- 
globin compounds  analogous  to  oxyhaemoglobin,  in  which  the  loosely- 
combined  oxygen  has  been  replaced  by  other  gases  (carbon  monoxide, 
nitric  oxide)  in  firmer  union.  Its  spectrum  shows  two  bands  very  like 
those  of  oxyhaemoglobin,  but  a  little  nearer  the  violet  end.  Carbonic 
oxide  haemoglobin  is  formed  in  poisoning  with  coal-gas.  Owing  to  the 
great  stability  of  the  compound,  the  haemoglobin  can  no  longer  be 
oxidized  in  the  lungs,  and  death  may  take  place  from  asphyxia.  It 
is,  however,  gradually  broken  up,  and  therefore  artificial  respiration 
may  be  of  use  in  such  cases.  Inhalation  of  oxygen  and  especially 
transfusion  of  blood  are  also  of  great  value. 

Methcsmoglobin  is  a  derivative  of  oxyhaemoglobin  which  can  be 
formed  from  it  in  various  ways — e.g.,  by  the  addition  of  ferricyanide  of 
potassium  or  nitrite  of  amyl  (Gamgee),  by  electrolysis  (in  the  neigh- 
bourhood of  the  anode),  or  by  the  action  of  the  oxidizing  ferment 
'  echidnase  '  in  the  poison  of  the  viper  (Phisalix) .  It  very  often  appears 
in  an  oxyhaemoglobin  solution  which  is  exposed  to  the  air.  It  has  been 
found  in  the  urine  in  cases  of  haemoglobinuria,  in  the  fluid  of  ovarian 
cysts,  and  in  haematoceles.  The  strongest  band  in  its  spectrum  is 
in  the  red,  between  C  and  D,  but  nearer  C,  nearly  in  the  same  position 
as  the  band  of  acid-haematin.  Reducing  agents,  such  as  ammonium 
sulphide,  change  methaemoglobin  first  into  oxyhaemoglobin  and  then 
into  reduced  haemoglobin.  It  has  by  some  been  regarded  as  a  more 
highly  oxidized  haemoglobin  than  oxyhaemoglobin.  Rebutting  evidence 
has,  however,  been  offered  to  the  effect  that  the  same  quantity  of 
oxygen  is  required  to  saturate  both  pigments,  and  this  evidence  appears 
to  be  sound.  The  difference  lies  rather  in  the  manner  in  which  the 
oxygen  is  united  to  the  haemoglobin  in  the  methaemoglobin  molecule 
than  in  the  quantity  of  oxygen  which  it  contains.     For  methacmo- 


54 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


globin,  unlike  oxyluinioglobin,  parts  with  no  oxygen  to  the  vacuum, 
while,  on  the  other  hand,  in  the  presence  of  reducing  agents  it  yields  up  its 
oxygen  even  more  readily  than  oxyhaemoglobin  does  (Haldahe)  (p.  248). 
F5y  the  action  of  acids  or  alkalies  oxyhai^moglobin  is  split  into  a  pig- 
ment, haematin,  and  a  protein,  globin,  belonging  to  the  histon  group. 
It  is  easily  precipitated  from  solution  by  ammoma.     On  hydrolysis,  it 


r-i 


uc^^ 


Hh 


Tu/ff 
banJf 


n 


^'^ 


0x1/ ^b 

Carljcntc  OyCideffh 

Ha  emc  ch  to  mo  tfi  tt  I 

Haematijiicrphijrtn  (actdj\ 

Mcthaemci^lohirt  \ 

field  Haematm  I    '^"^ 

Alkaline  Haemal m    \t'^^j 

Reduced  hk.  J^''"^ 


rig  15. — Diagram  to  show  the  Chief  Characteristics  by  which  Haemoglobin  and 
some  of  Its  Derivatives  may  be  recognized  Spectroscopically.  The  position  of 
the  middle  of  each  band  is  indicated  rougiily  by  a  vertical  line. 

yields  a  large  amount  of  histidin,  to  which  its  basic  properties  are  chiefly 
due  From  100  grammes  of  oxyhaemoglobin  about  4  grammes  of  hae- 
matin  arc  obtained.  As  to  the  pigment  moietv,  when  haemoglobin  is 
acted  on  by  acids  in  the  absence  of  oxvgen,  hcemochromogen  is  first 
formed,  which  then  gradually  loses  its  iron  and  is  changed  into  haemato- 
,  porphyrin.      If   oxy- 

TTvicks  29-2 

OreaT'  ve.i»»ls,ke<irT\ lungs    22'7 

Bones  8z 

hlealinesY  qeniM  organs  63 

^kizL  21 

Kidneys  16 

Nerve  cenTlres  12. 

Spleen  '2. 

Fig.  i6. — Diagram  to  illustrate  the  Distribution  of  the 
Blood  in  the  Various  Organs  of  a  Rabbit  (after  Ranke's 
Measurements).  The  numbers  are  percentages  of  the 
total  blood. 


gen  be  present,  h«E- 
matin  is  the  final 
product.  Ha;matin 
may  be  considered 
as  the  compound 
which  haemocliro- 
mogen  forms  with 
oxygen.  By  the 
action  of  alkalies  re- 
duced haemoglobin 
yields  ha?mochro- 
mogen,  which  is  stable  in  alkaline  solution,  and  gives  a  beautiful 
spectrum  with  two  bands,  bearing  some  resemblance  to  those  of  oxy- 
haemoglobin, but  placed  nearer  the  violet  end.  The  band  next  the  red 
end  is  much  sharper  than  the  other  (p.  76).  Hirmochromogen  binds 
exactly  the  same  amount  of  oxygen  as  the  hamoglobin  from  which  it  is 
derived,  and  it  is  flue  to  the  haemochronK>gcn  in  its  molecule  that  the 
blood-pigment  fulfils  its  function  of  taking  up  and  transporting  oxygen. 
H (D>natin  (C:j.)H;,.,()4X4.Fe()H  1,  the  most  frequent  result  of  the  splitting 
up  of  haemoglobin,  is  gcnerallv  obtained  as  an  amorphous  substance 
with  a  bluish-black  colour  and  a  metallic  lustre,  insoluble  in  water, 
but  soluble  in  dilute  alkalies  and  acids,  or  in  alcohol  containing  them. 
In  addition  to  the  iron  of  the  haemoglobin,  lucmatin  contains  the  four 
chief  elements  of  proteins — carbon,  hydrogen,  nitrogen,  and  oxgyen 
(Practical  Exercises,  p.  75). 

H cBtnatoporphyrin  (C33H3gOflN4),  or  iron-free  hsematin,  may'  be  ob- 
tained from  blood  or  hsemoglobin  by  the  action  of  strong  sulphuric 
acid,  from  haematin  or  ha;min  by  the  action  of  hydrobromic  acid.     It 


QUANTITY  AND  DISTRIBUTION  01-   liLOOl)  55 

is  distinguished  from  tliese  pigments  by  the  fact  that  it  contains  no 
iron.  When  strong  sulphuric  acid  is  allowed  to  act  on  blood  or  haemo- 
globin solution,  ha'matoporphyrin  is  also  pnxluced,  as  may  be  easily 
shown  by  the  spectroscope.  Its  spectrum  in  acid  solution  shows  two 
bands,  one  just  to  the  left  of  D,  the  other  about  midway  between  D 
and  E.  Like  oxyha?mogl(jbin,  reduced  haemoglobin,  carbonic  oxide 
haemoglobin,  methaemoglobin,  and  other  derivatives  of  haemoglobin, 
it  also  has  a  band  in  the  ultra-violet. 

H(pmi>i  (C.j.,FI;j.,()4N4.FeCl)  is  readily  obtained  from  hsmatin  and 
also  from  luemoglobin  by  heating  with  dilute  hydrochloric  acid,  and  also 
directly  from  blood,  as  described  in  the  Practical  Exercises,  p.  78.  It 
crystallizes  in  the  form  of  small  rhombic  plates,  of  a  brownish  or 
brownish-black  colour  (Fig.  24,  p.  78).  They  are  insoluble  in  water, 
but  readily  soluble  in  dilute  alkalies  (Practical  Exercises,  p.  79). 

Chemistry  of  the  White  Blood-Corpuscles. — The  composition  of  pus- 
cells  and  the  leucocytes  of  lymphatic  glands  has  alone  been  investigated. 
The  chief  constituents  of  the  latter  are  a  globulin  coagulating  by  heat 
at  48°  to  50°  C. ;  a  nucleo-protein  coagulating  in  5  per  cent,  magnesium 
sulphate  solution  at  75°  C.,  and  causing  coagulation  of  the  blood  on 
injection  into  the  veins  of  rabbits;  an  albumin  coagulating  at  73°  C. ; 
and  a  ferment  with  powers  like  the  pepsin  of  the  gastric  juice.  In  pus- 
cells  glycogen  has  been  found,  and  it  can  be  demonstrated  micro- 
chemically  in  the  leucocytes  of  blood  by  the  iodine  reaction  in  various 
conditions.  Fats,  cholesterol,  and  lecithin  are  also  present,  as  well 
as  the  so-called  protagon.  The  ordinary  inorganic  constituents  have 
been  demonstrated — namely,  potassium,  sodium,  calcium,  magnesium, 
and  iron,  united  with  chlorine  and  phosphoric  acid.  The  total  solids 
amount  to  11  to  12  per  cent. 

Section  IV. — Quantity  and  Distribution  of  the  Blood. 

The  Quantity  of  Blood. — The  quantity  of  blood  in  an  animal  is 
most  accurately  determined  by  the  method  of  Welcker.  The  animal 
is  bled  from  the  carotid  into  a  weighed  flask.  When  blood  has 
ceased  to  flow  the  vessels  are  washed  out  with  water  or  physiological 
saline  solution,  and  the  last  traces  of  blood  are  removed  by  chopping 
up  the  body,  after  the  intestinal  contents  have  been  cleared  away, 
and  extracting  it  with  water.  The  extract  and  washings  are  mixed 
and  weighed;  a  given  quantity  of  the  mixture  is  placed  in  a  haema- 
tinometer  (a  glass  trough  with  parallel  sides,  e.g.),  and  a  weighed 
quantity  of  the  unmixed  blood  diluted  in  a  similar  vessel  till  the  tint 
is  the  same  in  both.  From  the  amount  of  dilution  required,  the 
quantity  of  blood  in  the  watery  solution  can  be  calculated.  This  is 
added  to  the  amount  of  unmixed  blood  directly  determined.  Since 
haemorrhage  is  immediately  followed  by  the  entrance  of  liquid  into 
the  bloodvessels  from  the  lymph  and  tissue  fluids,  somewhat  too 
high  a  result  will  be  obtained  if  the  bleeding  is  at  all  prolonged.  It 
is  well,  therefore,  to  take  only  a  moderate  amount  of  blood  for  direct 
estimation,  and  to  compute  the  balance  by  the  colorimetric  method. 

Many  other  methods  have  been  devised  on  the  principle  of  in- 
jecting a  known  quantity  of  some  substance  into  the  circulating 
blood,  and  then,  after  an  interval  has  been  allowed  for  mixture, 
determining  the  change  produced  in  a  sample.     Thus,  the  specific 


56  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

gravity  of  a  drop  of  blood  having  been  measured,  a  certain  quantity 
of  a  solution  of  sodium  chloride  isotonic  with  the  plasma  may  be 
injected  into  a  vein,  and  the  specific  gravity  again  determined.  Or 
the  electrical  resistance  of  a  small  sam])le  of  blood  may  be  measured 
before  and  after  injection  of  a  given  quantity  of  isotonic  salt  solution. 

The  total  mass  of  blood  in  a  living  man  has  been  estimated  by  caus- 
ing the  person  to  inhale  a  mixture  of  carbon  monoxide  with  oxygen 
or  air.  The  amount  of  carbon  monoxide  taken  up  is  determined  and 
also,  in  a  sample  of  blood  taken  from  the  finger  the  percentage 
amount  to  which  the  haemoglobin  has  become  saturated  with  carbon 
monoxide.  All  that  remains  is  to  estimate  the  volume  of  carbon 
monoxide  (or,  what  is  precisely  the  same  thing,  the  volume  of 
oxygen)  which  lOO  c.c.  of  blood  will  take  up.  This  latter  quantity 
is  called  the  percentage  oxygen  capacity.  From  these  data  the 
total  volume  of  the  blood  can  be  calculated.  If  the  volume  is 
multiplied  by  the  specific  gravity  the  mass  is  obtained.  Notwith- 
standing the  elegance  of  this  method  in  principle,  it  is  by  no  means 
easy  to  obtain  accurate  results  with  it  in  practice.  It  unques- 
tionably gives  values  for  the  total  quantity  of  blood  which  are  too 
low.  A  better  method  is  to  inject  into  a  vein  a  measured  quantity 
of  a  solution  of  a  pigment  ("  vital  red  "),  which  is  only  slowly  elimin- 
ated and  is  not  taken  up  to  a  sensible  degree  by  the  erythrocytes. 
Samples  of  blood  are  drawn  before  and  a  short  time  after  the  injec- 
tion and  the  plasma  separated  from  each  by  the  centrifuge.  The 
amount  of  pigment  is  then  determined  which  must  be  added  to  the 
first  sample  of  plasma  to  make  its  tint  the  same  as  that  of  the 
second.  The  total  quantity  of  plasma  can  thus  be  calculated  and 
from  it,  by  determining  the  relative  proportion  of  corpuscles  and 
plasma  in  the  blood,  the  total  quantity  of  blood  (Rowntree,  etc.). 

The  quantity  of  blood  in  the  body  was  greatly  over-estimated  by 
the  ancient  physicians.  Avicenna  put  it  at  25  lb.,  and  many  loose 
statements  are  on  record  of  as  much  as  20  lb.  being  lost  by  a  patient 
without  causing  death.  By  Welcker's  method  the  proportion  of 
blood  to  body-weight  has  been  found  to  be  in  the  dog  i :  13,  cat  i :  14, 
horse  1:15,  frog  1:17,  rabbit  1:19,  fowl  1:20.  In  new-born 
children  the  proportion  was  i :  ig,  in  adult  human  beings  (executed 
criminals)  i  :  13.  By  the  '  vital  red  '  method,  the  amount  of 
plasma  was  found  to  be  one-twentieth  and  that  of  blood  one- 
eleventh  to  one-twelfth  of  the  body-weight. 

According  to  Dreyer,  the  blood  vohinic  is  a  function  of  the  surface 
of  the  body,  so  that  the  smaller  and  lighter  animals  in  any  given  species 
have  a  relatively  greater  blood  volume  than  the  larger  and  heavier 
individuals.  Accordingly,  he  considers  that  the  practice  of  expressing 
the  volume  of  blood  as  a  percentage  of  the  body-weight  should  be 
abandoned. 

Fig.  16  (p.  54)  illustrates  the  distribution  of  the  blood  in  the 
various  organs  of  a  rabbit.  The  liver  and  skeletal  muscles  each  con- 
tain rather  more  than  one-fourth;  the  heart,  lungs,  and  great  vessels 


LYMPH  AND  CHYLE 


57 


rather  loss  than  one- fourth;  and  the  rest  of  the  body  about  one-lifth, 
of  the  total  blood.  The  kidney  and  spleen  of  the  rabbit  each  contain 
one-eighth  of  their  own  weight  of  blood,  the  liver  between  one-third 
and  one-fourth  of  its  weight,  the  muscles  only  one-twentieth  of  their 
weight. 

Section  V. — ^Lymph  and  Chyle. 

Lymph  has  been  defined  as  blood  without  its  red  corpuscles 
(Johannes  Miiller) ;  it  resembles,  in  fact,  a  dilute  blood-plasma, 
containing  leucocytes,  some  of  which  (lymphocytes)  are  common  to 
lymph  and  blood,  others  (coarsely  granular  basophile  cells,  present 
only  in  small  numbers)  are  absent  from  the  blood.  I-ymph  also 
contains  thrombocytes.  The  reason  of  this  similarity  appears  when 
it  is  recognized  that  the  plasma  of  tissue-lymph  (p.  460)  is  derived, 
in  large  part  at  any  rate,  from  the  plasma  of  blood  by  a  process  of 
physiological  filtration  (or  secretion)  through  the  walls  of  the 
capillaries  into  the  lymph-spaces  that  everywhere  occupy  the  inter- 
stices of  areolar  tissue,  while  the  lymph  of  the  lymphatic  vessels  is 
in  turn  derived  from  the  tissue  fluid.  But  in  addition  to  the  con- 
stituents of  the  plasma,  lymph  contains  substances  produced  in  the 
metabolism  of  the  tissues  which  pass  into  it  directly.  As  collected 
from  one  of  the  large  lymphatic  vessels  of  the  Hmbs,  or  from  the 
thoracic  duct  of  a  fasting  animal,  lymph  is  a  colourless  or  some- 
times yellowish  or  slightly  reddish  liquid  of  alkaline  reaction.  Its 
specific  gravity  is  much  less  than  that  of  the  blood  (1015  to  1030). 
It  coagulates  spontaneously,  but  the  clot  is  always  less  firm  and  less 
bulky  than  that  of  blood.  The  plasma  contains  fibrinogen,  from 
which  the  fibrin  of  the  clot  is  derived.  Serum-albumin  and  serum- 
globulin  are  present  in  much  the  same  relative  proportion  as  in  blood, 
although  in  smaller  absolute  amount.  Neutral  fats,  urea,  and  sugar 
are  also  found  in  small  quantities.  The  inorganic  salts  are  the  same 
as  those  of  the  blood-serum,  and  exist  in  about  the  same  amount, 
sodium  preponderating  among  the  bases,  as  it  does  in  serum.  The 
following  table  shows  the  results  of  analyses  of  lymph  from  man  and 
the  horse  (Munk) : 


Man. 

Horse. 

Water               .... 

/"Fibrin           .         -         - 

Other  proteins     - 

Solids  <  Fat     -         -         -         - 

Extractives* 

I^Salts    -        -         -         - 

95 -0  per  cent. 

O-I       ^ 

4-1 

trace     5-0 

0-3 

0-5      ) 

95-8  per  cent. 

O'l       \ 
2-9 

trace  -  4*2 

O-I 

i-i     j 

1 

•  The  term  '  extractives  '  is  somewhat  loosely  applied  to  organic  substances 
which  exist  in  so  small  an  amount,  or  have  such  indefinite  chemical  characters, 
that  they  cannot  be  separately  estimated,  and  are  extracted  together  from  the 
residue  by  various  solvents. 


58 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


Chyle  is  merely  the  name  given  to  the  lymph  coming  from  the 
alimentary  canal.  The  fat  of  the  food  is  absorbed  by  the  lym- 
phatics, and  during  digestion  the  chyle  is  crowded  with  fine  fatty 
globules,  which  give  it  a  milky  appearance.  There  may  also  be  in 
chyle  a  few  red  blood-corpuscles,  carried  into  the  thoracic  duct  by  a 
back-flow  from  the  veins  into  which  it  opens.  Chyle  clots  like 
ordinary  lymph,  the  size  of  the  clot  varying  according  to  the  quantity 
of  fat  present  and  enmeshed  by  the  fibrin.  Wounds  of  the  thoracic 
duct  or  of  lymphatics  opening  into  it  are  occasionally  produced  in 
operations  on  the  neck,  and  when  these  remain  open  chyle  may  be 
readily  collected.  In  samples  obtained  from  a  patient  onlj'  a  week 
after  the  section  of  a  branch  of  the  duct  during  an  operation  for  the 
removal  of  tubercular  glands,  water  constituted  928-90  parts  in 
1,000,  total  solids  71-10,  inorganic  solids  6-04,  organic  solids  65-06, 
proteins  18-52,  ether  extract  (fatty  substances)  19-30  (Sollmann). 
The  following  is  the  composition  of  a  sample  analyzed  by  Paton,  and 
obtained  from  a  fistula  of  the  thoracic  duct  in  a  man: 

Water  -  .  _  .     953-4 

Solids  -  -  -  .       ^5.5 

Inorganic  -  -  -  -         6-5 

Organic     -  -  -  .  ^o-i 

Proteins  -  -  -  iS"? 

Fats       .  -  -  -  24-06 

Cholesterin  -  -  -         0-6 

Lecithin  -  .  _         0*36 

The  quantity  of  chyle  flowing  from  the  fistula  was  estimated  at  as 
much  as  3  to  4  kilos  per  twenty-four  hours,  or  nearly  as  much  as  the 
whole  of  the  blood.  The  flow  has  been  calculated  in  various  animals 
at  one-eighteenth  to  one-seventh  of  the  body-weight  in  the  twenty- 
four  hours.  The  quantity  of  lymph  in  the  body  is  unknown,  but  it 
must  be  very  great — perhaps  two  or  three  times  that  of  the  blood. 

Allied  to  tissue-lymph,  but  not  identical  with  it,  are  the  fluids 
present  in  health  in  very  small  amount  in  such  serous  ca\nties  as  the 
pericardium.  The  synovial  fluid  of  the  joints  differs  from  lymph 
especially  in  containing  a  small  amount  of  a  mucin-like  substance. 

The  aqueous  humour,  and  still  more  the  cerebro-spinal  fluid,  arc 
characterized  by  a  marked  deficiency  in  solids,  especially  protein. 
In  the  following  table  (from  Spiro)  the  differences  in  the  composition 
of  lymph  and  alHed  fluids  from  different  parts  of  the  body  are  illus- 
trated. 


Man  :  Ly:nph  from 
Fistisa  in  Thigh. 

Horse :  T>yinph 

from  Nr-ik  during 

Mastication. 

Aqueous 
Humour. 

Cerebro-Spinal 
Fluid. 

99  to  99-2 

0-02   to  0-16 

Water  -     - 
Salts    -     - 
Fat      -     - 
Protein     - 

oG-4    to  94-3 
0-7     ,,     0-87 
0'06  .,     0-22I 
2-8     ,.     4-8  / 

95 
075 

37 

98-7 

0-5  to  0-8 

0-72 

FUNCTIONS  OF  BLOOD  AND  LYMPH  59 

The  gases  of  the  blood  and  lyinpli  will  be  treated  of  in 
Chapter  IV.,  the  formation  of  lymph  in  Chapter  VIII.,  its  circulation 
in  Chapter  III. 


Section  VI. — The  Funxtions  of  Blood  and  Lymph, 

We  have  already  said  that  these  liquids  provide  the  tissues  with 
the  materials  they  require,  and  carry  away  from  them  materials 
which  have  served  their  turn  and  are  done  with.  These  materials 
are  gaseous,  liquid,  and  solid.  Oxygen  is  brought  to  the  tissues  in 
the  red  corpuscles ;  carbon  dioxide  is  carried  away  from  them  partly 
in  the  erythrocytes,  but  chiefly  in  the  plasma  of  the  blood  and 
lymph.  The  water  and  solids  which  the  cells  of  the  body  take  in 
and  give  out  are  also,  at  one  time  or  another,  constituents  of  the 
plasma.  The  heat  produced  in  the  tissues,  too,  is,  to  a  large  extent, 
conducted  into  the  blood  and  distributed  by  it  throughout  the  body. 
The  leucocytes,  as  will  be  seen  farther  on,  aid  in  some  measure  in  the 
absorption  of  certain  of  the  food  substances  from  the  intestine.  It  is 
not  known  whether,  apart  from  this,  they  play  any  role  in  the  normal 
nutrition  of  other  cells,  although  it  is  probable  that  they  exercise  an 
influence  on  the  plasma  in  which  they  live.  But  they  have  impor- 
tant functions  of  another  kind,  to  which  it  is  necessary  to  refer  briefly 
here. 

Phagocytosis. — Certain  of  the  amoeboid  cells  of  blood  and  lymph, 
and  the  cells  of  the  splenic  pulp,  are  able  to  include  or  '  eat  up  ' 
foreign  bodies  with  which  they  come  in  contact,  in  the  same  way  as 
the  amoeba  takes  in  its  food.  Such  cells  are  called  phagocytes;  and 
it  is  to  be  remarked  that  this  term  neither  comprises  all  leucocytes 
nor  excludes  all  other  cells,  for  some  fixed  cells,  such  as  those  of  the 
endothelial  Hning  of  bloodvessels,  are  phagocytes  in  \-irtue  of  their 
power  of  sending  out  protoplasmic  processes,  while  the  small, 
relatively  immobile  lymphocyte  is  not  a  phagocyte. 

Although  it  is  not  at  present  possible  to  assign  a  physiological 
value  to  all  the  phenomena  of  phagocjrtosis,  either  as  regards  the 
phagocytes  themselves  or  as  regards  the  organism  of  which  they 
form  a  part,  there  seems  little  doubt  that  under  certain  circumstances 
the  process  is  connected  with  the  removal  of  structures  which  in  the 
■course  of  development  have  become  obsolete,  or  wath  the  neutral- 
ization or  elimination  of  harmful  substances  introduced  from  with- 
out, or  formed  by  the  activity  of  bacteria  within  the  tissues.  During 
the  metamorphosis  of  some  larvae,  groups  of  cilia  and  muscle-fibres 
may  be  absorbed  and  eaten  up  by  the  leucocytes.  In  the  metamor- 
phosis of  maggots,  for  example,  the  muscular  fibres  of  the  abdominal 
wall,  which  are  used  in  creeping,  and  are  therefore  not  required  in 
the  adult,  degenerate,  and  are  devoured  by  swarms  of  leucocytes 
"which  migrate  into  them.     In  the  human  subject  an  example  of 


6o  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

absorption  of  tissue  by  the  aid  of  leucocytes  is  the  removal  of  the 
necrosed  decidua  reflexa,  the  fold  of  uterine  mucous  membrane 
which  envelops  the  ovum  (Minot). 

The  behaviour  of  phagocytes  towards  pathogenic  micro-organisms 
is  of  even  greater  interest  and  importance.  Metchnikoff  laid  the 
foundation  of  our  knowledge  of  this  subject  by  his  researches  on 
Daphnia,  a  small  crustacean  with  transparent  tissues,  which  can  be 
observed  under  the  microscope.  When  this  creature  is  fed  with  a 
fungus,  Monospora,  the  spores  of  the  latter  find  their  way  into  the 
body-cavity.  Here  they  are  at  once  attacked  by  the  leucoc3H:es, 
ingested,  and  destroyed.  But  after  a  time  so  many  spores  get 
through  that  the  leucocj^es  are  unable  to  deal  with  them  all;  some 
of  them  develop  into  the  first  or  '  conidium  '  stage  of  the  fungus;  the 
conidia  poison  the  leucocytes,  instead  of  being  destroyed  by  them, 
and  the  animal  generally  dies.  Occasionally,  however,  the  leuco- 
cytes are  able  to  destroy  all  the  spores,  and  the  life  of  the  Daphnia  is 
preserved.  This  battle,  ending  sometimes  in  victory,  sometimes  in 
defeat,  is  believed  by  Metchnikoff  to  be  tj^'pical  of  the  struggle  which 
the  phagocytes  of  higher  animals  and  of  man  seem  to  engage  in 
when  the  germs  of  disease  are  introduced  into  the  organism.  He 
supposes  that  the  immunity  to  certain  diseases  possessed  naturally 
by  some  animals,  and  which  may  be  conferred  on  others  by  vaccina- 
tion with  various  protective  substances,  is,  to  a  large  extent,  due  to 
the  early  and  complete  success  of  the  phagocytes  in  the  fight  with 
the  bacteria;  and  that  in  rapidly- fatal  diseases — such  as  chicken- 
cholera  in  birds  and  rabbits,  and  anthrax  in  mice — the  absence  of 
any  effective  phagocytosis  is  the  factor  which  determines  the  result. 
Others  have  laid  stress  on  the  action  of  protective  substances  sup- 
posed to  exist  in  the  plasma  itself.  It  is  possible  that  such  sub- 
stances are  manufactured  by  the  leucocytes,  and  either  given  off  by 
them  to  the  plasma  by  a  process  of  '  excretion,'  or  liberated  by  their 
complete  solution. 

The  most  recent  investigations  go  to  show  that  Metchnikoff's 
phagocytic  theory  of  immunity  requires  modification,  at  any  rate  in 
the  case  of  the  higher  animals  and  man,  although  the  brilliant 
biological  observations  on  which  it  was  originally  built  retain  all 
their  value.  He  supposed  that  in  the  immunizing  process  the 
leucocytes  underwent  certain  changes,  acquired,  so  to  speak,  a  sort 
of  '  education  '  that  enabled  them  to  cope  with  bacteria  against 
which  they  were  previously  powerless.  It  seems  more  probable 
that  in  the  presence  of  the  substances  that  confer  imnumity,  not  only 
the  leucocytes,  but  other  cells,  are  stimulated  to  produce  bodies 
which  cut  short  the  life,  or  inhibit  the  growth,  of  the  bacteria 
(alexins),  or  prepare  them  for  being  taken  up  by  the  phagocytes 
(opsonins).  It  has  been  shown  that  bacteria  which  have  been  in 
contact  with  serum  containing  the  appropriate  opsonins  are  taken 


FUNCTIONS  OF  BLOOD  AND  LYMPH  6i 

up  readily  by  leucocytes  washed  free  from  serum  constituents  by 
physiological  salt  solution,  whereas  the  washed  leucocytes  either  do 
not  ingest  bacteria  which  have  not  been  acted  on  by  serum,  or  take 
them  up  in  much  smaller  numbers.  There  is  some  evidence  that  in 
certain  bacterial  infections — for  example,  chronic  furunculosis,  a 
condition  in  which  crops  of  boils  continue  to  appear — the  grip  of  the 
bacteria  on  the  body  is  perpetuated  by  a  deficiency  in  the  amount  or 
in  the  activity  of  opsonins  capable  of  acting  specifically  upon  the 
micro-organisms  in  question.  A  numerical  expression,  which  in 
certain  cases,  perhaps,  gives  a  measure  of  the  patient's  resistance  to 
the  infection,  has  been  worked  out  by  Wright  under  the  name 
'  opsonic  index.'  This  index  is  the  ratio  between  the  average 
number  of  bacteria  taken  up,  under  certain  fixed  conditions,  by  each 
polymorphonuclear  leucocyte  in  an  emulsion  made  with  the  patient's 
serum,  and  the  average  number  taken  up  by  similar  leucocytes  in  an 
emulsion  made  with  normal  serum.  The  significance  of  this  index 
and  even  the  practicability  of  the  methods  used  to  ascertain  it,  are 
still  the  subject  of  discussion. 

Diapedesis. — The  fact  that  leucocytes  can  pass  out  of  the  blood- 
vessels into  the  tissues  has  a  very  important  bearing  on  the  subject 
of  phagocytosis.  The  phenomenon  is  called  diapedesis,  and  is  best 
seen  when  a  transparent  part,  such  as  the  mesentery  of  the  frog,  is 
irritated.  The  first  effect  of  irritation  is  an  increase  in  the  flow  of 
blood  through  the  affected  region.  If  the  irritation  continues,  or  if 
it  was  originally  severe,  the  current  soon  begins  to  slacken,  the 
corpuscles  stagnate  in  the  vessels,  and  inflammatory  stasis  is  pro- 
duced. The  leucocj^es  adhere  in  large  numbers  to  the  walls  of  the 
capillaries,  and  particularly  of  the  small  veins,  and  then  begin  to  pass 
slowl}^  through  them  by  amoeboid  movements,  the  passage  taking 
place  at  the  junctions  between,  or  it  may  be  through  the  substance  of, 
the  endothelial  cells.  Plasma  is  also  poured  out  into  the  tissues, 
the  whole  forming  an  inflammatory  exudation.  Even  red  blood- 
corpuscles  may  pass  out  of  the  vessels  in  small  numbers.  The 
exudation  may  be  gradually  reabsorbed,  or  destruction  of  tissue 
may  ensue,  and  a  collection  of  pus  be  formed.  The  cells  of  pus  are 
emigrated  leucocytes  (Practical  Exercises,  Chap.  III.,  p.  193). 

Their  emigration  is  connected  \\dth  the  defence  of  the  organism 
against  the  entrance  of  certain  forms  of  bacteria  at  the  seat  of 
injury,  and  with  the  repair  of  the  injured  tissue,  but  the  nature  of 
the  summons  which  gathers  them  there  is  not  yet  clearly  under- 
stood. It  is  probably  some  sort  of  chemical  attraction  (chemio- 
taxis)  between  constituents  of  the  bacteria  or  decomposition  prod- 
ucts of  the  injured  tissue  on  the  one  hand,  and  constituents  of  the 
leucocytes  on  the  other. 

As  for  the  blood-plates,  it  will  suffice  to  say  by  way  of  summary 
that  their  important  function  in  the  sealing  of  wounded  vessels  (p.  46) 


6i  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

is  the  sole  office  which  at  present  can  be  attributed  to  them.  And 
if  it  is  permissible  to  consider  the  leucocytes  as  a  patrol  for  the 
defence  of  the  tissues  in  general  against  invading  micro-organisms,  it 
may  perhaps  not  be  too  far-fetched  an  idea  to  look  upon  the  blood- 
plates  as  essentially  a  patrol  in  the  interests  of  the  anatomical 
integrity  of  the  vascular  system  itself.  This  does  not  exclude  the 
possibility  that  the  clo'^ting  of  extravasated  plasma  may  furnish  a 
more  favourable  medium  for  the  processes  of  repair  in  all  injured 
tissues. 


PRACTICAL  EXERCISES  ON  CHAPTER  II. 

N.B. — In  the  following  exercises  all  experiments  on  animals  which 
would  cat^e  the  slightest  pain  are  to  be  done  under  complete  ancesthesia. 

1.  Reaction  of  Blood. — (i)  Put  a  drop  of  fresh  dog's  or  ox  blood  on 
a  piece  of  glazed  neutral  litmus  paper  (the  litmus  paper  can  be  glazed 
by  dipping  it  into  a  neutral  solution  of  gelatin  and  allowing  it  to  dry). 
Wash  the  blood  ofiE  in  lo  to  30  seconds  with  distilled  water.  A  bluish 
stain  will  be  left,  showing  that  fresh  blood  is  alkaline.  (2)  Repeat  with 
dog's  or  ox  serum.  It  is  not  necessarv'  to  wash  the  serum  off,  as  it 
does  not  obscure  the  change  of  colour.  (3)  Repeat  (i)  with  human 
blood.  With  a  clean  suture-needle  or  a  good-sized  sewing-needle 
which  has  been  sterilized  in  the  flame  of  a  Bunsen  burner,  prick  one  of 
the  fingers  behind  the  nail.  Bandaging  the  finger  with  a  handkerchief 
from  above  downwards,  so  as  to  render  its  tip  congested,  will  often 
facilitate  the  getting  of  a  good-sized  drop,  but  for  quantitative  experi- 
ments, like  2.  10,  and  i  7  (4).  this  should  not  be  done. 

2.  Specific  Gravity  of  Blood — Hammerschlag's  Method. — (i)  Put  a 
mixture  of  chloroform  and  benzol  of  specific  gravity  i-o6o  into  a  small 
glass  cylinder.  Put  a  drop  of  dog's  or  o.x  defibrinated  blood  into  the 
mixture  by  means  of  a  small  pipette.  If  the  drop  sinks  add  chloroform, 
if  it  rises  add  benzol,  till  it  just  remains  suspended  when  the  liquid  has 
been  well  stirred.  Then  with  a  small  hydrometer  measure  the  specific 
gravity  of  the  mixture,  which  is  now  equal  to  that  of  the  blood.  Filter 
the  liquid  to  free  it  from  blood,  and  put  it  back  into  the  stock-bottle. 
(2)  Obtain  a  drop  of  human  blood  as  in  i,  and  repeat  the  measurement 
of  the  specific  gravity. 

3.  Coagulation  of  Blood.* — (i)  Take  three  tumblers  or  beakers,  label 
them  a.  ;i.  and  7.  and  measure  into  each  100  c.c.  of  water.  Mark  the 
level  of  the  water  by  strips  of  gummed  paper,  and  pour  it  out.  (If  a 
sufficient  number  of  graduated  cylinders  is  available,  they  may  of 
course  be  used,  and  this  measurement  avoided.)  Into  a  put  25  c.c 
of  a  saturated  solution  of  magnesium  sulphate,  into  ^  25  c.c.  of  a  i  per 
cent,  solution  of  potassium  or  ammonium  oxalate  in  0-9  per  cent, 
solution  of  sodium  chloride,  and  into  y  25  c.c.  of  a  i'2  per  cent,  solution 
of  sodium  fluoride  in  0-9  per  cent,  salt  solution  If  the  dog  provided 
is  a  large  one,  these  quantities  may  be  all  doubled ;  for  a  small  dog  they 
may  be  all  halved. 

•  This  experiment  requires  two  laboratory  periods,  the  various  blood  mix- 
tures being  obtained  during  the  first  and  worked  up  during  the  second. 


PRACTICAL  EXERCISES  63 

(2)  Insert  a  cannula  into  the  central  end  of  the  carotid  artery  of  a 
dog  anaesthetized  with  morphine*  and  ether,  or  A.C.E.  mixture. f 

To  put  a  Cannula  into  an  Artery. — Select  a  glass  cannula  of  suitable 
size,  feel  for  the  artery,  make  an  incision  in  its  course  through  the 
skin,  then  isolate  about  an  inch  of  it  with  forceps  or  a  blunt  needle, 
carefully  clearing  away  the  fascia  or  connective  tissue.  Next  pass  a 
small  pair  of  forceps  under  the  arterj\  and  draw  two  ligatures 
through  below  it.  If  the  cannula  is  to  be  inserted  into  the  central 
end  of  the  artery,  tie  the  ligature  which  is  farthest  from  the  heart, 
and  cut  one  end  short.  Then  between  the  heart  and  the  other 
ligature  compress  the  artery  with  a  small  clamp  (often  spoken  of  as 
'  bulldog  '  forceps).  Now  lift  the  arter^^  by  the  distal  ligature,  make  a 
transverse  slit  in  it  with  a  pair  of  fine  scissors,  insert  the  cannula,  and 
tie  the  ligature  over  its  neck.  Cut  the  ends  of  the  ligature  short.  If 
the  cannula  is  to  be  put  into  the  distal  end  of  the  ^.ttevy,  both  ligatures 
must  be  between  the  clamp  and  the  heart,  and  the  bulldog  must  be  put 
on  before  the  first  ligature  (the  one  nearest  the  heart)  is  tied,  so  that 
the  piece  of  bloodvessel  between  it  and  the  ligature  may  be  full  of 
blood,  as  this  facilitates  the  opening  of  the  artery. 

(3)  Run  into  a,  /3,  and  y  enough  blood  to  fill  them  to  the  mark. 
Shake  the  vessels,  or  stir  up  once  or  twice  with  a  glass  rod,  to  mix  the 
blood  and  solution. 

(4)  Take  a  small  thin  copper  or  brass  vessel,  and  place  it  in  a  freezing 
mixture  of  ice  and  salt.  Run  into  it  some  of  the  blood  from  the  artery. 
It  soon  freezes  to  a  hard  mass.  Now  take  the  vessel  out  of  the 
freezing  mixture  and  allow  the  blood  to  thaw.  It  will  be  seen  that  it 
remains  liquid  for  a  short  time  and  then  clots. 

(5)  Run  some  of  the  blood  into  a  porcelain  capsule,  stirring  it 
vigorously  with  a  glass  rod.  The  fibrin  collects  on  the  rod;  the  blood 
is  defibrinated  and  will  no  longer  clot. 

(6)  Now  let  some  blood  run  into  a  small  beaker  or  jar.  Notice  that 
the  blood  begins  to  clot  in  a  few  minutes,  and  that  soon  the  vessel 
can  be  tilted  without  spilling  it.  Note  the  time  required  for  clotting 
to  occur.  Set  the  coagulated  blood  aside,  and  observe  next  day  that 
clear  yellow  serum  has  separated  from  the  clot. 

(7)  Weigh  out  a  quantit}'  of  Witte's  '  peptone  '  equivalent  to 
0'5  gramme  for  every  kilo  of  bodj^- weight  of  the  dog.  Dissolve  the 
peptone  in  about  twenty  times  its  weight  of  0-9  per  cent,  salt  solution. 
Put  a  cannula  into  the  central  end  of  a  crural  vein  (p.  212).  Fill  the 
cannula  with  the  peptone  solution  and  connect  it  with  a  burette.  Put 
15  drops  of  the  peptone  solution  into  a  test-tube  labelled  '  Peptone  A.' 
Put  the  rest  into  the  burette,  and  see  that  the  connecting  tube  is  filled 
with  the  solution  and  free  from  air.  Run  into  the  test-tube  about 
5  c.c.  of  blood  from  the  cannula  in  the  carotid.  Now  let  the  peptone 
solution  flow  from  the  burette  into  the  vein.  Feel  the  pulse  o\'er  the 
heart  as  the  solution  is  running  in.  If  the  heart  becomes  very  weak, 
stop  the  injection ;  otherwise  the  animal  may  die  from  the  great  lower- 
ing of  blood-pressure  (p.  214).  As  soon  as  the  injection  is  finished, 
draw  off  a  sample  of  5  c.c.  of  blood  into  a  test-tube  labelled  '  Pep- 
tone B,'  and  let  it  stand.  In  ten  minutes  collect  five  further  samples 
of  5  c.c.  ('  Peptone  C,  D,  E,  F,  G  '),  and  a  large  one,  H;  in  half  an  hour 

*  One  to  2  centigrammes  of  morphine  hydrochlorate  per  kilogramme  of 
body-weight  should  be  injected  subcutaneously  about  half  an  hour  before 
the  operation.  Ten  c.c.  of  a  2  per  cent,  solution  is  sufficient  for  a  dog  of 
good  size.  Note  that  diarrhoea  and  salivation  are  caused  by  such  a  dose. 
For  directions  for  fastening  the  dog  on  the  holder,  see  footnote  on  p.  199. 

t  A  mixture  of  i  part  of  alcohol,  2  of  ether,  and  3  of  chloroform. 


64 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


another  set  of  five  small  samples,  and  at  as  long  an  interval  as  possible 
thereafter  five  more.  Now  letting  the  dog  bleed  to  death,  observe  that 
the  flow  of  blood  is  temporarilj'  increased  by  pres.sure  on  the  abdominal 
walls,  which  squeezes  it  towards  the  heart,  by  passive  movements  of 
the  hind-legs,  and  also  during  the  convulsions  of  asphyxia,  which  soon 
appear.  Add  to  the  peptone  blood  D  5  c.c.  of  serum,  to  H  a  little 
sodium  chloride  extract  of  liver,  to  F  a  little  extract  of  muscle,  and  to 
G  15  drops  of  a  2  per  cent,  solution  of  calcium  chloride,  and  put  C,  D, 
E.  F,  and  G  into  a  water-bath  at  40°  C.     Treat  the  other  sets  of  small 

samples  in  the  same  way.  Note 
liow  long  each  specimen  takes  to 
clot,  and  report  your  results.* 

(8)  Observe  that  the  blood  in  a, 
8,  and  y  has  not  coagulated.  Label 
four  test-tubes  '  Oxalate  A,  B,  C, 
D.'  and  put  into  each  about  5  c.c. 
of  the  oxalated  blood.  Add  to  A 
and  B  5  or  6  drops  of  a  2  per  cent, 
solution  of  calcium  chloride,  to  C  12 
drops,  and  to  D  as  much  as  there 
is  of  the  blood.  Leave  A  at  the 
ordinary  temperature,  put  the  other 
test-tubes  in  a  water-bath  at  40"  C, 
and  note  when  clotting  occurs. 

(9)  To  10  c.c.  of  the  fluoride  blood 
add  a  little  more  CaCl2  than  is  re- 
quired to  combine  with  the  excess 
of  fluoride  present.  Label  four  test- 
tubes  '  Fluoride  A,  B,  C,  D,'  and 
into  each  put  about  2  c.c.  of  this 
'  recalcified  '  fluoride  blood.  To  B 
add  I  c.c.  liver  extract  to  C  1  c.c. 
muscle  extract,  and  to  D  4  c.c. 
water.  Label  two  more  test-tubes 
'  Fluoride  E  and  F.'  Into  each  put 
2  c.c.  of  the  fluoride  blood  without 
CaCl2.  Add  also  to  E  i  c.c.  liver 
extract  and  to  F  i  c.c.  serum.  Put 
all  the  tubes  in  a  bath  at  about 
40°  C,  and  observe  in  which  and  in 
what  time  coagulation  takes  place. 

(10)  By  means  of  a  centrifuge 
(Fig.  1 7)  separate  the  plasma  from 
the  corpuscles  in  a,  ji,  and  y,  and 
also  from  the  peptone  blood. 

With  the  oxalate  plasma  from  /3, 
and  the  fluoride  plasma  from  y,  repeat  the  observations  in  (8)  and 
(9),  using  smaller  quantities  of  the  plasma,  if  necessarj',  in  small  test- 
tubes.  With  the  plasma  from  a  perform  the  following  experiments: 
Put  a  small  quantity  of  the  plasma  (i  c.c.)  into  four  test-tubes,  labelling 

•  Sometimes  the  injection  of  peptone  hastens  coagulation  instead  of  hinder- 
ing it.  It  has  been  asserted  that  this  is  only  the  case  when  small  doses  are 
used  (less  than  0-02  gramme  per  kilo  of  body-weight).  But  in  2  dogs  out  of 
ri  a  dose  of  0*5  gramme  per  kilo  has  been  seen  to  hasten  coagulation,  and  in 
I  out  of  12  to  leave  it  unaffected;  in  the  other  9  coagulation  was  markedly 
retarded 


Fig.  I/. — Centrifuge  (Jung).  The  four 
cylinders  shown  at  the  top  of  the 
figure  are  so  swung  that  they  become 
horizontal  as  soon  as  speed  is  up. 


PRACTICAL  EXERCISES  65 

them  '  Magnesium  Sulphate  A,  B,  C,  D.'  Dilute  B  with  four  times,  C 
with  eight  times,  and  D  with  twenty  times  as  much  distilled  water  as 
was  taken  of  the  plasma.  Observe  in  which,  if  any,  coagulation  occurs, 
and  the  time  of  its  occurrence,  and  report  the  result. 

(11)  With  peptone  plasma  from  H  and  from  the  peptone  blood 
obtained  later  repeat  the  experiments  done  in  (7).  In  addition  tlilute 
I  c.c.  of  the  plasma  with  three  volumes  of  water  and  i  c.c.  of  it  with 
ten  volumes  of  water,  and  put  in  the  bath  at  40°  C.  Observe  whether 
clotting  occurs. 

Instead  of  dog's  blood,  the  blood  of  an  ox  or  pig  may  be  obtained  at 
the  slauglitcr-housc. 

4.  Preparation  of  Fibrin-Ferment. — Precipitate  blood-serum  with 
ten  times  its  volume  oi  ;ilcohol.  Let  it  stand  for  several  weeks,  then 
extract  the  precipitate  with  water.  The  water  dissolves  out  the  fibrin- 
ferment,  but  not  tlie  coagulated  serum  proteins. 

3.  Preparation  of  Tissue  Extracts  containing  Thrombokinase. — In  a 
dog  or  rabbit  killed  by  bleeding  insert  a  cannula  into  the  lower  end  of 
the  thoracic  aorta.  Fill  the  cannula  with  0-9  per  cent,  salt  solution, 
and  connect  it  with  a  bottle  also  containing  salt  solution.  Wash 
out  the  vessels  of  the  lower  portion  of  the  body,  making  an  opening 
in  the  inferior  vena  cava  above  the  diaphragm  to  allow  the  liquid 
to  escape.  For  the  sake  of  cleanliness,  a  cannula  armed  with  a 
piece  of  rubber  tubing  should  be  inserted  for  this  purpose  into  the 
inferior  vena  cava.  Continue  the  injection  till  the  liquid  issues  colour- 
less. Then  remove  portions  of  liver  and  muscle.  Mince  each  separately. 
Rub  up  with  sand  in  a  mortar.  Add  o-g  per  cent,  sodium  chloride 
solution  and  rub  up  again.  Put  into  bottles  and  keep  in  the  ice-chest. 
For  use  take  off  some  of  the  liquid  from  the  top  with  a  pipette,  or  strain 
through  cheese-cloth. 

6.  Serum. — Test  the  reaction,  and  determine,  both  by  the  hydrom- 
eter and  the  pycnometer,  or  specific  gravity  bottle,  the  specific 
gravity  of  the  serum  provided,  or  of  the  serum  obtained  in  experi- 
ment 3. 

Serum  Proteins. — (i)  Saturate  serum  with  magnesium  sulphate 
crv'stals  at  30°  C.  The  serum-globulin  is  precipitated.  Filter  off. 
Wash  the  precipitate  on  the  filter  with  a  saturated  solution  of  mag- 
nesium sulphate.  Dissolve  the  precipitate  by  the  addition  of  a  little 
distilled  water,  and  perform  the  following  tests  for  globulins :  (a)  Satu- 
rate with  magnesium  sulphate.  A  precipitate  is  obtained.  (6)  Drop 
into  a  large  quantity  of  water,  and  a  flocculent  precipitate  falls  down, 
(c)  Heat.  Q>agulation  occurs.  Determine  the  temperature  of  coagfu- 
lation  (p.  9). 

(2)  To  a  portion  of  the  filtrate  from  (i)  add  sodium  sulphate  to 
saturation.  The  serum-albumin  is  precipitated.  (Neither  magnesium 
sulphate  nor  sodium  sulphate  precipitates  serum-albumin  alone,  but 
the  double  salt  sodio-magnesium  sulphate  precipitates  it,  and  this  is 
formed  when  sodium  sulphate  is  added  to  magnesium  sulphate.) 

(3)  Dilute  another  portion  of  the  filtrate  from  (i)  with  its  own  bulk 
of  water.  Very  slightly  acidulate  with  dilute  acetic  acid,  and  de- 
termine the  temperature  of  heat  coagulation. 

(4)  Precipitate  the  serum-globulin  from  another  portion  of  scrum  by 
adding  to  it  an  equal  volume  of  saturated  solution  of  ammonium 
sulphate.  Filter.  Precipitate  the  serum-albumin  from  the  filtrate  by 
saturating  with  ammonium  sulphate  cr\-stals. 

(5)  Dilute  serum  with  ten  to  twenty  times  its  volume  of  distilled 
water,  and  pass  through  it  a  stream  of  carbon  dioxide.  The  serum- 
globulin  is  partially  precipitated. 

5 


66  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

(6)  Acidulate  some  scrum  with  dilute  acetic  acid  and  boil.  Filtei 
off  the  coagulum.  and  to  the  filtrate  add  silver  nitrate.  A  non-protein 
precipitate  insoluble  in  nitric  acid,  but  soluble  in  ammonia,  indicates 
the  presence  of  clilorides. 

7.  Action  of  Serum  on  Artery  Rings. — Cut  a  number  of  rings  about 
li  millimetres  wide  from  a  fresh  carotid  artery  of  the  sheep,  obtained 
from  the  slaughter-house.  Keep  the  rings  in  a  dish  in  Ringer's  solu- 
tion.* They  should  be  as  nearly  as  possible  of  uniform  width.  A  small 
cylindrical  glass  vessel  is  supported  on  a  stand  in  such  a  way  that  it 
can  be  easily  lowered  into  a  bath  of  water  kept  at  a  temperature  of 
about  39°  to  40".  A  stock  of  Ringer's  solution  is  kept  in  a  beaker 
or  bottle  immersed  in  the  bath.  A  ring  of  the  artery  is  put  into  the 
small  cylinder,  where  it  is  held  between  two  aluminium  hooks,  one 
fastened  to  the  bottom  of  the  cylinder,  the  other  (the  upper  one)  con- 
nected with  the  short  arm  of  a  lever,  the  long  arm  of  which  is  arranged 
to  write  on  a  slowly  revolving  drum.  A  time-trace,  say  in  half- 
minutes,  is  recorded  below.  The  small  cylinder  is  now  filled  with 
warm  Ringer's  solution  and  lowered  into  the  bath.  Oxygen  is  bubbled 
through  the  solution  by  means  of  a  side-tube  near  the  bottom  of  the 
cylindrical  vessel.  The  artery-  ring  is  now  stretched  for  five  minutes 
by  a  weight  of  10  grammes  attached  to  the  long  arm  of  the  lever  at  the 
same  distance  from  the  axis  as  that  at  which  the  ring  is  attached. 
After  the  stretching  period  the  weight  is  removed,  and  a  little  time 
allowed  to  elapse  till  the  writing-point  traces  a  horizontal  line  on  the 
drum.  Then  a  bent  pipette  is  filled  with  serum  already  heated  to  bath 
temperature  in  a  vessel  immersed  in  the  bath.  The  pipette  is  intro- 
duced into  the  small  cylinder  so  tliat  its  point  is  at  the  bottom,  without 
disturbing  the  ring,  and  tlie  serum  is  allowed  to  run  in  till  the  Ringer 
solution  is  displaced.  The  ring  shortens  under  the  influence  of  the  con- 
strictor substance  in  the  serum,  and  the  tracing  is  continued  till  the 
shortening  has  reached  its  maximum  and  the  trace  is  again  horizontal 
(Fig.  3,  p.  46). 

^  arious  dilutions  of  the  serum  are  now  made  with  Ringer's  solution, 
and  the  greatest  dilution  in  which  the  serum  will  still  cause  a  percep- 
tible constriction  of  the  rings  is  determined.  This  affords  a  measure 
of  comparison  with  other  sera  of  the  strength  of  the  constrictor  action. 
For  each  dilution  of  serum  a  separate  ring  must  be  used.  It  must  be 
remembered  that  comparisons  of  this  kind  can  only  be  made  with 
arteries  of  the  same  sensitiveness,  and  different  arteries  vary  much  in 
this  regard. 

8.  Comparison  of  the  Action  of  Serum  and  Adrenalin  (Epinephrin)  on 
Artery  Rings. — Tracings  showing  the  effect  of  \  arious  dilutions  of 
adrenalin  chloride  on  artery  rings  may  now  be  taken  for  comparison 
with  the  serum  effects.  The  adrenalin  dilutions  should  be  made  just 
before  use,  as  adrenalin  is  rapidly  oxidized.  Or  a  separate  experiment 
on  the  action  of  adrenalin  may  be  made  under  '  Circulation,'  as  on 
p.  216. 

9.  Comparison  of  the  Action  of  Serum  and  Plasma  on  Artery  Rings. — 
Citrate  ])lasma  is  obtained  as  follows:  A  cannula  and  attached  rubber 
tube  are  boiled,  oiled  inside  with  fresh  olive-oil,  and  filled  with  a  citrate 

*  This  is  the  name  given  to  a  solution  containing  the  most  important  of 
the  inorganic  constituents  of  blood-serum  in  approximately  the  normal  pro- 
portions. The  various  '  Ringer's  solutions  '  used  by  different  workers  have 
varied  slightly.  That  recommended  by  Locke  (for  perfusion  of  the  isolated 
heart)  contains  NaCl,  0-9  per  cent.;  KCl,  0*042  per  cent.;  CaCl2.  0-024  P^r  cent.; 
NaHC03,  o-oi  to  0-03  per  cent.;  with  in  addition  o'l  per  cent,  of  dextrose, 
which  can  be  omitted  lor  such  experiments  as  7. 


PRACTICAL  EXERCISES 


f>7 


solution  made  by  dissolving  sodium  citrate  in  Ringer's  solution  to  the 
extent  of  2  per  cent.  The  solution  is  prevented  from  escaping  by  a 
clip  on  the  tube.  The  cannula  is  inserted  into  the  carotid  of  a  dog, 
the  end  of  the  rubber  tube  dipped  below  a  quantity  of  citrate- 
Ringer  solution  in  a  beaker  and  a  volume  of  blood  equal  to  that  of  the 
solution  run  in.  Then  the  blood  and  solution  are  at  once  stirred  gently, 
but  sufficiently  to  insure  proper  admixture. 

Some  blood  is  now  run  into  another  vessel,  defibrinated,  and 
measured.  An  equal  volume  of  the  citrate-Ringer  solution  is  added  to 
it  while  the  mass  of  fibrin  is  still  floating  in  the  blood,  .\fter  mixing, 
the  fibrin  is  removed.  Plasma  is  then  separated  by  the  centrifuge  from 
the  first  specimen  of  blood,  and  serum  from  the  second,  and  comparison 
experiments  are  made  with  each  on  artery  rings.  If  the  plasma  has 
been  properly  obtained,  it  will  have  little  constrictor  effect  on  the 
rings  in  comparison  with  the  serum.  In  making  the  comparison, 
arteries  which  give  a  decided  effect  with  serum  should  be  employed. 
The  defibrinated  blood  and  the  unclotted  citrate  blood  may  also  be 
used  for  tlie  comparison. 


Fig.  I&.  —  Thoma-Zeiss  Ha-mocytometer.  M,  mouthpiece  of  lube  G,  by  which 
blood  is  sucked  into  S;  E,  bead  for  mixing;  a,  view  of  slide  from  above;  b,  in 
section;  c,  squares  in  middle  of  B,  as  seen  under  microscope. 

10.  Enumeration  of  the  Blood  -  Corpuscles.  —  Use  the  Thoma-Zeiss 
apparatus  (Fig.  18).  (i)  Suck  a  drop  of  ox  or  dog's  blood  up  into 
the  capillary  tube  5  to  the  mark  i.  Wipe  off  any  blood  which 
may  adhere  to  the  end  of  the  tube.  Then  fill  it  with  3  per 
cent,  sodium  chloride  to  the  mark  loi.  This  represents  a  dilution  of 
100  times.  Mix  the  blood  and  solution  thoroughly,  then  blow  out  a 
drop  or  two  of  the  liquid  to  remove  all  the  solution  which  remains  in 
the  capillary-  tube.  Now  fill  the  shallow  cell  B  with  the  blood  mixture. 
Put  the  cover-glass  on,  taking  care  that  it  does  not  float  on  the  liquid, 
but  that  the  cell  is  exactly  filled.  Put  the  slide  under  the  microscope 
(say  Leitz's  oc.  III.,  obj.  5),  and  count  the  number  of  red  corpuscles 
in  not  less -tlitei' ten 'to  twenty  squares.  Sixteen  squares  is  a  good 
routine  number.  The  greater  the  number  of  squares  counted,  the 
nearer  will  be  the  approximation  to  the  truth.  Now  take  the  average 
number  in  a  square.  The  depth  of  the  cell  is  ^'^  mm.,  the  area  of  each 
square  j^^  sq.  mm.  The  volume  of  the  column  of  liquid  standing 
upon  a  square  is  ^oVht  cub.  mm.  One  cub.  mm-  of  the  diluted  blood 
would  therefore  contain  4,000  times  as  many  corpuscles  as  one  square. 
But  the  blood  has  been  diluted  100  times,  therefore  i  cub.  mm.  of  the 


68 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


undiluted  blood  would  contain  400,000  times  the  number  of  corpuscles 
in  one  square.  Suppose  the  average  for  a  square  is  found  to  be  13. 
This  would  correspond  to  5,200,000  corpuscles  in  i  cub.  mm.  of  blood. 
Compare  your  result  with  the  true  number  supplied  by  the  demon- 
strator. (2)  Prick  the  finger  to  obtain  a  drop  of  blood,  and  repeat 
the  crunt  as  in  (i).* 

To  Count  the  White  Corpuscles. — Add  to  i  part  of  blood  9  parts  of 
\  per  cent,  acetic  acid,  in  order  to  lake  the  coloured  corpuscles  and 
render  it  easy  to  see  the  leucocytes. 

II.  Relative  Volume  of  Corpuscles  and  Plasma  by  Haematocrite. — 
(i)  For  pructice,  fill  the  two  graduated  glass  tubes  with  the  defibrinated 
blood  of  an  animal.  The  rubber  tube  with  mouthpiece  supplied  with 
the  apparatus  is  to  be  attached  to  the  glass  tube,  and  the  blood  sucked 
up.  Press  the  tip  of  the  index-finger  against  the  pointed  end,  and  care- 
fully remove  the  rubber  tube.  Place  the  tube  in  the  haematocrite  frame, 
blunt  end  outwards — that  is,  farthest  from  the  axis  of  rotation — and 
then  slip  the  pointed  end  down  into  position  against  the  spring.  Instead 
of  the  rubber  tube,  a  special  suction  pipette  for  automatically  filling 
the  graduated  tubes  may  be  employed  (Daland).  Attach  the  haemato- 
crite frame  to  the  centrifuge,  and  rotate  till  the  volume  of  sediment 


Fig.  19. 


3 

-Hfpmatocrite.      A,  haematocrite  attachment  with  graduated  tubes;  B,  auto- 
matic pipette  for  filling  the  tubes  (Daland). 


(corpuscles)  ceases  to  diminish.  The  graduations  are  best  read  with  a 
hand  lens.  The  leucocytes  will  be  seen  to  form  a  thin  whitish  line 
proximal  to  the  column  of  red  corpuscles. 

(2)  Prick  the  finger  or  the  lobe  of  the  ear,  fill  the  tubes  as  in  (i),  and 
centrifugalize.  Evciything  must  be  done  as  rapidly  as  possible,  so 
that  the  blood  may  not  clot  till  the  separation  of  plasma  and  corpuscles 
is  completed.  The  centrifuge  must  rotate  very  rapidly  (about  10,000 
revolutions  a  minute)  for  two  or  three  minutes.  For  clmical  purposes 
it  is  best  to  rotate  the  centrifuge  always  at  the  same  speed  for  the 
same  length  of  time  rather  than  to  aim  at  reaching  a  constant  length 
of  the  column  of  corpuscles.  In  this  way  useful  comparative  results 
can  be  obtained.  It  is  well,  to  avoid  the  risk  of  accident,  to  rotate  the 
centrifuge  imder  a  guard. 

12.  Electrical  Conductivity  of  Blood. — (i)  Fill  a  small  U-tube  with 
blood  up  to  a  mark.     In  each  limb  insert  a  platinum  electrodef  con- 

*  If  the  tube  has  not  been  properly  filled,  blow  the  blood  out  immediately. 
On  no  account  permit  it  to  clot  in  the  capillary  tube. 

t  If  the  platmum  electrodes  are  of  good  size  and  the  resistance  of  the  tube 
of  liquid  considerable,  it  is  not  necessau-y  to  platinize  them — i.e..  to  cover  them 
by  electrolysis  of  a  solution  of  platinic  chloride  with  a  layer  of  platinum-black. 


PRACTICAL  EXERCISES  69 

nected  with  a  holder,  which  insures  that  the  electrode  shall  always  dip 
to  the  same  depth  into  the  tube.  Arrange  the  U-tube  so  that  it  is 
immersed  at  least  to  the  mark  in  water  of  constant  temperature.  Water 
running  freely  from  the  cold-water  tap  into  and  out  of  a  large  vessel 
will  have  a  sufficiently  constant  temperature  for  the  purpose.  A  ther- 
mometer must  be  fixed  in  the  water  with  its  bulb  in  contact  with  the 
U-tube.  Connect  the  electrodes  with  a  resistance-box  in  the  Wheat- 
stone's  bridge  arrangement  (Fig.  231,  p.  726),  so  that  the  U-tube 
occupies  the  position  of  the  unknown  resistance  CD.  Instead  of  the 
battery  F,  connect  the  poles  of  the  secondary  of  a  small  induction-coil, 
arranged  for  an  interrupted  current,  with  A  and  C,  and  instead  of  tlie 
galvanometer  G  insert  a  telephone.  The  resistances  AB  and  AD  will 
be  obtained  by  taking  out  two  plugs  from  the  appropriate  part  of  the 
resistanoe-box.  Whether  AB  and  AD  should  be  equal  (say,  10  :  10, 
100  :  100,  or  1,000  :  1,000  ohms)  or  unequal  (say,  10  :  100,  or 
100  :  1,000,  or  10  :  1,000  ohms)  will  depend  upon  the  resistance  of 
the  tube  of  liquid  to  be  measured.  Take  out  from  the  part  of  the  box 
corresponding  to  BC  a  plug  representing  a  resistance  something  like 
that  which  the  tube  of  blood  is  expected  to  have.  Close  the  primary 
circuit  of  the  induction-coil,  and  apply  the  telephone  to  the  ear.  A 
buzzing  sound  will  be  heard,  which  will  be  louder  the  farther  from  the 
true  resistance  of  the  tube  the  resistance  taken  out  of  the  box  is.  Go 
on  altering  the  resistance  in  the  box  by  taking  out  or  putting  in  plugs 
till  the  sound  disappears,  or  is  reduced  to  a  minimum.  The  tempera- 
ture of  the  water  should  now  be  read  off.  The  resistance  of  the  tube  of 
blood  for  this  temperature  can  easily  be  calculated  from  the  formula 
on  p.  726.  It  increases  about  2  per  cent,  for  each  degree  Centigrade  of 
diminution  of  temperature.  The  conductivity  is  the  reciprocal  of  the 
resistance.  By  determining  once  for  all  the  resistance  of  the  tube 
when  filled  with  a  standard  solution  of  a  salt  whose  conductivity  is 
known,  the  specific  conductivity  of  the  blood  can  be  expressed  in 
definite  units,  but  this  is  not  necessary  for  the  purposes  of  the  student. 
Compare  the  resistances  of  defibrinated  blood,  serum,  o-q  per  cent, 
sodium  chloride  solution,  and  a  sediment  of  blood-corpuscles  separated 
by  centrifugalization. 

(2)  Instead  of  the  resistance-box  a  wire  mounted  on  a  scale  may  be 
used  for  the  resistances  AB,  AD,  the  ends  of  the  wire  being  connected 
at  B  and  D.  A  slider  with  an  insulated  handle  moving  along  the 
graduated  wire  is  joined  by  a  flexible  wire  with  one  pole  of  the  secondary 
coil,  the  other  pole  being  connected  at  C.  The  resistance  BC  is  consti- 
tuted by  a  rheostat  from  which  a  fixed  resistance  can  be  taken  out. 
Instead  of  obtaining  the  minimum  sound  in  the  telephone  by  varying 
the  resistance  BC  in  the  box,  the  measurement  is  made  by  varydng  the 
position  of  the  slider;  in  other  words,  by  changing  the  ratio  AB:  AD. 

(3)  If  no  rheostat  is  available  instructive  comparative  measurements 
may  still  be  made  with  the  graduated  wire  by  substituting  for  the 
resistance  BC  a  U-tube  of  another  liquid. 

If  the  tubes  are  of  the  same  dimensions,  and  the  liquids  with  which 
they  are  filled  are  approximately  at  the  same  initial  temperature,  it 
is  not  necessary  to  immerse  them  in  water  at  constant  temperature.  It 
is  sufficient  to  place  them  side  by  side  in  the  air.  Perform  the  following 
experiments  in  this  way: 

(a)  Label  the  tubes  A  and  B.  Fill  them  both  to  the  mark  with 
0-9  per  cent.  NaCl  solution.  Connect  as  in  the  figure,  and  move  the 
slider  along  the  wire  till  the  sound  is  a  minimum.  Probably  the  two 
tubes  are  not  exactly  of  the  same  dimensions,  and  therefore  the  slider 
will  not  be  exactly  in  the  middle  of  the  wire.       Suppose  it  is  at  49-0 


TO  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

the  total  length  of  the  wire  being  loo.     Then  resistance  of  A :  resistance 

49 
of  B::  4Q'0 :  si-o,  i.e.,  resistance  of  A  =  --  resistance  of  B. 

[b)  Fill  A  with  defibrinated  blood,  keeping  B  filled  with  NaCl  solu- 
tion, and  repeat  the  measurement.  The  slider  must  now  be  moved 
much  farther  away  from  the  zero  of  the  scale.  Suppose  the  minimum 
sound  is  obtained  with  the  slider  at  70-0.     Then  resistance  of  blood  = 

3  CI 

X  -^  resistance  of  the  NaCl  solution. 
7     49 

(c)  Compare  in  the  same  waji-  the  resistance  of  scrum  with  that  of 
the  NaCl  solution.     It  will  be  found  much  less  tlian  that  of  the  blood. 

{d)  Centrifugalize  some  of  the  blood  for  as  long  as  is  convenient,  and 
compare  the  resistance  of  tlie  blood  from  the  top  of  the  tubes  and  from 
the  bottom  of  the  tubes  with  that  of  the  NaCl  solution.  The  resistance 
of  the  blood  from  the  bottom  of  the  tubes  will  be  found  much  greater 
than  that  of  the  blood  from  the  top. 

13.  Opacity  of  Blood. — Smear  a  little  fresh  blood  on  a  glass  slide,  and 
hold  the  slide  above  some  i)rinted  matter.  It  will  not  be  possible  to 
read  it,  because  the  light  is  reflected  from  the  corpuscles  in  all  directions, 
and  little  of  it  passes  tlirough. 

14.  Laking  of  Blood  by  Chemical  and  Physical  Agents. — (i)  Put  a 
little  fresh  blood  into  three  test-lubes,  A,  B,  and  C.  Dilute  A  with  an 
equal  volume,  B  with  two  volumes,  and  C  with  three  volumes,  of  dis- 
tilled water,  and  repeat  experiment  9.  The  print  can  now  be  read 
probably  through  a  layer  of  A,  but  certainly  through  B  and  C,  since 
the  haemoglobin  is  dissolved  out  of  the  corpuscles  by  the  water  and 
goes  into  solution,  the  blood  becoming  transparent  or  laked.  That  the 
difference  is  not  due  merely  to  dilution  can  be  shown  by  putting  an 
equal  quantity  of  blood  in  two  test-tubes,  and  gradually  diluting  one 
with  distilled  water  and  the  other  with  a  0'9  per  cent,  solution  of 
sodium  chloride,  which  does  not  dissolve  out  the  haemoglobin.  Print 
can  be  read  through  the  first  with  a  smaller  degree  of  dilution  than 
through  the  second.  Examine  the  laked  blood  with  the  microscope 
for  the  '  ghosts,'  or  shadows  of  the  red  corpuscles.  The  addition  of  a 
drop  or  two  of  methylene  blue  will  render  them  somewhat  more  distinct. 

(2)  Heat  a  little  dog's  or  ox  blood  in  a  test-tube  immersed  in  a  water- 
bath.  Put  a  thermometer  in  the  test-tube,  taking  care  that  there  is 
enough  blood  to  cover  the  bulb.  Keep  the  temperature  about  60°  C. 
In  a  few  minutes  the  blood  becomes  dark  and  laking  occurs. 

(3)  [a)  Put  a  little  blood  into  each  of  four  test-tubes.  To  one  add  a 
little  ether,  to  another  a  little  chloroform,  to  the  third  dilute  acetic 
acid  in  0-9  per  cent.  NaCl,  and  to  the  fourth  a  dilute  solution  of  bile 
salts  (or  of  sodium  taurocholatc)  in  0-9  per  cent.  NaCl  solution.  Laking 
occurs  in  all. 

[b)  To  5  c.c.  of  blood  add  0-5  c.c.  of  a  3  per  cent,  solution  of  saponin 
in  0'9  per  cent.  NaCl  solution,  and  put  the  mixture  at  40°  C.  Laking 
soon  occurs. 

(c)  Using  a  10  per  cent,  dilution  of  blood  (blood  to  which  nine  volumes 
of  NaCl  solution  have  been  added)  or  a  5  per  cent,  suspension  of  washed 
corpuscles  in  NaCl  solution  {i.e..  a  suspension  of  corpuscles  which  have 
been  washed  free  from  serum  by  being  repeatedly  mixed  with  NaCl 
solution  and  centrifugalized),  determine  the  minimum  dose  of  0-3  per 
cent,  saponin  solution  which  will  just  cause  complete  laking.  Keep  the 
tubes  at  about  40°  C,  and  observe  them  from  time  to  time.  Now  add 
to  some  of  the  10  per  cent,  dilution  or  the  5  per  cent,  suspension  of  blood 
an  equal  volume  of  scrum  from  the  same  kind  of  blood,  and  repeat  the 
determination  of  the  minimum  dose  of  saponin  necessary  for  laking. 


PRACTICAL  EXERCISES  71 

It  will  be  found  that  more  is  now  required.      The  cholestcrin  in  the 
serum  neutralizes  the  action  of  some  of  the  saponin. 

(4)  {a)  Put  I  c.c.  of  blood  into  each  of  two  tost-tubcs.  To  one  add 
I  c.c.  of  2  per  cent,  aqueous  solution  of  urea,  and  to  the  other  3  c.c. 
Laking  will  take  place  in  the  second,  whether  this  has  been  the  case  in 
the  first  or  not. 

{b)  Repeat  the  experiment  with  a  2  per  cent,  solution  of  urea  in 
0'9  per  cent.  NaCl  sohition.  Laking  docs  not  occur.  'Ihis  shows  that 
the  urea  in  the  first  experiment  did  not  act  as  a  haemolytic  agent. 
Laking  occurred  because  urea  penetrates  the  corpuscles  easily,  and 
therefore,  although  the  freezing-point  of  the  urea  solution  is  not  verj- 
different  from  that  of  the  NaCl  solution,  its  actual  osmotic  pressure, 
in  relation  to  the  envelopes  of  the  corpuscles,  is  very  much  less,  and  the 
laking  is  really  water-laking. 

(5)  Put  some  blood  into  a  flask  or  test-tube,  cork  up,  and  let  it  stand 
till  it  begins  to  putrefy.  It  becomes  laked.  The  same  occurs  when 
the  blood  is  collected  aseptically  in  a  sterile  tube  and  sealed  up,  although 
it  takes  a  longer  time  for  the  laking  to  become  complete. 

(6)  With  blood  containing  nucleated  corpuscles  (necturus,  frog  or 
chicken)  diluted  with  isotonic  salt  solution,  perform  the  following 
experiments  imder  the  microscope  : 

(a)  With  a  glass  rod  drawn  to  a  fine  point  put  a  small  drop  of  blood 
on  a  slide,  and  near  it  a  drop  of  distilled  water.  Carefully  lower  the 
cover-slip  and  observe  the  interface  with  the  microscope,  first  with  the 
low  and  then  with  the  high  power.  Then  mix  and  see  complete  laking. 
Add  a  little  methylene  blue.     Note  that  the  nuclei  still  stain. 

(6)  Place  a  small  drop  of  a  3  per  cent,  solution  of  saponin  in  isotonic 
salt  solution  on  a  slide,  and  near  it  a  small  drop  of  blood.  Observe  as 
in  (a).  Repeat  with  a  2  per  cent,  solution  of  sodium  taurocholate  in 
salt  solution.  If  necturus  corpuscles,  which  are  splendid  objects  for 
such  experiments  on  account  of  their  great  size,  have  been  used, 
intracorpuscular  crystallization  of  the  haemoglobin  may  be  observed. 

(c)  Repeat  (a)  and  [b)  with  mammalian  blood.  Note  that  the  cor- 
puscles swell  before  being  laked  by  the  saponin.  If  any  of  the  corpuscles 
are  crenated,  it  may  be  seen  that  before  being  laked  by  the  saponin 
the  crenations  disappear,  the  corpuscles  becoming  round,  while  in  the 
taurocholate  solution  they  may  remain  crenated  till  laking  has  occurred. 
This  indicates  that  the  permeability  of  the  envelopes  is  not  affected  in 
the  same  way  by  the  two  laking  agents. 

15.  Haemolysis  and  Agglutination  by  Foreign  Serum. — (i)  To  a  small 
quantity  of  rabbit's  blood  add  an  equal  volume  of  dog's  serum.  Mix 
and  let  stand  at  40°  C.  The  colour  of  tlie  blood  is  soon  darker  than 
before,  and  it  can  be  seen  to  be  laked.     Examine  microscopically. 

(2)  Place  a  small  drop  of  rabbit's  blood  and  a  somewhat  larger  drop 
of  the  dog's  serum  on  a  slide,  near,  but  not  quite  in  contact  with,  each 
other.  Now  put  on  a  cover-slip,  so  that  the  drops  just  come  together, 
and  examine  at  once  with  the  microscope  with  a  moderately  high  power. 
Where  the  two  drops  mingle,  the  red  corpuscles  will  be  seen  first  to 
become  agglutinated  into  groups,  and  then  to  fade  out,  leaving  only 
their  '  ghosts.'  A  few  of  the  corpuscles  which  come  into  contact  witn 
the,  as  yet,  undiluted  serum  may  be  entirely  dissolved. 

(3)  Heat  some  of  the  dog's  serum  to  60°  C.  for  ten  minutes,  and 
repeat  (i)  and  (2).  No  laking  will  now  be  produced  in  the  rabbit's 
corpuscles,  but  agglutination  may  be  observed  as  before. 

(4)  Repeat  (i)  and  (2)  with  dog's  blood  and  rabbit's  serum.  The 
blood  will  not  be  laked.  although  sometimes  the  dog's  corpuscles  may 
become  crenated.     There  will  be  no  agglutination. 


72  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

(5)  With  a  5  per  cent,  suspension  of  rabbit's  washed  corpuscles 
perform  the  following  experiments:* 

Put  into  each  of  six  small  test-tubes  i  c.c.  of  the  suspension.  Label 
the  tubes  A,  A',  B,  B',  C,  C 

(a)  To  A  and  A'  add  respectively  o-i  c.c.  and  0'5  c.c.  ox  serum. 

(b)  To  B  and  B'  add  respectively  O'l  c.c.  and  0'5  c.c.  dog's  serum. 

(c)  To  C  and  C  add  respectively  ci  c.c.  and  0-5  c.c.  of  0-9  per  cent, 
sodium  chloride  solution. 

Put  all  the  tubes  in  a  bath  at  40°  C.  Compare  the  amount  of  laking 
and  agglutination  in  the  various  tubes  at  intervals  of  two  minutes  or 
less.  Repeat  (a),  (&),  and  (c)  with  guinea-pig's  washed  corpuscles  and 
serum  of  ox  and  dog.  Determine  which  of  these  sera  has  the  strongest 
haemolytic  power.| 

(6)  Heat  I  c.c.  o:(  ox  and  dog's  serum  respectively  to  56°  C,  keeping 
it  at  tiiat  temperature,  or  not  more  than  a  couple  of  degrees  above  it, 
for  tenj  minutes,  and  repeat  experiment  (5),  labelling  the  tubes  D,  D', 
E,  E',  F,  F'.  Save  the  rest  of  the  heated  sera  for  (8).  There  is  no 
laking  in  any  of  the  tubes,  but  probably  agglutination  in  D,  D',  and 
E,  E'.  (The  complement  is  destroyed,  but  not  the  intermediary  body 
or  amboceptor,  or  the  agglutinin — p.  28.) 

(7)  Put  half  of  the  contents  of  tubes  D,  D',  E,  E',  into  four  separate 
test-tubes,  and  add  to  each  0-2  c.c.  of  rabbit's  serum.  If  there  is  laking 
now  it  is  because  the  rabbit's  serum  contains  complement.  Save  the 
balance  of  D,  D',  E  and  E'  for  (8). 

(8)  Allow  0'5  c.c.  of  ox  serum  to  act  at  o*  C.  on  the  rabbit's  washed 
corpuscles  contained  in  5  c.c.  of  the  5  per  cent,  suspension  after  removal 
of  the  sodium  chloride  solution.  The  ox  serum  and  rabbit's  corpuscles 
are  separately  cooled  to  0°  C.  before  being  mixed,  and  the  mixture  is 
then  kept  at  0°  C.  for  one  hour.  Centrifugalize  the  serum  off  rapidly. 
Label  it  '  Serum  S.'  To  0-2  c.c.  of  the  original  5  per  cent,  suspension 
of  rabbit's  washed  corpuscles  add  o-i  c.c.  of  this  serum  (labelling  the 
tube  G),  and  put  at  40°  C.  with  a  control-tube  containing  the  same 
amount  of  suspension  plus  salt  solution  instead  of  serum.  Add  the 
rest  of  the  serum  S,  cooled  to  0°  C,  to  the  same  cooled  rabbit's  cor- 
puscles, and  leave  for  a  further  period  at  0°  C.  Then  centrifugalize 
rapidly,  and  to  0*2  c.c.  of  the  original  suspension  of  washed  rabbit's 
corpuscles  add  o-i  c.c.  of  serum  S  (labelling  the  tube  H),  and  put  at 
40°  C.  with  a  sodium  chloride  tube  as  control.     There  may  be  no 

•  The  material  obtained  from  one  medium-sized  dog.  two  rabbits,  and  one 
guinea-pig  is  enough  for  fifty  or  sixty  students,  working  together  in  sets  of 
two,  to  perform  experiments  (5)  to  (8).  In  order  to  obtain  a  serum  more 
strongly  haemolytic  for  rabbit's  corpuscles  than  normal  dog's  serum,  a  dog 
may  be  '  immunized  '  by  previous  injection  of  all  the  washed  corpuscles 
obtainable  from  a  rabbit.  The  injection  should  be  made  under  the  skin  or, 
better,  into  the  peritoneal  cavity — of  course,  with  aseptic  precautions.  It 
should  be  repeated  not  less  than  twice,  with  an  interval  of  ten  days  between 
the  successive  injections,  and  the  dog's  blood  should  be  drawn  off  about  ten 
days  after  the  last  injection. 

f  To  determine  the  amount  of  laking  at  any  given  moment,  drop  the  small 
test-tubes  into  the  metallic  centrifuge  cups  after  shaking  them  up,  cind  centrif- 
ugalize. A  ver>'  short  time  is  sufficient  to  separate  a  clear  supernatant 
liquid,  from  the  tint  of  which  the  extent  of  the  haemolysis  can  be  deduced. 
Before  replacing  the  tubes  in  the  thermostat,  they  should,  of  course,  be  shaken 
up.  Small  test-tubes  of  about  8  mm.  internal  diameter  and  short  enough  to 
go  conveniently  into  the  centrifuge  cups  are  the  most  serviceable. 

I  For  exact  work  a  longer  time  is  recommended.  But  for  the  student  the 
time  is  made  as  short  as  possible,  and  it  is  only  in  exceptional  cases  that  ten 
minutes  is  not  enough. 


PRACTICAL  EXERCISES  7j 

laking  in  either  G  or  H,  or  if  there  is  laking  it  may  be  greater  in  G  than 
in  H.  The  amboceptor  has  been  removed  from  serum  S  by  the  rabbit's 
corpuscles.  Add  o-i  c.c.  of  this  '  inactivated  '  serum  to  the  balance 
of  D,  D',  and  E,  E'  (left  from  6).  Laking  will  occur  because  the  serum  S 
contains  complement,  and  the  heated  serum  added  in  (6)  to  these  tubes 
contains  amboceptor.  Wash  the  rabbit's  corpuscles  which  have  been 
treated  with  ox  scrum  at  o°  C.  with  cooled  sodium  chloride  solution. 
Add  to  them  some  of  serum  S  (that  from  the  top  of  tube  H  will  do  if 
no  more  is  left),  and  put  at  40°  C.  Laking  will  occur,  showing  that  the 
amboceptor  was  fixed  by  the  rabbit's  corj)uscles  at  0°  C.  To  a  further 
portion  of  the  washed  rabbit's  corpuscles  which  were  treated  with  ox 
serum  at  0°  C.  add  normal  rabbit's  serum,  and  put  at  40°  C.  If  laking 
occurs  it  is  because  the  rabbit's  serum  contains  complement. 

Dog's  serum  may  be  used  instead  of  ox  serum  for  experiment  (8). 

16.  Osmotic  Resistance  of  the  Coloured  Corpuscles. — Fill  a  burette 
with  a  I  per  cent,  solution  of  sodium  chloride  and  another  with  dis- 
tilled water.  Take  a  series  of  ten  test-tubes  and  run  into  the  first 
6  c.c.  of  the  NaCl  solution,  into  the  second  5 -8  c.c,  into  the  third 
5-6  c.c,  and  so  on,  always  making  a  difference  of  0-2  c.c.  between 
successive  test-tubes.  From  the  other  burette  run  in  enough  distilled 
water  to  make  up  10  c.c.  of  solution  in  each  tube — that  is,  4  c.c.  of  dis- 
tilled water  for  the  first  tube,  4-2  c.c.  for  the  second,  and  so  on.  Shake 
up.  The  tubes  now  contain  a  series  of  solutions  of  salt  differing  in 
strength  by  0-02  per  cent,  in  successive  tubes,  the  strongest  being  o*6 
per  cent.,  and  the  weakest  0-42  per  cent.  Number  the  tubes  i  to  10, 
beginning  with  the  strongest  solution.  Put  into  each  tube  one  drop  of 
perfectly  fresh  blood.  Shake  moderately  so  as  to  mix  the  blood  and 
salt  solution,  and  allow  the  tubes  to  stand  for  ten  to  thirty  minutes. 
Observe  the  colour  of  the  clear  liquid  above  the  sediment  of  corpuscles. 
Determine  in  which  tube  the  first  tinge  of  haemoglobin  appears.  The 
next  higher  concentration  of  the  salt  solution  is  that  in  which  all  the 
corpuscles  are  just  able  to  retain  their  haemoglobin,  and  is  a  measure  of 
the  minimum  osmotic  resistance  of  the  corpuscles,  or  the  resistance 
of  the  weakest  corpuscles.  Repeat  with  blood  which  has  stood  at  room 
temperature  for  twelve  to  twenty-four  hours.  For  clinical  purposes 
tubes,  each  containing  5  c.c  of  salt  solution,  may  be  used.  A  single 
drop  of  blood  can  then  be  distributed  between  the  tubes  with  a  fme 
pipette  or  a  glass  rod,  beginning  with  the  most  concentrated  solution, 
and  passing  do%vn  to  the  less  concentrated.  The  blood  must  be  dis- 
tributed rapidly  before  coagulation  occurs.  Only  such  concentrations 
of  the  salt  solution  as  are  known  to  correspond  to  the  possible  variations 
of  the  osmotic  resistance  for  any  particular  disease  or  for  any  particular 
variety  of  blood  need  be  employed. 

17.  Blood-Pigment — (i)  Preparation  of  Haemoglobin  Crystals. — [a) 
To  a  little  dog's  blood  in  a  narrow  test-tube  add  its  own  volume  or 
twdce  its  volume  of  chloroform.  Invert  the  tube  ten  or  twelve  times 
so  as  to  allow  the  chloroform  to  act  on  the  blood,  but  avoid  violent 
shaking.  When  the  tube  is  now  allowed  to  stand  for  a  few  minutes 
the  laked  blood  all  rises  to  the  top.  Remove  a  little  of  the  layer  of 
blood  without  taking  with  it  any  of  the  chloroform  layer,  and  examine 
the  oxyhaemoglobin  crystals  with  the  microscope.  They  form  long 
rhombic  prisms  and  needles  (Fig.  14,  p.  ^2). 

{b)  Add  a  little  crude  saponin  to  dog's  blood  in  a  test-tube.  Shake 
up  well,  and  allow  it  to  stand  till  the  colour  becomes  dark.  Then  shake 
vigorously,  and  a  mass  of  haemoglobin  crystals  will  be  formed. 

(c)  Put  a  small  drop  of  guinea-pig's  blood  on  a  slide.     Mix  with  a 


74  THE  ClRCUl.AriNG  LIQUIDS  OF  THE  liODY 

drop   of    Canada    balsam    and    cover.     Tetrahedral   crystals   of    oxy- 
haemoglobin  will  form  after  a  time.     The  slide  may  be  kept. 

(2)  Spectroscopic  Examination  of  Haemoglobin  and  its  Derivatives. 
— (a)  With  a  small,  direct-vision  spectroscojjc  look  at  a  bright  part  of 
the  sky  or  a  white  cloud.  Focus  by  pulling  out  or  pushing  in  the  eye- 
piece until  the  numerous  fine  dark  lines  (Fraunhofcr's  lines),  running 
verticallj-  across  the  spectrum,  are  seen.  Narrow  the  slit  by  moving 
the  milled  edge  till  the  lines  are  as  sharp  as  they  can  be  made.  Note 
especially  the  line  D  in  the  orange,  the  lines  K  and  b  in  the  green, 
and  F  in  the  blue.  Always  hold  the  spectroscope  so  that  the  red  is 
at  the  left  of  the  field.  Now  dip  an  iron  or  platinum  wire  with  a 
loop  on  the  end  of  it  into  water,  and  then  into  some  common  salt  or 
sodium  carbonate,  and  fasten  or  hold  it  in  the  flame  of  a  fishtail  burner. 
On  examining  the  flame  with  the  spectroscope,  a  bright  yellow  line 
will  be  seen  occupying  the  position  of  the  dark  line  D  in  the  solar 
spectrum.  This  is  a  convenient  line  of  reference  in  the  spectrum,  and 
in  studying  the  spectra  of  haemoglobin  and  its  derivatives,  the  position 
of  the  absorption  bands  with  regard  to  the  D  line  should  always  be 
noted.  The  dark  lines  in  the  solar  spectrum  are  due  to  the  absorption 
of  light  of  a  definite  range  of  wave-lengths  by  metals  in  a  state  of  vapour 
in  the  ?un's  atmosphere,  and  of  course  no  dark  lines  arc  seen  in  the 
spectrum  of  a  gas-flame.     Put  some  defibrinated  blood  into  a  test-tube. 


B 
Fig.  20. — Direct  Vision  Spectroscope  ot  Simple  Type.     A ,  slot  in  which  a  pin  on  the 
eyepiece  C  slides  in  focussing  the  spectrum :    B,  milled  head,  by  the  rotation 
of  which  the  slit  is  narrowed  or  widened. 

Fasten  it  vertically  in  a  clamp  in  front  of  the  flame  and  examine  it 
with  the  spectroscope,  holding  the  latter  in  one  hand  with  the  slit  close 
to  the  test-tube,  and  focussing  the  eyepiece  with  the  other.  Or  arrange 
the  spectroscope,  test-tube  and  gas-flame  on  a  stand  as  in  Fig.  21. 
Nothing  can  be  seen  till  the  blood  is  diluted.  Pour  a  little  of  the  blood 
into  another  test-tube,  and  go  on  diluting  till,  on  focussing,  two  bands  of 
oxyhcpmoglobin  are  seen  in  the  position  indicated  in  Fig.  13,  p.  51 .  Draw 
the  spectrum;  then  dilute  still  more,  and  observe  which  of  the  bands 
first  disappears.  Now  put  5  c.c.  of  the  blood  into  another  test-tube, 
and  dilute  it  with  four  times  its  volume  of  water.  Take  5  c.c.  of  this 
dilution,  and  again  add  four  times  as  much  water,  and  so  on  till  the 
solution  is  only  faintly  coloured.  Note  with  what  degree  of  dilution 
the  bands  disappear.  Then  examine  each  of  the  solutions  with  the 
spectroscope  and  draw  its  spectrum. 

(ft)  Make  a  solution  of  blood  which  shows  the  oxyhaemoglobin  bands 
sharply.  Add  some  ammonium  sulphide  solution  to  reduce  the  oxy- 
haemoglobin. Heat  gently  to  about  body  temperature.  A  single, 
ill-defined  band  now  appears,  occupying  a  position  midway  between 
the  oxyhaemoglobin  bands,  and  the  latter  disappear.  This  is  the 
band  01  reduced  hcrmoglobin  (Fig.  13). 

(c)  Carbonic  Oxide  Hamoglobin. — Pass  coal-gas  through  blood  for 


PRACTICAL  EXERCISES 


75 


Test'  tub 


a  considerable  time.  Examine  some  of  the  blood  (after  dilution) 
with  the  spectroscope.  Two  bands,  almost  in  the  position  of  the 
oxyhncmoglobin  bands,  are  seen ;  but  no  change  is  caused  by  the 
addition  of  ammonium  sulphide,  since  carbonic  oxide  haemoglobin  is 
a  more  stable  compound  than  oxy haemoglobin. 

(d)  Metlurmoglobin. — Put  .some  blood  into  a  test-tube,  add  a  few 
drops  of  a  solution  of  fcrricyanidc  of  potassiimi,  and  heat  gently.  On 
diluting  a  well-marked  band  will  be  seen  in  the  red.  On  addition  of 
ammonium  sulphide  this  band  disappears;  the  oxyliaemoglolnn  bands 
are  seen  for  a  moment,  and  then  give  place  to  the  band  of  reduced 
haemoglobin  (Fig.  13.  p.  51). 

[e)  Acid  Hcrmatin. — To  a  little  diluted  blood  add  strong  acetic  acid 
and  heat  gently.  The  colour  becomes  brownish.  Tlie  spectrum 
sliows  a  band  in  the  red  between  C  and  D,  not  far  from  the  position 
of  the  band  of  methaemoglobin.  The  addition  of  a  drop  or  two  of 
ammonium  sulphide  causes  no  change  in  the  spectrum,  and  this  is  a 
means  of  distinguishing  acid  hasmatin  from  methaemoglobin.  If  more 
ammonium  sulphide  be  added, 
haematin  will  be  precipitated 
when  the  acid  solution  has  been 
rendered  neutral,  and  a  further 
addition  of  ammonium  sulphide 
or  sodium  hydroxide  will  cause 
the  haematin  to  be  again  dis- 
solved, a  solution  of  alkaline 
hasmatin  being  formed.  This 
in  its  turn  may  be  reduced  by 
an  excess  of  ammonium  sul- 
phide, and  the  spectrum  of 
haemochromogen  may  be  ob- 
tained (Fig.  13,  p.  51). 

Since  the  watery  solution 
of  acid  haematin  obtained  as 
above  is  usually  somewhat  tur- 
bid, a  solution  in  acid  ether  is 
sometimes  employed  for  spec- 
troscopic examination.  Add  to 
a  little  undiluted  dcfibrinated 
blood  about  half  its  volume  of 
glacial  acetic  acid,  and  then  not 
less  than  an  equal  volume  of 
ether.  ]\Iix  well,  pour  off  the  ethereal  extract  and  examine  it  with  the 
spectroscope,  diluting,  if  necessar3^  with  ether  and  glacial  acetic  acid. 
It  shows  a  strong  band  in  the  red  somewhat  farther  from  the  D  line 
than  the  methaemoglobin  band.  On  dilution,  three  additional  fainter 
bands  may  be  seen. 

(/)  Alkaline  Htematin. — To  diluted  blood  add  strong  acetic  acid  and 
warm  gently  for  a  few  minutes.  Then,  when  the  spectroscopic  ex- 
amination of  a  sample  shows  that  acid  haematin  has  been  formed, 
neutralize  with  sodium  hydroxide.  A  brownish  precipitate  of  haematin 
is  thrown  down,  which  dissolves  in  an  excess  of  sodium  hydroxide, 
giving  a  solution  of  alkaline  haematin  (or  alkali  haematin). 

Or  add  sodium  hydroxide  to  blood  directlJ^  and  warm  for  a  couple  of 
minutes  after  the  colour  has  changed  decidedly  to  brownish-black. 
The  spectrum  of  alkaline  haematin  is  a  broad  but  ill-defined  band  just 
overlapping  the  D  line,  and  situated  chiefly  to  the  red  side  of  it  (Fig.  13). 
The  solution  should  be  shaken  up  with  air  before  being  examined,  as 


Spectroscope 
Solution 


Fig.  21. — Spectroscopic  Examination  of 
Blood -Pigment. 


76  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

some  of  the  alkali  haematin  is  changed  into  haemochromogen  by  re- 
ducing substances  formed  by  the  action  of  the  alkali  on  the  blood. 

{g)  Hcemochromogen. — To  a  solution  of  alkaline  haematin  add  a  drop 
or  two  of  ammonium  sulphide.  The  band  near  D  disappears,  and  two 
bands  make  their  appearance  in  the  green  (Fig.  13,  p.  31). 

(A)  Hamatoporphyyin. — Put  some  strong  sulphuric  acid  into  a  test- 
tube.  Add  a  few  drops  of  blood,  agitate  the  test-tube  till  the  blood 
di.-solves,  and  examine  the  purple  liquid,  diluting  it,  if  necessary, 
with  sulphuric  acid.  Its  spectrum  shows  two  well-marked  bands,  one 
just  to  the  left  of  D,  and  the  other  midway  between  D  and  E  (Fig.  13). 

(3)  Guaiacum  Test  for  Blood. — A  test  for  blood — much  used  in 
hospitals,  and,  indeed,  a  delicate  one,  but  quite  untrustworthy  unless 
certain  precautions  be  taken — is  the  guaiacum  test.  A  drop  of  freshly- 
prepared  tincture  of  guaiacum  is  added  to  the  liquid  to  be  tested,  and 
then  peroxide  of  hydrogen.  If  blood  be  present,  the  guaiacum  strikes 
a  blue  or  greenish-blue  colour.  The  decomposition  of  the  peroxide 
by  the  blood  is  due  mainly  to  the  hnemoglobin  of  the  corpuscles.  Any 
derivative  of  haemoglobin  which  still  contains  the  iron  will  act,  and 
boiling  does  not  abolish  this  power.  On  the  other  hand,  oxydases  or 
oxidizing  ferments  present,  not  only  in  the  formed  elements  of  blood, 
but  elsewhere,  e.g.,  in  fresh  vegetable  protoplasm,  milk,  seminal  fluid, 
and  pus,  will  cause  the  same  colour  (p.  271),  but  not  if  they  have  been 
previously  boiled.*  The  test  has  been  considered  chiefly  of  value  as 
a  negative  test.  When  the  blue  colour  is  not  obtained,  we  have  good 
evidence  that  blood  is  absent.  But,  according  to  Buckmastcr,  if  the 
precaution  of  first  boiling  the  liquid  suspected  to  contain  blood  be 
adopted,  it  is  also  a  good  positive  test.  It  is.  however,  far  inferior  to 
the  haemin  test  (p.  7«)  where  that  can  be  obtained,  and  of  course  in- 
ferior to  the  identification  of  erythrocytes  with  the  microscope,  or  to 
the  spectroscopic  identification  of  the  blood-pigment  where  the  material 
is  suitable  for  this. 

(4)  Quantitative  Estimation  of  Haemoglobin — [a)  By  Haldane's  Modi- 
fication of  Gowers  1 1  crnioglobinomctey . — Place  in  the  graduated  tube  B 
(Fig.  22)  an  amount  of  water  less  than  will  ultimately  be  required  to 
dilute  the  blood  to  the  required  tint.  Puncture  the  finger  or  lobe  of 
the  ear  with  one  of  the  small  lancets  in  F,  and  fill  the  capillary  pipette  D 
to  a  little  beyond  the  mark  20.  Wipe  the  p)oint  of  the  pipette  and  dab 
it  on  a  piece  of  filter-paper  till  the  blood  stands  exactly  at  the  mark. 
Blow  the  blood  into  the  water  in  B,  and  rinse  the  pipette  with  the  water. 
Attach  the  cap  of  tube  G  to  a  gas-burner.  Introduce  the  rubber  tube 
into  B  nearly  to  the  level  of  the  water,  and  allow  gas  to  pass  for  a  few 
seconds.  Withdraw  the  tube  while  the  gas  is  still  passing.  Immediately 
close  the  end  of  B  with  the  finger,  and  move  the  tube  so  that  the 
liquid  passes  from  end  to  end  of  it  at  least  a  dozen  times,  to  saturate 
the  haemoglobin  with  carbonic  oxide.  While  this  is  being  done,  the 
tube  should  be  held  in  a  cloth,  otherwise  it  will  become  heated,  and 
liquid  will  spurt  out  when  the  finger  is  removed.     Water  is  now  added 

*  The  formed  elements  of  blood  really  contain  no  less  than  three  ferments 
of  interest  in  this  connection:  (i)  A  catalase  which  decomposes  peroxide  of 
hydrogen  into  water  and  molecular  oxygen  {i.e.,  oxygen  not  in  the  atomic 
or  nascent  state).  This  reaction  is  given  by  both  blood  and  pus.  (2)  An 
oxydase  (also  spelled  oxidase),  which  oxidizes  guaiacum  and  similar  substances 
without  the  presence  of  hydrogen  peroxide.  This  reaction  is  obtainable  even 
from  aqueous  extracts  of  leucoc3i;es.  (3)  A  peroxydase  (also  spelled  peroxi- 
dase) which  causes  the  oxidation  of  these  substances  only  in  the  presence  of 
hydrogen  peroxide,  a  reaction  also  given  by  leucocytes.  These  ferments  are 
all  inactivated  Iby  boiling  (Kastle). 


PRACTICAL  EXERCISES 


71 


drop  by  drop  with  the  pipette  stopper  of  the  bottle  E,  which  is  used 
for  holding  the  water,  the  tube  being  inverted  after  each  addition, 
till  the  tint  in  B  is  the  same  as  tliat  in  A.  In  comparing  the  tubes, 
they  should  be  held  against  the  light  from  the  sky  or  from  an  opal 
glass  lamp-shade.  It  is  necessary  to  transpose  the  tubes  repeatedly. 
The  level  at  which  the  tints  are  equal  is  read  off  on  B  half  a  minute 
after  the  addition  of  the  last  drop  of  water.  Water  is  now  again  added 
by  drops  till  the  tint  in  B  is  just  roticeably  weaker  than  in  A,  and  the 
mean  of  the  two  readings  is  taken.  The  result  is  the  percentage  actually 
present  of  the  average  proportion  of  haemoglobin  in  the  blood  of  healthy 
adult  males.  Healthy  women  give  an  average  of  only  89  per  cent., 
and  healthy  children  an  average  of  only  87  per  cent.,  of  the  proportion 
in  men.  The  liquid  in  A  is  a  i  per  cent,  solution  of  blood  containing 
the  average  percentage  of  haemoglobin  found  in  the  blood  of  healthy 


Fig.  22. — Haldane's  Modification  of  Gowers'  HaBmoglobinometer. 


adult  males,  and  having  an  oxygen  capacity  of  18  5  per  cent. — i.e.. 
100  c.c.  of  the  blood  with  which  the  standard  was  made  would  take 
up  in  combination  from  air  18*5  c.c.  of  oxygen.  The  solution  in  A  has 
been  saturated  with  carbonic  oxide. 

This  method  is  probably  more  accurate  than  any  other  used  in  clinical 
work,  the  error,  in  the  hands  of  an  experienced  observer,  not  exceeding 
I  per  cent. 

[b)  By  Fleischl's  HcBtnometer  (Fig.  23). — Fill  with  distilled  water  that 
compartment  a'  of  the  small  cylinder  (above  tlie  stage)  which  is  over 
the  tinted  wedge.  Put  a  little  distilled  water  into  the  other  compart- 
ment a.  Now  prick  the  finger  and  fill  one  of  the  small  capillary  tubes 
with  blood.  See  that  none  of  the  blood  is  smeared  on  the  outside  of 
the  tube.  Then  wash  all  the  blood  into  the  water  in  compartment  a, 
gild  fill  it  to  the  brim  with  distilled  water.     By  means  of  the  milled 


78 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


head  T  move  the  tinted  wedge  K  till  the  depth  of  colour  is  the  same 

in  the  two  compartments.  The  percentage  of  the  normal  quantity 
of  haemoglobin  is  given  by  the  graduated  scale  P.  For  example,  if  the 
reading  is  90,  the  blood  contains  90  per  cent,  of  the  normal  amount; 
if  100,  it  contains  the  normal  quantity.  The  ob.servations  should  be 
made  in  a  dark  room,  the  white  surface  S,  arranged  below  the  compart- 
ments a  and  a',  being  illuminated  by  a  lamp.  Or  the  instrument  may 
be  placed  in  a  small  box,  lighted  by  a  candle.  It  is  best  that  each  result 
should  be  the  mean  of  two  readings,  one  just  too  large  and  the  other 
just  too  small.  In  any  case  the  instrument  does  not  give  readings 
accurate  to  less  than  5  per  cent. 

(c)  Hoppe-Seyley's  Method. — Two  parallel-sided  glass  troughs  are 
used.  In  one  is  put  a  standard  solution  of  oxy haemoglobin  of  known 
strength,    in    the    other    a    measured    quantity    of    the    blood    to    be 

tested.  The  latter  is  diluted 
with  water  until  its  tint 
appears  the  same  as  that 
of  the  standard  solution, 
when  the  troughs  are  placed 


Fig.  23. — Fleisclil's  Haemometer. 


Crystals  of  Haemin 
(Frey). 

side  by  side  on  white  paper. 
From  the  quantity  of  water 
added  it  is  easy  to  calculate 
the  proportion  of  haemo- 
globin in  the  undiluted 
blood.  Greater  accuracy  is  obtained  if  the  haemoglobin  in  the  standard 
solution  and  that  of  tlic  blood  are  converted  into  carbonic  oxide  haemo- 
globin by  passing  a  stream  of  coal-gas  through  them. 

{d)  1  allquisi's  Method. — In  this  method  the  tint  produced  by  a 
drop  of  blood  on  a  piece  of  white  filter-paper  is  compared  with  a  scale 
representing  10  percentages  of  haemoglobin  (from  10  to  100  per  cent.). 
The  standard  filter-paper  is  supplied  in  the  form  of  a  book  with  the 
scale.  To  make  an  estimation,  all  that  is  necessary  is  to  toucli  a  drop 
of  blood  with  a  piece  of  the  filter-paper,  and  allow  the  blood  to  diffuse 
slowly  through  the  paper,  so  as  to  give  an  even  stain.  The  position 
of  the  stain  is  then  determined  by  the  scale;  e.g..  it  may  be  deeper 
than  90.  but  fainter  than  100,  in  which  case  the  percentage  of  haemo- 
globin hes  between  90  and  100.  The  method  is  by  no  means  a  very 
accuratconc,  but  more  accurate  than  it  appears  at  first  sight. 

(5)  Microscopic  Test  for  Blood-Pigment. — Put  a  drop  of  blood  on  a 
slide.  Allow  the  blood  to  dry,  or  heat  ii-  gently  over  a  flame,  so  as  to 
evaporate  the  water.     Add  a  drop  of  glacial  acetic  acid  ;  put  on  a  cover- 


PRACTICAL  EXERCISES  jg 

glass,  and  again  heat  slowly  till  the  liquid  just  begins  to  boil.  Take 
the  slide  away  from  the  flame  for  a  few  seconds,  then  heat  it  again  for 
a  moment ;  and  repeat  this  process  two  or  three  times.  Now  let  the 
slide  cool,  and  examine  with  the  microscope  (high  power).  The  small 
black,  or  brownish-black,  crystals  of  hcemin  will  be  seen  (Fig.  24,  p.  78). 
This  is  an  important  test  where  only  a  minute  trace  of  blood  is  to  be 
examined,  as  in  some  medico-legal  cases.  If  a  blood-stain  is  old,  a 
minute  crystal  of  sodium  chloride  should  be  added  along  with  the 
glacial  acetic  acid.     Fresh  blood  contains  enough  sodium  chloride. 

A  blood-stain  on  a  piece  of  cloth  may  first  of  all  be  soaked  in  a  small 
quantity  of  distilled  water,  and  the  liquid  examined  with  the  spectro- 
scope or  the  micro-spectroscope  (a  microscope  in  which  a  small  spectro- 
scope is  substituted  for  the  eyepiece).  Then  evaporate  the  liquid  to 
dryness  on  a  water-bath,  and  apply  the  haemin  test.  Or  perform  the 
haemin  test  directly  on  the  piece  of  cloth.  In  a  fresh  stain  the  blood- 
corpuscles  might  be  recognized  under  the  microscope.  Very  few 
liquids,  however,  are  available  for  washing  out  the  blood,  as  all  ordinary 
solutions,  and  even  serum  itself,  cause  laking  of  dried  corpuscles 
(Guthrie).  Absolute  alcohol,  or  35  per  cent,  potassium  hydroxide, 
may  be  used  to  soak  and  rub  up  the  cloth  in. 


CHAPTER  III 

THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

The  blood  can  only  fulfil  its  functions  by  continual  movement. 
This  movement  implies  a  constant  transformation  of  energy';  and  in 
the  animal  body  the  transformation  of  energy  into  mechanical  work 
is  almost  entirely  allotted  to  a  special  form  of  tissue,  muscle.  In 
most  animals  there  exist  one  or  more  rhythmically  contractile 
muscular  organs,  or  hearts,  upon  which  the  chief  share  of  the  work 
of  keeping  up  the  circulation  falls. 

Section  I. — Preliminary  Anatomical  and  Physical  Dat.\. 

Comparative. — In  Echinus  a  contractile  tube  connects  the  two  vascu- 
lar rings  that  surround  the  beginning  and  end  of  the  alimentary  canal , 
and  plays  the  part  of  a  heart.  In  the  lower  Crustacea  and  in  insects 
the  heart  is  simply  the  contractile  and  generally  sacculated  dorsal 
bloodvessel;  in  the  higher  Crustacea,  such  as  the  lobster,  it  is  a  well- 
defined  muscular  sac  situated  dorsally.  A  closed  vascular  system  is 
the  exception  among  invertebrates.  In  most  of  them  the  blood 
passes  from  the  arteries  into  irregular  spaces  or  lacunae  in  the  tissues, 
and  thence  finds  its  way  back  to  the  heart.  In  the  primitive  vertebrate 
heart  five  parts  can  be  distinguished  as  we  proceed  from  the  venous 
to  the  arterial  end:  (i)  The  sinus  venosus,  into  which  the  great  veins 
open ;  (2)  the  auricular  canal,  from  the  dorsal  wall  of  which  is  developed 
— (3)  the  auricle;  (4)  the  ventricle;  (5)  the  bulbus  arteriosus,  from  which 
the  chief  artery  starts  (Fig.  25,  p.  81).  Amphioxus,  the  lowest  verte- 
brate, has  a  primitive  lacunar  vascular  system;  a  contractile  dorsal 
bloodvessel  serves  as  ai'tcrial  or  systemic  heart,  a  contractile  ventral 
vessel  as  venous  or  respiratory  heart.  From  the  latter,  vessels  go  to 
the  gills.  Fishes  possess  only  a  respiratory  heart,  consisting  of  a  venous 
sinus,  auricle,  ventricle,  and  bulbus  arteriosus.  This  drives  the  blood 
to  the  gills,  from  which  it  is  gathered  into  the  aorta;  it  has  thence  to 
find  its  way  without  further  propulsion  through  the  systemic  vessels. 
Amphibians  have  a  venous  sinus,  two  auricles,  a  single  'C"?tricle,  and 
an  arterial  bulb;  reptiles,  two  auricles  and  two  incompletely-separated 
ventricles.  In  birds  and  mammals  the  respiratory  and  systemic 
hearts  are  completely  separated.  The  former,  consisting  of  the  right 
auricle  and  ventricle,  propels  the  blood  through  the  lungs;  the  latter, 
consisting  of  the  left  auricle  and  ventricle,  receives  it  from  the  pul- 
monary veins,  and  sends  it  through  the  systemic  vessels. 

The  sinus  venosus  seems  to  be  represented  in  the  mammalian  heart 
by  certain  small  portions  of  tissue,  especially  the  so-called  sino-auricular 
node,  a  little  knot  of  primitive  fibres  near  the  mouth  of  the  superior 

80 


AN.-iTOMlCAL  AND  PHYSICAL  DATA 


vena  cava.  The  auricular  canal  is  probably  represented  by  the 
auriculo-vcntricular  bundle  (conveniently  designated  as  the  a. -v.  bundle), 
which  will  again  be  referred  to  in  relation  to  the  conduction  of  the  heart- 
beat from  auricles  to  ventricles  (p.  147).  This  bundle  starts  from  a 
clump  of  primitive  tissue,  the  auriculo-ventricular  node  (a. -v.  node) 
at  the  base  of  the  interauricular  septum  on  the  right  side,  below  and 
to  the  right  of  the  coronarj'  sinus,  and  runs  down  the  interventricular 
septum.  The  sino-auricular  and  tlie  auriculo-\-entricular  nodes  are 
connected  by  fibres  which  run  in  tiie  interauricular  septum,  so  that  it 
may  be  considered  that  the  primitive  cardiac  tube  is  still  represented 
from  base  to  apex  of  the  adult 
mammalian  heart,  although  onlj- 
by  very  slender  threads  of  tissue, 
amidst  the  massive  secondary 
developments  of  auricular  and 
ventricular  muscle  (Keith  and 
Flack) . 

General  View  of  the  Circulation 
in  Man. — The  whole  circuit  of  the 
blood  is  divided  into  two  portions, 
very  distinct  from  each  other, 
both  anatomically  and  function- 
ally— the  respiratory  or  lesser 
circulation,  and  the  systemic  or 
greater  circulation.  Starting  from 
the  left  ventricle,  the  blood  passes 
along  the  systemic  A-essels — ar- 
teries, capillaries,  veins — and,  on 
returning  to  the  heart,  is  poured 
into  the  right  auricle,  and  thence 
into  the  right  ventricle.  From 
the  latter  it  is  driven  through  the 
pulmonary  artery  to  the  lungs, 
passes  through  the  capillaries  of 
these  organs,  and  returns  through 
the  pulmonar}'  veins  to  the  left 


■  K         J  J.  •  1        Tu    „   _4-„i    Fiff.  2%. — Diagram  of  Primitive  Vertebrate 

auricle  and  ventricle.    The  portal    ^ '°;    •';  t-  •  „  c  of, ,,-„..  4^„^a  :,,  +1,^ 

^      -  Heart,  combmmg  Features  tound  in  the 

Eel,    Dogfish,    and    Frog    (Flack,    after 

Keith),     a.    Sinus    venosus;    b,  auricular 


canal;  c,  auricle;  <i,  ventricle ;  e,  bulbus 
cordis;  /,  aorta;  i-i,  sino-auricular  junc- 
tion and  venous  valves;  2-2,  junction  of 
canal  and  auricle;  3-3,  annular  part  of 
auricle;  5,  bulbo-ventricular  junction. 


system,  which  gathers  up  the 
blood  from  the  intestines,  forms 
a  kind  of  loop  on  the  sj-stemic 
circulation.  The  lymph-current 
is  also  in  a  sense  a  slow  and  stag- 
nant side-stream  of  the  blood- 
circulation;  for  substances  are 
constantly     passing    from    the 

bloodvessels  into  the  lymph-spaces,  and  returning,  although  after  a  com- 
paratively long  interval,  into  the  blood  by  the  great  lymphatic  trunks. 
Physiological  Anatomy  of  the  Vascular  System. — The  heart  is  to  be 
looked  upon  as  a  portion  of  a  bloodvessel  which  has  been  modified  to 
act  as  a  pump  for  driving  the  blood  in  a  definite  direction.  IMorpho- 
logically  it  is  a  bloodvessel;  and  the  physiological  property  of  auto- 
matic rhythmical  contraction  which  belongs  to  the  heart  in  so  eminent 
a  degree  is,  as  has  been  mentioned  (p.  80),  an  endowment  of  blood- 
vessels in  many  animals  that  possess  no  localized  heart.  Even  in 
some  mammals  contractile  bloodvessels  occur;  the  veins  of  the  bat's 
wing,  for  example,  beat  with  a  regular  rhythm,  and  perform  the  func- 
tion of  accessorv  hearts. 


82  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

The  whole  vascular  system  is  lined  with  a  single  layer  of  endothelial 
cells.  In  the  capillaries  nothing  else  is  present;  the  endothelial  layer 
forms  the  whole  tliickness  of  the  wall.  In  young  animals,  at  any  rate, 
the  endothelial  cells  of  the  capillaries  are  capable  of  contracting  when 
stimulated ;  and  changes  in  the  calibre  of  these  vessels  can  be  brought 
about  in  this  way.  The  walls  of  the  arteries  and  veins  are  chiefly 
made  up  of  two  kinds  of  tissue,  which  render  them  distensible  and 
elastic :  non-striped  muscular  fibres  and  j'cUow  clastic  fibres.  The 
muscular  fibres  are  mainly  arranged  as  a  circular  middle  coat,  which, 
especially  in  the  smaller  arteries,  is  relatively  thick.  One  conspicuous 
layer  of  elastic  fibres  marks  the  boundary  between  the  middle  and 
inner  coats.  In  the  larger  arteries  elastic  laminae  are  also  scattered 
freely  among  the  muscular  fibres  of  the  middle  coat.  The  outer  coat 
is  composed  chiefly  of  ordinary'  connective  tissue.  The  veins  differ 
from  the  arteries  in  having  thinner  walls,  with  the  layers  less  distinctly 
marked,  and  containing  a  smaller  proportion  of  non-striped  muscle 
and  elastic  tissue ;  although  in  some  veins,  those  of  the  pregnant  uterus, 
for  instance,  and  the  cardiac  ends  of  the  large  thoracic  veins,  there  is 
a  greater  development  of  muscular  tissue.  Further,  and  this  is  of  prime 
physiological  importance,  valves  are  present  in  many  veins.  These 
are  semilunar  folds  of  the  internal  coat  projecting  into  the  lumen  in 
such  a  direction  as  to  favour  the  flow  of  blood  towards  the  heart, 
but  to  check  its  return.  In  some  veins,  as  the  venae  cavae,  the  pulmonary 
veins,  the  veins  of  most  internal  organs,  and  of  bone,  there  are  no  valves ; 
in  the  portal  system  they  are  rudimentary  in  man  and  the  great  majority 
of  mammals.  The  valves  are  especially  well  marked  in  the  lower  limbs, 
where  the  venous  circulation  is  uphill.  When  a  valve  ceases  to  perform 
its  function  of  supporting  the  column  of  blood  between  it  and  the 
valve  next  above,  the  foundation  of  varicose  veins  is  laid;  the  valve 
immediately  below  the  incompetent  one,  having  to  bear  up  too  great 
a  weight  of  blood,  tends  to  yield  in  its  turn,  and  so  the  condition  spreads. 
The  smallest  veins,  or  venules,  are  ver\-  like  the  smallest  arteries,  or 
arterioles,  but  somewhat  wider  and  less  muscular.  The  transition 
from  the  capillaries  to  the  arterioles  and  venules  is  not  abrupt,  but 
may  be  considered  as  marked  bj^  the  appearance  of  the  non-striped 
muscular  fibres,  at  first  scattered  singly,  but  gradually  becoming  closer 
and  more  numerous  as  we  pass  away  from  the  capillaries,  until  at  length 
they  form  a  complete  layer. 

In  the  heart  the  muscular  element  is  greatly  developed  and  differ- 
entiated. Both  histologically  and  physiologically  the  fibres  seem  to 
stand  between  the  striated  skeletal  muscle  and  the  smooth  muscle.  In 
the  mammal  the  cardiac  muscular  fibres  are  generally  described  as 
made  up  of  short  oblong  cells,  devoid  of  a  sarcolcmma,  often  branched, 
and  arranged  in  anastomosing  rows,  each  cell  ha\ing  a  single  nucleus 
in  the  middle  of  it.  But  it  has  recently  been  shown  that  the  muscle 
fibrils  run  right  through  the  apparent  cell  boundaries,  and  form  a  con- 
tinuous sheet  of  tissue  anastomosing  in  everj'  direction.  The  fibres 
are  transversely  striated,  but  the  striae  are  not  so  distinct  as  in  skeletal 
muscle.  A  sarcolemma  is  not  absent,  although  it  is  more  delicate 
than  in  skeletal  muscle,  and  perhaps  of  a  different  nature.  Many 
fibres  pass  from  one  auricle  to  the  other,  and  from  one  ventricle  to  the 
other. 

In  the  frog's  heart  the  muscular  fibres  are  spindle-shaped,  like  those 
of  smooth  muscle,  but  transversely  striated,  like  those  of  skeletal 
muscle.  From  the  sinus  to  the  apex  of  the  ventricle  there  is  a  con- 
tinuous sheet  of  muscular  tissue. 


ANATOMICAL  AND  PHYSICAL  DATA  83 

The  problems  of  the  circulation  are  partly  physical,  partly  vital. 
Some  of  the  phenomena  observed  in  the  blood-stream  of  a  living 
animal  can  be  reproduced  on  an  artificial  model ;  and  they  may  justly 
be  called  the  physical  or  mechanical  phenomena  of  the  circulation. 
Others  are  essentially  bound  up  with  the  properties  of  living  tissues ; 
and  these  may  be  classified  as  the  vital  or  physiological  phenomena  of 
the  circulation.  The  distinction,  although  by  no  means  sharp  and 
absolute,  is  a  convenient  one — at  least,  for  purposes  of  description; 
and  as  such  we  shall  use  it.  But  it  must  not  be  forgotten  that  the 
physiological  factors  play  into  the  sphere  of  the  physical,  and  the 
physical  factors  modify  the  physiological.  Considered  in  its 
physical  relations,  the  circulation  of  the  blood  is  the  flow  of  a  liquid 
along  a  system  of  elastic  tubes,  the  bloodvessels,  under  the  influence 
of  an  intermittent  pressure  produced  by  the  action  of  a  central 
pump,  the  heart.  But  the  branch  of  d}Tiamics  which  treats  of  the 
movement  of  liquids,  or  hydrodynamics,  is  one  of  the  most  difficult 
parts  of  physics,  and  even  in  the  physical  portion  of  our  subject  we 
are  forced  to  rely  chiefly  on  empirical  methods.  It  would,  therefore, 
not  be  profitable  to  enter  here  into  mathematical  theory,  but  it  may 
be  well  to  recall  to  the  mind  of  the  reader  one  or  two  of  the  simplest 
data  connected  with  the  flow  of  liquids  through  tubes: 

Torricelli's  Theorem. — Suppose  a  vessel  filled  with  water,  the  level 
of  which  is  kept  constant;  the  velocity  with  which  the  water  will 
escape  from  a  hole  in  the  side  of  the  vessel  at  a  vertical  depth  h  below 
the  surface  will  be  t;=  \/2gh,  where  g  is  the  acceleration  produced  by 
gravity.*  In  other  words,  the  velocity  is  that  which  the  water  would 
have  acquired  in  falling  in  vacuo  through  the  distance  h.  This  formula 
was  deduced  experimentally  by  Torricelli,  and  holds  only  when  the 
resistance  to  the  outflow  is  so  small  as  to  be  negligible.  The  reason  of 
this  restriction  will  be  easily  seen,  if  we  consider  that  when  a  mass 
tn  of  water  has  flowed  out  of  the  opening,  and  an  equal  mass  m  has 
flowed  in  at  the  top  to  maintain  the  old  level,  everything  is  the  same 
as  before,  except  that  energy  of  position  equal  to  that  possessed  by 
a  mass  m  at  a  height  h  has  disappeared.  If  this  has  all  been  changed 
into  kinetic  energy  E,  in  the  form  of_visible  motion  of  the  escaping 
water,  then  'E  =  imv^=mgh,  i.e.,  v=  sj'^gh.  If,  however,  there  has  been 
any  sensible  resistance  to  the  outflow,  any  sensible  friction,  some  of 
the  potential  energy-  (energ\-  of  position)  will  have  been  spent  in  over- 
coming this,  and  will  have  ultimately  been  transformed  into  the  kinetic 
energy  of  molecular  motion,  or  heat. 

Flow  of  a  Liquid  through  Tubes. — Next  let  a  horizontal  tube  of  imi- 
form  cross-section  be  fitted  on  to  the  orifice.  The  velocity  of  outflow 
will  be  diminished,  for  resistances  now  come  into  play.  When  the 
liquid  flowing  through  a  tube  wets  it,  the  layer  next  the  wall  of  the 
tube  is  prevented  by  adhesion  from  moving  on.  The  particles  next 
this  stationary  layer  rub  on  it,  so  to  speak,  and  are  retarded,  although 
not  stopped  altogether.  The  next  layer  rubs  on  the  comparatively 
slowl)-  moving  particles  outside  it,  and  is  also  delayed,  although  not 
so  much  as  thiat  in  contact  with  the  immovable  layer  on  the  walls  of 

*  I.e.,  the  amount  added  per  second  to  the  velocity  of  a  falling  body 
(^  =  32  feet). 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


the  tube.  In  this  way  it  comes  about  that  every  particle  of  the  liquid 
is  hindered  by  its  friction  against  others — those  in  the  axis  of  the  tube 
least,  those  near  the  peripliery  most — and  part  of  the  energy  of  position 
of  the  water  in  the  reservoir  is  used  up  i.i  overcoming  this  resistance, 
only  the  remainder  being  transformed  into  the  visible  kinetic  energy 
of  the  liquid  escaping  from  the  open  end  of  the  tube. 

If  vertical  tubes  be  inserted  at  different  points  of  the  horizontal 
tube,  it  will  be  found  that  the  water  stands  at  continually  decreasing 
heights  as  we  pass  away  from  the  reservoir  towards  the  open  end  of 
the  tube.  The  height  of  the  liquid  in  any  of  the  vertical  tubes  indicates 
the  lateral  pressure  at  the  point  at  which  it  is  inserted;  in  other  words, 
the  excess  of  potential  energy,  or  energy  of  position,  which  at  that 
point  the  liquid  possesses  as  compared  with  the  water  at  the  free  end, 
wlicre  the  pressure  is  zero.  If  the  centre  of  the  cross-section  of  the 
free  end  of  the  tube  be  joined  to  the  centres  of  all  the  menisci,  it  will 
be  found  that  the  line  is  a  straight  line.  The  lateral  pressure  at  any 
point  of  the  tube  is  therefore  proportional  to  its  distance  from  the  free 
end.  Since  the  same  quantity  of  water  must  pass  through  each  cross- 
section  of  the  horizontal  tube  in  a  given  time  as  flows  out  at  the  open 
end,  the  kinetic  energy  of  the  liquid  at  every  cross-section  must  be 

constant  and  equal  to  ^mv^, 
where  v  is  the  mean  velocity 
(the  quantity  which  escapes  in 
umt  of  dme  divided  by  the 
cross-section)  of  the  water  at 
the  free  end. 

Just  inside  the  orifice  the 
total  energy  of  a  mass  m  of 
water  is  mgh;  just  beyond  it 
at  the  first  vertical  tube,  mgh' 
+  lniv'^,  where  h'  is  the  lateral 
pressure.  On  the  assumption 
that  between  the  inside  of  the 
orifice  and  the  first  tube  no 
energy  has  been  transformed 
into  heat  (an  assumption 
the  more  nearly  correct  tlie 
smaller  the  distance  between 
it  and  the  inside  of  the  orifice  is  made),  we  liave  mgh  =  mgh'  +  \mv'^. 
i.e.,  Imv- -^  mg{h  -  h') .  In  other  words,  the  portion  of  the  energy  of 
position  of  the  water  in  the  reservoir  which  is  transformed  into  the 
kinetic  cncrg\'^  of  the  water  flowing  along  the  horizontal  tube  is  measured 
by  the  difference  between  the  height  of  the  level  of  the  reservoir  and 
the  lateral  pressure  at  the  beginning  of  the  horizontal  tube — that  is, 
the  height  at  which  the  straight  line  joining  the  menisci  of  the  vertical 
tubes  intersects  the  column  of  water  in  the  reservoir.  Let  H  represent 
the  height  corresponding  to  that  part  of  the  energy  of  position  which 
is  transformed  into  the  kinetic  energy  of  the  flowing  water.  H  is  easily 
calculated  when  the  mean  velocity  of  efflux  is  known.  For  v=  ^2gH 
by  TorriccUi's  theorem  (since  none  of  the  energy  corresponding  to  H 

IS  supposed  to  be  used  up  in  overcoming  friction),  or  H=      .    At  the 

second  tube  the  lateral  pressure  is  only  h".  The  sum  of  the  visible 
kinetic  and  potential  energy  here  is  therefore  hnv-  +  mgh" .  A  quantity 
of  energy  mg{h'  —  h")  must  have  been  transformed  into  heat  owing  to 
the  resistance  caused  by  fluid  friction  in  the  portion  of  the  horizontal 


(^^E 

I 

' 

^^m 

\          ^^ 

C^ 

^^^A^: 

^ 

\  ^ 

?  h"  ^^""^ 

^ 

^~^^~"'^"^  "- 

:-  

==s= 

^            ~"- 

h"" 

Fig.  26. — Diagram  to  illustrate  Flow  of 
Water  along  a  Horizontal  Tube  connected 
with  a  Reservoir. 


ANATOMICAL  AND  PHYSICAL  DATA  85 

tube  between  the  first  two  vertical  tubes.  In  general  the  energy  of 
position  represented  by  the  lateral  pressure  at  any  point  is  equal  to 
the  energy  used  up  in  overcoming  the  resistance  of  the  portion  of  the 
path  beyond  tliis  point. 

Velocity  of  Outflow. — It  has  been  found  by  experiment  that  v,  the 
mean  velocity  of  outflow,  when  the  tube  is  not  of  very  small  calibre, 
varies  directly  as  the  diameter,  and  therefore  the  volume  of  outflow 
as  the  cube  of  the  diameter.  In  fine  capillary  tubes  the  mean  velocity 
is  proportional  to  the  square,  and  the  volume  of  outflow  to  the  fourth 
power  of  the  diameter  (Poiscuille).  If,  for  example,  the  linear  velocity 
of  the  blood  in  a  capillary  of  10  /x  in  diameter  is  \  mm.  per  sec,  it  will 
be  four  times  as  great  (or  2  mm.  per  sec.)  in  a  capillary  of  20  /x  diameter, 
and  one-fourth  as  great  (or  ^  mm.  per  sec.)  in  a  capillary  of  5  /i  diameter, 
the  pressure  being  supposed  equal  in  all.  The  volume  of  outflow  per 
second  is  obtained  by  multiplying  the  cross-section  by  the  linear 
velocity.  The  cross-section  of  a  circular  capillary,  10  /n  in  diameter, 
is  TT  (5XTjfjjj)2  -=,  say,  j^o^  sq.  mm.  The  outflow  will  be  i^UqX^ 
=  ogJuo  cub.  mm.  per  sec.  The  outflow  from  the  capillary  of  .>o  n 
diameter  would  be  sixteen  times  as  much,  from  the  5  fj.  capillary  only 
one-sixteenth  as  much.  Some  idea  of  the  extremely  minute  scale 
on  which  the  blood-flow  through  a  single  capillary  takes  place  may 
be  obtained  if  we  consider  that  for  the  capillary  of  10  ^  diameter  a 
flow  of  05^00  cub.  mm.  per  sec.  would  scarcely  amount  to  i  cub.  mm 
in  six  hours,  or  to  i  c.c.  in  250  days. 

When  the  initial  energy  is  obtained  in  any  other  way  than  by  means 
of  a  '  head  '  of  water  in  a  reservoir — say,  by  the  descent  of  a  piston 
which  keeps  up  a  constant  pressure  in  a  cylinder  filled  with  liquid — 
the  results  are  exactly  the  same.  Even  when  the  horizontal  tube  is 
distensible  and  elastic,  there  is  no  difference  when  once  the  tube  has 
taken  up  its  position  of  equilibrium  for  any  given  pressure,  and  that 
pressure  does  not  vary^ 

Flow  with  Intermittent  Pressure. — When  this  acts  on  a  rigid  tube, 
everything  is  the  same  as  before.  When  the  pressure  alters,  the 
flow  at  once  comes  to  correspond  with  the  new  pressure.  Water 
thrown  by  a  force-pump  into  a  system  of  rigid  tubes  escapes  at  every 
stroke  of  the  pump  in  exactly  the  quantity  in  which  it  enters,  for 
water  is  practically  incompressible,  and  the  total  quantity  present 
at  one  time  in  the  system  cannot  be  sensibly  altered.  In  the  intervals 
between  the  strokes  the  flow  ceases;  in  other  words,  it  is  intermittent. 
It  is  very  different  with  a  system  of  distensible  and  elastic  tubes. 
During  each  stroke  the  tubes  expand,  and  make  room  for  a  portion 
of  the  extra  liquid  thrown  into  them,  so  that  a  smaller  quantity  flows 
out  than  passes  in.  In  the  intervals  between  the  strokes  the  distended 
tubes,  in  virtue  of  their  elasticity,  tend  to  regain  their  original  calibre. 
Pressure  is  thus  exerted  upon  the  liquid,  and  it  continues  to  be  forced 
out,  so  that  when  the  strokes  of  the  pump  succeed  each  other  with 
sufficient  rapidity,  the  outflow  becomes  continuous.  This  is  the  state 
of  affairs  in  the  vascular  system.  The  intermittent  action  of  the 
heart  is  toned  down  in  the  elastic  vessels  to  a  continuous  steady  flow. 

Section  II. — The  Beat  of  the  Heart  in  its  Physical  or 
Mechanical  Relations. 

Events  in  the  Cardiac  Cycle. — In  the  frog's  heart  the  contraction 
can  be  seen  to  begin  about  the  mouths  of  the  great  veins  which  open 
into  the  sinus  venosus.     Thence  it  spreads  in  succession  over  the 


86  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

sinus  and  auricles,  hesitates  for  a  moment  at  the  auriculo-ventric- 
ular  junction,  and  then  with  a  certain  suddenness  invades  the 
ventricle.  In  the  mammalian  heart  the  contraction  likewise  com- 
mences, so  far  as  can  be  ascertained  by  inspection  or  the  study  of 
tracings,  in  the  region  near  the  mouths  of  the  veins  opening  into  the 
auricles.  It  will  be  seen,  when  the  question  of  the  origin  of  the 
rhythmical  beat  is  being  discussed  (p.  141),  that  the  actual  starting- 
point  is  probably  the  sinus  tissue  of  the  right  auricle  (p.  142)  near  the 
opening  of  the  superior  vena  cava,  which  is  richly  provided  with 
muscular  fibres  ak  n  to  those  of  the  heart.  But  the  wave  advances 
so  rapidly  that  it  is  difficult  to  trace  in  its  course  a  regular  progress 
from  base  to  apex,  although  the  ventricular  beat  undoubtedly 
follows  that  of  the  auricle,  and  in  a  heart  beating  normally  the 
electrical  change  associated  with  contraction  of  the  ventricle 
begins  at  the  base,  then  reaches  the  apex  (p.  853),  and  finally  passes 
towards  the  orifices  of  the  great  arteries. 

The  most  conspicuous  events  in  the  beat  of  the  heart,  in  their 
normal  sequence,  are:  (i)  the  auricular  contraction  or  systole,  (2)  the 
ventricular  contraction  or  systole,  each  followed  by  relaxation,  (3)  the 
pause.  The  auricles,  into  which,  and  beyond  which  into  the  ven- 
tricles, blood  has  been  flowing  during  the  pause  from  the  great 
thoracic  veins,  contract  sharply,  the  right,  perhaps,  a  little  before 
the  left.  The  contraction  begins  in  the  muscular  tissue  that 
surrounds  the  orifices  of  the  veins,  so  that  these,  destitute  of  valves 
as  they  are,  are  functionally,  at  least,  if  not  anatomically,  sealed  up 
for  an  instant,  and  regurgitation  of  blood  into  them  is  to  a  great 
extent,  if  not  entirely,  prevented.  Apparently,  complete  closure 
of  the  inferior  cava  is  unnecessary,  the  pressure  of  the  blood  in  it 
being  sufficiently  high  to  hinder  any  important  back-flow.  The 
action  of  the  circular  fibres  of  the  veins  in  closing  their  orifices  is 
reinforced  by  the  contraction  of  a  band  of  muscle  (the  tcBuia  ter- 
minalis)  in  the  roof  of  the  right  auricle.  This  band  compresses 
especially  the  mouth  of  the  superior  vena  cava.  The  filling  of  the 
ventricles  is  thus  completed.  The  actual  amount  of  extra  blood 
injected  into  the  ventricles  by  the  auricular  contraction  is  not  large. 
The  ventricles  are  already  nearly  charged,  but  the  auricles,  so  to 
speak,  ram  the  charge  home.  The  ventricular  contraction  follows 
hard  on  the  relaxation  of  the  auricles.  The  mitral  and  tricuspid 
valves,  whose  strong  but  delicate  curtains  have  during  the  diastole 
been  hanging  down  into  the  ventricles  and  swinging  freely  in  the 
entering  current  of  blood,  are  floated  up  as  the  intraventricular 
pressure  begins  to  rise,  so  that,  in  the  first  moment  of  the  sudden 
and  powerful  ventricular  systole,  the  free  edges  of  their  segments 
come  together,  and  the  auriculo-ventricular  orifices  are  completely 
closed  (Fig.  98,  p.  206).  In  the  measure  in  which  the  pressure  in  the 
contracting  ventricles  increases,  the  contact  of  the  valvular  seg- 


MECHANICS  OF  THE  HEART-BEAT  87 

monts  becomes  closer  and  more  extensive;  and  their  tendency  to 
belly  into  the  auricles  is  opposed  by  the  pull  of  the  chorda.*  tendinea;, 
whose  slender  cords,  inserted  into  the  valves  from  border  to  base,  are 
kept  taut,  in  spite  of  the  shortening  of  the  ventricles  by  the  con- 
traction of  the  papillary  muscles.  The  arrangement  and  connec- 
tions of  the  muscular  fibres  of  the  heart  are  such  that  during  the 
auricukir  systole  the  auriculo-ventricular  groove  moves  towards  the 
base  of  the  heart,  while  during  the  systole  of  the  ventricles  it  moves 
towards  the  apex,  which  constitutes  a  relatively  fixed  point  on 
account  of  the  mutual  action  of  the  numerous  fibres  which  converge 
here  and  constitute  the  '  whorl.'  The  hnc  joining  the  apex  and 
the  origin  of  the  aorta  does  not  shorten  when  the  ventricles  contract, 
but  all  parts  of  the  heart  are  drawn  towards  this  line.  The  apex  is, 
therefore,  pushed  forwards,  while  the  rest  of  the  ventricular  surface 
is  being  drawn  inwards.  During  the  systole,  the  ventricles  change 
their  shape  in  such  a  way  that  their  combined  cross-section — which 
in  the  relaxed  state  is  a  rough  ellipse  with  the  major  axis  from  right 
to  left — becomes  approximately  circular,  and  they  then  form  a  right 
circular  cone.  As  soon  as  the  pressure  of  the  blood  within  the  con- 
tracting ventricles  exceeds  that  in  the  aorta  and  pulmonary  artery 
respectively,  the  semilunar  valves,  which  at  the  beginning  of  the 
ventricular  systole  are  closed,  yield  to  the  pressure,  and  blood  is 
driven  from  the  ventricles  into  these  arteries. 

The  ventricles  are  more  or  less  completely  emptied  during  the 
contraction,  which  seems  still  to  be  maintained  for  a  short  time  after 
the  blood  has  ceased  to  pass  out.  The  contraction  is  followed 
by  sudden  relaxation.  The  intraventricular  pressure  falls.  The 
lunules  of  the  semilunar  valves  slap  together  under  the  weight  of  the 
blood  as  it  attempts  to  regurgitate,  the  corpora  Arantii  seal  up  the 
central  chink,  and  the  aorta  and  pulmonary  artery  are  thus  cut  off 
from  the  heart.  Then  follows  an  interval  during  W'hich  the  w^hole 
heart  is  at  rest,  namely,  the  interval  between  the  end  of  the  relaxa- 
tion of  the  ventricles  and  the  beginning  of  the  systole  of  the  auricles. 
This  constitutes  the  pause.  The  whole  series  of  events  is  called  a 
cardiac  cycle  or  revolution  (see  Practical  Exercises,  p.  201). 

It  will  be  easily  understood  that  the  time  occupied  by  any  one  of 
the  events  of  the  cardiac  cycle  is  not  constant,  for  the  rate  of  the 
heart  is  variable.  If  we  take  about  70  beats  a  minute  as  the  average 
normal  rate  in  a  man,  the  ventricular  systole  will  occupy  about 
0*3  second;  the  diastole,*  including  the  ventricular  relaxation,  about 

•  The  term  '  diastole  '  is  variously  used,  as  meaning  the  pause,  the  pause 
plus  the  period  during  which  relaxation  is  occurring,  or  the  period  of  re- 
laxation alone.  We  shall  employ  it  in  the  second  sense.  Henderson  refers 
to  the  period  during  which  the  ventricular  muscle  is  at  rest,  from  the  end  of 
its  relaxation  to  the  onset  of  the  auricular  systole,  as  the  'diastasis'  and  the 
period  during  which  the  relaxation  is  taking  place  as  the  'diastole,'  a  termin- 
ology which  seems  worthy  of  general  adoption. 


88  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

0-5  second.  The  systole  of  the  auricle  is  one-third  as  long  as  that  of 
the  ventricle. 

This  rhythmical  beat  of  the  heart  is  the  ground  phenomenon  of 
the  circulation.  It  reveals  itself  by  certain  tokens — sounds,  surface- 
movements  or  pulsations,  alterations  of  the  pressure  and  velocity  of 
the  blood,  changes  of  volume  in  parts — all  periodic  phenom^a, 
continually  recurring  with  the  same  period  as  the  heart -beat,  and  all 
fundamentally  connected  together.  And  if  we  hold  fast  the  idea 
that  when  we  take  a  pulse-tracing,  or  a  blood-pressure  curve,  or  a 
plethysmographic  record,  we  are  really  investigating  the  same  fact 
from  different  sides,  we  shall  be  able,  by  following  the  cardiac  rhythm 
and  its  consequences  as  far  as  we  can  trace  them,  to  hang  upon  a 
single  thread  many  of  the  most  important  of  the  phj^sical  phenom- 
ena of  the  circulation. 

The  Sounds  of  the  Heart. — When  the  ear  is  applied  to  the  chest,  or 
to  a  stethoscope  placed  over  the  cardiac  region,  two  sounds  are 
heard  with  every  beat  of  the  heart.  They  follow  each  other  closely, 
and  are  succeeded  by  a  period  of  silence.  The  dull  booming  '  first 
sound  '  is  heard  loudest  in  a  region  which  we  shall  afterwards  have 
to  speak  of  as  that  of  the  '  cardiac  impulse  '  (p.  90) ;  the  short,  sharp, 
'  second  sound  '  over  the  junction  of  the  second  right  costal  cartilage 
with  the  sternum. 

The  heart-sounds  can  be  registered  by  placing  over  the  chest  a 
microphone  receiver  connected  with  a  string  galvanometer.  The 
magnified  sounds  are  translated  into  electrical  changes  which  cause 
movements  of  the  fibre  of  the  galvanometer,  and  the  movements  are 
photographed  on  a  travelling  plate  (Eitithoven) .  The  record  is  called 
a  cardiophonogram.  When  this  is  studied,  a  third  sound  can  be 
detected,  and  it  is  probable  that  it  is  present  in  all  persons,  although  it 
is  as  a  rule  inaudible  to  auscultation.  It  occurs  early  in  diastole  very 
shortly  after  the  second  sound.  In  those  persons  in  whom  it  is  audible 
it  is  most  distinct  over  the  region  of  cardiac  impulse.  It  is  described 
as  softer  and  of  lower  pitch  than  the  second  sound  (Thayer). 

There  has  been  much  discussion  as  to  the  cause  of  the  first  sound. 
That  a  sound  corresponding  with  it  in  time  is  heard  in  an  excised 
bloodless  heart  when  it  contracts  is  certain ;  and  therefore  the  first 
sound  cannot  be  exclusively  due,  as  some  have  asserted,  to  vibra- 
tions of  the  auriculo-ventricular  valves  when  they  are  suddenly 
rendered  tense  by  the  contraction  of  the  ventricles,  for  in  a  bloodless 
heart  the  valves  are  not  stretched.  Part  of  the  sound  must  accord- 
ingly be  associated  with  the  muscular  contraction  as  such. 

Again,  the  fact  that  the  first  sound  is  heard  during  the  whole,  or 
nearly  the  whole,  of  the  ventricular  systole  is  against  the  idea  that 
it  is  exclusivelv  due  to  the  vibrations  of  membranes  like  the  valves, 
which  would  speedily  be  damped  by  the  blood  and  rendered  in- 
audible. But  while  there  is  good  reason  to  believe  that  the  vibra- 
tion of  the  suddenly-contracted  ventricles  is  the  fundamental  factor, 
the  shock  sets  up  vibrations  also  in  the  blood,  the  chest-wall,  and 


MECHANICS  OF  THE  HEARl'-HEAT  8y 

perhaps  the  resonant  tissue  of  the  lungs.  Further,  as  we  shall  see 
later  on  (p.  760),  the  sound  caused  by  a  contracting  muscle  readily 
calls  forth  sympathetic  resonance  in  the  ear,  and  the  peculiar  boom- 
ing character  of  the  hrst  sound  may  be  due  to  the  superpositi(jn  of 
these  VcU"ious  resonance  tones  upon  the  muscular  note.  But,  in 
addition,  the  vibration  of  the  auriculo-ventricular  valves  un- 
doubtedly contributes  to  the  production  of  the  sound,  and  some 
observers  have  been  able  to  distinguish  in  the  first  sound  the  valvular 
and  the  muscular  elements,  the  fomier  being  higher  in  pitch  than  the 
latter,  but  a  minor  third  below  the  second  sound.  In  the  excised 
empty  heart  the  deeper  tone  of  the  first  sound  is  alone  heard,  while 
the  higher  note  is  elicited  when  in  a  dead  heart  the  auriculo-ventric- 
ular valves  are  suddenly  put  under  tension  (Haycraft).  When  the 
mitral  valve  is  prevented  from  closing  by  experimental  division  of 
the  chordae  tendineae,  or  by  pathological  lesions,  the  first  sound  of 
the  heart  is  altered  or  replaced  by  a  '  murmur.'  This  evidence  is 
not  only  important  as  regards  the  physiological  question,  but  of 
great  practical  interest  from  its  bearing  on  the  diagnosis  of  cardiac 
disease.  It  may  be  added  that  the  point  of  the  chest-wall  at  which 
the  first  sound  is  most  easily  recognized  is  also  the  point  at  which  a 
changed  sound  or  murmur  connected  with  disease  of  the  mitral  valve 
is  most  distinctly  heard.  The  sound  is,  therefore,  best  conducted 
from  the  mitral  valve  along  the  heart  to  the  point  at  which  it  comes 
in  contact  with  the  wall  of  the  chest.  Changes  in  the  first  sound  con- 
nected with  disease  of  the  tricuspid  valve  are  heard  best,  in  the  com- 
paratively rare  cases  where  they  can  be  distinctly  recognized,  in  the 
third  to  the  fifth  interspace,  a  Httle  to  the  right  of  the  sternum. 

The  second  sound  is  caused  by  the  vibrations  of  the  semilunar 
valves  when  suddenly  closed, '  the  recoiUng  blood  forcing  them  back, 
as  one  unfurls  an  umbrella,  and  with  an  audible  check  as  they 
tighten  '  (Watson).  The  sharpness  of  its  note  is  lost,  and  nothing 
but  a  rushing  noise  or  bruit  can  be  heard,  when  the  valves  are  hooked 
back  and  prevented  from  closing.  It  is  altered,  or  replaced  by  a 
murmur,  when  the  valves  are  diseased.  As  there  is  a  mitral  and  a 
tricuspid  factor  in  the  first  sound,  so  there  is  an  aortic  and  a  pul- 
monary factor  in  the  second.  The  place  where  the  second  sound  is 
best  heard  (over  the  junction  of  the  second  right  costal  cartilage  and 
sternum)  is  that  at  which  any  change  produced  by  disease  of  the 
aortic  valves  is  most  easily  recognized.  The  sound  is  conducted  up 
from  the  valves  along  the  aorta,  which  comes  nearest  to  the  surface 
at  this  point.  Changes  connected  with  disease  of  the  pulmonary 
valves  are  most  readily  detected  over  the  second  left  intercostal 
space  near  the  edge  of  the  sternum,  for  here  the  pulmonary  artery 
most  nearly  approaches  the  chest-wall.  The  first  sound  is  '  systolic  ' 
— that  is,  it  occurs  during  the  ventricular  systole;  the  second  is 
'  diastolic,'  beginning  at  the  commencement  of  the  diastole 


90 


THE  CIRCULATION  OF  THE  BLOOD  A\D  LYMPH 


Various  explanations  of  the  third  sound  have  been  given,  but,  as 
the  authors  who  have  studied  it  are  not  even  agreed  as  to  whether  it 
is  produced  at  the  auriculo-ventricular  orifices  or  at  the  aortic  and 
puhnonary  orifices,  it  would  not  be  useful  to  discuss  them  at  present. 
The  Cardiac  Impulse. — A  surface-movement  is  seen,  or  an  impulse 
felt,  at  every  cardiac  contraction  in  various  situations  where  the 
heart  or  arteries  approach  the  surface.  The  pulsation,  or  impulse, 
of  the  heart,  often  stj'led  the  apex-beat,  is  usually  most  distinct  to 
sight  and  touch  in  a  small  area  lying  in  the  fifth  left  intercostal 
space,  between  the  mammary  and  the  parasternal  line,*  and  gener- 
.alh',  in  an  adult,  about  an  inch  and  a  half  to  the  sternal  side  of  the 
former.  It  is  due  to  the  systolic  hardening  of  the  ventricles,  which 
are  here  in  contact  with  the  chest-wall,  the  contact  being  at  the 
same  time  rendered  closer  by  their  change  of  shape,  and  by  a  slight 

movement  of  rotation  of 
the  heart  from  left  to  right 
during  the  contraction 
(Practical  Exercises, 
p.  207).  When  the  left 
ventricle  is  in  contact  with 
the  chest  at  the  position  of 
the  apex-beat,  as  is  usually 
the  case,  an  important 
element  in  the  impulse  is 
the  actual  forward  thrust 
of  the  apex.  WTien  the 
apex-beat  corresponds  in 
position  wnih  the  right 
ventricle,  there  is  no 
actual  forward  movement, 
although  the  hardening  of 
the  ventricle  may  be  felt  as  a  tlirust  by  the  finger.  Even  in  health 
the  position  of  the  impulse  varies  somewhat  with  the  position  of 
the  body  and  the  respirator^'  movements.  In  children  it  is  usually 
situated  in  the  fourth  intercostal  space.  In  disease  its  displacement 
is  an  important  diagnostic  sign,  and  may  be  very  marked,  especially 
in  cases  of  effusion  of  fluid  into  the  pleural  cavity.  It  is  sometimes, 
though  not  invariably,  a  little  lower  in  the  standing  than  in  the 
sitting  position,  and  shifts  an  inch  or  two  to  the  left  or  right  when 
the  person  hes  on  the  corresponding  side. 

Various  instruments,  called  cardiographs,  have  been  devised  for 
magnifying  and  recording  the  movements  produced  by  the  cardiac 
impulse.     Marey's  cardiograph  (Fig.  27)  consists  essentially  of  a  small 

*  The  mammary  line  is  an  imaginary  vertical  line  supposed  to  be  drawn 
on  the  chest  through  the  middle  point  of  the  clavicle.  It  usually,  but  not 
necessarily,  parses  through  the  nipple.  The  parasternal  line  is  the  vertical 
line  lying  midway  between  the  mammary  line  and  the  corresponding  border 
of  the  sternum. 


27. — Diagram  of  Marey's  Cardiograph. 


MECHANICS  OF  THE  HEART- BEAT 


91 


chamber,  or  tambour,  filled  with  air,  and  closed  at  one  end  by  a  flexible 
membrane  carrying  a  button,  which  can  be  adjusted  to  the  wall  of  the 
chest.  This  receiving  tambour  is  connected  by  a  tube  with  a  recording 
tambour,  the  flexible  plate  of  which  acts  upon  a  lever  writing  on  a 
travelling  surface — a  uniformly-rotating  drum,  for  example — covered 
with  smoked  paper.  Any  movement  communicated  to  the  button 
forces  in  the  end  of  the  tambour  to  which  it  is  attached,  and  thus 
raises  the  pressure  of  the  air  in  it  and  in  the  recording  tambour;  the 
flexible  plate  of  the  latter  moves  in  response,  and  the  lever  transfers 
the  movement  to  the  paper.  The  tracing,  or  cardiogram,  obtained  in 
this  way  shows  a  small  elevation  corresponding  to  the  auricular  systole, 
succeeded  by  a  large  abrupt  rise  corresponding  to  the  beginning  of 
the  first  sound,  and  caused  by  the  ventricular  systole.  This  ventricular 
elevation  is  the  essential  portion  of  the  curve;  it  is  alone  felt  by  the 
palpatmg  hand,  and  the  auricular  elevation  is  often  absent  from  the 
cardiogram  in  man.  The  rise  is  maintained,  with  small  secondary 
oscillations,  for  about  o-;;  of  a  second  in  a  tracing  from  a  normal  man, 
then  gives  way  to  a  sudden  de- 
scent, that  marks  the  relaxation 
of  the  ventricles,  the  beginning 
of  the  second  sound,  and  the 
closure  of  the  semilunar  valves. 
An  interval  of  about  0-5  second 
elapses  before  the  curve  begins 
again  to  rise  at  the  next  auricular 
contraction. 

Such  was  the  interpretation 
which  Chauveau  and  Marey  put 
upon  their  tracings.  Although 
neither  their  resiilts  nor  their 
deductions  from  them  have 
escaped  the  criticism  of  succeed- 
ing investigators,  it  is  doubtful 
whether  any  adequate  reason 
has  been  brought  forward  for 
discarding  them,  and  Chauveau  has  furnished  further  proofs  of  their 
accuracy.  The  difficulties  that  beset  the  subject  are  great,  for  the 
cardiogram  is  a  record  of  a  complex  series  of  events.  The  very  rapid 
variation  of  pressure  within  the  ventricles,  the  change  of  volume  and 
of  shape  of  the  heart,  the  slight  change  of  position  of  its  apex,  must 
all  leave  their  mark  upon  the  curve,  which  is  besides  distorted  by  the 
resistance  of  the  elastic  chest-wall,  the  inertia  of  the  recording  lever, 
and  the  compression  of  the  air  in  the  connecting  tubes.  It  is  only  by 
comparing  in  animals  the  cardiographic  record  with  the  changes  of 
blood-pressure  in  the  heart  and  arteries  that  our  present  degree  of 
knowledge  of  the  human  cardiogram  has  been  attained.  Could  we 
register  directly  the  fluctuations  of  pressure  in  the  interior  of  the  human 
heart,  the  cardiographic  method  would  be  rarely  employed.  For 
cl.nical  purposes  the  receiving  tambour  can  be  advantageously  replaced 
by  a  small  glass  funnel  or  a  small  metal  cup,  the  open  end  of  which  is 
applied  without  a  membrane  over  the  cardiac  impulse,  the  stem  being 
connected  with  the  recording  tambour.  In  cases  in  which  the  right 
ventricle  is  in  contact  with  the  chest-wall  at  the  position  of  the  apex- 
beat  the  cardiogram  is  '  inverted  ' — that  is  to  say,  the  chest-wall  is 
drawn  in  during  systole  and  protruded  during  diastole  of  the  ventricles. 
Inversion  of  the  cardiogram  is,  therefore,  not  an  infallible  sign  of  the 
pathological  condition  known  as  adherent  pericardium  (Mackenzie). 


Fig.  28. — Cardiogram  taken  with  Marey"~ 
Cardiograph.  A,  auricular  systole  ; 
V,  ventricular  systole ;  D,  diastole. 
The  arrow  shows  the  direction  in  which 
the  tracing  is  to  be  read. 


92 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


Endocardiac  Pressure. — The  function  of  the  heart  is  to  maintain 
an  excess  of  pressure  in  the  aorta  and  puhnonary  artery  sufficient  to 
overcome  the  friction  of  the  whole  vascular  channel,  and  to  keep  up 
the  flow  of  blood.  So  long  as  the  semilunar  valves  are  closed,  most 
of  the  work  of  the  contracting  ventricles  is  expended  in  raising  the 
pressure  of  the  blood  within  them.  At  the  moment  when  blood 
begins  to  pass  into  the  arteries,  nearly  all  the  energy  of  this  blood  is 
potential;  it  is  the  energy  of  a  liquid  under  pressure.  During  a 
cardiac  cycle  the  pressure  in  the  cavities  of  the  heart,  or  the  endo- 
cardiac pressure,  varies  from  moment  to  moment,  and  its  variations 

afford  important 
(lata  for  the  study 
of  the  mechanics  of 
the  circulation. 

Manometers.  — For 
the  study  of  the  endo- 
cardiac pressure,  the 
ordinary       mercurial 
manometer    (p.    no) 
is    unsuitable,    since, 
owing    to    the     rela- 
tively great   amount 
of   work   required    to 
produce  a  given  dis- 
placement of  the  mer- 
cury,    it     does     not 
readily   follow    rapid 
changes   of  pressure, 
and     the      mercurial 
column,     once      dis- 
placed, continues  for 
a    time    to     execute 
vibrations  of  its  own, 
which  are  compoun- 
ded with  the  true  oscillations  of  blood-pressure.     But  by  introducing 
in  the  connection  between  the  manometer  and  the  heart  a  valve  so 
arranged  as  to  oppose  the  passage  of  blood  towards  the  heart,  while  it 
favours  its  passage  towards  the  manometer,  the  maximum  pressure 
attained  in  the  cardiac  cavities  during  the  cycle  may  be  measured  with 
considerable   accuracy.     When  the   valve   is   reversed  the  apparatus 
becomes  a  minimum  manometer.     In  this  way  it  has  been  found  that 
in  large  dogs  the  pressure  in  the  left  ventricle  may  rise  as  high  as  230 
to  240  mm.  of  mercury,  and  sink  as  low  as  -  30  to  -  50  mm. ;  while  in 
the  right  ventricle  it  may  be  as  much  as  70  mm.,  and  as  little  as 
—  25  mm.     In  the  right  auricle  a  maximum  pressure  of  20  mm.  of 
mercury  has  been  recorded,  and  a  minimum  pressure  of   -  10  mm.  or 
even  less.     But  these  results  were  obtained  under  somewhat  exceptional 
experimental  conditions,  and  the  normal  maximum  pressures  in  the 
heart  cavities  in  man  are  probably  not  so  high,  especially  in  the  right 
auricle  and  ventricle. 

Our  knowledge  of  the  maximum  and  minimum  pressure  attained 
in  the  cavities  of  the  heart,  even  if  it  were  far  more  precise  than  it 
actually  is,  would  only  carry  us  a  little  way  in  the  study  of  the  endo- 
cardiac pressure-curve,  for  it  would  merely  tell  us  how  far  above  the 


Fig.  29. — Curves  of  Enducardiac  Pressure  takeu  with 
Cardiac  Sounds.  Aur.,  auricular  curve;  Vent.,  ven- 
tricular curve;  AS,  period  of  auricular  systole,  in- 
cluding relaxation;  VS,  of  ventricular  systole, including 
relaxation;  D,  pause. 


MECHANICS  OF  THE  HEART-BEAT 


93 


J,        -^ 

pjg  30. — Diagram  of  Hurthle's  Elastic  Mano- 
meter. T,  small  chamber  covered  by  mem- 
brane; t,  tube  communicating  with  interior 
of  heart;  L,  compound  lever  to  magnify  the 
movements  of  the  membrane. 


base-line  of  atmospheric  pressure  the  curve  ascends,  and  how  far  below 
the  base-line  it  sinks.  To  exhaust  the  problem,  we  require  to  have 
tracings  of  the  exact  form  of  the  curve  for  each  of  the  cavities  of  the 
heart,  and  to  know  the  time-relations  of  the  curves  so  as  to  be  able  to 
compare  them  with  each  other,  and  with  tlie  pressure-curves  of  the  great 
arteries  and  great  veins.  To  obtain  satisfactory  tracings  of  the  swiftly- 
changing  cndocardiac  pressure 
is  a  task  of  the  highest  techni- 
cal difliculty,  and  it  is  only  in 
very  recent  years  that  it  has 
been  accomplished,  with  an  y  ap- 
proach to  accuracy  by  the  use 
of  clastic  manometers,  in  which 
the  blood-pressure  is  counter- 
balanced, not  by  the  weight  of 
a  column  of  liquid,  as  in  the 
mercurial  manometer,  but  by 
the  resistance  to  compression 
of  a  small  column  of  air  or  the 
tension  of  an  elastic  disc  or  of 
a  spring.     Modifications  in  the 

nature  and  dimensions  of  the  clastic  resistance  of  the  recordmg  apparatus 
and  of  the  size  of  the  cavity  have  produced  successive  improvements,  as, 
e.g.,  in  the  manometers  of  Hiirthle  (Fig   30). 

The  penetrating  analysis  of  the  principles  of  manometer  construction 
by  Frank  has  recently  stimulated  renewed  investigation  of  the  whole 
subject  with  the  aid  of  instruments  whose  movements  are  optically  re- 

pjg  3i_ — Diagram  of  Optical  Manometer  (Wiggers). 
A  is  a  vertical  glass  tube  surmounted  by  a  hollow 
brass  cylinder,  B,  which  contains  a  stopcock,  C 
whose  lumen  comes  into  apposition  with  a  plate, 
a,  having  a  small  opening  in  it.  By  opening  the 
stopcock  more  or  less,  the  pulsations  will  be  '  damped ' 
to  a  smaller  or  greater  extent.  Above  a  the  cylinder 
ends  in  a  segment  capsule  b  [i.e.,  a  capsule  cut  away 
at  one  side)  3  mm.  in  diameter,  covered  with  rubber 
dam.  Upon  this  a  small  piece  of  celluloid  carr>'ing 
a  little  mirror,  c,  is  fastened,  so  that  it  pivots  on  the 
chord  side  of  the  capsule.  Over  the  capsule  and  its 
recording  mirror  is  mounted  a  support  bearing  an 
inclined  reflecting  mirror,  E,  adjustable  about  a 
horizontal  axis  by  a  screw,  so  that  the  image  of  the 
lecording  mirror  appears  within  it.  Upon  this 
image  a  strong  light  is  focussed.  The  incident  rays 
are  doubly  reflected,  as  shown  in  the  figure,  and  the 
movements  of  the  capsule  are  thus  greatly  magnified. 
The  beam  of  light  is  photographed  on  a  moving 
plate. 

corded  on  a  photographic  plate,  so  as  to  eliminate  all  unnecessary  fric- 
tion. Fig.  31  is  a  diagram  of  the  manometer  devised  by  Wiggers  on 
this  principle.  ,      -.li 

Hiirthle's  spring  manometer  consists  of  a  small  drum  covered  with 
an  indiarubber  membrane,  loosely  arranged  so  as  not  to  vibrate  with 
a  period  of  its  own.  The  drum  is  connected  with  the  heart  or  with 
a  vessel,  and  the  blood-pressure  is  transmitted  to  a  steel  spring  by 
means  of  a  light  metal  disc  fastened  on  the  membrane.     The  spring 


94  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

acts  on  a  writing  lever.  The  instrument  is  so  constructed  that  for  a 
given  change  of  pressure  the  quantity  of  liquid  displaced  is  as  small 
as  possible,  and  it  is  on  this  that  its  capacity  to  follow  sudden  varia- 
tions of  pressure  chiefly  depends.  The  manometer  is  connected  with 
the  cavity  of  the  heart  by  an  appropriately  curved  cannula  of  metal 
or  glass,  which,  after  being  filled  with  some  liquid  that  prevents  co- 
agulation (Practical  Exercises,  p.  211),  is  pushed  through  the  jugular 
vein  into  the  right  auricle  or  ventricle,  or  through  the  carotid  artery 
and  aorta  into  the  left  ventricle.  Some  observers  fill  only  the  cannula 
with  fluid,  and  leave  the  capsule  of  the  elastic  niimomcter  and  as  much 
of  the  connections  as  possible  full  of  air.  Others  fill  the  whole  system 
with  liquid.  And  around  the  question  of  the  relative  merits  of  '  trans- 
mission '  by  liquid  and  by  air  has  raged  a  controversy  which,  however, 
now  shows  signs  of  coming  to  an  end.  For  there  is  reason  to  suppose 
that  the  character  of  the  curves  obtained  is  modified  among  other 
circumstances  by  the  manner  in  which  the  pressure  is  transmitted,  as 
it  is  certainly  modified  by  the  dimensions  and  mass  of  the  moving  parts 
and  the  method  of  recording.  As  Wiggers  has  pointed  out,  the  differ- 
ences in  the  records  obtained  by  different  observers,  even  with  the  latest 
methods  of  optical  registration,  are  determined  largely  by  the  sensitive- 
ness and  degree  of  damping  of  the  manometer. 

The  Ventricular  Pressure-Curve. — Thus,  the  pressure-curve  of  the 
ventricle,  according  to  most  of  those  who  have  employed  mano- 
meters with  hquid  transmission  and  small  inertia  of  the  moving 
parts  (Fig.  33),  remains  after  the  first  abrupt  rise,  which  undoubtedly 
corresponds  to  the  ventricular  systole,  well  above  the  abscissa  line 
for  a  considerable  time,  and  then  descends  somewhat  less  suddenly 
than  it  rose.  This  systohc  '  plateau,'  although  usually  broken  by 
minor  heights  and  hollows,  which  may  be  partly  due  to  inertia  oscilla- 
tions of  the  liquid  or  the  recording  apparatus,  would  indicate  that 
the  ventricular  pressure,  after  its  first  swift  rise,  maintained  itself  at 
a  considerable  height  throughout  the  greater  part  of  the  systole. 
The  tracings  yielded  by  most  of  the  manometers  with  air  trans- 
mission show  the  same  suddenness  in  the  first  part  of  the  upstroke 
and  the  last  part  of  the  descent — that  is,  the  same  abruptness 
in  the  beginning  of  the  contraction  and  the  end  of  the  relaxa- 
tion. But  they  differ  totally  in  the  intermediate  portion  of  the 
curve,  which,  climbing  ever  more  gradually  as  it  nears  its  apex, 
remains  but  a  moment  at  the  maximum,  then  immediately  descend- 
ing forms  a  '  peak,'  and  not  a  plateau.  It  ought  to  be  distinctly 
understood,  however,  that  the  use  of  the  term  '  plateau  '  must  not  be 
taken  to  imply  that  the  pressure  remains  constant  and  the  curve 
parallel  to  the  abscissa  during  this  interval. 

Wiggers,  using  the  optical  method  of  recording  the  pressure- 
curve  in  the  right  ventricle  (p.  93),  finds  that  when  the  auricular 
pressure  and  the  pressure  in  the  pulmonary  artery  are  normal  the 
curve  of  intraventricular  pressure  may  be  divided  into  (i)  an  auric- 
ular period;  (2)  a  period  of  rising  pressure  while  the  ventricle  is 
contracting  and  its  cavity  is  closed  by  the  auriculo- ventricular  and 
semilunar  valves;  (3)  an  ejection  period  during  which  the  pressure 


MECHANICS  OF  THE  HEART-BEAT 


95 


still  rises,  reaches  a  summit,  and  then  slowly  falls;  and  (4)  a  relaxa- 
tion period  (Fig.  32). 

Without  entering  further  into  a  technical  discussion,  we  may  say 


CiirotifJ 


e 

■     r 

d'  , 
<i  ;       , 

!             1 

\ 

Fig.  32. —  Intraventricular  Pressure  Curves  with  Optical  Recording  (Wiggers).  Three 
types  of  normal  curves  are  reproduced,  taken  with  manometers  of  different 
degrees  of  sensitiveness.  The  second  at  the  left-hand  side  was  taken  with  the 
least  sensitive,  a — b,  auricular  systolic;  b — d,  isometric  period,  during  which 
the  auriculo-ventricular  and  the  semilunar  vaU'es  are  both  closed;  d — f,  ejection 
period;  after/,  diastole. 

the  bulk  of  the  evidence  goes  to  show  that  the  plateau  is  not,  as  the 
advocates  of  the  peak  have  claimed,  an  artificial  phenomenon,  but 
does  in  reality  correspond  to  that  continuation  of  the  systole  of  the 


Fig.  33. — Simultaneous  Record  of  Pressure  in  Left  Ventricle  (V)  and  Aorta  (A). 
(Hiirthle.)  The  tracings  were  fallen  with  elastic  manometers;  0  indicates  a 
point  just  before  the  closure  of  the  mitral  valve;  i,  the  opening  of  the  semilunar 
valve;  2,  beginning  of  the  relaxation  of  the  ventricle;  3,  the  closure  of  the  semi- 
lunar valve;  4,  the  opening  of  the  mitral  valve.  The  ventricular  curve  shows 
a  *  plateau.' 

ventricle,  that  dogged  grip,  if  we  may  so  phrase  it,  which  it  seems  to 
maintain  upon  the  blood  after  the  greater  portion  of  it  has  been 
expelled. 


qg        the  circulation  of  the  blood  and  lymph 

This  conclusion  is  essentially  in  accordance  with  the  results  of 
Chauveau  and  Marej',  obtained  long  ago  by  means  of  their  '  cardiac 
sound,'  which  was  in  principle  an  elastic  manometer. 

It  consisted  of  an  ampulla  of  indiarubbcr,  supported  on  a  frame- 
work, and  communicating  with  a  long  lube,  which  was  connected  with 
a  recording  tambour.  The  ampulla  was  introduced  into  the  heart  (ot 
a  horse)  through  the  jugular  vein  or  carotid  arter\'  in  the  way  already 
described.  Sometimes  a  double  sound  was  employed,  armed  witli 
two  ampullae,  placed  at  such  a  distance  from  each  other  that  when 
one  was  in  the  right  ventricle  the  other  was  in  the  auricle  of  the  same 
side.  Each  ampulla  communicated  by  a  separate  tube  in  the  common 
stem  of  the  instrument  with  a  recording  tambour,  and  the  writing 
points  of  the  two  tambours  were  arranged  in  the  same  vertical  line. 
When  any  change  in  the  blood-pressure  takes  place,  the  degree  of 
compression  of  the  ampullae  is  altered,  and  the  change  is  transmitted 
along  the  air-tight  connections  to  the  recording  tambours. 

On  most  of  the  endocardiac  pressure  tracings  taken  with  modern 
manometers,  whether  the  curves  belong  to  the  tj^pe  of  the  peak  or  of 
the  plateau,  no  sudden  change  of  curvature,  no  nick,  or  crease,  or 
undulation  reveals  the  moment  of  opening  or  closure  of  any  valve. 
This  has  been  considered  by  some  writers  a  striking  tribute  to  the 
smooth  working  of  the  cardiac  pump.  There  is  reason  to  think, 
however,  that  the  smoothness  of  the  curve  is  still  in  some  degree 
artificial,  and  on  some  of  the  records  obtained  by  optical  methods 
(Fig.  32)  indications  of  changes  of  curvature,  associated  with  the 
action  of  the  valves,  may  be  observed.  But  even  in  the  absence  of 
such  indications,  by  experimentally  graduating  a  pair  of  elastic 
manometers,  and  obtaining  with  them  simultaneous  records  of  the 
pressure  in  auricle  and  ventricle,  or  by  using  a  '  differential  '  mano- 
meter, in  which  the  pressures  in  two  ca\nties  are  opposed  to  each 
other,  so  that  the  movement  of  the  membrane  corresponds  to  their 
difference,  we  can  calculate  at  what  points  of  the  ventricular  curve 
the  pressure  is  just  greater  than  and  just  less  than  the  pressure  in  the 
auricle.  The  first  point,  it  is  evident,  will  correspond  to  the  instant 
at  which  the  mitral  or  tricuspid  valve,  as  the  case  may  be,  is  closed, 
and  the  second  to  the  instant  at  which  it  is  opened.  And  in  like 
manner,  by  comparing  the  pressure-curve  of  the  aorta  with  that  of 
tht.;  left  ventricle,  the  moment  of  opening  and  closure  of  the  semi- 
lunar valves  may  be  determined  (Figs.  33  and  34).  According  to  the 
best  observations,  the  closure  of  the  semilunar  valves  takes  place  at 
a  time  corresponding  to  a  point  on  the  upper  portion  of  the  descend- 
ing limb  of  the  intraventricular  curve. 

On  the  blood-pressure  curve  of  the  aorta,  simultaneously  registered, 
the  corresponding  point  is  near  the  bottom  of  the  so-called  '  aortic  ' 
notch  (p.  105)  which  precedes  the  dicrotic  elevation.  For  clinical 
purposes,  in  man  the  moment  of  closure  of  the  semilunar  valves 
(denoted  by  the  abbreviation  S.C.  point)  may  be  taken  as  0-03  second 
before  the  bottom  of  the  aortic  notch  in  sphygniographic  tracings 
from  the  carotid,  this  being  approximately  the  a\erage  time  occupied 


MECHANICS  OF  THE  HEART-BEAT  97 

by  the  pulse-wave  in  travelling  from  the  aorta  to  the  carotid.  The 
S.C.  point,  the  A.O.  point,  or  moment  of  opening  of  the  auriculo- 
ventricular  valves,  and  the  Leginnhig  of  the  ventricular  systole,  are 
three  important  points  of  reference  in  the  measurement  and  inter- 
pretation of  pulse -tracings  in  clinical  work.  The  A.O.  point  in  man 
may  be  taken  as  a  point  '  0-03  second  in  advance  of  the  summit  of 
the  dicrotic  wave  '  on  the  carotid  pulse-tracing  (Lewis).  But  this  is 
the  most  difficult  of  the  three  standard  points  to  determine  clinically 
with  anything  like  accuracy. 

The  study  of  tlie  curves  of  endocardiac  pressure  enables  us  to  add 
precision  in  certain  points  to  the  description  of  the  events  of  the 
cardiac  cycle  which  we  have  already  given,  and,  as  regards  the 
ventricles,  to  divide  the  cycle  into  four  periods: 

(i)  A  period  during  which  the  pressure  is  lower  in  the  ventricles  than 
either  in  the  auricles  or  the  arteries,  and  the  auricido -ventricular  valves 
are  consequently  open,  and  the  semilunar  valves  closed.  This  is  the 
period  of  '  filling  '  of  the  heart,  or  the  pause. 

(2)  A  period,  beginning  with  the  ventricular  systole,  during  which  the 
pressure  is  increasing  abruptly  in  the  ventricles,  while  they  are  as  yet 
completely  cut  off  from  the  auricles  on  the  one  hand  and  the  arteries  on 
the  other  by  the  closure  of  both  sets  of  valves.  This  is  the  period  of 
'  rising  pressure,'  during  which  the  ventricles  are,  so  to  say,  '  getting  up 
steam.'  The  interval  between  the  beginning  of  the  ventricular  systole 
and  the  opening  of  the  semilunar  valves  is  termed  the  '  presphygmic  ' 
interval. 

(3)  A  period  during  which  the  pressure  in  the  ventricles  overtops  that 
in  the  arteries,  and  the  semilunar  valves  are  open,  while  the  auriculo- 
ventricular  valves  remain  shut.  This  is  the  period  of  '  discharge  '  or 
*  sphygmic  '  period. 

(4)  A  period  during  which  the  pressure  in  the  ventricles  is  again  less 
than  the  arterial,  while  it  still  exceeds  the  auricular  pressure,  and  both 
sets  of  valves  are  closed.  This  is  the  period  of  rapid  relaxation.  The 
interval  between  the  closure  of  the  semilunar  and  the  opening  of  the 
auric  ulo-ventricular  valves  is  sometimes  called  the  '  post-sphygmic  ' 
interval. 

Of  the  four  periods,  the  second  and  fourth  are  exceedingly  brief. 
The  third  is  relatively  long  and  constant,  being  but  slightly  depen- 
dent on  either  the  pulse-rate  or  the  pressure  in  the  arteries.  The 
duration  of  the  first  period  varies  inversely  as  the  frequency  of  the 
heart ;  with  the  ordinary  pulse-rate  it  is  the  longest  of  all. 

From  records  taken  in  a  person  with  a  defect  in  the  chest-wall  which 
rendered  the  heart  accessible  the  following  results  were  obtained  as 
to  the  duration  of  the  various  events  of  the  cardiac  cycle :  First  and 
fourth  periods  together,  0-445;  third  period,  0*254;  second  period  (pre- 
sphygmic interval),  0'05i  second,  the  pulse-rate  being  80  a  minute 
(Tigerstedt).  In  another  case  with  a  similar  defect  the  first  period 
lasted  0-32,  the  fourth  period  (post-sphygmic  interval)  0'o6,  the  second 
and  third  periods  together  0-4,  and  the  auricular  systole  0*1  second, 
the  pulse-rate  being  66. 

7 


98 


Tlin  CIRCULATION  OF  THE  BLUOD  ASD  LYMPH 


The  Auricular  (and  Venous)  Pressure-Curve. — The  fluctuations  of 
pressure  in  the  aurieUs,  allhou^'h  cfjn fined  witliin  narrower  hmits 
tlian  in  the  ventricles,  are  of  equal  interest.  They  have  been  studied 
in  considerable  detail  both  in  animals  and  by  indirect  methods  in 
man.  No  fewer  than  three  distinct  elevations  or  '  positive  waves,' 
separated  or  followed  by  three  depressions  or  '  negative  waves,' 
have  been  described  on  the  curve  of  intra-auricular  pressure. 

The  first  elevation  corresponds  to  the  systole  of  the  auricle.  The 
second  coincides  with  the  onset  of  the  ventricular  systole,  and  is 


Fig.  34. — Schematic  Comparison  of  Pressure  Curves  in  the  Auricle  (or  Superior 
Vena  Cava),  the  Ventricle  and  the  .\orta  in  the  1  )og  (Fredericq).  In  the  auricular 
curve  are  to  be  distinguished  ab,  the  first  positive  or  pres>-stolic  wave,  corre- 
sponding to  the  auricular  systole  (o  wave);  6ft'  or  be,  second  positive  wave  or 
fcrst  systolic  wave,  which  corresponds  with  the  beginning  of  the  ventricular 
systole  (c  wave);  b'cd,  the  steep  negative  wave  of  which  the  beginning  corre- 
sponds to  the  opening  of  the  semilunar  valves;  def.  the  third  positive  wave 
(v  wave),  more  or  less  serrated,  ending  at  /.  the  point  of  opening  of  the  auriculo- 
ventricular  valves:  fg,  a  negative  wave  corresponding  to  the  relaxation  of  the 
ventricle.  The  time  is  indicated  along  the  abscissa  in  tenths  of  a  second,  the 
pressure  along  the  vertical  axis  at  the  left  in  mm.  of  mercury. 

probably  due  to  the  sudden  bulging  of  the  auriculo- ventricular  valve 
into  the  auricle,  or  even  to  a  slight  regurgitation  of  blood  from  the 
ventricle  through  the  valve  before  it  has  completely  closed.  The 
cause  of  the  third  elevation,  which  occurs  during  the  period  occupied 
in  the  ventricular  pressure-curve  by  the  plateau,  is  less  clearly  made 
out.     In  man,  the  events  taking  place  in  the  right  auricle  during  its 


MECHANICS  OF  THE  HEART-BEAT 


99 


?.ystole  can  be  followed  to  some  extent  by  recording  the  venous  pulse 
in  the  jugular  veins,  especially  the  internal  jugular,  at  the  root  of  the 
the  neck  (Fig.  36).  Successful  tracings  can  be  obtained,  not  only  in 
certain  pathological  conditions,  but  in  many  normal  individuals,  and 
it  is  probably  only  a  matter  of  improved  technique  to  obtain  them 
in  all.  The  jugular  venous  pulse-tracing,  like  the  intra-auricular 
pressure-curve,  shows  in  general  three  well-marked  elevations  and 
three  depressions,  and  there  is  good  evidence  that,  broadly  speaking, 
these  features  of  the  jugular  curve  corre- 
spond as  regards  their  origin  with  the 
changes  of  pressure  in  the  auricle. 

Identical  features  are  observed  on  records 
of  the  normal  venous  pulse  taken  from  veins 
of  dogs  near  the  heart,  and  on  records  of  tlie 
pulse  taken  by  a  sound  in  the  oesophagus. 
The  oesophagus  pulse  is  related  to  the  pul- 
sation of  the  left  auricle,  the  venous  pulse  to 
the  changes  of  pressure  in  the  right  auricle. 
The  first  elevation,  called  the  a  (auricular) 
or  p  (presystolic)  wave,  begins  with,  and  is 
the  result  of,  the  auricular  systole.  It  is 
probably  produced  by  stasis  in  the  veins  due 
to  the  contraction  of  the  auricle,  as  well  as 
to  the  effect  of  the  impact  of  the  auricular 
systole.  The  downstroke  on  the  curve  which 
succeeds  this  first  elevation  corresponds  to 
the  first  negative  wave  or  presystolic  fall, 
which  is  due  to  the  auricular  relaxation .   This 

Fig.  35. — Schema  of  Events  in  the  Cardiac  Cyclt, 
in  Relation  to  the  Venous  Pulse  (Ewing).  i.  Tracing 
from  Vena  Cava,  showing  presystolic  rise  and  fall, 
PR.  PF  (a  wave)  ;  SR.  systolic  rise  and  fall 
(c  wave);  O',  first  onflow  wave  and,  DR,  diastolic 
rise  and  fall  (t;  wave);  O*,  second  onflow  wave; 
2.  auricular  myogram  (tracing  of  contraction  of 
auricle);  3,  ventricular  myogram  (tracing  of  con- 
traction of  ventricle);  4,  record  of  the  movement 
of  the  aurictilo-ventricular  septum;  5,  ventricular 
volume  curve  (plethysmographic  curve  of  dis- 
charge of  the  ventricles ) ;  6,  curve  of  aortic  pressure ; 
7,  intraventricular  pressure -curve. 

fall  of  pressure  is  terminated  by  a  rise — the  second  positive  wave — which 
begins  at  the  same  moment  as  the  ventricular  systole,  and  is  the  ex- 
pression on  the  venous  pulse-curve  of  that  second  elevation  of  the 
intra-auricular  pressure  whose  probable  cause  has  already  been  found 
in  the  sharp  protrusion  of  the  auriculo-ventricular  valve  into  the 
auricular  cavity  under  the  stress  of  the  ventricular  systole  while  the 
semilunar  valve  are  still  closed.  In  addition  to  the  actual  bulgmg  of 
the  auriculo-ventricular  valves,  the  impact  of  the  sudden  contraction 
of  the  ventricle  on  its  contents  transmitted  through  the  valve  to 
the  contents  of  the  auricle  may  aid  in  producing  the  rise  of  venous 
pressure.     The  second  elevation  has  been  termed  the  c  wave  by  certain 


too  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

writers,  who  studRci  it  on  jugular  tracings,  because  they  supposed  it 
to  be  simply  transmitted  from  the  pulse  in  the  acijacent  carotid  artery. 
This,  however,  has  been  shown  to  be  erroneous,  although  it  is  true 
enough  that  pulsations  transmitted  from  the  great  arteries  of  the 
thorax  and  neck  may  augment  or  distort  the  second  elevaticjn  of  the 
venous  pulse.  It  has  been  proposed  tiiat  the  second  positive  wave 
should  be  called  the  s  (systolic)  wave.  It  lasts  practicallv  throughout 
the  presphygmic  period  of  the  ventricular  systole;  the  opening  of  the 
semilunar  valves,  as  indicated  by  the  appearance  of  the  pulse  in  the 
innominate  artery,  occurs  just  before  the  end  of  the  second  elevation 
(Porter,  Ewing,  etc.).  The  rapid  discharge  of  the  ventricle  through  the 
open  semilunar  valves,  and  its  consequent  diminution  in  size,  especially 
in  its  longitudinal  diameter,  is  associated  with  a  dilatation  of  the 
auricular  cavity  and  a  fall  of  intra-auricular  pressure  which  is  expressed 
on  the  venous  pul^-^ -curve  as  the  downstroke  succeeding  the  second 
positive  wave.  Thi:i  second  negative  wave  gives  place  to  the  third 
positive  wave,  due  to  the  steady  inflow  of  blood  into  the  auricle 
from  the  veins.     According  to  Ewing,  the  third  positive  wave,  the  v 

V£_Yvix^^    Pulse  »"  ^^  M^^ 

Fig.  36. — Normal  .\p(X  and  Vonous  Pulses,  Photographically  Recorded  (reduced 
nine-tenths)  (Niles  and  Wipgers).  P,  presystolic  (or  a)  wave  ;  S,  systolic  (or  c) 
wave  ;  Dj,  first  diastolic  (v)  wave.  In  this  venous  record  a  second  diastolic 
wave,  D2,  is  present.  S*,  vibrations  corresponding  to  first  sound  ;  S^,  to  second 
sound. 

wave  of  Mackenzie,  really  consists  of  t%vo  waves,  the  "  first  onflow 
wave  "  and  the  "  diastolic  rise  "  or  rf  wave.  This  last  is  terminated  by 
the  third  negative  wa\e  or  diastolic  fall  of  venous  pressure  coincident 
with  the  opening  of  the  auriculo- ventricular  valves.  The  re-examina- 
tion of  the  venous  pulse  with  apparatus  of  which  the  moving  parts 
have  an  exceedinglv  small  mass  and  optical  methods  of  recording  (see 
p.  93)  has  confirmed  the  existence  on  the  phlebogram  of  three  essential 
waves.  A  fourth  is  sometimes  added  when  the  cardiac  cycle  is  long. 
The  first  wave  is  clearly  presystolic,  the  second  systolic,  as  agreed  by 
all  observers  who  have  used  polygraph  tracings.  The  third  wave, 
however,  is  diastolic,  as  is,  of  course,  the  fourth  when  it  exists.  The 
position  of  these  waves  can  be  definitely  fixed  by  simultaneous  heart 
apex  tracings,  since  on  such  optically  recorded  cardiograms  the  heart- 
sounds  are  represented  by  distinct  vibrations,  except  where  the  chest 
wall  is  too  thick  or  the  heart  overlaid  by  emphysematous  lung  Some- 
times heart-sound  vibrations  may  be  present  also  on  the  record  of  the 
venous  pulse  (Wiggers). 


MECHANICS  OF  THE  CIRCULATION  I\   THE   VESSELS     loi 

The  jugular  curve,  when  properly  interpnted,  affords  valuable 
information  as  to  the  action  of  the  auricle,  information  of  the  same 
kind  as  that  afforded  by  the  arterial  pulse-tracing  and  the  cardiogram 
as  to  the  action  of  the  ventricle.  In  the  interpretation  of  the  venous 
piilse-tracings,  a  simultaneous  record  of  tlie  radial  or.  better,  the 
carotid  pulse  or  of  the  apex-beat  is  always  important,  and  often 
indispensable,  for  it  enables  the  time  of  onset  of  the  ventricular 
systole  to  be  marked  upon  the  phlebogram  (the  venous  trace),  and 
this  facihtates  the  identification  of  the  a  wave,  which  must  immedi- 
ately precede,  and  the  c  or  s  wave,  which  should  coincide  with  the 
beginning  of  the  contraction  of  the  ventricle.  The  student  must, 
however,  be  warned  that  the  proper  interpretation  of  such  tracings 
in  the  study  of  cardiac  disease  is  often  difficult  and  requires  special 
knowledge  and  training.* 

Suction  Action  of  the  Ventricle. — We  have  alrea<1y  said  that  a 
negative  pressure  may  be  detected  in  the  cardiac  cavities  by  means  of 
a  special  form  of  mercurial  manometer.  This  is  confirmed  by  an 
examination  of  the  tracings  written  by  good  elastic  manometers,  for 
the  curves  of  both  ventricles  may  often  descend  below  the  line  of 
atmospheric  pressure.  The  cause  of  this  negative  pressure  has  been 
much  discussed.  In  part  it  may  be  ascribed  to  the  aspiration  of  the 
thoracic  cage  when  it  expands  during  inspiration  (p.  226).  But  since 
the  pressure  in  a  vigorously-beating  heart  may  still  become  negative, 
when  the  thorax  has  been  opened,  and  the  influence  of  the  respiratory 
movements  eliminated,  we  must  conclude  that  the  recoil  of  the  some- 
what narrowed,  or  at  least  distorted,  auriculo-ventricular  rings,  and  of 
elastic  structures  in  the  walls  of  the  ventricles,  exerts  of  itself  a  certain 
suction  upon  the  blood.  This,  however,  is  not  an  important  factor  in 
the  maintenance  of  the  circulation. 

Section  III. — Physical  or  Mechanical  Phenomena  of  the 
Circulation  in  the  Bloodvessels. 

The  Arterial  Pulse. — At  each  contracton  of  the  heart  a  quantity  of 
blood,  probably  varjang  within  rather  wide  limits  (p.  139),  is  forced 
into  the  already  full  aorta.  If  the  walls  of  the  bloodvessels  were 
rigid,  it  is  evident  (p.  85)  that  exactly  the  same  quantity  would  pass 
at  once  from  the  veins  into  the  right  auricle.  The  work  of  the 
ventricle  would  all  be  spent  within  the  time  of  the  systole,  and  only 
while  blood  was  being  pumped  out  of  the  heart  would  any  enter  it. 
Since,  however,  the  vessels  are  extensible,  some  of  the  blood  forced 
into  the  aorta  during  the  systole  is  heaped  up  in  the  arteries,  beyond 
which,  in  the  narrow  arterioles  and  in  the  capillary  tract,  with  its 
relatively  great  surface,  the  chief  resistance  lies.  The  arteries  are 
accordingly  distended  to  a  greater  extent  than  before  the  systole, 
and,  being  elastic,  they  keep  contracting  upon  their  contents  until 
the  next  systole  over-distends  them  again.  In  this  way,  during  the 
pause,  the  walls  of  the  arteries  are  executing  a  kind  of  elastic  sj^stole, 

*  The  necessary  details  must  be  sought  in  such  works  as  Mackenzie'* 
'  Diseases  of  the  Heart.' 


I02  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

and  driving  the  bhxjd  on  into  the  capillaries.  The  W(jrk  done  by  the 
ventricle  is,  in  fact,  i)artly  stored  up  as  potential  energy  in  tiie  tense 
arterial  wall,  and  this  energy  is  being  continually  transformed  into 
work  upon  the  blood  during  the  pause,  the  heart  continuing,  as  it 
were,  to  contract  by  proxy  during  its  diastole.  Thus,  the  blood 
progresses  along  the  arteries  in  a  series  of  waves,  to  which  the  name 
of  '  blood-waves  '  or  '  pulse-waves  '  may  be  given.  Wherever  the 
pulse-wave  spreads  it  manifests  itself  in  various  ways — by  an  increase 
of  blood-pressure,  an  increase  in  the  mean  velocity  of  the  blood-flow, 
an  increase  in  the  volume  of  organs,  and  by  the  visible  and  palpable 
signs  to  which  the  name  of  pulse  is  commonly  given  in  a  restricted 
sense.  The  intermittence  in  the  flow  with  which  the  pulse-wave  is 
necessarily  associated  is  at  its  height  at  the  beginning  of  the  aorta. 
In  middle-sized  arteries,  such  as  the  radial,  it  is  still  well  marked,  but 
it  dies  away  as  the  capillaries  are  reached,  and  only  under  special 
conditions  passes  on  into  the  veins,  where,  however,  as  has  just  been 
mentioned,  pulsatory  phenomena  of  a  different  origin  maybe  detected. 

The  pulse  was  well  known  to  the  Greek  physicians,  and  used  by 
them  to  a  certain  extent  as  an  indication  in  practical  medicine. 
Harvey  demonstrated  with  some  clearness  the  relation  of  the  pulse 
to  the  contraction  of  the  heart,  but  Thomas  Young  was  the  fir.st  to 
form  a  proper  conception  of  it  as  the  outward  token  of  a  wave  prop- 
agated from  heart  to  periphery. 

When  the  finger  is  placed  over  a  superficial  artery  like  the  carotid, 
the  radial,  or  the  temporal,  a  throb  or  beat  is  felt,  which,  without 
measurement,  seems  to  be  exactly  coincident  with  the  cardiac 
impulse.  In  certain  situations  the  pulse  can  be  seen  as  a  distinct 
rhythmical  rise  and  fall  of  the  skin  over  the  vessel.  The  throbbing 
of  the  carotid,  especially  after  exertion,  is  familiar  to  everyone,  and 
the  beat  of  the  ulnar  artery  can  be  easily  rendered  \'isible  by  extend- 
ing the  hand  sharply  on  the  wrist.  When  the  pulse  is  felt  by  the 
finger,  it  is  not  the  expansion,  but  the  hardening  of  the  wall  of  the 
vessel,  due  to  the  increase  of  arterial  pressure,  that  is  perceived ;  and 
even  a  superficial  artery,  when  embedded  in  soft  tissues  so  that  it 
cannot  be  compressed,  gives  no  token  of  its  presence  to  the  sense  of 
touch.  Sometimes  an  artery  is  longitudinally  extended  by  the 
pulse- wave,  and  this  extension  may  be  far  more  conspicuous  than 
the  lateral  dilatation.  This  is  particularly  seen  when  one  point  of 
the  vessel  is  fixed  and  a  more  distal  point  offers  some  obstruction  to 
the  blood-flow,  as  at  a  bifurcation  or  in  an  artery  which  has  been 
ligatured  and  divided. 

By  means  of  the  sphygmograph,  the  lateral  movements  of  the 
arterial  wall,  or,  rather,  in  man,  the  movements  of  the  skin  and  other 
tissues  lying  over  the  bloodvessel,  can  be  magnified  and  recorded. 

It  would  be  very  unprofitable  to  enumerate  all  the  sphygmographs 
which  ingenuity  has  invented  and  found  names  for.     The  first  attempt 


MECHANICS  OF  THE  CIRCULATION  IN  THE    VESSELS 


if^3 


Fig-  37- — Scheme  of  Marey's  Sphygmo- 
graph.  A,  toothed  wheel  connected  with 
axle  H.  and  gearing  into  toothed  upright 
B;  C.  ivory  pad  which  rests  over  blood- 
vessel and  is  pressed  on  it  by  moving  G. 
a  screw  passing  through  the  sprin'g  J ; 
E,  writing-lever  attached  to  axle  H,  and 
moved  by  its  rotation.  E  writes  on  D,  a 
travelling  surface  moved  bv  clockwork  F. 


to  magnify  the  movements  of  the  pulse  was  made  by  loosely  attaching 

a  thin  fibre  of  glass  or  wax  to  the  skin  with  a  little  Jard,  in  order  to 

demonstrate  the  venous  pulse  which  appears  under  certain  conditions. 

In  all  modem  sphygmographs  there  is  a  part,  usually  button-shaped, 

which  is  pressed  over  the  artery  by  means  of  a  spring,  as  in  Marey's 

and   Dudgeon's  sphygmographs, 

or  by  a  weight,  or  by  a  column  of 

liquid.     In  Marey's   instrument, 

the  button  acts  upon  a  toothed 

rod  gearing  into  a  toothed  wheel, 

to  which  a  lever,  or  a  system  of 

levers,  is  attached.    The  lever  has 

a  writing-point  which  records  the 

movement  on  a  smoked  plate,  or 

a    plate    covered    with   smoked 

paper,  drawn  uniformly  along  by 

clockwork  (Figs.  37,  loo).  Special 

forms  of  sphygmographs  (poly- 
graphs) have  been  devised,  which. 

by  the  addition  of  one  or  more 

recording  tambours,   permit  the 

simultaneous  record  of  movements  from  two  or  more  points  of  the 

vascular  system — for  example,  the  radial  artery  and  the  jugular  vein, 

or  the  radial  or  carotid  artery,  jugular  vein,  and  the  apex  of  the  heart. 

In  rare  cases,  with  de- 
fect of  the  chest  wall, 
a  tracing  may  be  ob- 
tained even  from  the 
aorta  (Fig.  40). 

In  a  normal  arterial 
pulse-tracing  (Fig.  38) 
the  ascent  or  ana- 
crotic limb  is  abrupt 
and  unbroken;  the 
descent  or  katacrotic 
limb  is  more  gradual, 
and  is  interrupted  by 
one,  two,  or  even 
three  or  more,  second- 
SiTy  wavelets.  The 
most  important  and 
constant  of  these  is 
the  one  marked  3, 
which  has  received  the 
name  of  the  dicrotic 
wave.  Usually  less 
marked,    and    some- 


Fig.  38. — Pulse-Tracings,  i,  primary  elevation ;  2,  predi- 
crotic  or  first  tidal  wave  ;  3,  dicrotic  wave.  The 
depression  between  2  and  3  is  the  dicrotic  or  aortic 
notch;  3  is  better  marked  in  B  than  in  A.  C,  dicrotic 
pulse  with  low  arterial  pressure;  D,  pulse  with  high 
arterial  pressure — summit  of  primary  elevation  in  the 
form  of  an  ascending  plateau.  E,  systolic  anacrotic 
pulse;  the  secondary  wavelet  a  occurs  during  the 
upstroke  corresponding  to  the  ventricular  systole. 
F,  presystolic  anacrotic  pulse;  a  occurs  just  before 
the  systole  of  the  ventricle.  In  this  rarer  form  of 
anacrotism,  a  may  sometimes  be  due  to  the  auricular 
systole  when  the  aortic  valves  are  incompetent. 


times  absent,  is  the 
wavelet  2  between  the  dicrotic  elevation  and  the  apex  of  the  curve. 
It  is  generally  termed  the  predicrotic  wave.  Oscillations,  due  to 
vibrations    of    the   recording   apparatus,  appear  on   many  pulse- 


I04  TUi:  CIRCULATIOS  Ul-   THE  liLOOD  AND  LYMFH 

tracings,  and  it  is  important  to  rt'cognizc  their  cause,  so  that  no 
weight  may  be  given  to  them. 

In  the  explanation  of  the  pulse-tracing,  a  fundamental  fact  to  be 
borne  in  iniiul  is  the  elasticity  of  the  vessels.     When  an  incompres- 
sible fluid  like  water  is  injected  bj-  an  intermittent  pump  into  one  end 
ol  an  elastic  tube  a  wave  is  set  up,  which  is  transmitted  to  the  other 
end  of  the  tube.     It  is  a  jw.sitive  wave — tliat 
is,  it  causes  an   increase  of  pressure  and  an 
expansion  of   the    tube   wherever  it  arrives; 
and  if  a  series  of  levers  be  placed  in  contact 
with    the    tube,    they  will    rise  and   sink    in 
succession  as  the  wave  passes  them.     After 
the  passage  of  this  primary  wave  the  walls  of 
the  tube,  instead  of  coming  instantly  to  rest 
in  their  original  position,  regain  it  by  a  series 
of  oscillations,  first  shrinking  too  much,  then 
expanding  too  much,  but  at  each  movement 
coming  nearer  to  the  position  of  equilibrium. 
Each  vibration  of  the  elastic  wall  is  of  course 
accompanied  by  a  change  of  pressure  in  the 
contents  of  the  tube.     This  change  of  pressure 
runs  along  the  tube  as   a   wave;   and   such 
waves,  succeeding  the  primarj'  one,  may  be 
1  ig.      ■(     -  Pulse  -  Tracmgs    t;a-llcd   secondary  waves  of  oscillation.     These 
from  ^  Different     Arteries    secondary  waves  will  be  set  up  in  an  elastic 
(V.  Frey).      T,  temporal;    sj^stem  whether  the  distal  end  of  the  system 
i?,  radial :  P,  artery  of  foot,     be  closed  or  open.     But   if   it  is   closed,    or 
sufficiently  obstructed   without   being   actu- 
ally closed,  secondary  waves  of  another  kind  may  also  be  generated, 
the  primar)-^  waNC  on  arri^•ing  at  the  distal  end  being  reflected  there. 
The  reflected  wave  running  back  towards  the  central  end  may  there 
again  undergo  reflexion,  and  pass  out  once  more  towards  the  distal  end 
as  a  centrifugal,  twice-reflected  wave.     When  the  liquid  ceases  to  enter 
the  tube  at  the  end  of  the  stroke,  a  wave  of  diminished  pressure^a 
negative  wave — is  generated  at  the  central 
end,  and  is  propagated  to  the  distal  end, 
where  it  may  be  reflected  just  like  the  posi- 
tive wave. 

AlthouG^li  under  certain  conditions  the 
dicrotic  wave  is  so  marked  tliat  the  double 
beat  of  the  pulse  was  discovered  and 
named  by  physicians  long  before  the  in- 
vention of  any  sphygmograph,  perhaps 
no  physiological  question  has  been  more 
discussed  or  is  less  understood  than  the  F»g-  40.  — Puise-Curve  from 
mechanism  of  its  production.  Two  ^^*°  "^""^^  (^^^"  '^'8«''- 
points,  however,  seem  to  be  clear :  (i)  That 

it  is  a  centrifugal,  and  not  a  centripetal,  wave — that  is  to  say,  it 
travels  away  from,  and  not  towards,  the  heart ;  (2)  that  the  aortic 
semilunar  valves  have  something  to  do  with  its  origin. 

It  is  not  a  centripetal  wave,  for  in  tracings  taken  at  all  parts  of  the 
arterial  path,  no  matter  what  the  distance  from  the  heart  and  the 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS       105 

capillaries  {e.g.,  the  origin  of  the  carotid  and  the  radial  at  the  wrist), 
the  dicrotic  wave  is  separated  by  the  same  interval  from  the  begin- 
ning of  the  primary  elevation.  This  can  only  be  explained  by 
supposing  that  it  has  the  same  point  of  origin,  and  travels  with  the 
same  velocity  and  in  the  same  direction  as  the  primary  wave.  It  is 
not,  then,  a  wave  reflected  directly  from  the  peripheral  distribution 
of  the  artery  from  which  the  pulse-tracing  is  taken. 

Some  writers  have  contended  that  it  is  a  centrifugal  twice -re  fleeted 
wave,  and,  indeed,  traces  of  such  waves  may  be  detected  in  the  vessels 
of  newly-killed  animals  when  changes  of  pressure  of  the  same  order 
of  magnitude  as  the  arterial  pulse  are  artificially  produced  by  a  pump 
and  recorded  by  elastic  manometers  connected  with  the  interior  of 
an  artery.  It  has  been  supposed  that  these  secondary  waves  are 
reflected  first  from  peripheral  points  at  which  the  blood-flow  is  particu- 
larly obstructed  (the  bifurcations  of  the  larger  arteries,  and  the  small 
arteries  and  capillaries  in  general),  and  that,  running  towards  the  heart, 
they  are  again  reflected  outwards  from  the  semilunar  valves.  It  has 
been  urged  in  support  of  this  view  that  in  very  small  animals  (guinea- 
pigs)  no  dicrotic  elevation  occurs  on  the  pulse-tracing,  since  the  path 
which  the  reflected  wave  has  to  follow  is  so  short  that  it  arrives  at  the 
root  of  the  aorta  before  the  primary  elevation  is  over.  But  this 
argument  is  by  no  means  conclusive,  and,  indeed,  the  great  difference 
in  the  distance  from  the  heart  of  the  numerous  points  at  which  reflection 
must  take  place  is  one  of  the  chief  difficulties  of  the  hypothesis.  For 
it  is  not  easy  to  understand  how  the  reflected  fragments  of  the  primary 
wave,  arriving  at  different  intervals  at  the  heart,  can  be  integrated  into 
the  single  considerable  dicrotic  elevation. 

The  explanation  that  best  takes  account  of  the  facts  and  renders 
most  clear  the  role  of  the  semilunar  valves  is  somewhat  as  follows: 
When  the  systole  abruptly  comes  to  an  end  and  the  outflow  from  the 
ventricle  ceases,  the  column  of  blood  in  the  aorta  tends  still  to  move 
on  in  virtue  of  its  inertia,  and  a  diminution  of  pressure,  accom- 
panied by  a  corresponding  contraction  of  the  aorta,  takes  place 
behind  it,  just  as  a  negative  wave  is  set  up  in  the  central  end  of  the 
elastic  tube  when  the  stroke  of  the  pump  is  over.  At  the  same 
moment,  and  while  the  semilunar  valves  are  still  for  an  instant  in- 
completely closed,  the  diminution  of  pressure  in  the  beginning  of  the 
aorta  is  intensified  by  the  aspiration  of  the  relaxing  ventricle,  which 
sucks  the  blood  back  against  the  valves,  and  draws  them  a  little  way 
into  its  cavity.  A  negative  wave,  therefore — a  wave  of  diminished 
pressure,  represented  in  the  pulse-curve  by  the  '  aortic  notch  ' — 
travels  out  towards  the  periphery.  The  diminution  of  pressure  is 
quickly  followed  by  a  rebound,  as  always  happens  in  an  elastic 
system.  The  recoiUng  blood  meets  the  closed  semilunar  valves. 
The  aorta  expands  again,  and  the  expansion  is  propagated  once  more 
along  the  arteries  as  the  dicrotic  elevation.  It  is  possible  that  this 
elevation  may  be  reinforced  by  a  reflected  wave  produced  in  the 
manner  described. 


lo6  THE  Clh'CULATJON  OF  THE  BLOOD  ASD  LYMPH 

When  the  semilunar  valve  beromes  incompL-tcnt  in  disease,  or  is 
rendered  insulin  it  nt  in  animals  by  tlie  artilit  ial  rupture  of  one  or 
more  of  its  segments,  the  dicrotic  wave,  as  will  be  readily  understood 
from  the  manner  in  which  it  is  produced,  eitlier  disappears  altogether 
or  is  markedly  enfeebled.  But  apart  from  any  anatomical  lesion  or 
functional  defect  in  the  aortic  valves,  the  prominence  of  the  wave 
varies  with  a  great  number  of  circumstances,  some  of  which  are  in  a 
measure  understood,  while  others  remain  obscure.  It  varies  in  par- 
ticular with  the  abruptness  of  discharge  of  the  ventricle  and  the  ex- 
tensibility of  the  arteries.  The  conditions  are  usually  favourable  when 
the  arterial  pressure  is  low,  for  the  blood  then  passes  quickly  from  the 
ventricle  into  the  arteries,  which,  already  only  moderately  tense,  are 
easily  dilated  by  the  primary  wave,  then  sharply  collapse,  and  are  again 
abruptly  distended  when  the  dicrotic  wave  arrives.  And,  in  fact,  an 
exaggeration  of  the  dicrotic  wavelet  may  be  artificially  produced  by 
nitrite  of  amyl  (Fig.  lo  j,  p.  209),  a  drug  which  lessens  the  blood-pressure 
by  dilating  the  small  arteries.  Muscular  exercise  (Fig.  loi,  p.  209), 
running  or  bicycling,  for  instance,  has  a  similar  effect  on  the  sphygmo- 
gram,  although  the  explanation  can  scarcely  be  the  same,  since  the  blood- 
pressure  mounts  rapidly  when  moderate  exercise  begins,  and  only 
gradually  falls  during  its  continuance,  with  an  abrupt  decline  to  normal 
or  below  it  on  cessation  of  work  (Bowen).  The  increase  in  the  pulse- 
rate  may  have  something  to  do  in  this  case  with  the  exaggeration  of  the 
dicrotism,  which  is  very  frequently,  although  by  no  means  invariably, 
associated  with  a  rapidly-beating  heart,  and  therefore  is  often  seen  in 
fever.  On  the  other  hand,  in  certain  diseases  associated  with  a  high 
arterial  pressure,  the  dicrotic  elevation  almost  disappears.  Ather- 
omatous arteries,  being  very  inextensible,  do  not  allow  a  dicrotic  pulse. 

Since  the  pulse  represents  a  periodical  increase  and  diminution  in 
the  amount  of  distension  of  an  artery  at  any  point,  the  line  joining 
all  the  minima  of  the  pulse-curve  will  vary  in  its  height  above  the 
base-line,  or  line  of  no  pressure,  according  to  the  amount  of  permanent 
distension,  i.e.,  permanent  blood-pressure,  which  the  heart  in  any  given 
circumstances  is  able  to  maintain.  Any  circumstance  that  tends  to 
lessen  the  permanent  distension  will  cause  a  fall  of  the  line  of  minima, 
and  any  circumstance  tending  to  increase  the  distension  will  cause  that 
line  to  rise.  If,  for  example,  the  arm  be  raised  while  a  pulse-tracing 
is  being  taken  from  the  wrist,  the  line  of  minima  falls  because  the 
permanent  pressure  in  the  radial  artery  is  diminished. 

The  form  of  the  pulse-curve  varies  in  the  different  arteries,  and 
therefore  in  making  conipurisons  the  same  artery  should  be  used. 
When  the  wave  of  blood  only  enters  an  artery  slowly,  the  ascending 
part  of  the  curve  will  be  oblique.  This  is  normally  the  case  in  a 
pulse-curve  of  a  distant  artery,  such  as  the  posterior  tibial.  The 
heiglit  of  the  wave  is  also  less  than  in  an  artery  nearer  the  heart,  such 
as  the  carotid,  or  even  the  axillary,  where  the  primary  elevation  is 
relatively  abrupt  (Fig.  39,  p.  104). 

Anacrotic  Pulse. — As  a  rule,  the  ascent  of  the  tracing  is  unbroken 
by  secondary  waves,  but  in  certain  circumstances  these  may  appear 
on  it.  This  condition,  which,  when  well  marked  at  any  rate,  may 
be  considered  pathological,  is  called  anacrotism  (Fig.  38).  It  is  seen 
when  the  disclKirge  of  the  left  ventricle  into  the  aorta  is  slow  and 
difficult — e.g.,   in   cases  where  the   orifice   of  the   aorta  has   been 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSEL!^       107 

narrowed  from  disease  oi  tlie  semilunar  valvi's  (aortic  stenosis). 
Since  this  condition  is  associated  with  hypertrophy  and  dilatation 
of  the  li'ft  ventricle,  the  slow  emptyiiif.^  of  the  ventricle  is  partly  due 
to  the  greater  quantity  of  blood  which  it  contains.  In  whatever 
way  the  delay  in  the  emptjnng  of  the  ventricle  is  brought  about,  the 
most  probable  explanation  of  the  anacrotic  pulse  is  that  the  delay 
affords  time  for  one  or  more  secondary  waves  to  be  developed  in  the 
arterial  system  before  the  summit  of  the  curve  has  been  reached,  and 
that  these  are  superposed  upon  the  long-drawn  primary  elevation. 
In  aortic  insuHiciency,  where  the  left  side  of  the  heart  is  never  cut  off 
entirely  from  the  aorta,  the  auricular  impulse  is  sometimes  marked 
on  the  pulse-curve  as  a  distinct  elevation;  and  this  gives  rise  to  a 
peculiar  kind  of  anacrotic  pulse,  especially  in  the  arteries  nearest  the 
heart  (Fig.  38,  F,  p.  103). 

Frequency  of  the  Pulse. — In  health,  the  working  of  the  cardiac 
pump  is  so  smooth  and  apparently  so  self-directed  that  it  needs  a 
certain  degree  of  attention  to  perceive  that  the  rate  of  the  stroke  is 
not  absolutely  constant.  It  is,  in  reahty,  affected  by  many  internal 
conditions  and  external  influences. 

At  the  end  of  foetal  hfe  the  rate  is  given  as  144  to  133;  from  birth 
till  the  end  of  the  first  year,  140  to  123 ;  from  10  to  15  years,  91  to  76; 
from  20  to  25  years,  73  to  69.  It  remains  at  this  till  60  years,  and 
increases  again  somewhat  in  old  age.*  At  all  ages  the  pulse  is  some- 
what quicker  in  the  female  than  in  the  male,  the  excess  amounting  to 
about  8  beats  a  minute.  So  that  if  we  take  the  average  rate  for  a 
man  (in  the  sitting  position)  as  72,  the  average  for  a  woman  will  be 
80.  The  difference  is  partly  due  to  the  fact  that  the  average  man 
is  taller  than  the  average  woman;  and  it  is  known  that  in  persons  of 
the  same  sex  and  age  the  pulse-rate  has  an  inverse  relation  to  the 
stature.  But  there  may  be,  in  addition,  a  real  sexual  difference. 
It  must  not  be  forgotten  that  a  certain  number  of  perfectly  healthy 
persons,  who  may  even  be  noted  for  their  powers  of  physical  en- 
durance, have  an  habitually  slow  pulse,  not  above  50  in  the  minute. 
The  position  of  the  body  exercises  a  slight,  but  relatively  constant, 
influence  on  the  rate,  which  is  greater  in  the  standing  than  in  the 
sitting  posture,  and  greater  in  the  latter  than  in  the  recumbent 
position.  And  this  is  true  even  when  muscular  action  is  as  far  as 
possible  ehminated  by  fastening  the  person  to  a  board.     The  pulse 

*  It  must  be  remembered  that  these  numbers  are  merely  averages.  Some 
healthy  individuals  have  a  much  lower  pulse-rate  than  72  per  minute,  and 
some  a  rate  considerably  greater.  Thus,  while  the  average  pulse-rate  (taken 
in  the  sitting  position)  of  87  healthy  (male)  students,  whose  ages  ranged  from 
18  to  36  years,  was  73,  the  extreme  variation  was  from  54  to  89.  In  the 
standing  position  the  average  was  80,  and  the  variations  64  to  105.  In 
the  supine  position,  average  69,  and  variations  48  to  98.  After  a  short  spell 
of  muscular  exercise  (generally  running  up  and  down  some  flights  of  stairs) 
the  average  in  the  standing  position  was  119,  the  variations  75  to  164,  and 
the  average  increase  32. 


lo8  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

is  further  affected  by  tho  respiratory  movements,  especially  when 
they  are  exaggerated  in  forced  breathing,  being  accelerated  during 
each  inspiration  (p.  293).  It  is  also  increased  by  the  taking  of  food, 
and  especially  of  alcoholic  stimulants,  by  muscular  i-xercise,  in  fever 
and  many  other  pathological  conditions,  and  by  a  high  external 
temperature.  A  warm  bath,  for  example,  causes  a  very  distinct 
acceleration  of  the  heart;  and  Delaroche  found  that  in  air  at  the 
temperature  of  65°  C  his  pulse  went  up  to  160.  A  cold  bath  may 
depress  the  pulse-rate  to  60,  or  even  less.  During  sleep  it  may  fall 
to  50.  It  is  greatly  influenced  by  psychical  events,  and  that  in  the 
direction  either  of  an  increase  or  a  decrease.  Finally,  it  ought  to  be 
remembered  as  of  some  practical  importance  that  the  pulse-rate  in 
women  and  children,  but  particularly  in  the  latter,  is  less  steady 
than  in  men,  and  more  apt  to  be  affected  by  trivial  causes.  And  it 
is  a  good  general  rule  to  let  a  short  interval  elapse  after  the  finger  is 
laid  on  the  artery  before  beginning  to  count  the  pulse,  so  that  the 
acceleration  due  to  the  agitation  of  the  patient  may  have  time  to 
subside. 

Rate  of  Propagation  of  the  Pulse-Wave. — When  pulse-tracings  are 
taken  simultaneously  at  two  points  of  the  arterial  system  unequally 
distant  from  the  heart,  by  two  sphygmographs  whose  writing-points 
move  in  the  same  vertical  straight  line,  it  is  found  that  the  ascent 
of  the  curve  begins  later  at  the  more  distant  than  at  the  nearer  point. 
Since  waves  hke  the  pulse-wave  travel  with  approximately  the  same 
velocity  in  different  parts  of  an  elastic  system  like  the  arterial '  tree,' 
this  '  delay  '  must  be  due  to  the  difference  in  the  length  of  the  two 
paths.  The  difference  in  length  can  be  measured;  the  time- value  of 
the  '  delay  '  can  be  deduced  from  the  rate  of  movement  of  the  re- 
cording surface;  dividing  the  length  by  the  time,  we  arrive  at  the 
rate  of  propagation  of  the  pulse-wave.  The  average  rate  has  been 
found  to  be  about  7  metres  per  second  in  man  in  the  arteries  of  the 
upper  limb,  and  8  metres  in  those  of  the  lower  limb,  the  difference 
being  due  to  the  smaller  distensibihty  of  the  latter.  In  sleep  the 
velocity  diminishes  almost  a  metre  a  second.  It  increases  in  arterio- 
sclerosis, where  the  distensibihty  of  the  arteries  is  diminished,  and 
in  chronic  nc^phritis  with  hypertrophy  of  the  heart,  in  which  the 
blood-pressure  is  increased.  The  mean  velocity  of  the  pulse- wave 
is  about  the  same  as  the  speed  of  a  moderately  fast  steamship  (say, 
17  miles  an  hour),  but  less  than  that  of  a  wave  of  the  sea  in  a  strong 
gale.  The  velocity  of  the  pulse-wave  must  not  be  confounded  with 
that  of  the  blood-stream  itself,  which  is  not  one-thirtieth  as  great. 
A  ripple  passes  over  the  surface  of  a  river  at  its  own  rate — a  rate 
that  is  independent  of  the  velocity  of  the  current.  The  passage  of 
the  ripple  is  not  a  bodily  transference  of  the  particles  of  water  of 
which  at  any  given  moment  the  wave  is  composed,  but  the  propaga- 
tion of  a  change  of  relative  position  of  the  particles.     The  mere  fact 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      105 

that  the  ripple  can  pass  upstream  as  well  as  down  is  sufficient  to 
illustrate  this.  The  pulse-wave  does  not,  however,  correspond  in 
every  respect  to  a  ripple  on  a  stream,  for  the  bodily  transfer  of  the 
blood  depends  upon  the  series  of  blood- waves  which  the  heart  sets 
travelling  along  the  arteries.  Every  particle  of  blood  is  advanced, 
on  the  whole,  by  a  certain  distance  with  every  pulse- wave  in  which 
for  the  time  it  takes  its  place.  But  no  particle  continues  in  the 
front  of  the  pulse- wave  from  beginning  to  end  of  the  arterial  system. 
The  '  delay  '  or  '  retardation  '  of  the  pulse  (the  interval,  say,  between 
the  beginning  of  the  ascent  of  the  carotid  and  radial  curves)  is 
practically  constant  in  the  same  individual,  not  only  in  health,  but 
also  in  most  diseases.  But  the  retardation  is  markedly  increased 
when  the  pulse-wave  has  to  pass  through  a  portion  of  an  artery 
whose  lumen  is  either  greatly  widened  (in  aneurism)  or  greatly 
constricted  (in  endarteritis  obliterans). 

The  Blood- Pressure  Pulse  in  the  Arteries.— In  man  it  is  only 
possible  to  trace  the  pulse-wave  along  the  arteries  by  movements  of 
the  walls  of  the  vessels  transmitted  through  the  overlying  tissues. 
In  animals  the  changes  of  pressure  that  occu-  in  the  blood  itself  can 
be  directly  registered,  and  these  changes  may  be  spoken  of  as  the 
blood-pressure  pulse.  At  bottom,  as  already  pointed  out,  the 
phenomenon  is  exactly  the  same  as  that  we  have  been  dealing  with 
in  our  study  of  the  external  pulse.  We  are  only  now  to  follow,  by 
a  more  direct,  and  in  some  respects  a  more  perfect  method,  the  same 
wave  of  blood  along  the  same  channel. 

Measurement  of  the  Arterial  Blood-Pressure. — Hales  was  the  first  to 
measure  the  blood-pressure.  This  he  did  by  connecting  a  tall  glass 
tube  with  the  crural  artery  of  a  horse.  The  height  to  which  the  blood 
rose  in  the  tube  indicated  the  pressure  in  the  vessel.  Poise uille,  nearly 
half  a  century  later,  applied  the  mercury  manometer,  which  had  already 
been  used  in  physics,  to  the  measurement  of  blood-pressure.  Ludwig 
and  others  improved  this  method  by  making  the  manometer  self- 
registering  by  means  of  a  float  in  the  open  limb,  supporting  a  style 
which  writes  on  a  revolving  drum,  or  kymograph.  (For  the  method 
of  taking  a  blood-pressure  tracing,  see  p.  210.) 

For  reasons  already  mentioned,  the  mercurial  manometer  is  better 
suited  for  measuring  the  mean  blood-pressure,  or  for  recording  changes 
in  the  pressure  which  last  for  some  time,  than  for  following  the  rapid 
variations  of  the  pulse-wave.  For  the  latter  purpose,  one  of  the  class 
of  elastic  manometers  is  required  (p.  93). 

A  blood-pressure  tracing  taken  from  an  artery  with  a  manonieter 
of  this  sort  yields  the  truest  picture  of  the  pulse-wave  which  it  is 
possible  to  obtain,  because  the  reproduction  of  it  is  the  most  direct. 
The  fact  that  such  a  tracing  shows  a  close  agreement  with  the  trace 
of  a  good  sphygmograph  properly  applied  to  the  corresponding  artery 
on  the  other  side  is  a  striking  proof  of  the  general  accuracy  of  the 
sphygmographic  method  for  physiological  purposes,  and  enables  us  to 
guide  ourselves  in  transferring  to  man,  in  whom,  of  course,  the  sphyg- 
mograph can  alone  be  used,  the  information  derived  from  direct 
manometric  observations  in  animals. 


no  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


For  the  same  reason  it  is  unnecessary  to  discuss  the  nianometric 
tracings,  as  regards  the  pulsatory  phenomena,  in  all  their  details. 
It  will  be  sufficient  to  say  that,  while  the  form  of  the  blood- pressure 
pulse-curve  varies  with  the  mean  blood-pressure,  th'-  dicrotic  wave 
is  always  marked  on  it,  preceded  by  one  or  more  oscillations  falling 
within  the  period  of  the  systole,  and  followid  by  one  or  more  within 
the  period  of  the  diastole.  When  the  blooil-pn-ssure  is  low,  the  tirst 
or  primary  elevation  is  the  highest  of  the  whole  curve  (Fig.  42).  When 
the  blood-pressure  is  high,  the  maximum  falls  later  coinciding  with 

one  of  the  secondary 
systolic  waves,  but 
always  preceding  the 
dicrotic  wave;  and  the 


^==^ 


curve  assumes  an 
erotic  character. 


ana- 


That  all  the  secondary 
oscillations,  including  the 
dicrotic  wavelet,  arc  cen- 
trifugal, and  not  centrip- 
etal, may  be  shown,  just 
as  in  the  sphygmographic 
method,  by  recording  the 
blood -pressure  simultane- 
ously at  two  points  of  the 
arterial  sj-stcm  at  differ- 
ent distances  from  the 
heart — e.g..  in  the  crural 
and  carotid  arteries.  The 
secondary  waves  are 
found,  by  measuring  the 
tracings,  to  reach  the 
more  distal  point  later 
than  the  more  central. 

The  increase  of  pres- 
sure during  the  systole, 
as  indicated  by  the  height 
of  the  primary  elevation, 
is  always  very  large ,  much 
larger  than  it  appears  in  a 
tracing  taken  with  a  mer- 
cury manometer.  In  the 
rabbit  this  pulsatory  variation  is  one-third  to  one -fourth  of  the  minimum 
pressure.  In  the  dog  it  is  still  greater,  owing  to  the  slower  rate  of  the 
heart,  and  often  amounts  to  50  mm.  of  mercury,  while  under  favourable 
conditions  (low  minimum  pressure  and  slowly  -  beating  heart)  the 
systolic  increase  of  pressure  may  be  actually  more  than  double  the 
minimum  (Hiirthlc).  Pick  found  also,  by  means  of  his  spring  man- 
ometer, that  the  pulsatory  variations  of  blood-pressure  were  greater 
than  the  respiratory  variiltions  (p.  2Su).  although  in  the  records  of 
the  mercury  manometer  the  reverse  appears  often  to  be  the  case. 
Landois,  too,  in  the  course  of  experiments  in  which  a  divided  artery 
was  allowed  to  spout  against  a  moving  surface,  and  to  trace  on  it  a 
sort  of  pulse-curve  painted  in  blood  (a  hieniautogram  as  it  is  called). 


Fig.  41. — .\rrangement  for  taking  a  Blood-Pressure 
Tracing.  M,  manometer;  Hg,  niercun-;  F,  float 
armed  with  writing-point;  A.  thread  attached  to 
a  wire  projecting  from  the  drum  and  supporting 
a  small  weight.  The  thread  keeps  the  writing- 
point  in  contact  with  the  smoked  paper  on  the 
drum.  B  is  a  strong  rubber  tube  connecting  the 
manometer  with  the  artery;  C  a  pinchcock  on 
the  rubber  tube,  which  is  taken  off  when  a  tracing 
is  to  be  obtained. 


MECHANICS  OF  THE  CIRCULATION  IN  THE  VI-SSELS      in 


observed  that  the  rate  of  escape  of  the  blood  was  nearly  50  per  cent, 
greater  during  the  systole  than  during  the  pause  of  the  heart.  The 
existence  of  the  dicrotic  wave  on  this  tracing  was  long  looked  on  as  the 
best  proof  that  it  was  not  an  artificial  phenomenon. 

The  wave  of  increased  pres- 
sure, as  it  runs  along  the  arterial 
system,  carries  with  it  wherever 
it  arrives  an  increase  of  potential 
energy.  But  this  excess  of  po- 
tential energy  is  continually  being 
worn  down,  owing  to  the  friction 
of  the  vascular  bed;  and  although 
in  the  comparatively  large  arteries 
the  loss  of  energy  is  not  great,  it 
rapidly  increases  as  the  arteries 
approach  their  termination,  and 
begin  to  break  up  into  the  narrow 
arterioles  which  feed  the  capillary 
network.  For  not  only  is  the  ratio 
of  the  total  surface  to  the  total 
cross-section,  and  therefore  the 
friction,  increased  with  every 
bifurcation,  but  the  mere  change 
of  direction  and  division  of  the 
wave  cannot  take  place  without 
loss  of  energy.  For  this  reason 
the  fluctuations  of  blood-pres- 
sure are  greater  in  the  large  arteries  near  the  heart  than  in  arteries 
smaller  and  more  remote.  In  the  wide  and  much-branched  capillary 
bed  the  pulse-wave  disappears  altogether,  and  the  blood-pressure 
becomes  relatively  constant  or  permanent.     And  it   is   for  some 

purposes  convenient  to  look  upon 
the  blood -pressure  in  the  arteries  as 
made  up  of  a  permanent  element, 
with  pulsatory  oscillations  super- 
posed on  it.  Since  no  portion  of  the 
arterial  system  is  more  than  partially 
emptied  in  the  interval  between  two 
blood-waves,  the  minimum  or  per- 
manent pressure  is  always  positive 
—i.e.,  always  above  that  of  the  atmosphere,  the  beats  of  the  heart 
succeeding  each  other  so  rapidly  that  the  successive  waves  over- 
lap or  '  interfere,'  and  are  only  separated  at  their  crests. 

If  the  heart  is  stopped  while  a  blood-pressure  tracing  is  being 
taken — and  we  shall  see  later  on  how  this  can  be  done  (p.  157) — the 
minimum  Hne  of  the  tracing  goes  on  falhng  towards  the  zero-line. 


Fig.  42. — Curves  of  Blood-l*ressure  taken 
with  a  Spring  Manometer  from  the 
Carotid  Artery  of  a  Dog  (Hiirthle). 
When  I  was  taken  the  blood-pressure 
was  high;  2  corresponds  to  a  medium, 
3  to  a  low,  and  4  to  a  very  low,  blood- 
pressure;  p  is  the  primary  elevation 
— this  and  the  succeeding  elevations 
between  p  and  a  are  called  systolic 
waves;  the  systolic  waves  are  followed 
by  a  marked  elevation  d,  which  corre- 
sponds to  the  dicrotic  wave. 


v'VWWV'^ 


Fig.  43.  —  Blood  -  Pressure  Tracing. 
The  horizontal  straight  line  inter- 
secting the  curves  is  the  line  of 
mean  pressure. 


112         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

When  the  heart  begins  beating  again,  the  pressure-curve  rises,  not 
by  a  continuous  ascent,  but  by  successive  leaps,  each  corresponding 
to  a  beat  of  the  heart,  and  each  overtopping  its  predecessor,  tiU  the 
old  line  of  minimum  or  of  mean  pressure  is  again  reached. 

The  mean  arterial  blood -pressure  is  the  permanent  pressure  plus 
one-half  of  the  average  pulsatory  oscillation.  In  a  blood-pressure 
tracing  the  line  of  permanent  pressure  joins  all  the  minima;  the  line 
of  maximum  pressure  joins  all  the  maxima ;  the  line  of  mean  pressure 
is  drawn  between  them  in  such  a  way  that,  of  the  area  included 
between  it  and  the  blood- pressure  curve,  as  much  lies  above  as  below 
it  (Fig.  43).  As  has  been  said,  a  tracing  taken  with  a  mercury  man- 
ometer gives  approximate!}' the  mean  blood-pressure.  Each  beat  of 
the  heart  is  represented  on  it  by  a  single  elevation  of  variable  size, 
sometimes  not  amounting  to  more  than  one-twentieth  of  the  height 
of  the  curve  above  the  line  of  zero  or  atmospheric  pressure,  but  some- 
times much  larger.  The  oscillations  due  to  the  heart-beat  are 
superposed  upon  much  longer,  and  often,  as  registered  in  this  way, 
larger  waves,  caused  by  the  movements  of  respiration.  So  much 
having  been  said  by  way  of  definition,  we  have  now  to  consider  the 
amount  of  the  mean  arterial  pressure,  the  variations  which  it  under- 
goes, and  the  factors  on  which  its  maintenance  depends. 

As  to  its  amount,  it  will  be  sufficiently  accurate  to  say  that  in  the 
systemic  arteries  of  warm-blooded  animals  in  general  (including 
birds),  and  of  man  in  particular,  the  mean  pressure  does  not,  under 
ordinary  conditions,  descend  much  below  100  mm.  of  mercury,  nor 
rise  much  above  200  mm. ;  while  in  cold-blooded  animals  it  seldom 
exceeds  50  mm.,  and  may  fall  as  low  as  20  mm. 

It  does  not  seem  possible,  at  least  with  our  present  data,  to  further 
subdivide  these  two  great  groups;  nor  do  we  know  precisely  whether 
the  distinction  depends  mainly  on  morphological  or  mainly  on  physio- 
logical dififerences,  whether,  that  is  to  say,  the  warm-blooded  animal 
has  a  higher  blood-pressure  than  the  cold-blooded  chiefly  because  its 
vascular  system  (and  especially  its  heart)  is  anatomically  more  perfect, 
or  because  its  heart  beats  faster  and  works  harder.  It  may  be  that 
it  is  for  both  of  these  reasons  that  the  birds,  which  in  certain  other 
respects  are  more  nearly  related  to  the  reptiles  than  to  the  mammals, 
mount,  as  regards  the  pressure  of  the  blood,  into  the  mammalian  class, 
and  that  a  manometer  in  the  carotid  of  a  goose  will  rise  as  high,  or 
almost  as  high,  as  in  the  carotid  of  a  horse,  a  sheep,  or  a  dog,  while  the 
pressure  in  the  aorta  of  a  tortoise  is  no  higher  than  in  the  aorta  of  a  frog. 
But  we  know  that  the  mere  average  rate  of  the  heart  has  of  itself  com- 
paratively little  influence  on  the  blood-pressure  within  either  group, 
for  the  heart  of  a  rabbit  beats,  on  the  average,  very  much  faster  than 
the  heart  of  a  dog.  and  yet  the  arterial  pressure  in  the  dog  is  certainly 
at  least  as  great  as  in  the  rabbit.  Nor  docs  the  size  of  the  body  seem 
to  have  any  definite  relation  to  the  mean  pressure,  even  in  animals 
of  the  same  species;  and  there  is  no  reason  to  suppose  that  the  pressure 
is  materially  less  in  the  radial  artery  of  a  dwarf  than  in  the  radial  artery 
of  a  giant. 


MFCflAXICS  OF  Tin-:  CIRCULATION  IN  THE   VESSELS 


"3 


Measurement  of  the  Blood-Pressure  in  Man  .—In  man  the  blood- 
pressuiv  has  been  estiinatid  hy  adjusting  over  an  artery  an  instru- 
ment known  as  a  sj^liygmomanometer  or  sphygmometer,  which,  in 
its  most  modern  form,  consists  essentially  of  a  hollow  rubber  pad  or 
bag  containing  air,  and  connected  with  a  metallic  pressure  gauge  or 
a  mercurial  manometer. 

The  simplest  method  is  that  devised  by  Riva-Rocci  (Fig.  44).  An 
armlet  in  the  form  of  a  broad  rubber  bag,  supported  externally  by 
canvas  or  leatlicr,  is  adjusted  round  the  upper  arm.  The  interior  of  the 
bag  is  connected  with  a  mercury  manometer,  and  also  with  a  strong 
rubber  bulb  provided  with  a  valve.  By  rhythmical  compression  of 
the  bidb  the  pressure  can  be  raised.  Between  the  pressure  bulb  and 
the  rest  of  the  system  is  a  thin  rubber  balloon,  which  by  its  distension 
renders  the  changes  of  pressure  more  gradual.  The  finger  of  the 
observer  is  placed  (>\er  the  radial  artery,  and  the 
pressure  is  raised  luitil  the  pulse  disappears.  Then 
the  pressure  is  allowed  to  fall  gradually,  and  the 
manometer  reading  at  the  moment  when  the  pidse 
first  reappears  in  the  radial  gives  the  maximum  or 
systolic  pressure  in  the  brachial  artery. 

Instead  of  palpating  the  radial  artery,  a  stetho- 
scope may  be  placed  over  the  brachial  just  below 
the  edge  of  the  armlet,  according  to  the  method  of 
Korotkoff,  by  which,  in  addition  to  the  systolic,  the 
minimimi  or  diastolic  pressure  may  be 
determined.  This  is  much  the  best  of 
all  the  methods  of  measuring  the  arterial 
pressures  in  man.  The  pressure  is 
raised  somewhat  above  that  necessary 
to  obliterate  the  pulse,  and  then  allowed 
to  fall  slowly.  At  the  moment  when 
pulsations  first  begin  to  break  through 
below  the  armlet,  a  succession  of  sharp 
taps,  synchronous  with  the  pulse,  is 
heard.  The  tapping  sound  grows  rapidly 
louder  as  the  artery  opens  up  more  and 
more,  then  abruptly  diminishes  and 
changes  its  character,  and  gradually  dis- 
appears. Several  pha.ses  have  been  distinguished  after  the  first  maxi- 
mum. Everybody  agrees  that  the  pressure  shown  by  the  manometer 
when  the  sound  is  first  heard  is  the  sj^stolic  pressure.  This  corresponds 
closely  with  the  systolic  pressure  as  determined  by  palpating  the  radial ; 
and  it  can  be  shown  experimentally  that  at  pressures  in  the  armlet 
exceeding  this  the  lumen  of  the  brachial  artery  is  actually  obliterated 
and  not  merely  narrowed  to  such  a  degree  as  to  prevent  the  passage  of 
the  pulse  wave,  while  still  permitting  the  passage  of  some  blood  (see 
Practical  Exercises,  p.  213). 

The  diastolic  pressure  is  the  pressure  at  which  a  sudden  weakening 
and  dulling  of  the  sound  occurs  (beginning  of  the  fourth  phase),  and  not 
the  pressure  at  which  the  sound  becomes  altogether  inaudible  (Mac- 
William,  etc.).  The  sound  seems  t(j  be  due  to  vibrations  set  up  in  the 
walls  of  the  artery  and  the  structures  in  contact  with  it  when  it  is 
suddenly  opened  by  the  pul.se  waves.  According  to  Erlanger,  the  essen- 
tial thing  is  the  '  water  hammer  '  action  of  the  blood  when,  moving 
through  the  artery  under  compression  in  the  armlet,  it  strikes  the  stag- 
nant blood  in  the  uncompressed  artery  below  and  distends  it. 


Fig.  44. — Riva-Rocci  Apparatus. 
a,  armlet;  b,  manometer  tube; 
c,  bottle  containing  mercury, 
into  which  b  dips  ;  d,  thin 
rubber  bulb  ;  e,  thick  rubber 
bulb  for  getting  up  pressure. 


114 


THE  CIRCULATIOX  <>I-   THE  BLOOD  AND  LYMPH 


Various  instnimenls  have  been  dcvisecl  for  dctcnniuiiig  the  blood 
pressure  from  tlie  changes  in  the  oscillations  communicated  to  the  arm- 
let by  the  artery  as  the  pressure  in  the  armlet  is  allowed  to  fall  or  caused 
to  rise.     The  sphygmomanometer  of  Erlanger  (Fig.  45)  is  arranged  to 

obtain  graphic  records  of  the  pulse 
from  which  both  the  maximum 
and  the  minimum  blood-pressures 
may  be  deduced.  The  mean  pres- 
sure cannot  be  directly  measured, 
but  must  lie  much  nearer  to  the 
minimuin  than  to  the  maximum, 
since  the  line  of  mean  pressure  bi- 
sects the  area  enclosed  by  the 
pulse  curve,  and  this  area  is  broad 
at  the  base  and  narrow  at  the  apex. 
The  rubber  bag  is  applied  in  the 
form  of  a  cuff  or  armlet  to  the  arm 
above  the  elbow  over  the  brachial 
artery.  It  communicates  with  a 
mercury  manometer,  which  gives 
the  pressure  exerted  upon  the  arm. 
It  is  also  connected  with  a  rubber 
bulb,  B,  enclosed  in 
a  glass  bulb,  G,  and 
through  a  stopcock 
with  a  syringe  bulb, 
V,  provided  with  a 
^  valve.  The  space 
between  B  and  G 
communicates  (1) 
with  the  tambour; 
(2)  with  the  exterior 
through  the  stopcock 
by  the  tube  E,  and 
also  through  a  pin- 
point opening  in  the 
membrane  of  the 
tambour.  While  the 
armlet  is 
being  ad- 
justed the 
sto]K-ock  is 
turned  so 
that  the  rubber  bag  is 
in  communication  with 
the  external  air  through 
1".  The  same  is  true  of 
the  space  TS  in  the 
glass  bulb.  The  tam- 
bour is  thus  protected 
against  undue  strain  during  adjustment.  The  stopcock  is  now  rotated 
so  as  to  cut  off  the  armlet  from  the  exterior  and  to  permit  the  entrance 
of  air  through  I*"  from  V,  which  is  used  as  a  pump  to  raise  the  pressure, 
the  space  TS  and  the  tambour  being  still  in  communication  with  the 
exterior.  When  the  desired  pressure  has  been  reached,  the  stopcock 
is  turned  into  an  intermediate  position,  which  cuts  off  both  the  armlet 
and  the  space  TS  from  the  exterior,  and  the  pulse  is  then  transmitted  to 
the  tambour  and  recorded  on  the  drum.    By  certain  adjustments  of  the 


Fig.  45. — Sphygmomanometer  of  Erlanger. 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS  115 


stopcock  air  can  be  allowcil  to  escape  more  or  less  rapidly  from  the 
armlet. 

To  determine  the  maximum  or  systolic  blood-pressure,  the  air- 
pressure  in  the  armlet  is  raised  considerably  (about  50  mm.  Ilg)  above 
what  it  is  expected  to  be.  While  the  lever  is  writing  on  the  drum 
the  small  oscillations  due  to  the  impact  on  the  bag  of  the  pulse-waves 
in  the  central  portion  of  the  obliterated  artery,  the  pressure  is  gradually 
diminished  by  allowing  air  to  escape.  At  the  moment  when  the 
pressure  upon  the  arm  falls  below  the  maximum  blood-pressure,  and 
the  pulse-wave  is  first  able  to  break  through  the  brachial  artery,  the 
oscillations  of  the  lever  will  more  or  less  abruptly  increase  in  amplitude. 
The  pressure  shown  by  the  manometer  at  this  point  is  the  systolic 
blood-pressure.  To  obtain  the  minimum  or  diastolic  pressure,  the  air- 
pressure  in  the  armlet  is  raised  somewhat  (to  to  15  mm.  Hg)  above  the 
pressure  expected.  The  pressure  is  diminished  by  5  mm.  Hg  at  a  time, 
records  of  the  oscillations  being  taken  on  the  drum.  The  manometer 
reading  at  the  point  at  which  the  oscillations,  after  reaching  the  maxi- 
mum, begin  abruptly  to  diminish,  corresponds  to  the  minimum  blood- 
pressure. 

According  to  Brooks  and  Luckhardt,  the  criteria  which  are  supposed 
to  fix  the  systolic  and  diastolic  pressures  in  these  and  similar  methods 
yield  results  which  are  too  high.  The  personal  equation  also  seems  to 
introduce  a  considerable  error  in  the  selection  of  the  points  on  the  trac- 
ings at  which  the  characteristic  changes  are  supposed  to  occur  (Kilgore). 

In  using  the  sphygmometer  of  Hill  and  Barnard  (Fig.  46),  the  bag 
is  inflated  till  the  pulsation  indicated  by  the  gauge  reaches  a  maxi- 
mum. The  mean 
pressure  shown 
at  this  point  is 
assumed  to  be 
equal  to,or  some- 
what greater 
than,  the  dia- 
stolic pressure. 

The  effect  of 
muscular  exer- 
cise upon  the 
pressure  is  in- 
fluenced by  the 
nature  of  the 
work.  Such  an 
effort  as  the  lift- 
ing of  a  heavy 
weight  causes 
a  sudden  and 
great  increase, 
which  is  very 
transient.  Thus, 

the  average  arterial  pressure  in  a  number  of  men  was  11 1  before, 
180  during,  and  no  two  to  three  minutes  after  the  lift  (McCurdy).  The 
rise  of  pressure  in  this  case  is  dvie  largely  to  the  marked  diminution  of 
the  calibre  of  the  bloodvessels  mechanically  produced  by  the  strong 
and  sustained  contraction  of  the  muscles.  This  increases  the  resistance 
to  the  passage  of  the  blood  along  the  arteries,  while  the  veins  are  emptied 
by  the  pressure,  and  more  blood  thus  reaches  the  right  side  of  the  heart. 
It  is  obvious  that  the  heart  and  vessels  may  easily  be  exposed  to  an 
injurious  strain  during  such  eftorts.  In  such  an  exercise  as  running, 
while  the  pressure  mounts  to  some  extent  at  first,  as  already  mentioned, 


Fig.  46. — Sphygmometer  of  Hill  and  Barnard.  It  consists  of 
a  broad  armlet,  A,  connected  by  a  T-tube,  B,  with  a  pressure 
gauge,  C,  and  a  small  compressing  air-pump,  D,  fitted  with 
a  valve. 


ii6  THE  CIRCULATION  OF  THE  BLOOD  AXD  LYMPH 

the  rise  is  not  mainlaineil.  owing  to  the  dilatation  of  the  cutaneous 
vessels.  In  the  antcrif)r  tibial  artcrj-  of  a  boy  whose  leg  was  to  Ix: 
amputated,  the  blood-pressure,  measured  by  means  of  a  manometer 
connected  directly  with  the  artery,  was  found  to  vary  from  loo  to 
i6o  mm.,  according  to  the  position  of  the  body  and  other  circum- 
stances. In  a  woman  sixty  years  old,  in  good  health,  the  following 
readings  were  obtained  with  a  sphygmomanometer: 

June  28  .         _         -         .         -     126^130  mm.  of  mercury. 

,,     29         -         -         -         -         -     126 — 136 
Aug.      3 132—144 

,.7 134—140 

,.12 136 — 144 

Such  mcasurcMiients  on  man  show  that  the  mean  blood-pressure 
under  similar  conditions  in  one  and  the  same  artery,  and  in  one  and 
the  same  indivndual,  may  vary  for  a  considerable  time  only  within 
comparatively  narrow  limits. 

This  relative  constancy  of  the  general  arterial  pressure  is  the 
result  of  a  dehcate  adjustment  between  the  work  of  the  heart,  the 
resistance  of  the  vessels,  and  the  volume  of  the  circulating  liquid. 
The  quantity  of  the  blood  is  tolerably  steady  in  health,  and  con- 
siderable changes  may  be  artificially  produced  in  it  (p.  191)  without 
affecting  the  pressure  in  any  great  degree.  On  the  other  hand,  the 
work  of  the  heart  and  the  peripheral  resistance  are  highly  variable 
and  vastly  influential.  A  narrowing  of  the  arterioles  throughout 
the  bod\^  or  in  some  extensive  vascular  tract  increases  the  peripheral 
resistance;  and  if  the  heart  continues  to  beat  as  before,  the  pressure 
must  rise.  If  the  arterioles  are  widened,  while  the  heart's  action 
remains  unchanged,  the  pressure  must  fall.  In  like  manner  an 
increase  or  a  decrease  in  the  activity  of  the  heart,  in  the  absence  of  any 
change  in  the  peripheral  resistance,  will  cause  a  rise  or  a  fall  in  the 
blood-pressure.  But  if  a  slowing  of  the  heart  is  accompanied  by  an 
increase  in  the  peripheral  resistance,  or  a  dilatation  of  the  arterioles 
by  an  increase  in  the  activity  of  the  heart,  the  one  change  may  be 
partially  or  completely  balanced  by  the  other,  and  the  pressure  may 
vary  within  narrow  hmits  or  not  at  all. 

Not  only  is  the  mean  pressure,  as  measured  in  a  large  artery, 
tolerably  constant,  but  if  recorded  simultaneously  in  two  arteries  at 
different  distances  from  the  heart,  it  is  seen  to  decrease  very  gradu- 
ally so  long  as  the  arteries  remain  large  enough  to  hold  a  cannula. 
It  is  nearly  as  high,  for  instance,  in  the  crural  artery  of  a  dog  as  in 
the  carotid.  It  is  easy  to  see  that  this  must  be  so,  for  the  resistance 
of  the  arteries  between  the  point  where  the  arterioles  are  given  off 
and  the  heart  is  only  a  small  fraction  of  the  total  resistance  of  the 
vascular  path;  and  we  have  said  (p.  84)  that  the  lateral  pressure  at 
any  cross-section  of  a  system  of  tubes  through  which  liquid  is  flow- 
ing is  proportional  to  the  resistance  still  to  be  overcome.  This  is 
also  the  reason  why  the  pressure  is  always  much  lower  in  the  pul- 
monary artery  and  right  ventricle  than  in  the  aorta  and  left  ventricle 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      117 

(only  one -fifth  to  one-sixth  as  great),  for  the  total  resistance  of  the 
vascular  path  through  the  lungs  is  much  less  than  that  of  the 
systemic  circuit.  In  dogs  with  natural  respiration  the  pressure  in 
the  pulmonary  artery  was  found  to  vary  between  14  and  26  mm.  of 
mercury,  averaging  about  20  mm. 

The  Velocity-Pulse. — We  have  seen  that  the  blood  is  propelled 
through  the  arteries  in  a  series  of  waves  that  travel  from  the  heart 
towards  the  periphery.  The  particles  in  the  front  of  the  pulse-wave 
are  constantly  changing,  but  since  every  section  of  the  arterial  tree 
is  successively  distended,  every  section  contains  more  blood  while 
the  pulse-wave  is  passing  over  it  than  it  contained  immediately 
before.  And  since  there  is  always  a  fairly  free  passage  for  this  blood 
towards  the  periphery,  there  is  a  bodily  transfer  on  the  whole  of  a 
certain  quantity  with  every  wave. 

The  translation  of  the  blood,  instead  of  being  entirely  intermittent, 
as  it  would  be  in  a  rigid  tube  or  in  an  elastic  system  with  a  slow 
action  of  the  central  pump,  is  to  some  extent  constantly  going  on ; 
for  a  portion  of  a  blood-wave  is  always  passing  through  every  section 
of  the  arterial  channel.  Thus,  we  arrive  at  the  same  distinction  as 
to  the  onward  movement  of  the  blood  itself  as  we  previously  reached 
in  regard  to  the  blood-pressure,  the  distinction  between  the  constant 
or  permanent  factor  of  the  velocity  and  the  periodic  factor,  which 
we  may  call  the  velocity-pulse. 

The  Velocity  of  the  Blood. — By  the  velocity  or  rate  of  flow  of  a  river 
we  should  mean,  if  the  flow  were  uniform  throughout  the  whole  cross- 
section,  the  rate  of  movement  of  any  given  portion  or  particle  of  the 
water.  If  we  could  identify  a  portion  of  the  water,  we  could  determine 
the  velocity  by  measuring  the  distance  travelled  over  by  that  portion 
in  a  given  time.  If  the  velocity  was  uniform  over  the  channel,  we  could 
predict  the  actual  time  which  would  be  required  to  traverse  any 
fractional  part  of  the  measured  distance.  If,  however,  the  velocity 
of  the  current  changed  from  point  to  point,  then  we  could  only  deduce 
from  our  observation  the  mean  rate  of  the  river  for  the  measured  dis- 
tance. To  determine  the  actual  rate  for  any  given  portion  of  this 
distance  over  which  the  rate  was  uniform,  we  should  have  to  make  a 
separate  observation  for  this  portion  alone. 

But  as  soon  as  we  pass  from  an  ideal  frictionless  river  to  an  actual 
stream,  in  which  the  water  at  the  bottom  and  near  the  banks  flows 
more  slowly  than  that  in  the  middle  and  on  the  surface,  we  are  in  every 
case  restricted  to  the  notion  of  mean  velocity.  We  may  distinguish 
between  the  velocity  of  different  parts  of  the  current,  between  that  of 
the  mid-stream  and  the  side  current,  the  bottom  and  the  surface  layers; 
but  when  we  consider  the  river  as  a  whole,  we  take  cognizance  only 
of  the  mean  or  average  velocity.  And  at  any  cross-section  this  may 
be  defined  as  the  volume  of  water  passing  per  hour,  or  whatever  the 
unit  of  time  may  be,  divided  by  the  cross-section  of  the  current.  It  is 
evident  that  this  does  not  enable  us  to  determine  the  actual  velocity 
of  any  given  particle  of  the  water  at  any  given  moment  within  a 
measured  interval ;  nor  does  it  tell  us  whether  or  not  the  average  velocity 
of  the  current  has  itself  undergone  variations  within  the  period  of 
observation. 


Ii8  THF.   CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

Wc  lia\(!  dwelt  upon  this  point  because  the  measurement  of  the 
velocity  of  the  blood,  to  which  we  must  now  turn,  involves  the  same 
considerations.  Within  the  smaller  arteries,  as  the  microscope 
shows  us,  and  as  we  should  in  any  case  expect  from  what  we  know 
of  fluid  motion,  the  blood-current,  apart  from  the  periodical  varia- 
tions in  its  velocity,  due  to  the  action" of  the  heart,  varies  in  speed 
.  from  point  to  point  of  the  same  cross-section.  The  layer  next  the 
periphery  of  the  vessel,  the  so-called  peripheral  plasma-layer  or 
Poiseuille's  space,  moves  more  slowly  than  the  central  portion,  the 
axial  stream.  In  fact,  we  must  suppose  that  in  the  large  as  well  as 
in  the  small  vessels  the  layer  just  in  contact  with  the  vessel-wall  is 
at  rest,  while  the  stratum  internal  to  this  slides  on  it  and  has  its 
velocity  diminished  by  the  friction.  The  next  layer  again  slides  on 
the  last,  but  since  this  is  already  in  motion,  its  velocity  is  not  so 
much  diminished,  and  so  on.  The  velocity'  must  therefore  increase 
as  we  pass  towards  the  axis  of  the  bloodvessel,  and  reach  its  maxi- 
mum there  (p.  193). 

Again,  the  velocity  must  be  altered  wherever  an  alteration  occurs 
in  the  width  of  the  bed,  that  is,  in  the  total  cross-section  of  the 
vascular  system ;  for  since  as  much  blood  comes  back  in  a  given  time 
to  the  right  side  of  the  heart  as  leaves  the  left  side,  the  same  quantity 
must  pass  in  a  given  time  through  every  cross-section  of  the  circula- 
tion. Wherever  the  total  section  of  the  vascular  tree  increases,  the 
blood-current  must  slacken;  wherever  it  diminishes,  the  current 
must  become  more  rapid.  Now,  the  total  section,  increasing  some- 
what as  we  pass  from  the  heart  along  the  branching  arteries,  under- 
goes an  abrupt  augmentation,  and  reaches  its  maximum  in  the 
capillary  region.  It  suddenly  diminishes  again  at  the  venous  end 
of  the  capillar}^  tract,  and  then  more  gradually  as  we  pass  heart - 
wards  along  the  veins,  but  never  becomes  so  small  as  in  the  arterial 
tract.  We  must,  therefore,  expect  the  mean  velocity  to  be  greatest 
in  the  large  arteries,  less  in  the  veins,  and  least  in  the  arterioles, 
capillaries,  and  venules.  It  must,  of  course,  be  remembered  that  the 
total  section  varies  from  time  to  time  at  any  given  distance  from  the 
heart.  The  capillary  tract  is  especially  variable  in  its  area,  and 
capillaries  full  of  blood  at  one  moment  may  be  collapsed  and  empty 
at  another,  according  to  the  changes  of  calibre  and  pressure  in  the 
arteries  which  feed  and  the  veins  which  drain  them. 

Although  in  strictness  we  are  only  at  present  concerned  with  the 
arteries,  it  will  be  well  to  consider  here  what  a  change  of  velocity  at 
any  part  of  the  vascular  channel  really  implies.  To  say  that  when 
the  channel  widens  the  velocity  diminishes  is  not  to  explain  the 
meaning  of  this  diminution.  A  diminution  of  velocity  implies  a 
diminution  of  kinetic  energy,  and  it  is  necessary  to  know  what  becomes 
of  the  energy  that  disappears.  The  stock  of  energy  imparted  by  the 
contraction  of  the  heart  to  a  given  mass  of  blood  constantly  diminishes 
as  it  passes  round  from  the  aorta  to  the  right  side  of  the  heart,  for 
friction  is  constantly  being  overcome  and  heat  generated.     Tliis  energy, 


Mechanics  of  the  circulation  in  the  vessels      iir> 

as  \vc  have  seen,  exists  in  a  moving  liquid  in  two  forms,  potential  and 
kinetic,  the  former  being  measured  by  the  lateral  pressure,  the  latter 
var^-ing  directly  as  the  square  of  the  velocity.  Whenever  the  velocit}', 
and  therefore  the  kinetic  energy,  of  a  given  mass  of  the  blood  is 
diminished  without  a  corresponding  increase  in  the  potential  energy, 
some  of  the  total  stock  of  energy  must  have  been  used  up  to  overcome 
resistance  (p.  84). 

In  a  uniform,  rigid,  horizontal  tube,  as  has  been  already  remarked, 
the  velocity  (and  consequently  the  kinetic  energy)  is  the  same  at 
ever^'  cross-section  of  the  tube,  while  the  potential  energy,  represented 
by  the  lateral  pressure,  diminishes  regularly  along  the  tube.  When 
the  calibre  of  the  tube  varies,  it  is  different.  Suppose,  for  instance, 
that  the  liquid  passes  from  a  narrower  to  a  wider  part,  the  velocity 
must  diminish  in  the  latter.  The  kinetic  energy  of  visible  motion 
which  has  disappeared  must  liave  left  something  in  its  room.  Here 
there  are  three  possibilities:  (i)  The  kinetic  energy  that  has  disappeared 
may  be  just  enough  to  overcome  the  extra  friction  in  the  wider  part  of 
the  tube  due  to  eddies  and  consequent  change  of  direction  of  the  lines 
of  flow;  in  this  case  the  potential  energy  of  a  given  mass  of  the  liquid 
will  be  the  same  at  the  beginning  of  the  wider  part  as  in  the  narrower 
part.  The  lost  kinetic  energy  will  have  been  transformed  into  heat. 
(2)  The  kinetic  energv'  which  has  disappeared  may  be  greater  than  is 
enough  to  overcome  the  extra  resistance  ;  a  portion  of  it  must,  therefore, 
have  gone  to  increase  the  potential  energy,  and  the  lateral  pressure  will 
be  greater  in  the  wide  than  in  the  narrow  part.  (3)  The  lost  kinetic 
energ}'  may  be  less  than  enough  to  overcome  the  extra  resistance ;  in 
this  case  both  the  lateral  pressure  and  the  velocity  will  be  less  in  the 
wide  than  in  the  narrow  part.  It  has  been  experimentally  shown  that 
when  a  narrow  portion  of  a  tube  is  succeeded  by  a  considerably  wider 
portion,  and  this  again  by  a  narrow  part,  case  (2)  holds;  and  the  liquid 
may,  under  these  conditions,  actually  flow  from  a  place  of  lower  to  a 
place  of  higher  lateral  pressure. 

In  the  vascular  s\-stein  the  conditions  are  not  the  same.     The 
widening  of  t  le  bed  which  takes  place  as  we  proceed  in  the  direction 
of  the  arterial  current  is  not  due  to  the  widening  of  a  single  trunk, 
but  to  the  branching  of  the  channel  into  smaller  and  smaller  tubes. 
In  the  larger  arteries  the  increase  of  resistance  is  so  gradual  that  both 
the  potential  and  the  kinetic  energy  diminish  only  slowly,  and  the 
lateral  pressure  and  velocity  are  not  much  less  in  the  femoral  artery 
than  in  the  aorta  or  carotid.     But  in  the  arterioles  the  friction 
increases  so  greatly  that  although  the  velocity,  and  therefore  the 
kinetic  energy,  in  the  capillary  region  is  much  less  than  in  the 
arteries,  the  amount  of  kinetic  energy  lost  is  not  upon  the  whole 
equivalent  to  the  energy  consumed  in  overcoming  the  extra  resis- 
tance; the  potential  energy  of  the  blood  is  also  drawn  upon,  and  the 
lateral  pressure  falls  sharply  in  the  capillary  region,  as  well  as  the 
velocity.     Where  the  capillaries  open  into  the  veins,  the  lateral  pres- 
sure again  sinks  abruptly,  while  the  velocity  begins  to  increase,  tiU  in 
the  largest  veins  it  is  probably  about  half  as  great  as  in  the  aorta. 
Where  does  the  extra  kinetic  energy  of  the  blood  in  the  veins  come 
from  ?     To  say  that  the  vascular  channel  again  contracts  as  the 
blood  passes  from  the  capillaries  into  the  veins,  and  that,  since  the 


120  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

same  quantitj'  must  How  tlirough  every  cross-section  of  the  channel, 
the  velocity  must  necessarily  be  greater  in  the  narrower  than  in  the 
wider  part,  docs  not  answer  the  question.  The  greater  portion  of 
tlie  kinetic  energy  of  the  arterial  blood  is,  as  we  have  seen,  destroyed, 
or,  rather,  changed  into  an  unavailable  form,  into  heat,  in  the  capil- 
lary region.  The  mean  velocity  of  the  blood  in  the  capillaries  is  not 
more  than  -5^-^  to  77^  of  the  velocity  in  the  aorta;  the  kinetic  energy 
of  a  given  mass  of  blood  in  the  capillaries  cannot  therefore  be  more 
than  („  J^)2,  or  4-5  075-0  o^  ^^^  kinetic  energy  in  the  aorta.  In  the  veins, 
taking  the  velocity  at  half  the  arterial  velocity,  the  kinetic  energy 
of  the  mass  would  be  one-fourth  of  that  in  the  aorta,  or  at  least 
10,000  times  as  great  as  in  the  capillary  region.  This  extra  kinetic 
energy  comes  partly  from  the  transformation  of  some  of  the  poten- 
tial energy  of  the  blood.  The  resistance  in  the  veins  is  very  small 
compared  with  that  in  the  capillaries;  less  of  the  potential  energy 
represented  by  the  lateral  pressure  at  the  end  of  the  capillary  tract 
is  required  to  overcome  this  resistance,  and  some  of  it  is  converted 
into  the  kinetic  energy  of  visible  motion,  the  lateral  pressure  at  the 
same  time  falling  somewhat  abruptly.  Contributory  sources  of 
kinetic  energy  in  the  veins  are  the  aspiration  caused  by  the  respira- 
tory movements  and  the  pressure  caused  by  muscular  contraction 
in  general,  which,  thanks  to  the  valves,  always  aids  the  flow  towards 
the  heart.  From  these  two  sources  new  energy  is  supplied,  to  rein- 
force the  remnant  due  to  the  cardiac  systole  (p.  133). 

Measurement  of  the  Velocity  of  the  Blood — i.  Direct  Observation. — 
(a)  This  method  can  be  applied  to  transparent  parts  by  observing  the 
rate  of  flow  of  the  corpuscles  under  the  microscope.  But  it  is  only 
where  the  blood  moves  slowly,  as  in  the  capillaries,  that  the  method 
is  of  use .  (b)  Part  of  the  path  of  the  blood  through  a  large  vessel  may 
be  artificially  rendered  transparent  by  the  introduction  of  a  glass  tube, 
of  approximately  the  same  bore  as  the  vessel  (Volkmann).  The  tube 
is  filled  with  salt  solution,  and  the  blood  admitted  by  means  of  a  stoji- 
cock  at  the  moment  of  observation.  The  time  which  the  blood  takes 
to  pass  from  one  end  of  the  tube  to  the  other  is  noted,  and  the  length 
divided  by  the  time  gives  the  velocity  of  the  blood  in  the  tube.  If  the 
calibre  of  the  tube  is  the  same  as  that  of  the  artery,  tliis  is  also  the 
velocity  in  the  vessel;  but  if  the  calibre  is  different,  a  correction  would 
have  to  be  made.  The  method  is  not  a  good  one,  for  the  reason,  among 
others,  that  the  long  tube  introduces  an  extra  resi.stance. 

2.  Ludwig's  Stromuhr. — This  instrument  measures  the  quantity  of 
blood  which  passes  in  a  given  time  through  the  vessel  at  the  cross- 
section  where  it  is  inserted.  It  consists  of  a  U-shaped  tube,  with  the 
limbs  widened  into  bulbs,  but  narrow  at  the  free  ends,  which  are  con- 
nected with  a  metal  disc.  By  rotating  the  instrument,  these  ends 
can  be  placed  alternately  in  communication  with  a  cannula  in  the 
central,  and  another  in  the  peripheral,  portion  of  a  divided  artery; 
or  they  can  be  placed  so  that  none  of  the  blood  passes  through  the  bulbs, 
but  all  goes  by  a  short-cut.  One  limb  of  the  instrument  is  filled  with 
oil,  and  the  other  with  defibrinated  blood.  The  limb  containing  the 
oil  is  first  put  into  communication  with  the  central  end.  and  that  con- 
taining the  blood  witli  the  peripheral  end,  of  the  artery.     The  blood 


MECHANICS  OF  THE  CIRCULATION  IN  THE    VESSELS       121 


from  the  artery  rushes  in  and  displaces  the  oil  into  the  other  limb,  tlie 
defibrinated  blood  passing  on  into  the  circuhition.  As  soon  as  the  bloofl 
has  reached  a  certain  height,  indicated  by  a  mark,  the  instrument  is 
reversed  and  the  oil  is  again  displaced  into  the  limb  it  originally 
occupied.     This  process  is  repeated  again  and  again,  the  time  from 

beginning  to  end  of  an  experiment  being 
carefully  noted.  The  number  of  times 
the  blood  has  filled  a  bulb  in  that 
period,  the  capacity  of  the  bulb  and  the 
cross-section  of  the  vessel  being  known, 
all  the  data  required  for  calculating  the 
velocity  of  the  blood  in  the  vessel  have 
been  obtained. 

Suppose,  for  example,  that  the  cap- 
acity of  the  bulb  up  to  the  mark  is  5  c.c, 
and  that  it  is  filled  twelve  times  in  a 
minute,  the  quantity  flowing  through 
the  cross-section  of  the  artery  is  i  c.c, 
or  1,000  cub.  mm.,  per  second.  Let  the 
diameter  of  the  vessel  be  3  mm.,  then  its 
/'3y_3-i4X9, 


sectional  area  is  tt  x 


-=J      lir~^ 


Fig.  47. — Stromuhr  of  Ludwig  and 
Dogiel.  A,  B,  glass  bulbs;  a,  a 
metal  disc,  to  which  A  and  G 
are  attached,  and  which  can  be 
rotated  on  the  disc  b;  E,  F,  can- 
nula attached  to  b,  and  con- 
nected with  the  peripheral  and 
central  ends  of  a  divided  blood- 
vessel. .\t  the  beginning  of  the 
experiment,  A  and  the  junction 
between  A  and  B  are  filled  with 
oil;  B  is  filled  with  physiological 
salt  solution  or  defibrinated 
blood:  a  being  turned  into  the 
position  shown  in  the  figure,  the 
blood  passes  through  F  and  D 
into  A ,  and  the  oil  is  forced  into 
B.  As  soon  as  the  blood  has 
reached  the  mark  m,  the  disc  a, 
with  the  bulbs,  is  rapidly  ro- 
tated, so  that  C  is  now  opposite 
jF.  The  blood  now  passes  into 
B,  and  the  oil  is  again  driven 
into  A.  When  the  oil  has 
reached  D,  reversal  is  again 
made,  and  so  on. 


=  7-06 


sq.  mm.     The  velocity  is  — ;-^  =  141  mm 

per  second. 

Various  improvements  in  this  method 
have  been  made,  such  as  a  graphic  regis- 
tration of  the  reversals  of  the  stromuhr. 

3.  A  tube  or  box,  in  which  swings  a 
small  pendulum,  is  inserted  in  the  course 


Fig.  48.— Pitot'l-Tubes. 


of  the  vessel.  The  pendulum  is  deflected 
by  the  blood,  and  the  amount  of  the 
deflection  bears  a  relation  to  the  ve- 
locity of  the  stream  (Vierordt's  hcsmatachometer ;  Chauveau  and  Lortet's 
much  more  perfect  dromograph)  (Fig.  49). 

4.  Pilot's  Tubes.— li  two  vertical  tubes,  a  and  b,  of  the  form  sho\vn  in 
Fig.  48,  be  inserted  into  a  horizontal  tube  in  which  liquid  is  flowing  in 
the  direction  of  the  arrow,  the  level  will  be  higher  in  a  than  would  be 
the  case  in  an  ordinary  side-tube  without  an  elbow ;  in  6  it  will  be  lower. 
For  the  moving  liquid  will  exert  a  push  on  the  column  in  a,  and  a  pull 


nil-:  CIRCULATION  0I<   THE  BLOOD  AND  LYMPH 


tfffjL'Tj'j.^'g 


on  that  in  h.  The  amount  of  this  push  and  pull  will  vary  with  the 
velocity,  so  that  a  change  in  the  latt  r  will  correspond  to  an  alteration 
in  the  difference  of  level  in  the  two  tubes.  Instruments  on  this  prin- 
ciple have  been  constructed  by  Marey  and  Cybulski,  the  former  regis- 
tering the  movements  of  the  two  columns  of  blood  by  connecting  the 
tubes  to  tambours  provided  with  writing  levers,  the  latter  by  photo- 
graphy (Fig.  50). 

5.  7  he  electrical  method,  described  on  p.  135, 
for  the  measurement  of  the  circulation  time,  can 
also  be  applied  to  the  estimation  of  the  mean 
velocity  of  the  blood  between  two  cross-sections 
of  the  arterial  path  which  are  separated  by  a 
sufficient  distance.  For  example,  salt  solution 
can  be  injected  into  the  left  ventricle  or  the  be- 
ginning of  the  aorta,  and  the  interval  which  it 
takes  to  reach  a  pair  of  electrodes  in  contact  with, 
say,  the  femoral  artery  determined.  Kjiowing 
the  distance  between  the  point  of  injection  and 
the  electrodes,  we  can  then  calculate  the  mean 
velocity. 

6.  In  the  calorimetric  method  of  measuring  the 
quantity  of  blood  which  passes  through  such 
parts  as  the  hands  (or  feet)  in  man,  the  flow  is 
deduced  from  the  quantity  of  heat  given  off  by 
the  part  in  a  given  time,  and  the  difference  be- 
tween the  temperatures  of  the  blood  entering  and 
leaving  the  part.  The  hands  are  immersed  in  a 
large  bath  of  water  (a  few  degrees  below  arterial 
blood  temperature)  for  a  sufficient  time  to  permit 
any  change  of  temperature  of  the  parts  due  to 
the  difference  in  temperature  between  them  and 
the  water  to  be  estabhshed.  The  hands  are  then 
rapidly  transferred  to  calorimeters  previously 
filled  with  water  at  the  same  temperature  as  that 
of  the  bath.  All  the  heat  henceforth  given  off 
can  be  assumed  to  be  due  to  the  cooling  of  the 
blood  passing  through  the  hands,  since  the  small 
amount  of  heat  produced  in  the  resting  hands  is 
negligible  for  this  purpose.  The  temperature  of 
the  arterial  blood  at  the  wrist  is  taken  as  0*5°  C. 
below  that  of  the  rectum,  this  beuig  the  relation 
actually  found  in  a  normal  man.*  The  tempera- 
ture of  the  venous  blood  leaving  the  hand  is  taken 
as  that  of  the  calorimeter,  since  it  has  been  found 
that  blood  withdrawn  from  the  hand  veins  by 
puncture,  and  collected  with  suitable  precautions 
to  prevent  loss  of  heat  as  far  as  possible  and  to 
permit  the  calculation  of  the  unavoidable  loss, 
has   a  temperature    only   a    negligible    fraction 

of   a    degree    above    that    of    the    bath    in    which   the    hand   is   im- 
mersed.    The  flow  in  grammes  per  minute  is  obtained  from  the  formula 

H  I 

Q=      /-.  'YTy    "'  where  Q  is  the  quantity  of  blood,  H  the  number 

*  The  temperature  of  the  arterial  blootl  at  the  wrist  was  assumed  to  be  the 
calorimeter  temperature  at  which  the  calorimeter  neither  loses  heat  to  tlie  hand 
nor  gTJns  heat  from  it.  If  the  heat  production  in  the  resting  hand  is  negligible, 
this  must  correspond  to  the  temperature  of  the  entering  blood. 


Fig.  49.  —  Chauveau's 
Dromograph.  A,  tube 
connected  with  blood- 
vessel; B,  metal  cylin- 
der in  communica- 
tion with  A.  The  upper 
end  of  B  has  a  hole  in 
the  centre,  which  is 
covered  by  a  mem- 
brane, m,  through 
which  a  lever,  C, 
passes;  C  has  a  small 
disc,  p,  at  its  end, 
which  projects  into  the 
lumen  of  A,  and  is  de- 
flected in  the  direction 
of  the  blood  -  stream 
through  A.  The  de- 
flection is  registered  by 
a  recording  tambour  in 
communication  by  the 
tube  E  with  a  tambour 
D,  the  flexible  mem- 
brane of  which  is  con- 
nected with  the  lever 
or  pendulum  C. 


MECHANICS  OF  THE  CIRCULATION  IN  THE    VESSELS 


123 


of  small  calorics  (gramme-calories)  given  off  in  m  minutes,  T  the  tem- 
perature of  the  blood  entering  the  hand,  T^  the  temperature  of  the 
blood  leaving  the  hand,  and  s  the  specific  heat  of  blood  (o-g).  For 
purposes  of  comparison  the  volume  of  the  hands  is  measured,  and  the 
blood-flow  expressed  in  grammes  per  100  c.c.  of  hand  per  minute. 
Further  details  are  given  in  the  Practical  Exercises  (p.  219).  Fig.  51 
shows  one  of  the  calorimeters  on  its  adjustable  stand.  The  collar  of 
thick  felt  which  fits  closely  around  the  wrist,  and  prevents  loss  of  heat 
from  the  orifice  through  which  the  hand  is 
inserted,  is  shown  standing  on  the  top  of 
the  calorimeter,  as  also  the  thermometer 
with  the  small  sliding  lens,  or  '  reader.'  In 
Fig.  108,  p.  .220.  the  position  of  the  subject 
with  haads  in  the  calorimeters  is  shown. 


Fig-  50. — Cybulski's  Arrangement  for  recording 
Variations  in  the  Velocity  of  the  Blood.  A,  tube 
connected  with  central,  B  with  peripheral,  end 
of  divided  bloodvessel.  The  blood  stands  higher 
in  the  tube  C  than  in  D.  A  beam  of  light  passing 
through  the  meniscus  in  both  tubes  is  focussed  by 
the  lens  L  on  the  travelling  photographic  plate  E. 
The  velocity  at  any  moment  is  deduced  from  the 
height  of  the  meniscus  in  the  two  tubes  C  and  D. 


Fig.  51. — Calorimeter  with 
stand  for  measuring 
blood-flow  in  hand. 


Of  these  methods,  3  and  4  are  alone  suited  for  the  study  of  the 
velocity-pulse,  that  is,  the  change  of  velocity  occurring  with  every 
beat  of  the  heart.  The  curves  obtanied  by  Chauveau's  dromo- 
graph  show  a  general  agreement  with  blood-pressure  tracings  taken 
by  a  spring  manometer,  and  with  records  of  the  external  pulse 
obtained  by  a  sphygmograph.  There  is  a  primary  increase  of 
velocity  corresponding  with  the  ventricular  systole,  and  a  secondary 
increase  corresponding  wdth  the  dicrotic  wave  (Fig.  54).  Like  all 
the  other  pulsatory  phenomena,  the  velocity-pulse  disappears  in  the 
capillaries,  and  is  only  present  under  exceptional  circumstances  in 
the  veins. 


124  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

Fick,  from  a  comparison  of  sphygmographic  and  plethysmographic 
tracings  (p.  128).  taken  simultaneously  from  the  radial  artery  and 
the  hand,  has  demonstrated  that  in  man  the  vcItm  it\  pnlsc  exhibits 


tig.  52.  Fig.  53. 

Fig.  52. — The  highest  of  the  three  curves  is  a  plethysmographic  record  taken  from 
the  hand;  the  second  curve  is  a  sphygmogram  taken  simultaneously  from  the 
corresponding  radial  artery;  the  lowest  (interrupted)  curve  is  the  curve  of  velocity 
deduced  from  a  comparison  of  the  first  two  (Fick). 

Fig-  53- — Simultaneous  plethysmographic  and  sphygmographic  tracings. 


the  same  general  characters  as  in  animals  (Figs.  52  and  53).  And 
V.  Kries  has  confirmed  Fick's  conclusions  by  actual  records  of  the 
velocity-pulse  obtained  by  means  of  an  arrangement  called  a  gas 
tachograph  (Fig.  55). 


Fig.  54. — Simultaneous  Tracings  of  the  Velocity  (Upper  Curs'c)  and  I'rcssure  (Lower 
Curve)  (Lortet).  The  tracings  were  taken  from  the  carotid  artery  of  a  hersc. 
The  curve  of  velocity  was  obtained  by  the  dromograph.  The  dicrotic  wave  is 
marked  on  it.  The  slightly  curved  ordinates  drawn  through  the  cur\'es  indicate 
corresponding  points. 

This  consist.s  of  a  plethysmograph  connected  with  the  tube  of  a  gas- 
burner.  Wlicn  the  part  enclosed  in  the  plethysmograph  expands,  air 
issues  from  the  connecting  tube,  and  causes  an  increase  in  the  height  of 
the  flame.  When  the  part  shrinks,  air  is  dra\vn  in  from  the  flame, 
which  is  depressed.  Since  the  speed  of  the  blood  in  the  veins  may  be 
considered  constant  during  the  time  of  an  experiment,  the  rate  at  which 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        125 

the  volume  of  tlie  part  alters  at  any  moment  is  a  measure  of  the  pulsa- 
tory clumge  of  velocity  in  the  arteries  of  the  part.  And  by  photo- 
graphing the  movements  of  the  flame  on  a  travelling  sensitive  surface, 
the  velocity-pulse  is  directly  recorded. 

The  mean  velocity,  like  the  mean  blood-pressure,  is  more  variable 
in  the  large  arteries  near  the  heart  than  in  the  smaller  and  more 
di  stant  arteries. 
Dogiel  found  in 
measurements 
taken  with  the 
stromuhr  (a  good 
instrument  for  the 
estimation  of  mean 
speed),  within  a 
period  of  two 
minutes,  velocities 
ranging  from  over 
200  mm.  to  under 
100  mm.  per  second 
in  the  carotid  of  the 
rabbit,  and  from  over  500  mm.  to  less  than  250  mm.  in  the  carotid  of 
the  dog.  Chauveau,  with  the  dromograph,  found  the  velocity  in  the 
carotid  of  a  horse  to  be  520  mm.  per  second  during  systole,  150  mm. 
during  the  pause,  220  mm.  during  the  period  of  the  dicrotic  wave. 

It  is  probable,  however,  that,  if  these  numbers  are  at  all  accurate 
for  bloodvessels  in  the  immediate  neighbourhood  of  the  heart,  there 
must  be  a  rapid  diminution  in  the  velocity  even  while  the  arteries 
are  still  of  considerable  calibre.  For  it  has  been  found  by  the 
electrical  method  that,  in  anaesthetized  dogs  at  any  rate,  as  is  shown 
in  the  following  table,  the  mean  velocity  between  the  origin  of  the 
aorta  and  the  crural  artery  in  the  middle  of  the  thigh  is  usually  less 
than  100  mm.  per  second. 


Fig-  55- — Photographic  Record  of  the  Velocity-Pulse  ob- 
tained by  the  Gas  Tachograph  (v.  Kries).  The  upper 
curve  is  the  photographic  representation  of  the  move- 
ments of  the  flame,  and  corresponds  to  the  curve  of 
velocity. 


Distance 

Average  Time  be- 

Average 
Velocity 

Average 

No.  of 

Body- 

between  Point 

tween  Injection 

Average 

Distance 

traversed  per 

Heart-beat, 

in  Milli- 

Experi- 

weight 

of  Injection  and 

and  Arrival  of  the 

Pulse-rate 

per 
Secoi  d, 
in  Milli- 

ment. 

in  Kilos. 

Electrodes, 
in  Millimetres. 

Salt  Solution,  in 

per  Minute. 

metres. 

metres. 

I. 

34-55 

420 

4-62 

105 

90-9 

51-9 

II. 

17-5 

495 

5-7 

69 

86-8 

75-4 

III. 

14-99 

400 

5-0 

102 

8o-o 

47-0 

IV. 

10-32 

470 

7-12 

74-5 

72.9 

587 

V. 

7-165 

330 

7-83 

46-3 
(weak  beat) 

42-1 

54-5 

In  I.  the  injecting  cannula  was  in  the  descending  part  of  the  thoracic 
aorta,  in  V.  at  the  very  origin  of  the  aorta,  and  in  II.,  III.,  and  IV. 
in  the  left  ventricle. 


126 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


As  to  the  speed  of  the  blood  in  the  arteries  of  man,  our  data  are 
insufficient  for  more  than  a  loose  estimate.  But  it  does  not  seem 
likely  that  the  mean  velocity  of  a  particle  of  blood  in  moving  from 
the  heart  to  the  femoral  artery  can  exceed  150  mm.  per  second  for 
the  whole  of  its  path.  This  would  correspond  to  rather  more  than 
a  third  of  a  mile  per  hour.  In  the  arch  of  the  aorta  the  average 
speed  may  be  twice  as  great.  '  The  rivers  of  the  blood  '  are,  even 
at  their  fastest,  no  more  rapid  than  a  sluggish  stream.  A  red  cor- 
puscle, even  if  it  continued  to  move  with  the  velocity  with  which  it 
set  out  through  the  aorta,  would  only  cover  about  15  miles  in  twenty- 
four  hours,  and  would  require  five  years  to  go  round  the  world. 

The  average  flow  through  the  hands  of  a  healthy  young  man,  as 
determined  in  eighteen  experiments  on  different  dates  ranging  over 
two  years,  at  room  temperatures  varying  from  19°  to  27°  C,  was 
12-8  grammes  per  100  c.c.  of  hand  per  minute  for  the  right  hand,  and 
12*3  grammes  for  the  left.  Ten  of  the  observations  on  tliis  man  are  con- 
densed in  the  table. 


Date. 

Temperature  of — 

Blood-flow  in  Grammes 

per  100  c.c.  of  Hand 

per  Minute. 

Room. 

Arterial 
Blood. 

Calorim. 

Right. 

Left. 

November  30,  19 10  - 

December  22,  1910  - 
February  i,  191 1 
March  17,  191 1 
May  24,  191 1    - 
November  3,  191 1     - 
November  9,  1911     - 
November  15,  191 1  - 
December  11,  1911   - 
March  26,  1913 

20*2 
2I'I 
22-8 
2I-I 
27-0 
25-1 
24-1 
25-2 
24-5 
24-5 

36-6 
36-8 

36-9 
36-6 
36-8 
367 
36-7 
36-8 
36-6 
36-6 

28-0 
29.7 

30-3 
29-9 

30 -9 
30-0 
30-8 

30-8 
3I-I 
31-5 

lO-I 

137 
12-6 

II-8 
18-5 

I2-I 

13-7 
14-0 
12-4 

147 

9-4 

12-5 
12-7 

II-3 

17-5 

II-7 

1^-5 
13-8 

I2'0 

I5-I 

Since  the  great  function  of  the  circulation  in  the  skin  is  the  regulation 
of  the  temperature  of  the  body  (see  Chapter  XII. ),  the  blood-flow  in 
the  hands  is,  of  course,  much  influenced  by  the  external  temperature. 
Thus,  by  far  the  greatest  flow  in  the  above  table  corresponds  to  the 
high  room  temperature  of  27°  C.  With  a  given  external  temperature, 
the  degree  of  humidity  of  the  air  also  affects  the  flow.  Under  similar 
conditions  of  external  temperature  and  daily  routine,  including  diet, 
the  hand  flow  in  one  and  the  same  individual  does  not  ^■ary  greatly 
when  measured  at  about  the  same  hour  on  different  days.  Different 
individuals,  when  tested  under  apparently  similar  conditions,  show  a 
greater  range  in  the  blood-flow.  Some  normal  persons  know  and  say 
that  their  hands  are  habitually  cool  or  cold;  others,  like  the  man  on 
whom  the  above  results  were  obtained,  that  their  hands  are  habitually 
warm.  The  former  may  be  expected  to  show  a  relatively  small,  and 
the  latter  a  relatively  large,  flow  of  blood  through  the  liands.     It  is 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        127 

possible  that  such  habitual  differences  are  associated  with  differences 
in  the  total  heat  value  of  the  food  consumed  or  in  the  proportions  of 
the  various  food  substances,  especially  of  proteins  (sec  p  605), 
for  it  is  well  known  that  even  persons  engaged  in  the  same  work,  and 
living  under  similar  external  conditions,  may  differ  greatly  in  their 
dietetic  habits,  both  as  to  (juantity  and  quality  of  the  food.  And  since 
the  cutaneous  circulation  is  by  far  the  most  important  factor  in  the 
loss  of  heat  from  the  body,  the  hearty  eaters,  other  things  being  equal, 
may  be  expected  to  have  the  largest  blood-flow  through  parts  like  the 
hands.  The  importance  of  the  flow  through  the  skin  in  the  total  hand 
flow  is  illustrated  by  the  fact  that  the  flow  per  unit  of  volume  through 
the  distal  half  of  the  hand,  which,  of  course,  has  a  large  surface  in 
proportion  to  its  volume,  is  considerably  greater  than  through  the  hand 
as  a  whole.  For  the  forearm  the  flow  per  100  c.c.  is,  in  its  turn,  much 
less  than  in  the  hand  (ilewlett) .  In  the  foot  the  blood-flow,  as  estimated 
by  the  calorimetric  method,  is  smaller  per  unit  of  volume  of  the  part 
than  in  the  hand,  the  ratio  of  foot  flow  to  hand  flow  per  100  c.c.  of  the 
part  usually  lying  in  normal  persons  between  i  to  3  and  i  to  2.  This 
is  largely  due  to  the  proportionally  greater  proportion  of  skin  in  the 
hand,  as  well  as  to  the  smaller  proportion  of  bone,  which  has  not  an 
active  circulation.  In  the  sitting  position  the  following  results  were 
obtained  for  the  flow  in  the  feet  on  the  person  whose  hand  flows  have 
been  given  above : 


Dat«. 

Temperature  of-^ 

Blood-flow  in  Grammet 

per  loo  c.c.  of  Foot 

per  Minute. 

Room. 

Arterial 
Blood. 

Calorim.! 

Right. 

Left 

May  2,  191 1     -         -         - 
May  18,  1911   -         -         - 
June  17,1911    -         -         - 
March  26,  1913 

25-2 
26'4 
21-8 

24-5 

36-8 
36-9 

37-0 
36-5 

30-4 

31-4 
30-6 

31-4 

3-5 
3-5 

4-9 
3-9 

4-2 

4-1 

The  great  variations  in  the  vascularity  of  different  organs  and  parts, 
as  revealed  by  the  examination  of  injected  specimens  or  by  inspection 
of  the  organs  during  life,  indicate  that  there  must  be  great  differences 
in  the  blood-flow.  Observations  with  the  stromuhr  in  animals  have 
shown  that  this  is  the  case.  The  following  list  gives  the  number  of 
c.c.  of  blood  passing  per  minute  through  100  grammes  of  organ,  according 
to  the  results  of  Burton-Opitz,  Tigerstedt,  and  other  observers : 


Posterior  extremity. 

5 

Liver  (venous) 

59 

Skeletal  muscle 

....     12 

Liver  (total)    . . 

84 

Head 

..     20 

Brain    . . 

..      136 

Stomach 

. .     21 

Kidney 

..      150 

Liver  (arterial) 

...     25 

Adrenal 

500 

Intestines 

..     31 

Thyroid  gland 

..     560 

Spleen 

..     58 

The  Volume-Pulse. — When  the  pulse- wave  reaches  a  part  it  dis- 
tends its  arteries,  increases  its  volume,  and  gives  rise  to  what  may 
be  called  the  volume-pulse. 


128 


THE  CIRCULATION^    OF  THE   BLOOD  AND  LYMPH 


This  may  be  readily  recorded  by  means  of  a  plethysmograpli ,  an 
instrument  consisting  essentially  of  a  chamber  with  rigid  walls  which 
enclose  the  organ,  the  intervening  space  being  filled  up  with  liquid 
(Fig.  56).  The  movements  of  the  liquid  are  transmitted  either  through 
a  tube  filled  with  air  to  a  recording  tambour,  or  directly  to  a  piston  or 
float  acting  upon  a  writing  lever.  Special  names  have  been  given  to 
plethysmographs  adapted  to  particular  organs;  for  example,  Roy's 
oncometer  for  the  kidney.  The  method  has  been  successfully  applied 
to  the  investigation  of  circulatory  changes  in  man,  a  finger,  a  hand  or 
an  entire  limb  being  enclosed  in  the  plethysmograpli.  With  a  fairly 
sensitive  arrangement,  every  beat  of  the  heart  is  represented  on  the 
tracing  l>y  a  primary  elevation  and  a  dicrotic  wave  (Fig.  57). 

The  general  appearance  of  the 
curve  is  very  similar  to  that  of  an 
ordinary  pulse-tracing,  though 
there  are  some  differences  of  detail, 
especially  in  the  time  relations.  A 
volume-pulse  has  been  actually  ob- 
served not  only  in  limbs  and  por- 
tions of  hmbs,  but  also  (in  animals) 
in  the  spleen,  kidney  and  brain 
and  other  organs,  and  in  the  orbit. 


Fig.  56. — Plethysiujgraph  (MossOJ.  M,  balanced  test-tube,  in  communication  with 
the  glass  vessel,  D,  which  contains  the  arm,  escape  of  water  being  prevented  by 
the  rubber  cufi,  A.  When  water  passes  from  vessel  D  to  M.  or  from  M  to  D. 
M  moves  down  or  up,  and  its  movements  are  recorded  by  the  writing-point  .V. 
M  is  steadied  by  the  liquid  in  P,  into  which  it  dips. 

The  so-called  cardio-pneumatic  movements  also  constitute  a 
volume-pulse,  although  of  complex  origin.  This  name  is  given  to 
the  rhvthmical  changes  of  pressure  accompanying  the  beat  of  the 
heart,  which  can  be  detected  in  the  air  of  the  respiratory  passages 
when  one  nostril  is  connected  with  a  recording  tambour,  or  water 
manometer,  the  other  nostril  and  the  mouth  being  closed,  and  the 
respiration  suspended  in  inspiration,  with  the  glottis  open.      Or  the 


MECHANICS  OF  THE  CIRCULATION  IN  THE  VESSELS      129 

mouth  may  be  connected  with  the  recording  apparatus,  the  nostrils 
being  closed.  One  factor  in  the  production  of  these  movements  may 
be  the  change  of  lilood- volume  in  the  soft  tissues  of  the  mouth,  naso- 
pharynx, and  perhaps  also  in  the  lower  respiratory  passages  accom- 
panying the  heart-beat.  Another  factor,  and  a  more  influential  one, 
is  the  rhythmical  alteration  of  pressure  caused  directly  by  the  alter- 
nate systole  and  diastole  of  the  heart  in  the  air  contained  in  the 
lung-tissue  surrounding  it,  which  acts  as  a  kind  of  air  plethysmo- 
graph.  One  interesting  way  in  which  the  cardio-pneumatic  move- 
ments may  reveal  themselves  is  by  a  variation  with  each  beat  of  the 
heart  in  the  intensity  of  a  note  prolonged  in  singing,  especially  after 
fatigue  has  set  in.  Upon  the  whole,  the  air-pressure  falls  during 
systole,  owing  to  the  expulsion  of  blood  from  the  chest,  and  rises 
during  diastole.  The  main  cardio-pneumatic  movement  is,  there- 
fore, a  systolic  inspiration  and  a  diastolic  expiration  (Practical 
Exercises,  p.  303). 

Doubtless  the  weight  of  an  organ  would  also  show  a  pulse  correspond- 
ing to  the  beat  of  the  heart,  and  so  would  the  temperature — at  least, 
of  the  superficial  parts.     For  the  amount  of  heat  given  off  by  the  blood 


J'ig-  57- — Plethysmograph  Tracing  troia  Ann.  The  tracing  was  taken  by  means  oi 
a  tambour  connected  with  the  plethysmograph.  The  dicrotic  wave  is  distinctly 
marked. 

to  the  skin  increases  with  its  mean  velocity,  and,  therefore,  although 
the  difference  may  not  in  general  be  measurable,  more  heat  is  pre- 
sumably given  off  during  the  systolic  increase  of  velocity  than  during 
the  diastolic  slackening.  And  this,  along  with  other  considerations, 
suggests  that,  at  any  rate  in  certain  situations  and  under  certain  con- 
ditions, there  may  even  be  a  pulse  of  chemical  change ;  that  is,  a  slight 
and  as  yet  doubtless  inappreciable  ebb  and  flow  of  metabolism  corre- 
sponding to  the  rhythm  of  the  heart. 

The  Circulation  in  the  Capillaries. — From  the  arteries  the  blood 
passes  into  a  network  of  narrow  and  thin-walled  vessels,  the  capil- 
laries, which  in  their  turn  are  connected  with  the  finest  rootlets  of 
the  veins.  Physiologically-,  the  arterioles  and  venules  must  for 
many  purposes  be  included  in  the  capillary  tract,  but  the  great 
anatomical  difference — the  presence  of  circularly-arranged  muscular 
fibres  in  the   arterioles,  their  absence  in  the  capillaries — has  its 

9 


130  THE  ClJiCULATION  OF  THE  BLOOD  AND  LYMPH 

ph\'siological  correlative.  The  calibre  of  the  arterioles  can  be 
altered  by  contraction  of  these  fibres  under  nervous  influences;  the 
calibre  of  the  capillaries,  although  it  varies  passively  with  the  blood- 
pressure,  and  is  possibly  to  some  extent  affected  by  active  con- 
traction of  the  endothelial  cells,  cannot  be  under  the  control  of  vaso- 
motor nerves  acting  on  muscular  fibres  (but  see  p.  173). 

Harvey  had  deduced  from  his  observations  the  existence  of 
channels  between  the  arteries  and  the  veins.  Malpighi  was  the  first 
to  observe  the  capillary  blood-stream  with  the  microscope,  and  thus 
to  give  ocular  demonstration  of  the  truth  of  Harvey's  brilliant 
reasoning.  He  used  the  lungs,  mesentery  and  bladder  of  the  frog. 
The  web  of  the  frog,  the  tail  of  the  tadpole,  the  wing  of  the  bat,  the 
mesentery  of  the  rabbit  and  rat.  and  other  transparent  parts,  have 
also  been  frequently  employed  for  such  investigations.  From  the 
apparent  velocity  of  the  corpuscles  and  the  degree  of  magnification, 


Fig.  58. — Diagram  to  Illustrate  the  Slope  of  Pressure  along  the  Vascular  S\-stem. 
A,  arterial;  C,  capillary;  V,  venous  tract.  The  interrupted  line  represents  the 
line  of  mean  pressure  in  the  arteries,  the  \vav>'  line  indicating  that  the  pressure 
varies  with  each  heart-beat.  The  line  passes  below  the  abscissa  axis  (line  of 
zero  or  atmospheric  pressure)  in  the  veins,  indicating  that  at  the  end  of  the  venous 
system  the  pressure  becomes  negative. 

it  is  easy  to  calculate  the  velocity  of  the  capillary  blood-stream. 
It  has  been  estimated  at  from  02  to  08  mm.  per  second  in  different 
parts  and  different  animals. 

The  comparative  slowness  of  the  current  and  the  disappearance 
of  the  pulse  are  the  chief  characteristics  of  the  capillary  circulation. 
The  explanation  we  have  already  found  in  the  great  resistance  of 
the  narrow  arterioles  and  the  much-branched  capillary  vessels. 
Although  the  average  diameter  of  a  capillary  is  only  about  10  fi 
(5  to  20  yu  in  different  parts  of  the  body),  the  number  of  branches 
is  so  prodigious  that  the  total  cross-section  of  the  sj'stemic  capillary 
tract  has  been  estimated  at  500  to  700  times  that  of  the  aorta. 
Such  estimates  are,  of  course,  by  no  means  exact. 

The  total  cross-section  of  the  vascular  channel  gradually  widens 
as  it  passes  away  from  the  left  ventricle.     In  the  capillary  region 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      131 


it  undergoes  a  great  and  sudden  increase.  A  part  of  this  increase 
K  to  be  attributed  to  the  arterioles,  which,  although  individually 
very  narrow,  have  a  total  bed  considerably  greater  than  that  of  the 
arteries  from  which  they  spring.  Where  the  arterioles  pass  into 
the  capillaries  proper,  a  further  and  a  still  greater  and  more  abrupt 
increase  in  the  bed  occurs.  At  the  venous  end  of  this  region  the 
cross-section  is  again  somewhat  abruptly  contracted,  and  then 
gradually  lessens  as  the  right  side  of  the  heart  is  approached;  but 
the  united  sectional  area  of  the  large  thoracic  veins  is  greater  than 
that  of  the  aorta. 

Attempts  have  been  made  to  measure  the  blood-pressure  in  the 
capillaries  by  weighting  a  small  plate  of  glass  laid  on  the  back  of  one  of 
the  fingers  behind  the  nail,  until  the  capillaries  are  just  emptied,  as 
shown  by  the  paling  of  ihe  skin  (v,  Kries),  or  by  observing  the  height  of 
a  column  of  liquid  that 
just  stops  the  circula- 
tion in  a  transparent 
part  (Roy  and  Graham 
Brown).  The  last- 
named  observers  found 
that  a  pressure  of  100 
to  150  mm.  of  water 
(about  7  to  II  mm. 
of  Hg)  was  needed  to 
bring  the  blood  to  a 
standstill  in  the  capil- 
laries and  veins  of  the 
frog's  web;  that  is, 
about  a  third  of  the 
blood-pressure  in  the 
frog's  aorta.  The  pres- 
sure in  the  capillaries 
at  the  root  of  the  nail 
in    man     varies    from 

30  to  50  mm.  of  mercury,  as  estimated  by  the  method  of  v.  Kries.  But 
the  method  is  exposed  to  serious  errors.  The  method  of  measuring  the 
venous  pressure  described  on  p.  132  can  also  be  applied  to  the  capillaries, 
and  is  somewhat  more  satisfactory. 

Under  certain  conditions  the  pulse-wave  may  pass  into  the 
capillaries  and  appear  beyond  them  as  a  venous  pulse.  Thus,  we 
shall  see  that  when  the  small  arteries  of  the  submaxillary  gland  are 
widened,  and  the  vascular  resistance  lessened,  by  the  stimulation  of 
the  chorda  tympani  nerve,  the  pulse  passes  through  to  the  veins. 
And,  normally,  a  pulse  may  be  seen  in  the  wide  capillaries  of  the 
nail-bed — especially  when  they  are  partially  emptied  by  pressure — 
as  a  flicker  of  pink  that  comes  and  goes  with  every  beat  of  the  heart. 

We  have  seen  that  the  lateral  pressure  at  any  point  of  a  uniform 
rigid  tube  through  which  water  is  flowing  is  proportional  to  the  amount 
of  resistance  in  the  portion  of  the  tube  between  this  point  and  the  outlet. 
In  any  system  of  tubes  the  sum  of  the  potential  and  kinetic  energy 
must  diminish  in  the  direction  of  the  flow;  and  although  the  problem 


Fig.  59. — Relation  of  Blood- Pressure,  Velocity,  and 
Cross-Section.  The  cur\es  P,  V,  and  S  represent  the 
blood -pressure,  velocity  of  the  blood,  and  total  cross- 
section  respectively  in  the  arteries  A,  capillaries  C, 
and  veins  V. 


132  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

is  complicated  in  the  vascular  system  by  the  branching  of  the  channel 
and  the  variation  in  the  total  cross-section,  yet  theory  and  experiment 
agree  that  in  the  larger  arteries  the  lateral  pressure  diminishes  but 
slowly  from  the  heart  to  the  periphery',  the  resistance  being  small  com- 
pared with  the  resistance  of  the  whole  circuit.  In  the  capillary  region 
the  vascular  resistance  abruptly  increases;  the  velocity  (and  therefore 
the  kinetic  energy)  abruptly  diminishes,  and  the  lateral  pressure  falls 
much  more  steeply  between  the  beginning  and  the  end  of  this  region 
than  between  the  heart  and  its  commencement.  In  the  veins  onTj-  a 
small  remnant  of  resistance  remains  to  be  overcome,  and  the  lateral 
pressure  must  sink  again  rather  suddenly  about  the  end  of  the  capillary 
tract.  Fig.  59  shows  by  a  rough  diagram  the  manner  in  which  the 
pressure,  velocity  and  cross-section  probably  change  from  part  to  part 
of  the  vascular  system. 

The  Circulation  i.i  the  Veins. — The  slope  of  pressure,  as  we  have 
just  explained,  must  fall  rather  suddenly  near  the  beginning  and 
near  the  end  of  the  capillary  tract.  It  continues  falling  as  we  pass 
along  the  veins,  till  the  heart  is  again  reached.  In  the  right  heart, 
and  in  the  thoracic  portions  of  the  great  veins  which  enter  it,  the 
pressure  may  be  negative — that  is,  less  than  the  atmospheric 
pressure.  And  since  nowhere  in  the  venous  system  is  the  pressure 
more  than  a  small  fraction  of  that  in  the  arteries,  its  measurement 
in  the  veins  is  correspondingly  difficult,  because  any  obstruction 
to  the  normal  flow  is  apt  to  artificially  raise  the  pressure.  A  man- 
ometer containing  some  lighter  liquid  than  mercury,  such  as  water 
or  a  solution  of  sodium  citrate  or  magnesium  sulphate,  is  usually 
employed,  so  that  the  difference  of  level  may  be  as  great  as  possible. 
In  the  sheep  the  pressure  was  found  to  be  3  mm.  of  mercury  in  the 
brachial,  and  about  11  mm.  in  the  crural  vein.  Burton-Opitz 
obtained  the  following  pressures  in  dogs  (of  about  15  kilos) :  left 
facial  vein,  51;  right  external  jugular,  -011;  central  end  of  superior 
vena  cava,  —  2*8 ;  femoral  vein,  5-4;  renal  vein,  lo-g;  portal  vein, 
8-9  mm.  of  mercury. 

Estimation  of  Venous  Pressure  in  Man. — The  venous  pressure  in  man 
has  been  estimated  by  several  observers  with  more  or  less  satisfactory 
results.  The  best-known  method  is  that  of  v.  Recklinghausen.  A 
circular  rubber  bag.  with  a  central  opening,  is  laid  over  tlie  course  of 
a  vein,  so  that  the  vein  can  be  observed  through  the  opening,  as  in 
Fig.  60.  The  bag  is  smeared  with  glycerin.  A  glass  plate  is  laid  over 
the  opening  and  held  firmly,  so  that  the  vein  and  the  surrounding  skin 
are  in  a  closed  chamber.  The  bag  is  provided  with  a  side-tube,  which 
connects  it  with  a  pump  and  a  water  manometer.  By  means  of  the 
pump  air  is  forced  into  the  bag  till  the  vein  is  just  seen  to  collapse. 
The  pressure  indicated  on  the  manometer  at  this  moment  is  taken  as 
the  pressure  in  the  vein. 

By  means  of  a  modification  in  this  method,  Eyster  and  Hooker  have 
found  that  the  pressure  in  the  small  veins  of  the  arm  or  hand  generally 
varies  between  3  and  10  cm.  of  water.  In  conditions  of  congestion  of 
the  venous  system  the  pressure  may  rise  to  20  cm.  of  water  (say  15  mm. 
of  mercury^)  or  more. 

In  making  this  meatsurement  it  is  necessary  to  take  account  of  the 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      133 

position  of  the  vein,  since  the  hydrostatic  factor  (p.  iQo)  in  the  venous 
pressure  is  so  important.  Thus  it  is  obvious  that  the  pressure  in  the 
veins  of  the  hand  will  be  greater  when  it  is  hanging  down  than  when 
it  is  raised  to  level  of  the  heart  or  above  it.  Accordingly,  the  actual 
readings  of  the  manometer  must  always  be  corrected  for  the  vertical 
distance  between  the  vein  and  the  heart,  the  height  of  a  column  of 
blood  equal  to  this  distance  being  deducted  from  or  added  to  the 
manometer  reading,  according  to  whether  the  vein  is  below  or  above 
the  heart  level.  For  practical  purposes  the  heart  level  is  supposed  to 
correspond  to  the  lower  end  of  the  sternum  (costal  angle). 

For  the  measurement  of  the  pressure  in  the  right  auricle,  the  follow- 
ing simple  and  elegant  method  has  been  given  by  Gaertner,  following 
a  suggestion  of  Frey:  He  raises  the  arm  of  the  sitting  patient,  and 
observes  a  small  vein  on  the  back  of  the  hand.  At  the  moment  when  the 
vein  collapses  the  elevation  of  the  arm  is  stopped,  and  the  vertical 
distance  between  the  vein  and  the  heart  measured.  This  expressed  in 
millimetres  of  blood  {i.e..  approximately  of  water)  is  the  pressure  in 
the  auricle,  since  the  veins  of  the  arm  constitute  manometer  tubes 
connected  with  the  auricle. 

The  venous  pressure  being  so  low,  or,  in  other  words,  the  potential 
energy  which  the  systole  of  the  heart  imparts  to  the  blood  being  so 
greatly     exhausted 

before     it     reaches      Q  J^ 

the  veins,  other  in-  r  B>^-n_^  ^"^^^^^^^^^ 

fluences  begin  here 
appreciably  to 
affect  the  blood- 
stream : 

1.  Contraction    of      Fig.  60. — Diagram   of  Measurement  of  Venous  Pressure 

a^    M',j<:rJfl<:    This  (V.Recklinghausen).     H,  back  of  hand,  with  V,  a  vein ; 

me   mui>ue,^.         1  las  ^  ^^^  rubber  bag  with  central  opening;  T,  tube  leading 

COmpreseSS   the  from  bag  to  manometer  and  pump;  G,  glass  plate, 

neighbouring  veins, 

and  since  the  blood  is  compelled  by  the  valves,  if  it  moves  at 
all,  to  move  towards  the  heart,  the  venous  circulation  is  in  this 
way  helped. 

2.  Aspiration  of  the  Thorax. — In  inspiration  the  intrathoracic 
pressure,  and  therefore  the  pressure  in  the  great  thoracic  veins,  is 
diminished,  and  blood  is  drawn  from  the  more  peripheral  parts  of 
the  venous  system  into  the  right  heart  (p.  226). 

3.  Aspiration  of  the  Heart.— When  the  heart  after  its  contraction 
suddenly  relaxes,  the  endocardiac  pressure  becomes  negative,  and 
blood  is  sucked  into  it,  just  as  when  the  indiarubber  ball  of  a  syringe 
is  compressed  and  then  allowed  to  expand.  But  we  cannot  attribute 
any  great  importance  to  this ;  and,  of  course,  it  is  only  the  relaxa- 
tion of  the  right  ventricle  which  could  directly  affect  the  venous 
circulation. 

4.  Every  change  of  position  of  the  Umbs,  as  in  walking,  aids  the 
venous  circulation  (Braune),  and  this  independently  of  the  muscular 
contraction.   When  the  thigh  of  a  dead  body  is  rotated  outwards,  and 


134  ^^^  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

at  the  same  time  extended,  a  manometer  connected  with  the  femoral 
vein  shows  a  negative  pressure  of  5  to  10  mm.  of  water.  When  the 
opposite  movements  are  made,  the  pressure  becomes  positive. 

It  follows  from  the  number  of  casually-acting  influences  which 
affect  the  blood-flow  in  the  veins  that  it  cannot  be  very  regular  or 
constant.  We  have  seen  that  in  the  great  arteries  there  is  a  con- 
siderable variation  of  velocity  and  of  pressure  with  every  discharge 
of  the  ventricle,  and  although  this  variation  is  absent  from  the 
veins,  since  normally  the  pulse,  due  to  the  ventricular  discharge, 
does  not  penetrate  into  them,  the  venous  flow  is,  nevertheless,  as  a 
matter  of  fact,  more  irregular  than  the  arterial.  So  that  if  it  is 
difficult  to  give  a  useful  definition  of  the  term  '  velocity  of  the 
blood  '  in  the  case  of  the  arteries,  it  is  still  more  difficult  to  do  so  in 
the  case  of  the  veins.  Where  voluntary  movement  is  prevented, 
one  potent  cause  of  variation  in  the  venous  flow  is  eliminated;  and 
In  curarized  animals  certain  observers  have  found  but  little  differ- 
ence between  the  mean  velocity  in  the  veins  and  in  the  corre- 
sponding arteries.  Others  have  found  the  velocity  in  the  veins 
considerably  less,  which  is  indeed  what  we  should  expect  from  the 
fact  that  the  average  cross-section  of  the  venous  system  is  greater 
than  that  of  the  arterial  system.  Burton-Opitz,  by  means  of  a 
stromuhr,  obtained  a  mean  velocity  of  147  mm.  per  second  in  the 
external  jugular  vein  of  a  13-kilo  dog. 

To  sum  up,  we  may  conclude  that,  upon  the  whole,  the  blood 
passes  with  gradually-diminishing  velocity  from  the  left  ventricle 
along  the  arteries ;  it  is  greatly  and  somewhat  suddenly  slowed  in  the 
broad  and  branching  capillary  bed;  but  the  stream  gathers  force 
again  as  it  becomes  more  and  more  narrowed  in  the  venous  channel, 
although  it  never  acquires  the  speed  which  it  has  in  the  aorta. 

Venous  Pulse. — To  complete  the  account  of  the  circulation  in  the 
veins,  it  may  be  recalled  that,  in  addition  to  the  venous  pulse 
described  on  p.  131,  which,  as  an  occasional  phenomenon,  may 
travel  through  widened  arterioles  and  capillaries  from  the  arteries 
into  the  veins,  and  therefore  in  the  direction  of  the  blood-stream, 
a  so-called  venous  pulse,  travelling  from  the  heart  against  the  blood- 
stream and  depending  on  variations  of  pressure  in  the  right  auricle, 
may  be  detected  in  the  jugular  veins  in  healthy  persons,  and  more 
distinctly  in  certain  disorders  of  the  circulation,  where  indeed  it 
may  be  evident  at  a  greater  distance  from  the  heart — for  example, 
over  the  liver  as  the  so-called  li\er  pulse.  In  animals  a  venous 
pulse  of  this  nature  has  been  demonstrated  in  the  vence  cavae,  the 
jugular  vein,  and  with  a  delicate  manometer  even  in  the  large  veins 
of  the  Umbs.  It  moves  with  a  speed  of  i  to  3  metres  a  second 
(Morrow).  It  is  most  easily  observed  in  the  jugular  veins  in  man, 
because  of  their  proximity  to  the  heart.  We  have  already  pointed 
out  the  significance  of  the  study  of  this  venous  pulse  for  the  analysis 


MECHANICS  OF  THE  CIRCULATION  IN  THE    VESSELS      135 

of  cardiac  events  (p.  100).  A  jugular  venous  pulse  of  a  perfectly 
different  origin  is  seen  in  cases  of  incompetence  of  the  tricuspid 
valve.  Here  the  chief  elevation  is  synchronous  with  the  ventricular 
systole,  and  is  caused  by  the  regurgitation  of  blood  from  the  right 
ventricle  through  the  auricle  into  the  veins.  The  so-called  '  com- 
municated venous  pulse  '  is  simply  due  to  the  proximity  of  some 
large  artery,  especially  when  enclosed  in  a  common  sheath,  whose 
pulsations  are  directly  transmitted  to  the  vein.  The  changes  of 
pressure  in  the  great  veins  accompanying  the  respiratory  move- 
ments (p.  290)  are  also  sometimes  spoken  of  as  a  venous  pulse,  but 
they  are  produced  in  a  different  way — namely,  by  the  rhythmical 
alteration  in  the  intrathoracic  pressure,  which  alternately  favours 
and  hinders  the  venous  return  to  the  heart. 

The  Circulation-Time. — Hering  was  the  first  who  attempted  to 
measure  the  time  required  by  the  blood,  or  by  a  blood-corpuscle,  to 
complete  the  circuit  of  the  vascular  system.  He  injected  a  solution  of 
potassium  ferrocyanide  into  a  vein  (generally  the  jugular),  and  collected 
blood  at  intervals  from  the  corresponding  vein  of  the  opposite  side. 
After  the  blood  had  clotted,  he  tested  for  the  ferrocyanide  by  addition 
of  ferric  chloride  to  the  serum.  The  first  of  the  samples  that  gave  the 
Prussian  blue  reaction  corresponded  to  the  time  when  the  injected  salt 
had  just  completed  the  circulation.  This  method  was  improved  by 
Vierordt,  who  arranged  a  number  of  cups  on  a  revolving  disc  below  the 
\ein  from  which  the  blood  was  to  be  taken.  In  these  cups  samples  of 
the  blood  were  received,  and  the  rate  of  rotation  of  the  disc  being  known, 
it  was  possible  to  measure  the  interval  between  the  injection  and  appear- 
ance of  the  salt  with  considerable  accuracy.  Hermann  made  a  further 
advance  by  allowing  the  blood  to  play  upon  a  revolving  drum  covered 
with  paper  soaked  in  ferric  chloride,  and  by  using  the  less  poisonous 
sodium  ferrocyanide  for  injection. 

Even  as  thus  modified,  the  method  laboured  under  serious  defects. 
It  was  not  possible  to  make  more  than  a  single  observation  on  one 
animal,  at  least  without  allowing  a  considerable  interval  for  the  elimina- 
tion of  the  ferrocyanide,  and,  further,  the  method  was  unsuited  for  the 
estimation  of  the  circulation-time  in  individual  organs.  In  both  of 
these  respects  the  more  recently  introduced  electrical  method  presents 
considerable  advantages;  for  by  its  aid  we  can  not  only  obtain  satis- 
factory measurements  of  the  circulation-time  in  such  organs  as  the 
lungs,  liver,  kidney,  etc.,  but  we  can  repeat  them  an  indefinite  number 
of  times  on  the  same  animal. 

A  cannula,  connected  with  a  burette  (or  a  Mariotte's  bottle,  or  a 
syringe),  containing  a  solution  of  sodium  chloride  (usually  a  i'5  to 
2  per  cent,  solution),  is  tied  into  a  vessel — say  the  jugular  vein.  Sup- 
pose that  the  time  of  the  circulation  from  the  jugular  to  the  carotid  is 
required — that  is,  practically  the  time  of  the  lesser  or  pulmonary  circu- 
lation. A  small  portion  of  one  carotid  artery  is  isolated,  and  laid  on 
a  pair  of  hook-shaped  platinum  electrodes,*  covered,  except  on  the 
concave  side  of  the  hook,  with  a  layer  of  insulating  varnish.  To 
further  secure  insulation,  a  bit  of  very  thin  sheet-indiarubber  is  slipped 
between  the  artery  and  the  tissues.     By  means  of  the  electrodes  the 

*  The  electrodes  can  easily  be  made  by  beating  out  one  end  of  a  piece  of 
thick  platinum  wire  to  a  breadth  of  5  or  6  mm.,  and  then  bending  the  flattened 
part  into  a  hook,  or  by  bending  pieces  of  stout  platinum  foil. 


136 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


piece  of  artery  lying  bttwccn  them,  with  the  blood  that  flows  in  it,  is 
connected  up  as  one  of  the  resistiinccs  in  a  Whcatstonc's  bridge  (p.  726). 
The  secondary  coil  of  a  small  inductorium,  arranged  for  giving  an  inter- 
rupted current,  and  with  a  single  Daniell  or  dry  cell  in  its  primary,  is 
substituted  for  the  batter^',  and  a  telephone  for  the  galvanometer, 
according  to  Kohlrausch's  well-kno\"m  method  for  the  measurement  of 
the  resistance  of  electrol>i:es.  It  is  well  to  have  the  induction  machine 
set  up  in  a  separate  room  and  connected  to  the  resistance-box  by  long 
wires,  so  that  the  noise  of  the  Necf's  hammer  may  be  inaudible.  The 
bridge  is  balanced  by  adjusting  the  resistances  until  the  sound  heard 
in  the  telephone  is  at  its  minimum  intensity,  the  secondary  coil  being 
placed  at  such  a  distance  from  the  primary  that  there  is'  no  sign  of 
stimulation  of  muscles  or  ner\'es  in  the  neighbourhood  of  the  electrodes 


f  \u,r»KC"^-||'^*'' 


Fig.  61. 


-Measurement  of  the  Pulmonary  Circulation-Time  in  Rabbit  by  Injection 
of  Methvlene  Blue. 


when  the  current  is  closed.  A  definite,  small  quantity  of  the  salt  solu- 
tion is  now  allowed  to  run  into  the  vein  by  turning  the  stop-cock  of  the 
burette.  It  moves  on  with  the  velocity  of  the  blood,  and  reaching  the 
arter\'  on  the  electrodes  causes  a  diminution  of  its  electrical  resistance 
(p.  26).  This  disturbs  the  balance  of  the  bridge,  and  the  sound  in  the 
telephone  becomes  louder.  The  time  from  the  beginning  of  the  injec- 
tion to  the  alteration  in  the  sound  is  the  circulation  -  time  between 
jugular  and  carotid.  It  can  be  read  off  by  a  stop-watch,  or  more 
accurately  by  an  electric  time-maker  writing  on  a  revolving  drum 
(Fig.  62).  Instead  of  the  telephone  a  galvanometer  may  be  used,  the 
equal  and  oppositely  directed  induction  shocks  being  replaced  by  a 
weak  voltaic  current,  and  the  platinum  by  unpolarizable  electrodes 
(p.  731).     But  this  is  less  convenient. 


■    '  '.  I.  11/,  i: ; 
MECHANICS  OF  THE  CIRCULATION  IN  THE  VESSELS     137 

The  circulation-time  of  an  organ  like  the  kidney  can  be  measured  by 
adjusting  a  pair  of  clcctrodts  under  the  renal  artery  and  anotlier  under 
the  renal  vein,  and  reading  off  the  interval  required  by  the  salt  solution 
to  pass  from  the  point  of  injection  first  to  the  artery  and  then  to  the 
vein.     The  difference  is  the  circulation-time  through  the  kidney. 

For  certain  purposes,  and  particularly  for  measurements  on  small 
animals  like  the  rabbit,  or  on  organs  whose  vessels  are  too  delicate  to 
be  placed  on  electrodes  without  the  risk  of  serious  interference  with 
the  circulation,  anotlier  method  may  be  employed  with  advantage.  It 
depends  on  the  injection  of  a  pigment,  like  methylene  blue,  which  at 
first  overpowers  the  colour  of  the  blood  and  shows  through  the  walls  of 
the  bloodvessels,  but  is  soon  reduced  to  a  colourless  substance  (Fig.  61). 
The  details  of  the  method  are  given  in  the  Practical  Exercises  (p.  217.) 

It  may  be  said  in  general  terms  that  in  one  and  the  same  animal 
the  time  of  the  lesser  circulation  is  short  as  compared  with  the  total 
circulation-time,  relatively  constant,  and  but  little  affected  by  changes 
of  temperature.  In  animals  of  the  same  species  it  increases  with  the 
size,  but  more  slowly,  and  rather  in  proportion  to  the  increase  of 
surface  than  to  the  increase  of  weight. 

Thus  a  dog  weighing  2  kilogrammes  had  an  average  pulmonary 
circulation-time  of  4'05  seconds,  while  that  of  a  dog  weighing  11  8  kilos 
was  8'7  seconds,  and  that  of  a  dog  with  a  body-weight  of  i8"2  kilos  only 
io*4  seconds.  It  is  probable  that  in  a  man  the  pulmonary  circulation- 
time  is  not  usually  much  less  than  12  seconds,  nor  much  more  than 
15  seconds. 

The  circulation-time  in  the  kidney,  spleen  and  liver  is  relatively 
long  and  much  more  variable  than  that  of  the  lungs,  being  easily 
affected  by  exposure  and  changes  of  temperature  (increased  by 
cold,  diminished  by  warmth). 

In  a  dog  of  13-3  kilos  weight  the  average  circulation-time  of  the 
spleen  was  10 -95  seconds;  kidney,  13-3  seconds;  lungs,  8-4  seconds. 
The  circulation-time  of  the  stomach  and  intestines  is  (in  the  rabbit) 
comparatively  short,  not  exceeding  very  greatly  that  of  the  lungs, 
but  it  is  lengthened  by  exposure.  The  circulation-time  of  the 
retina  and  that  of  the  heart  (coronary  circulation)  are  the  shortest 
of  all. 

The  total  circulation-time  is  properly  the  time  required  for  the  whole 
of  the  blood  to  complete  the  round  of  the  pulmonary  and  systemic 
circulation.  But  there  are  many  routes  open  to  any  given  particle  of 
blood  in  making  its  systemic  circuit.  If  it  passes  from  the  aorta  through 
the  coronary-  circulation  it  takes  an  exceedingly  short  route.  If  it  passes 
through  the  intestines  and  liver,  or  through  the  kidney,  or  through  the 
lower  limbs,  it  takes  a  long  route.  So  that  to  determine  the  total  cir- 
culation-time by  direct  measurement  we  must  know  (i)  the  quantity 
of  blood  that  passes  on  the  average  by  each  path  in  a  given  time,  and 
(2)  the  average  circulation-time  of  each  path.  If  the  average  weight  of 
blood  in  each^jrgan  be  represented  by  wi,  w^,  w^,  etc.;  and  the  average 
circulation-times  by  1^,  t^,  t^,  etc. ;  and  /  be  the  total  systemic  circulation- 

t  t  t 

tmie;  then  iffy,  w^-: ,  "'37.  etc.,  will  represent  the  quantity  of  blood 

*1  *2  '3 

passing  through  each  organ  in  t  seconds,  since  in  the  average  circula- 


i3« 


THE  CIRCULATION  OF  THE  BLOOD  AXD  LYMPH 


tion-timc  of  an  organ  the  whole  of  the  blood  in  it  at  the  beginning  of 
the  period  of  observation  will  have  been  exchanged  for  fresh  blood. 
But  the  whole  of  the  blood  in  the  body,  which  we  may  call  VV,  passes 
once     round    the    systemic    circulation     in     t    seconds.       Therefore, 

w.r  +tt'oT  +w^-,  etc.,=W.     In  this  equation  everj-thing  can  be  de. 


/i 


''t. 


n 


JLJLJLJLJLJLJLJIJULJLJIJUUULJLJLX 


127 


tcrmined  by  experiment  except  /.  and  therefore  /  can  be  calculated. 
.A.dding  t  to  the  pulmonary  circulation -time,  we  arrive  at  the  tota 
circulation-time. 

Although  our  experimental  data  are  as  yet  too  meagre  to  make  the 
calculation  more  than  a  rough  approximation,  it  apjjcars  probable  that 
in  certain  animals  the  total  circulation-time  is  five  or  six  times  as  great 
as  the  pulmonary  circulation -time.  If  the  same  ratio  holds  good  in 
man.  the  total  circulation-time  is  unlikely  to  be  much  less  than  a  minute 

or  much  greater  than  a 

' J  L_ minute  and  a  quarter. 

We  shall  see  directly 
that  this  estimate  is 
confirmed  by  data  de- 
rived from  a  different 
source.  In  the  mean- 
time, we  may  use  it 
{provisionally  to  calcu- 
ate  the  work  done  by 
the  heart.  Let  us  take 
for  simplicity  the  total 
circulation  -  time  as  i 
minute  in  a  70  -  kilo 
man,  the  quantity  of 
blood  as  4^  kilos,*  and 
the  mean  pressure  in 
the  aorta  as  150  mm. 
of  mercury.  Up  to  the 
time  when  the  semi- 
lunarvalves  areopened, 
the  work  done  by  the 
left  ventricle  is  spent 
in  raising  the  intraven- 
tricular pressure  till  it 
is  sufficient  to  over- 
come the  pressure  in 
the  aorta.  If  a  vertical 
tube  were  connected 
with  the  left  ventricle, 
the  blood  would  rise  till 
the  column  was  of  the  same  weight  as  a  column  of  mercury  of  equal  section 
and  150  mm.  high.  This  column  of  blood  would  be  about  192  metres  in 
height.  If  a  reservoir  were  placed  in  communication  with  the  tube  at 
this  height,  a  quantity  of  blood  equal  to  that  ejected  from  the  ventricle 
would  at  each  systole  pass  into  the  reservoir;  and  the  work  which  the 
blood  thus  collected  would  be  capable  of  doing,  if  it  were  allowed  to 
fall  to  the  level  of  the  heart,  v.ould  be  equal  to  the  work  expended  by 
the  heart  in  forcing  it  up.  Thus,  in  i  minute  the  work  of  the  left  ven- 
tricle would  be  equal  to  that  done  in  raising  4^  kilos  of  blood  to  a  height 

*  The  mean  of  the  5^  kilos  given  by  most  writers,  and  of  the  3J  kilos  ob- 
tained by  Haldane  and  Smith  (p.  56). 


_JLJl_a_JLJLJl_Jl-JlJUn_n_JLJLJLJLJLJLJlJL 

Fig.  62. — Time  of  the  Lesser  Circulation.  Cat  anaes- 
thetized with  Ether.  Time-trace,  seconds.  The  line 
above  the  time-trace  was  written  by  an  electro- 
magnetic signal,  the  circuit  of  which  was  closed  at 
the  moment  when  injection  of  methylene  blue  into 
the  jugular  vein  was  begun,  and  opened  at  the 
moment  when  the  change  of  colour  in  the  carotid 
was  observed.  I.  normal  circulation-time;  II,  cir- 
culation-time after  section  of  both  vagi  (much 
diminished);  HI,  circulation-time  during  stimulation 
of  the  peripheral  end  of  one  vagtis  (much  increased). 


MLCflAMCS  OF  THE  CI HCIJLATION  IN   THE   VESSELS       139 

of  I  92  metres — that  is,  about  S()4  kilogramme-metres;  in  24  hours  it 
would  be,  say,  12,450  kilogrammt-mctrcs.  'Jaking  the  mean  pressure 
in  the  puhnonary  artery  at  one-third  of  the  aortic  pressure,  we  get  for 
the  daily  work  of  the  right  ventricle  about  4,150  kilogramme-metres. 
The  work  ol  the  two  ventricles  is  thus  about  16,600  kilogramme-metres,* 
which  is  enough  to  raise  a  weight  of  nearly  4  pounds  from  the  bottom 
of  the  deepest  mine  in  the  world  to  the  top  of  its  highest  mountain,  or 
to  raise  the  man  himself  to  ij^  times  the  height  of  the  spire  of  Strasburg 
Cathedral,  or  twice  the  height  of  the  loftiest  '  skyscraper  '  in  New  York. 
By  friction  in  the  bloodvessels  this  work  is  almost  all  changed  into  its 
equivalent  of  heat,  nearly  40,000  gramme-calories  (p.  688) .  Further,  since 
the  contraction  of  the  heart  is  always  maximal  (p.  154),  and  there  is 
reason  to  believe  that  the  quantity  of  blood  ejected  at  a  single  systole 
by  the  left  ventricle  (being  dependent  upon  the  inflow  from  the  pulmon- 
ary veins,  and  therefore  upon  the  inflow  into  the  right  side  of  the  heart 
from  the  systemic  veins)  varies  widely,  some  of  the  mechanical  effect 
of  the  contraction  must  be  wasted  when  the  quantity  is  less  than  the 
ventricle  is  capable  of  expelling. 

Output  of  the  Heart. — If  4J  kilos  of  blood  pass  through  the  heart  in 
I  minute  with  the  average  pulse-rate  of  72  per  minute,  the  quantity 

ejected  by  either  ventricle  with  every  systole  will  be  — —  =  62*5  grm., 

or  a  little  less  than  60  c.c.  The  output  may  be  expressed  in  grammes 
or  cubic  centimetres  per  minute  (the  minute  volume),  or  per  second,  or 
per  beat.  It  has  been  measured  in  animals  in  several  ways — e.g.,  by 
inserting  a  stromuhr  (p.  121)  on  the  course  of  the  aorta,  or  by  recording 
the  variations  in  the  volume  of  the  heart,  or,  better,  of  the  ventricles, 
by  means  of  a  plethysmograph  (cardiometer  of  Henderson),  in  which 
the  organ  is  enclosed.  Another  method,  which  does  not  entail  the 
opening  of  the  chest,  is  to  allow  a  salt  solution  to  riin  slowly,  for  a  de- 
finite number  of  seconds,  into  the  left  ventricle  through  a  tube  passed 
into  it  from  the  carotid  artery.  A  sample  of  the  mixture  of  blood  and 
salt  solution  is  collected  from  a  branch  of  the  femoral  artery,  where  its 
arrival  is  detected  by  the  change  of  electrical  resistance  (p.  135).  From 
the  amount  of  salt  solution  which  must  be  added  to  a  normal  sample 
of  blood  drawn  before  the  injection  to  make  its  conductivity  the  same 
as  that  of  the  sample  taken  during  the  passage  of  the  mixture,  the 
quantity  of  blood  with  which  the  solution  was  mixed  in  the  ventricle 
during  the  injection  can  be  approximately  determined.  By  this  method 
it  has  been  shown  in  a  series  of  experiments  on  more  than  twenty  dogs, 
ranging  in  weight  from  5  to  nearly  35  kilos,  that  the  output  of  the 
left  ventricle  per  kilo  of  body-weight  per  second  diminishes  as  the  size 
of  the  animal  increases ;  and  the  relation  between  body-weight  and  out- 
put is  such  that  in  a  man  weighing  70  kilos  we  can  hardly  suppose  that 
the  ventricle  discharges,  during  bodily  rest,  more  than  105  grm.  of 
blood  per  second,  or  87  grm.  (80  c.c.)  per  heart-beat  with  a  pulse-rate 
of  72.  Putting  this  result  along  with  that  deduced  from  the  circulation- 
time,  we  can  pretty  safely  conclude  that  the  average  amount  of  blood 
thrown  out  by  each  ventricle  at  each  beat  is  not  more  than  70  or  80  c.c. 
Zuntz,  from  the  quantity  of  oxygen  absorbed  by  the  blood  in  the  lungs 
in  a  definite  short  time,  and  the  difference  between  the  oxygen  content 
of  samples  of  the  arterial  and  venous  blood,  has  estimated  the  output 
per  beat  at  60  c.c.     But  according  to  him  this  may  be  doubled  during 

•  Since  the  blood  on  expulsion  is  moving  with  a  certain  velocity,  an  addi- 
tion might  be  made  for  its  kinetic  energy.  But  this  would  only  increase  the 
total  work  by  a  small  fraction  (about  i  per  cent.). 


140  77//;  CJRCULATIOS  Ol-    THE  BLOOD  AND  LYMPH 

severe  muscular  work,  wlicn,  as  a  matter  of  fact,  by  the  aid  of  the 
Rontgcn-rays  or  by  percussion  of  the  chest,  the  volume  of  the  heart 
may  be  shown  to  be  considerably  increased.  Tigcrstedt,  on  the  basis 
of  stromuhr  measurements  in  animals,  puts  the  ventricular  output  per 
beat  in  man  at  50  to  100  c.c;  Plesch,  on  the  basis  of  gasometric  ob- 
servations on  man,  at  59  c.c.  Recently  Krogh,  using  a  gasometric 
method  based  on  the  absorption  of  nitrous  oxide  gas  in  the  lungs,  found 
that  the  minute  volume  during  rest  may  vary  between  wide  limits 
(2-8  to  87  litres  of  blood  per  minute,  corresponding,  with  a  pulse-rate 
of  70,  to  40  c.c.  to  120  c.c.  per  beat).  During  muscular  work  there  is 
a  great  and  immediate  increase,  up  to,  it  may  be,  21-6  litres  per  minute. 
These  great  variations  in  the  output  of  the  ventricle  depend  primarily 
upon  variations  in  the  rate  of  return  of  the  blood  to  the  heart  by  the 
veins.  According  to  Henderson,  however,  such  great  variations  in  the 
output  per  beat  as  are  postulated  by  the  majority  of  physiologists  who 
have  worked  at  the  subject  do  not  occur,  and  the  fundamental  variable 
is  the  rate  of  the  beat. 

In  healthy  persons  in  whom  the  pulse-rate  is  permanently  much 
below  the  normal  (p.  107)  the  output  of  the  ventricle  per  beat  must,  of 
course,  be  correspondingly  increased.  In  a  man  with  a  pulse -rate 
always  below  40  during  rest  in  the  sitting  position,  the  flow  in  the  hands 
was  found  to  be  normal  in  amount,  and  all  the  signs  of  a  normal  delivery 
of  blood  from  the  left  ventricle  were  present.  Here  the  output  per 
beat  must  have  been  twice  the  usual  amount  during  rest. 


Section  IV. — The  Heart-Beat  in  its  Physiolog  cal 
Relations. 

So  far  we  have  been  considering  the  circulation  as  a  purely 
physical  problem.  We  have  spoken  of  the  action  of  the  heart  as 
that  of  a  force-pump,  and  perhaps  to  a  small  extent  that  of  a  suction- 
pump  too.  We  have  spoken  of  the  bloodvessels  as  a  system  of  more 
or  less  elastic  tubes  through  which  the  blood  is  propelled.  We  have 
spoken  of  the  resistance  which  the  blood  experiences  and  the  pressure 
which  it  exerts  in  this  system  of  tubes,  and  we  have  considered  the 
causes  of  this  resistance,  the  interpretation  of  this  pressure,  and  the 
physical  changes  in  the  vascular  system  that  may  lead  to  variations 
of  both.  But  so  far  we  have  not  at  all,  or  only  incidentally  and  very 
briefly,  dealt  with  the  physiological  mechanism  through  which  the 
physical  changes  are  brought  about.  We  have  now  to  see  that, 
although  the  heart  is  a  pump,  it  is  a  living  pump;  that,  although  the 
vascular  system  is  an  arrangement  of  tubes,  these  tubes  are  alive; 
and  that  both  heart  and  vessels  are  kept  constantly  in  the  most 
delicate  poise  and  balance  by  impulses  passing  from  the  central 
nervous  system  along  the  nerves. 

In  many  respects,  and  notably  as  regards  the  influence  of  nerves 
on  it,  we  may  look  upon  the  heart  as  an  expanded,  thickened  and 
rhythmically-contractile  bloodvessel,  so  that  an  account  of  its 
innervation  may  fitly  precede  the  description  of  vaso-motor  action 
in  general. 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS     141 

The  Relation  of  the  Heart  to  the  Nervous  System. — A  very  simple 
experiment  is  suthcient  to  prove  that  the  beat  of  the  heart  does  not 
depend  on  its  connection  with  tlie  central  nervous  system,  for  an 
excised  frog's  heart  may,  under  favourable  conditions,  of  which  the 
most  important  are  a  moderately  low  temperature,  the  presence  of 
oxygen,  and  the  prevention  of  evaporation,  continue  to  beat  for  days. 
The  mammalian  heart  also,  after  removal  from  the  body,  beats  for 
a  time,  and  indeed,  if  defibrinated  blood  be  artificially  circulated 
through  the  coronary  vessels,  for  several  or  even  many  hours.  But 
although  this  proves  that  the  heart  can  beat  when  separated  from 
the  central  nervous  system,  it  does  not  prove  that  nervous  influence 
is  not  essential  to  its  action,  for  in  the  cardiac  substance  nervous 
elements,  both  cells  and  fibres,  are  to  be  found. 

The  Intrinsic  Nerves  of  the  Heart. — In  the  heart  of  the  frog 
numerous  nerve-cells  occur  in  the  sinus  venosus,  especially  near  its 
junction  with  the  right  auricle  (Remak's  ganghon).  A  branch 
from  each  vagus,  or  rather  from  each  vago-sympathetic  nerve  (for 
in  the  frog  the  vagus  is  joined  a  Httle  below  its  exit  from  the  skull 
by  the  sympathetic),  enters  the  heart  along  the  superior  vena  cava 
(pp.  157,  198). 

Running  through  the  sinus,  with  whose  ganglion-cells  the  true  vagus 
fibres,  or  some  ol  them,  are  believed  to  make  physiological  junction 
(p.  163),  the  nerves  pursue  their  course  to  the  auricular  septum.  Here 
they  form  an  intricate  plexus,  studded  with  ganglion-cells.  From  the 
plexus  nerve-fibres  issue  in  two  main  bundles,  which  pass  down  the 
anterior  and  posterior  borders  of  the  septum  to  end  in  two  clumps  of 
nerve-cells  (Bidder's  ganglia),  situated  at  the  auriculo- ventricular 
groove.  These  ganglia  in  turn  give  off  fine  nerve-bundles  to  the  ven- 
tricle, which  form  three  plexuses — one  under  the  pericardium,  another 
under  the  endocardium,  and  a  third  in  the  muscular  wall  itself,  or  myo- 
cardium. From  the  last  of  these  plexuses  numerous  non-raedullated 
fibres  run  in  among  the  muscular  fibres  and  end  in  close  relation  with 
them.  Similar  plexuses  of  nerve-fibres  exist  in  the  mammalian  ventricle. 
But  while  scattered  ganglion-cells  are  found  in  the  upper  part  of  the 
ventricular  wall,  most  observers  have  been  unable  to  demonstrate  any 
either  in  the  mammal  or  the  frog  in  the  apical  half.  In  the  rat's  heart, 
according  to  the  careful  obser\'ations  of  Schwartz,  true  gangUon-cells 
are  confined  to  an  area  on  the  posterior  surface  of  the  auricles,  lying 
always  under  the  visceral  pericardium.  Other  writers,  however,  have 
stated  that  ganglion-cells  do  exist  in  the  apex  both  of  the  cat's  and  of 
the  frog's  heart.  In  connection  with  the  whole  question  it  must  be 
home  in  mind  that  in  other  organs  improved  histological  methods  have 
brought  typical  nerve-cells  to  light  in  situations  where  they  were  not 
suspected  or  were  denied  to  exist,  and,  further,  that  all  investigators 
are  not  agreed  upon  the  histological  criteria  by  which  ganglion-cells  are 
to  be  distinguished. 

Cause  of  the  Rhythmical  Beat  of  the  Heart. — Scarcely  any  physio- 
logical question  has  excited  greater  interest  for  many  years  than  the 
mechanism  of  the  heart-beat.  Several  properties  of  the  cardiac 
tissue  ought  to  be  distinguished  in  discussing  this  question:  (i)  Its 


I42  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

automatism — i.e.,  its  power  of  beating  in  the  absence  of  external 
stimuli;  (2)  its  rhythmicity — i.e.,  its  power  of  responding  to  con- 
tinuous stimulation  by  a  series  of  rhythmically  repeated  contrac- 
tions; (3)  its  conductivity — i.e.,  its  power  of  conducting  the  contrac- 
tion wave  or  the  impulse  to  contraction  once  it  has  been  set  up;  and 
(4)  the  power  of  co-ordination,  in  virtue  of  which  the  various  parts 
of  the  heart  beat  in  a  regular  sequence. 

The  excitability  of  the  cardiac  tissue — that  is,  its  power  of  appro- 
priate response  (namely,  by  contraction)  to  a  suitable  stimulus — 
does  not  particularly  concern  us  here,  since  it  is  in  no  wise  a  property 
special  to  the  heart.  Only,  as  we  shall  see  in  the  sequel,  the  time- 
relations  of  this  excitability  are  of  interest,  for  the  existence  of  a 
refractory  period — that  is,  an  interval  during  which  the  cardiac 
muscle  refuses  to  respond  to  excitation — throws  light  upon  the 
rhythmicity  of  the  heart-beat.  The  tonicity  of  the  heart — i.e.,  its 
power  of  remaining  contracted  to  a  certain  extent  in  the  intervals 
between  successive  beats — is  another  property  of  great  importance 
in  certain  aspects,  but  which  only  needs  to  bo  mentioned  at  present. 

Automatism  of  the  Heart-Beat — Neurogenic  and  Myogenic  Hypo- 
theses.— That  the  heart-beat  is  automatic  is  sufficiently  shown  by 
the  fact  that,  as  already  mentioned,  an  excised  and  empty  heart 
will  go  on  beating  for  a  time,  for  many  hours  or  even  for  days  in  the 
case  of  cold-blooded  animals.  When  blood,  or  even  a  suitable 
solution  of  such  inorganic  salts  as  exist  in  serum,  is  caused  to  circu- 
late through  the  coronary  vessels  of  the  excised  heart  of  a  warm- 
blooded animal,  it  also  continues  to  contract  for  a  long  time.  In 
trying  to  understand  the  real  significance  of  the  automatic  beat  of 
the  heart,  physiologists  have  endeavoured,  first,  to  compare  different 
portions  of  the  heart  as  regards  the  degree  in  which  they  possess  this 
property  of  automaticity;  and,  second,  to  associate,  if  possible,  one 
or  other  of  the  active  tissues  that  compose  the  organ,  muscle,  and 
nervous  tissue,  with  this  characteristic  property.  It  cannot  be 
pretended  that  a  final  answer  to  this  question  is  possible  at  present. 
Nor  is  the  historical  controversy  which  it  has  occasioned  perhaps  as 
important  in  itself  as  the  space  usually  devoted  to  it  in  textbooks 
might  imply.  Yet  it  is  probable  that  the  series  of  fundamental 
facts  in  the  physiology  of  the  heart  elicited  in  the  long  discussion  can 
be  best  presented,  even  for  the  purposes  of  the  elementary  student, 
as  they  were  originally  brought  forward  in  the  form  of  pros  and 
cons,  of  arguments  for  and  against  the  neurogenic  or  the  myogenic 
hypothesis.  There  is  good  evidence  that  as  in  the  amphibian 
heart  the  contraction  starts  in  the  sinus  venosus,  so  in  the  mam- 
malian heart  it  starts  in  the  sinus  tissue  of  the  right  auricle  in  the 
region  of  the  sino-auricular  node.  Attempts  have  been  made  to 
demonstrate  that  the  origination  of  the  impulses  which  are  after- 
wards conducted  to  all  parts  of  the  heart  is  normally  confined  to 


THE  HLART-BhAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      143 

the  node  itself,  and  the  sino-auricular  node  is  by  some  authors 
denominated  the  pace-maker  of  the  heart,  the  tissue  which  sets  the 
pace  for  the  rest  of  the  organ  and  gives  the  time  to  auricles  and 
ventricles  alike.  The  experimental  results,  however,  are  by  no 
means  harmonious,  some  observers  finding  that  destruction  of  the 
region  of  the  node  causes  no  change  in  the  rate  of  the  heart-beat, 
others  that  the  beat  is  permanently  slowed.  But  even  were  we  in 
a  position  to  sharply  delimit  a  given  region  of  the  heart  as  the  point 
at  which  the  strong  tendency  to  contraction  inherent  in  the  cardiac 
tissue  as  a  whole  first  breaks  into  an  actual  beat,  this  would  scarcely 
enable  us  to  decide  offhand  where  the  cause  of  the  automatism 
resides,  in  the  muscular  tissue  or  in  the  intrinsic  nervous  apparatus, 
because  in  nearly  all  animals  hitherto  investigated  the  muscular 
tissue,  ganglion-cells,  and  nerve-fibres  are  inseparably  intermingled. 
In  Limulus,  however,  the  horseshoe  or  king  crab,  the  cardiac 
ganglion-cells  are  collected  in  a  nerve-cord  running  longitudinally  in 
the  median  line  along  the  dorsal  surface  of  the  segmented  heart,  and 


z^^,::C:>^:^::^2:^^, 


Fig.  63. — -The  Heart  ana  che  Heart  Nerves  of  Limulus:  Dorsal  View  (Carlson).  (The 
heart  is  figured  one-half  the  natural  size  of  a  large  specimen.)  aa.  Anterior 
artery;  la,  lateral  arteries;  In,  lateral  nerves;  mnc,  median  nerve-cord;  os,  ostia. 


sending  off  at  intervals  branches  to  two  lateral  cords,  and  also 
branches  which  enter  the  heart  muscle  directly  (Fig.  63).  When 
the  median  nerve-cord  is  removed,  as  can  be  done  without  injuring 
the  muscle,  the  heart  ceases  for  ever  to  beat  spontaneously.  It 
still  contracts  when  directly  stimulated,  mechanically  or  electrically, 
but  the  contraction  never  outlasts  the  stimulation.  The  automatic 
power  therefore  resides  in  the  nerve-cord  alone,  and  not  in  the 
muscle.  The  same  is  true  of  the  rhjrthmical  power,  for  excitation 
of  the  nerves  that  pass  from  the  median  cord  to  the  muscle  produces, 
'  not  a  rhythmical  series  of  beats  in  the  resting,  and  an  acceleration 
of  the  rhythm  in  the  pulsating  heart,  but  a  tetanus  closely  resembling 
that  produced  in  skeletal  muscle  on  stimulation  of  a  motor  nerve  ' 
(Carlson).  Conduction  and  co-ordination  are  also  effected  in  this 
heart  through  the  nervous  mechanism,  and  essentially  through  the 
median  nerve-cord;  for  section  of  the  longitudinal  nerves  in  any 
segment  of  the  heart  abohshes  the  co-ordination  of  the  two  ends  of 
the  heart  on  either  side  of  the  lesion,  while  division  of  the  muscle 
in  any  segment  does  not  affect  the  co-ordination.  It  is  not  per- 
missible to  transfer  these  results  wholesale  to  higher  hearts,  and 


144  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

especially  the  conclusions  as  to  rhythm,  conduction,  and  co-ordina- 
tion. Nevertlu>less  the  Limulus  heart  affords  one  absolutely  un 
ambiguous  example  of  a  heart  whose  rhythmical  beat  is  sustained 
by  nervous  impulses.  And  in  the  case  of  the  higher  animals  also 
facts  may  be  adduced  in  favour  of  the  neurogenic  origin  of  the  beat. 
The  isolated  auricular  appendices  of  the  mammalian  heart,  in  which 
no  ganglion-cells  have  been  found,  refuse  to  beat  spontaneously. 
If  in  the  frog  we  divide  the  sinus,  which  is  conspicuously  rich  in 
ganglion-cells,  from  the  lower  portion  of  the  heart,  it  continues  to 
pulsate.  A  fragment  from  the  base  of  the  ventricle  will  go  on 
contracting  if  it  includes  Bidder's  ganghon,  but  not  otherwise.  We 
cut  off  the  lower  two-thirds  of  the  frog's  ventricle,  the  so-called 
apex  preparation,  which  either  contains  no  ganglion-cells  or  is 
relatively  poor  in  them,  and  it  remains  obstinately  at  rest.  Further, 
if,  without  actually  cutting  off  the  apex,  we  dissever  it  physiologically 
from  the  heart  by  crushing  a  narrow  zone  of  tissue  midway  between 
it  and  the  auriculo- ventricular  groove,  we  abolish  for  ever  its  power 
of  spontaneous  rh^'-thmical  contraction.  The  frog  may  hve  for 
many  weeks,  but  in  general  the  apex  remains  in  permanent  diastole. 
It  can  be  caused  to  contract  by  an  artificial  stimulus,  but  it  neither 
takes  part  in  the  spontaneous  contraction  of  the  rest  of  the  heart, 
nor  does  it  start  an  independent  beat  of  its  own. 

What  can  be  simpler  than  to  assume  that  the  sinus  beats  because 
it  has  numerous  ganglion-cells  in  its  walls,  and  that  the  apex  refuses 
to  beat  because  it  has  comparatively  few  or  none  ?  Could  we  pick 
out  the  nerve-cells  from  the  sinus,  without  injuring  the  muscular 
tissue,  as  easily  as  we  can  extirpate  the  median  nerve-cord  in 
Limulus,  we  may  well  suppose  that  it  would  lose  its  power  of  auto- 
matic contraction.  And  although,  if  we  pursue  our  investigations 
-a  little  farther,  facts  may  emerge  which  seem  to  contradict  the 
neurogenic  hypothesis,  the  contradiction  is  usually  only  apparent. 
Let  us  inquire,  for  instance,  what  happens  to  the  auricles  and  ven- 
tricle of  the  frog's  heart  when  the  sinus  is  cut  off.  The  answer  is 
that  as  a  rule,  while  the  sinus  goes  on  beating,  the  rest  of  the  heart 
comes  to  a  standstill,  in  spite  of  the  numerous  ganglion-cells  in  the 
auricular  septum  and  the  auriculo-ventricular  groove.  Not  only 
so,  but  if  the  ventricle  be  now  severed  from  the  auricles  by  a  section 
carried  through  the  groove,  it  is  the  former,  poor  in  nerve-cells 
though  it  be,  which  will  usually  first  begin  to  beat.  We  shall  again 
have  to  discuss  this  experiment  (p.  i6b).  It,  at  any  rate,  cannot  be 
interpreted  as  proving  that  the  automaticity  of  the  heart  does  not 
depend  upon  the  presence  of  ganglion-cells.  For  although  a  portion 
of  the  heart  rich  in  ganglion-cells  may,  under  the  circumstances 
mentioned,  refuse  for  a  time  to  beat,  there  is  good  evidence  that 
this  is  due  either  to  a  peculiar  condition  called  inhibition  into  which 
the  muscular  tissue  or  the  nerve-cells  of  the  lower  portions  of  the 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  liELATf()\S       145 

heart  have  been  thrown  by  the  first  section,  or  more  probably  to 
the  loss  of  the  accustomed  impulses  from  the  sinus  which  normally 
give  the  signal  for  the  auricular  contraction.  A  stronger  argument 
in  favour  of  the  myogenic  theory  is  the  fact  that  the  embryonic 
heart  beats  with  a  regular  rhythm  at  a  time  when  as  yet  no  ganglion- 
cells  have  settled  in  its  walls.  But  it  may  well  be  that  this  primitive 
automatic  power  of  the  cardiac  muscle,  absolutely  necessary  at  iirst, 
since  the  early  establishment  of  the  circulation  is  essential  for  the 
development  of  the  tissues  in  general  and  of  the  nervous  system  in 
particular,  falls  into  abeyance  when  the  intrinsic  cardiac  nervous 
mechanism  is  completed,  or  at  least  becomes  subordinated  to  the 
latter.  The  advocates  of  the  myogenic  theory  further  state  that 
the  isolated  bulbus  aortse  of  the  frog,  and  even  tiny  fragments  of  it, 
will  pulsate  spontaneously,  and  that  the  same  is  true  of  small 
portions  of  the  great  veins  which  open  into  the  sinus.  The  rhyth- 
mical contraction  of  the  veins  of  the  bat's  wing  has  also  been  con- 
sidered an  argument  in  favour  of  myogenic  automatism.  In  none 
of  these  cases,  however,  can  the  complete  absence  of  ganghon-cells 
be  considered  satisfactorily  demonstrated.  The  statement  that  a 
portion  of  the  apex  of  the  dog's  ventricle  continues  for  a  considerable 
time  to  beat  with  a  rhythm  of  its  own  when  connected  with  the  rest 
of  the  heart  by  nothing  but  its  bloodvessels  and  the  narrow  isthmus 
of  visceral  pericardium  and  connective  tissue  in  which  they  lie  has 
not  been  confirmed  by  all  observers.  But  even  if  it  be  accepted,  it 
can  hardly  be  used  as  a  decisive  argument  against  the  neurogenic 
theory  so  long  as  the  absence  of  ganglion-cells  from  such  a  ventricular 
strip  has  not  been  demonstrated. 

The  fact  that  under  the  influence  of  a  constant  stimulus  portions 
of  the  heart  can  be  made  to  beat  rhythmically  has  been  sometimes, 
though  erroneously,  brought  forward  as  evidence  of  myogenic 
automatism.  Thus  the  supposedly  ganglion-free  apex  of  the  frog's 
heart,  lifeless  as  it  seems  when  left  to  itself,  can  be  caused  to  execute 
a  long  and  faultless  series  of  pulsations  when  its  cavity  is  distended 
with  defibrinated  blood  or  serum,  or  certain  artificial  nutritive 
fluids,  or  even  physiological  salt  solution.  The  passage  of  a  constant 
current  through  the  preparation  may  also  start  a  regular  rhythm. 
But  apart  from  the  question  whether  nervous  elements  would  not 
be  subjected  to  the  constant  stimulus  impartially  with  the  muscular 
elements  (and  nerve-fibres,  at  any  rate,  are  acknowledged  to  be 
present),  the  beat  here  produced  ought  not  to  be  considered  as  an 
automatic  beat,  but  as  a  contraction  evoked  by  an  external  stimulus. 
Such  experiments,  in  fact,  throw  no  light  upon  the  automatism  of 
the  heart,  but  prove  clearly  its  rhythmicity — i.e.,  its  power  of 
responding  to  a  continuous  stimulus  by  regularly  recurring  con- 
tractions. While  we  are  hardly  at  present  in  a  position  to  dis- 
criminate sharply  between  the  influence  of  constant  stimulation 


146  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

upon  the  nervous  and  upon  the  muscular  elements  of  the  heart,  and 
certainly  not  in  a  position  to  deny  to  the  nervous  elements  the 
power  of  responding  to  such  stimulation  by  rhythmical  discharges, 
it  cannot  be  doubted  that  tin  cardiac  muscle  itself  possesses  rhythmi- 
cal power.  One  of  the  best  proofs  of  this  is  deri\-ed  from  observa- 
tions on  the  growth  of  tissue  cultures  containing  fragments  of  heart 
muscle.  A  group  of  heart  muscle  cells  which  had  become  entirely 
separated  from  the  rest  of  the  culture  continued  to  beat  rhythmically 
although  with  a  different  rhythm  from  that  of  the  original  piece. 
No  ganglion  cells  or  nerve  fibres  could  be  seen  in  it.  Rhythmical 
contraction  was  observed  even  in  a  single  isolated  heart  muscle  cell 
(Burrows).  The  power  of  rhythmical  contraction  is  a  property 
which  also  belongs  to  the  smooth  muscle  of  such  tubes  as  the  ureter, 
whose  rhythmical  contraction  is  affected  by  distension  much  as  that 
of  the  heart  is,  and  in  a  smaller  degree  even  to  ordinary  skeletal 
muscle,  which  can  contract  with  a  kind  of  rhythm  under  the  stimulus 
of  a  certain  tension  and  in  certain  saline  solutions.  But  just  as  the 
primitive  automatism  of  the  cardiac  muscle  may  have  become  sub- 
ordinated in  the  course  of  development  to  the  automatism  of  the 
nervous  elements,  so  the  primitive  rhythmical  power  of  the  muscle 
may  under  ordinary  conditions  remain  in  abeyance  and  yet  be 
capable  of  asserting  itself  in  favourable  circumstances,  and  when  the 
normal  rhythmical  impulses  from  the  nervous  apparatus  are  with- 
drawn. In  any  case,  in  the  normally  beating  heart  the  opportunity 
for  the  exercise  of  the  rhythmical  power  of  the  muscle  does  not 
arise,  at  least  in  the  case  of  the  lower  portions  of  the  heart.  For  the 
impulses  which  (in  the  frog's  heart),  descending  from  the  sinus, 
liberate  the  contraction  of  the  auricles,  and  the  impulses  which, 
descending  from  the  auricles,  liberate  the  contraction  of  the  ventricle, 
appear  to  be  discrete,  and  not  continuous;  in  other  words,  the  lower 
portions  of  the  heart  do  not  receive  from  the  upper  portions  a  con- 
tinuous stream  of  stimuli  to  which  they  respond  by  rhythmical  con- 
tractions, but  a  series  of  rhythmically  repeated  impulses,  each  of 
which  evokes  a  single  contraction.  One  of  the  best  proofs  of  this 
is  that  if  the  sinus  is  heated  the  ventricle  beats  much  more  rapidly  in 
unison  with  the  rapidly  beating  sinus  and  auricles,  while  if  the 
ventricle  itself  is  heated  no  change  takes  place  in  its  rhythm.  Now, 
if  the  ventricle  responds  to  a  constant  stimulus  by  rhythmical  beats, 
the  condition  of  the  ventricular  tissue  ought  to  affect  the  rate  of  its 
beat.  In  the  mammalian  heart,  too,  an  alteration  in  the  tempera- 
ture of  a  definite  area  of  the  wall  of  the  right  auricle  lying  between 
the  mouths  of  the  venae  cavae  produces  a  change  in  the  rate  of  the 
whole  heart,  while  no  effect  is  caused  by  altering  the  temperature 
of  any  other  portion  of  the  heart.  It  has  already  been  stated  that 
tlie  impulses  from  the  nerve-cord  which  maintain  the  rhythm  in  the 
Limulus  heart  are  also  discontinuous. 
Conduction  and  Co-ordination. — -The  question  of  the  conduction 


THi:  III    \RT  liF.AT  IK   ITS    PHVSIoiJU.IC AL  NI'.LATIOXS 


H7 


of  Iho  excitation  over  the  heart  and  the  co-ordination  of  its  ])arts 
is  in  tlie  same  position  as  the  question  of  the  automatism  and 
rhythmicity.     In   tlic   horseshoe   crab,  as   already   remarked,  the 
mechanism  appears  to  be  a  nervous  one.     In  higher  hearts,  on  the 
other  hand,  facts  have  been  discovered  whicii  favour  each  of  the 
rival  hypotheses.    In  the  frog's  heart  the  probability  that  the  con- 
traction wave  is  propagated  from  fibre  to  fibre  of  the  muscle  without 
the  intervention  of  nerves  has  been  much  insisted  upon,  since  the 
muscular   tissue,    although   presenting   certain    variations   in   its 
character  in  the  different  divisions  of  the  heart  and  at  their  junctions, 
forms  a  practically  continuous  sheet  over  the  whole  organ  from 
base  to  apex.     In  support  of  this  view  has  been  brought  forward 
the  observation  that  the  delay  of  the  wave  at  the  auriculo- ventricu- 
lar groove  is  much  greater  than  it  ought  to  be  if  the  excitation  were 
transmitted  by  nerves,  since  the  velocity  of   the  nerve-impulse  is 
exceedingly  great  (p.  793) ;  and  the  further  observation  that,  when 
the  ventricle  is  caused  to  contract  by  artificial  stimulation  of  the 
auricle,  this  delay  is  appreciably  greater  when  the  stimulus  is  appHed 
as  far  from  the  ventricle  as  possible  than  when  it  is  applied  as  near 
to  it  as  possible.     The  delay  has  been  attributed  to  the  '  embryonic  ' 
character  of  the  muscular  tissue  at  the  junction  of  the  sinus  with  the 
auricles  and  of  the  auricles  with  the  ventricles.     But  it  has  never 
been  demonstrated  that  muscular  fibres  with  the  histological  char- 
acters described  do,  as  a  matter  of  fact,  conduct  the   contraction 
wave  so  much  more  slowly  than  the  other  cardiac  muscular  fibres 
It  is  just  as  probable,  and  indeed  more  so,  that,  whether  the  con- 
traction travels  in  any  particular  division  of  the  heart  directly  from 
muscle-fibre  to  muscle-fibre  or  not,  the  impulse  to  contraction  is 
transferred  from  each  division  of  the  heart  to  the  next  by  a  nervous 
mechanism  whose  action  is  timed  with  the  very  object  of  securing 
a  certain  interval  between  the  systoles  of  successive  divisions.     In 
any  case,  since  we  know  that  the  velocity  of  the  nerve-impulse  is 
very  different  in  different  varieties  of  nerves,  the  question  cannot  be 
decided  by  general  arguments  of  this  kind.     In  Limulus,  as  a  matter 
of  fact,  the  velocity  in  the  intrinsic  heart  nerves  is  only  one-tenth  as 
great  as  in  the  ordinary  motor  (hmb)  nerves  of  the  animal  (Carlson). 
In  the  mammalian  heart  the  alleged  absence  of  muscular  con- 
nection between  the  auricles  and  ventricles  was  long  the  foundation 
of  the  general  belief  that  the  link  was  a  nervous  one.     Certainly 
there  is  no  dearth  of  nerves  which  might  serve  as  such  a  bridge. 
But  it  has  been  shown  (Kent,  His,  etc.)  that  in  the  mammahan 
heart,  too,  a  slender  band  of  muscular  fibres,  arising  at  a  definite 
point  (the  auriculo- ventricular  node)  near  the  coronary  sinus  on  the 
right  side  of  the  interauricular  septum  below  the  fossa  ovaUs,  passes 
forwards  and  downwards  through  the  fibrous  ring  between  the 
auricles  and  ventricles  under  the  septal  cusp  of  the  tricuspid  valve. 
It  then  divides  into  two  branches,  one  for  each  ventricle,  which  run 


148  THE  CIRCULATIOS  OF  THE  BLOOD  A\D  LYMPH 

down  till'  iuU'ivcntricular  st'j)tum  towards  the  apex,  spreading  out 
as  tlic  Purkinje  fibres  or  their  equivalent,  to  blend  at  last  with  the 
ordinary  muscle  of  the  ventricles,  and  particularly  of  the  inter- 
ventricukir  septum.  The  fibres  of  the  bundle  are  narrower  than  the 
other  fibres  of  the  auricles,  very  rich  in  nuclei,  and  only  slightly 
differentiated  into  fibrillae.  They  seem  to  represent  the  remains  ol 
the  primitive  cardiac  tube,  which  by  the  development  of  certain 
pouches  and  twists  becomes  transformed  into  a  multi-chambered 
heart.  Their  resemblance  to  embryonic  fibres  suggests  that  they 
may  have  retained  the  primitive  capacity  of  the  mesodermic  tissue 
of  the  embryonic  heart  to  conduct,   and  even  to  originate,   the 


Fig,  64. — Right  Auricle  and  Ventricle  of  Calf,  to  show  Auriculo-Ventricular  Band 
(Keitli).  I,  central  cartilage;  2,  main  auriculo-ventricular  bundle;  3,  auriculo- 
ventriculcU'  (A-V)  node;  4,  right  septal  division  of  the  bundle;  5,  moderator  band; 
6,  msdial  or  septal  cusp  of  tricuspid  valve;  8,  coronary  sinus. 

rhythmical  contraction.  But  while  there  is  no  decisive  evidence 
that  they  constitute  an  automatic  cardio- motor  centre,  as  some 
authors  have  supposed,  they,  or  at  least  the  narrow  bridge  of  tissue 
in  which  they  he,  do  play  an  important  part  in  the  conduction  of 
the  contraction  from  the  auricles  to  the  ventricles.  For  compres- 
sion of  the  band  produces  a  block,  just  as  the  pressure  of  a  clamp 
in  the  auriculo-ventricular  groove  does  in  the  frog's  heart  (Kent). 
With  a  certain  degree  of  pressure  the  ventricle  beats  only  once  for 
two  beats  of  the  auricle,  with  greater  pressure  only  once  for  three 
or  more  auricular  beats.  With  a  still  greater  pressure  or  after 
crushing  or  section  of  the  bundle  conduction  is  abolished,  and  the 
ventricle  either  remains  at  rest  for  a  time,  as  in  the  frog's  heart,  or 


THi:  HEART-BJiAT  IN  ITS  PHYSIOLOGICAL   RILLATlUSS     149 

what  is  much  mure  common,  imnicdiati'ly  slaits  btatiiif,'  with  an 
indepondent  rliythm,  which  is  slower  than  that  of  the  auricles 
(Erlanger).  It  can  be  considered  certain  that  in  these  obser\'ations 
ncr\es  may  have  been  involved  in  the  block  as  well  as  the  muscle  of 
the  auriculo-ventricular  band,  since  this  band   is  richly  provided 


rt       ft        0*      ^       a       a      a 


Fig.  65.— Jugular  (Upper)  and  Carotid  (Lower)  Pulse -Tracing  from  a  Case  of  Arterio- 
sclerosis,  showing  Partial  Failure  of  Conduction  in  the  Auriculo-Ventricular 
Bundle  (Cushny  and  Grosh).  The  ventricle  only  beats  once  to  two  beats  of  the 
auricle.     Time-trace,  fifths  of  a  second. 

with  nerve-fibres  as  well  as  ganglion-cells  (Wilson).  Yet  it  is 
unlikely  tliat  all  the  nerves  capable  of  conducting  the  impulses  to 
contraction  should  be'  gathered  into  such  a  narrow  compass,  and 
therefore  the  experiment  supports  the  view  that  the  conduction,  is 
carried  out  in  the  muscular  tissue.     And  if  the  conduction  of  the 


Fig  66.— Tracing  of  Jugular  (Upper)  and  Radial  (Lower)  Pulse  from  a  Maii  with 
Heart-Block  (Le^^ris  and  Macnalty).  In  the  cycles  marked  34.  35.  and  36  the 
ventricular  contraction,  although  less  frequent  than  the  auricular,  was  initiated 
from  the  auricle.  In  the  last  two  cycles  (37  and  38)  and  the  pause  of  36  complete 
heart -block  was  present.  On  the' jugular  trace  the  a-c  interval  (representing 
the  interval  between  the  onset  of  the  auricular  and  ventricular  contractions)  is 
given,  and  on  the  radial  trace  the  duration  of  a  cardiac  cycle,  both  in  fifths  of  a 
second. 

excitation  from  auricles  to  ventricles  is  accomplished  by  a  muscular 
connection,  it  is  natvual  to  suppose  that  the  co-ordination  of  sym- 
metrical portions  of  the  heart  on  either  side  of  the  longitudinal  axis, 
the  co-ordination  in  virtue  of  which  the  two  auricles  contract 
together  and  the  two  ventricles  together,  is  also  achieved  by  the 
passage  of  impulses  through  the  muscular  tissue.     In  accordance 


150  THE  CIRCULATION  OP  THE  BLOOD  A  WD  LYMPH 

with  this,  it  has  been  shown  that  the  wntriclts  in  the  d'»g  and  cat 
continue  to  boat  in  unison,  after  the  attempt  has  been  made  to 
sever  any  nerves  connecting  them  by  extensive  zigzag  incisions,  so 
long  as  they  are  united  by  a  narrow  bridge  of  muscle  (Porter). 

In  disease,  interference  with  the  conduction  of  the  stimulus  from 
auricles  to  ventricles  along  the  atrio-ventricular  bundle  is  a  not  un- 
common phenomenon.  According  to  the  degree  of  interference,  the 
ventricular  contraction  may  be  simply  delayed,  or  only  a  certain  pro- 
portion of  the  auricular  contractions  (every  second,  every  third,  or 
every  fourth)  may  be  conducted  to  the  ventricle,  or,  finally,  the  block 
may  be  complete,  and  the  ventricle  then  contracts  quite  independently 
of  the  auricle,  the  stimulus  to  contraction  originating,  perhaps,  in  the 
uninjured  portion  of  the  bundle  below  the  seat  of  the  block.  These 
conditions  are  most  easily  recognized  by  comparing  tracings  simul- 
taneously obtained  from  the  jugular  vein  and  the  radial  artery  or  apex- 
beat  (p.  90).  When  the  block  is  complete  the  rate  of  the  ventricle  is 
very  slow  (about  30  in  the  minute,  or  less),  the  time  of  the  ventricular 
beat  is  clearly  unrelated  to  that  of  the  auricular,  and  the  stability  of 
the  ventricular  rhythm  is  abnormally  great,  such  circumstances  as 
usually  cause  a  marked  increase  in  tlie  pulse-rate — mental  excitement, 
for  instance — affecting  it  little  or  not  at  all.     This  is  the  condition  in 


Fig.  67. — Polygraph  Tracing  £r  .in  a  Case  of  True  Bradycardia  (Carter).     The  lower 
trace  is  the  radial,  the  upper  the  jugular.     Time-trace,  fifths  of  a  second. 

the  so-called  Stokes-Adams  disease.  In  some  of  these  cases  pathological 
(syphilitic)  changes  in  the  A-V  bundle  have  actually  been  discovered 
at  necropsy.  In  others  there  is  some  reason  to  belie\'e  that  abnormal 
excitation  of  the  cardio-inhibitory  nerves  may  be  responsible  even  for 
long-continued  block,  especially  when  the  conductivity  of  the  bimdle 
has  been  already  permanently  diminished. 

Cases  of  slow  heart  are  also  known  in  which  there  is  no  block  in 
the  conduction  system,  but  the  original  rh>i:hm  of  the  auricle  is  slow 
(so-called  true  br.idycardia.  Fig.  67). 

Kent  ha^  pointed  out  that  the  muscular  connection  between  the 
auricles  and  ventricles  is  not  single  and  confii.cd  to  the  A-V  bundle, 
but  multiple,  and  that  the  co-ordinated  action  of  the  chambers  of  the 
heart  is  to  some  extent  dependent  upon  the  integrity  of  muscular 
connections  other  than  that  which  exists  in  the  A-V  bundle.  One  of 
these  he  describes  as  the  '  right  lateral  connection.'  at  the  junction  of 
the  right  auricle,  the  right  ventricle,  and  the  tricuspid  valve,  at  the 
right-hand  margin  of  the  heart.  The  existence  of  this  additional  con- 
nection, the  importance  of  which  relatively  to  that  of  the  A-V  bundle 
need  not  be  the  same  in  every  heart,  may  explain  otherwise  puzzling 


THi:  HEART-BEAT  /.V   ITS  PHYSfnEnClCAL   RIU.ATIOXS     151 

results  Ixith  cliniral  and  cxptMimental  c.^.,  lliat  sometimes  co-ordina- 
tion between  the  ventricles  and  auricles  has  continued  after  destruction 
of  the  A-V  bundle,  while  sometimes  co-ordination  has  been  upset  by 
lesions  not  affecting  the  bundle. 

Fibrillary  Contraction. — In  the  case  of  the  warm-blooded  Iicart  a 
coniph^tc  breakdown  of  co-ordination  occurs  under  certain  cinnnn- 
stanccs,  producing  the  phenomenon  known  as  fibrillary  contraction, 
or  delirium  cordis,  a  condition  in  which  each  minute  portion,  perhaps 
each  fibre,  of  the  whole  heart,  or  of  a  portion  of  it,  goes  on  contract- 
ing in  a  disorderly  manner,  quite  independently  of  the  rest.  The 
condition  is  often  seen  in  a  heart  that  has  been  exposed  for  some 
time,  particularly  in  the  ventricle,  and  can  be  induced  by  stimulating 
it  with  strong  induction  shocks  or  by  ligation  of  the  coronary 
arteries.  According  to  the  best  evidence,  the  condition  is  due  to 
the  fact  that  the  conductivity  of  the  fibrillating  muscle  is  interfered 
with  so  that  the  contraction  wave  is  prevented  from  running  its 
usual  course.  The  consequence  of  this  '  blocking  '  is  that  the 
normal  co-ordinated  action  of  the  musculature  gives  place  to  the 
confused  movement  characteristic  of  fibrillation  (Porter,  Garrey). 
There  is  no  reason  to  believe  that  fibrillary  contraction  is  connected 
with  the  loss  of  impulses  from  any  special  co-ordinating  centre,  for 
it  is  not  peculiar  to  the  heart,  but  is  typically  seen  in  the  tongue 
when  the  circulation  after  a  long  interruption  is  restored.  The 
peculiar  '  boiling  '  movement  is  exactly  similar  to  that  observed  in 
the  heart,  probably  because  the  tongue  also  contains  fibres  running 
in,  several  directions. 

The  confused  fibrillary  contractions  are  quite  ineffective  for  driving 
on  the  contents  of  the  heart.  Fibrillation  of  the  ventricle  is  therefore 
incompatible  with  life.  On  the  other  hand,  auricular  fibrillation,  far 
from  being  immediately  fatal,  is  one  of  the  most  common  of  the  chronic 
cardiac  disorders  in  man.  It  is  characterized  by  extreme  irregularity 
of  the  pulse,  due  to  the  fact  that  the  ventricles  are  played  upon  by  an 
irregular  stream  of  impulses  from  the  fibrillating  auricles  to  which  they 
respond  as  they  best  can.  The  auricular  wave  {a.  Figs.  65-67)  is  absent 
from  the  jugular  pulse-tracing  and  the  P  wave  (p.  836),  corresponding 
to  the  electrical  change  produced  by  the  normally  contracting  auricles, 
is  absent  from  the  electrocardiogram.  Auricular  flutter  is  a  condition 
which  must  be  distinguished  from  auricular  fibrillation.  When  a  weak 
stimulus  is  applied  to  the  auricle  of  a  dog  or  cat,  the  auricular  beats  are 
grcii.tly  increased  in  frequency  up  to  300  or  400  a  minute.  Although 
the  beats  are  so  rapid,  they  are  otherwise  normal  beats.  When  the 
strength  of  the  stimulus  is  increased,  this  condition  of  flutter 
(Mac William)  passes  into  fibrillation.  Auricular  flutter  is  also  recog- 
nized clinically.  In  the  majority  of  cases  the  ventricle  does  not  respond 
to  each  beat  of  the  auricle,  and  the  arterial  pulse  is  irregular;  but  each 
auricular  contraction  produces  its  appropriate  effect  upon  the  electro- 
cardiogram and  often  also  upon  the  jugular  tracing  (Mackenzie). 

Without  entering  further  into  a  discussion  of  the  rival  hypotheses, 
we  may  sum  up  by  saying  that  for  one  heart  {that  of  Limulus)  the 
automatism  and  the  rhythmical  power  have  been  clearly  shown  to  reside 


15^:        rni:  cinci'latjox  of  the  blood  axd  lymph 

in  the  local  nervous  apparalus  ;  for  the  hearts  of  other  animals  full  and 
formal  proof  of  the  neurogenic  theory,  so  far  as  those  tico  properties  of 
the  cardiac  tissue  are  concerned,  has  not  been  given.  As  regards  the 
conduction  and  co-ordination  of  the  contraction,  the  hulk  of  the  evidence 
(leaving  the  Limulus  heart  out  of  account)  points  to  the  muscular  tissue 
as  the  channel  throw^h  which  the  effective  impulses  pass.  The  normal 
order  or  sequence  in  which  the  different  parts  of  the  heart  contract  depends 
upon  the  fact  that  the  automatism  of  the  upper  portions  is  more  pro- 
nounced than  that  of  the  loiver,  so  that  under  strictly  physiological  con- 
ditions the  contraction  is  only  propagated,  and  not  originated,  by  the 
loicer  parts  of  the  heart.  When,  however,  the  signal  to  contraction 
normalh'  given  b\'  the  basal  region  is  prevented  from  reaching  the 
lower  parts,  an  independent  automatic  rhythm  of  the  latter  may  be 
developed,  as  in  the  case  of  the  mammalian  ventricle  mentioned 
above.  Here  we  may  suppose  that  the  automatic  mechanism  of  the 
lower  portions  of  the  heart  discharges  itself  as  soon  as  a  sufficient 
accumulation  of  energy  has  taken  place  in  it,  although  it  requires 
a  longer  time  to  reach  the  point  of  discharge  than  the  automatic 
mechanism  of  higher  parts,  and  therefore  is  normally  discharged 
from  above.  Under  certain  conditions  the  normal  sequence  can  be 
reversed.  In  the  heart  of  the  skate  it  is  eas}-,  by  stimulating  the 
bulbus  arteriosus,  to  cause  a  contraction  passing  from  bulbus  to 
sinus.  The  power  of  propagating  the  contraction  may  also  be 
artificially  altered.  As  already  mentioned,  it  may  be  diminished  or 
abolished  by  pressure.  The  same  effect  may  be  produced  by  fatigue 
or  cold,  while  heating  a  portion  of  the  heart  in  general  increases  its 
power  of  conducting  the  contraction. 

Chemical  Conditions  of  the  Beat.  When  we  have  localized  the 
essential  mechanism  of  the  rhythmical  beat  in  the  nervous  or  in  the 
muscular  elements,  the  question  may  still  be  asked  what  the 
chemical  and  physical  conditions  are  which  are  necessary  to  its 
maintenance.  While  it  is  known  that  a  supply  of  arterial  blood  at 
or  near  body-temperature,  and  under  a  sufficient  pressure,  is  required 
for  permanent  cardiac  contraction,  much  simpler  solutions  will 
suffice  to  maintain  the  activity  even  of  the  isolated  mammalian  heart 
for  a  considerable  time.  One  of  the  best  of  these  is  a  solution  contain- 
ing sodium  chloride, potassium  chloride, calcium  chloride,  and  sodium 
bicarbonate  in  the  proportions  in  which  they  exist  in  blood-serum, 
with  the  addition  of  a  small  quantity  of  dextrose  (Locke,  p.  66). 
When  this  solution,  properly  oxygenated  and  warmed,  is  circulated 
through  the  coronary  vessels  of  an  excised  rabbit's  or  cat's  heart, 
strong  and  regular  beats  may  be  observed  for  many  hours.  Some 
investigators  have  claimed  for  sodium  chloride,  and  even  for  sodium 
ions,  others  for  calcium  salts  or  calcium  ions,  a  special  role  in  the 
origination  or  maintenance  of  the  rhvtlmiical  beat.  There  is  no 
doubt  that  strips  from  the  ventricle  of  the  tortoise  or  turtle,  which 


THE  111: ART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIOSS      153 

after  isolation  have  ceased  beating,  and  if  left  to  themselves  in  a 
moist  chamber  do  not  develop  rhythmical  contractions,  begin  after 
a  while  to  beat  when  immersed  in  or  irrigated  with  a  solution  of 
sodium  chloride  or  a  solution  of  cane-sugar  containing  a  little  of  that 
salt.  They  refuse  to  beat  in  any  solution  which  does  not  contain 
sodium  chloride  (Lingle).  The  addition  of  calcium  chloride  to  the 
sodium  chloride  solution,  or  preliminary  treatment  of  the  strip  with 
a  solution  of  a  calcium  salt  before  its  immersion  in  the  sodium 
chloride  solution,  hastens  the  onset  of  the  contractions,  and  increases 
the  length  of  time  for  which  they  are  kept  up  (Erlanger).  It  is 
unquestionable  that  for  the  normal  beat  of  the  heart  the  presence 
of  both  salts  is  one  of  the  necessary  conditions,  but  there  is  at 
present  no  sufficient  foundation  for  the  view  that  either  the  one  or 
the  other  acts  as  a  special  chemical  excitant  of  the  automatic 
contraction.  Still  less  necessary  is  it  to  make  this  assumption  for 
potassium.  Certain  potassium  salts  are,  of  course,  beneficial  to 
the  heart  as  to  other  tissues.  This  might  be  assumed  from  their 
presence  in  blood  and  lymph,  and  it  has  been  shown  experi- 
mentally. But  a  terrapin's  heart  will  continue  beating,  and  beating 
well  for  a  considerable  time  when  irrigated  with  a  solution  con- 
taining sodium  and  calcium  salts  alone  and  free  from  potassium. 
That  the  reaction  of  the  perfusive  fluid  is  of  great  importance  in 
connection  with  the  origination  of  rhythm  is  well  established,  and 
it  is  an  interesting  fact  that  the  limits  of  H  ion  concentration 
within  which  the  development  of  spontaneous  beats  is  possible 
differs  for  the  hearts  of  different  kinds  of  animals  (Mines),  and  even 
for  the  different  portions  of  the  frog's  heart  (Dale  and  Thacker). 
While  these  facts  illustrate  the  importance  of  the  inorganic  com- 
position of  the  nutritive  Hquids  for  the  action  of  the  heart,  they 
leave  the  old  question  of  the  existence  and  the  nature  of  an  inner 
stimulus  to  the  rhythmic  contraction  very  much  where  it  was. 

Resuscitation  of  the  Heart. — Not  only  can  the  beat  of  the  freshly- 
excised  mammaUan  heart  be  long  maintained  by  artificial  circulation, 
but  many  hours  or  even  some  days  after  somatic  death  pulsation 
may  be  restored  by  the  perfusion  of  such  a  solution  of  inorganic 
salts  as  Locke's  through  the  coronary  vessels.  Kuliabko  in  this 
way  was  able  to  restore  a  rabbit's  heart  which  had  been  kept  forty- 
four  hom-s  in  the  ice-chest.  Even  after  an  interval  of  three  to  five 
days  from  the  death  of  the  animal,  in  other  experiments,  pulsation 
returned  in  certain  parts  of  the  heart,  while  twenty  hours  after 
death  from  double  pneumonia  the  heart  of  a  boy  three  months 
old  was  restored,  and  went  on  beating  for  over  an  hour.  He  obtained 
also  more  or  less  complete  restoration  of  the  beat  in  the  hearts  of 
persons  dead  from  bronchitis  combined  with  peritonitis  or  menin- 
gitis, and  from  cholera  infantum,  but  was  unsuccessful  in  cases  of 
diphtheria  complicated  with  septicaemia  or  erysipelas,  and  in  cases 


154  THE  circulation:  Oh'  THE  BLOOD  ASD  LYMl'JI 

of  pleurisy  witli  elfusioii.  It  is  to  be  remarked,  howevt-r,  that 
althougli  beats  of  a  kind  can  be  obtained  a  long  time  after  death, 
they  are  either  confined  to  tlic  auricles  or  to  jiortions  of  them,  or, 
if  they  involve  the  ventricles  too,  they  are  only  shallow  and  local 
contractions,  especially  seen  in  the  neighbourhood  of  the  larger 
coronary  vessels,  and  are  utterly  inadequate  to  the  maintenance 
of  an  eflicient  circulation.  The  heart  can  also  be  resuscitated  in  situ 
for  some  time  after  complete  stoppage  without  the  injection  of  any 
solution  by  clamping  the  aorta  in  the  thorax  and  practising  direct 
cardiac  massage,  the  lower  end  of  the  animal  at  the  same  time  being 
elevated  to  allow  blood  to  pass  out  of  the  engorged  abdominal  veins 
to  the  right  auricle.  The  clamping  of  the  aorta  permits  a  sufficient 
pressure  to  be  attained  for  the  filling  of  the  coronary  arteries.  The 
injection  of  adrenalin  into  the  blood  has  also  been  recommended  as 
a  means  of  raising  the  blood- pressure  by  constricting  the  small 
arteries,  and  stimulating  the  action  of  the  cardiac  muscle.  The 
possibility  of  restoration  of  the  mammahan  heart  many  hours  after 
somatic  death  has  been  considered  by  some  a  strong  argument  for 
the  myogenic  theory  of  cardiac  automatism,  since,  they  say,  it  is 
improbable  that  ganglion-cells,  elsewhere  such  physiologically 
fragile  structures,  should  in  the  heart  retain  their  vitality  for  so 
long  a  time.  But  it  is  easy  to  overdo  this  argument,  and  we  must 
not  assume  without  proof  that  ganglion-cells  in  all  parts  of  the  body 
have  an  equal  capacity  of  survival.  Indeed,  we  know  that  there 
are  great  differences,  the  nerv^ous  mechanism  concerned  in  respira- 
tion, eg.,  being  capable  of  restoration  when  the  circulation  is  re- 
newed after  total  anamia  of  the  brain  and  cervical  cord  lasting  for 
as  much  as  an  hour  (in  cats),  while  the  nervous  mechanism  con- 
cerned in  voluntary  movements  cannot  be  completely  restored  even 
after  a  much  shorter  interval.  It  is  very  probable  that  the  cardiac 
ganglia,  if  the  all-important  automatic  function  of  the  heart  depends 
upon  them,  are,  like  the  cardiac  muscle,  endowed  with  exceptional 
powers  of  resistance  to  those  changes  which  constitute  death. 
The  possibility  also  must  not  be  overlooked  that  the  contractions 
obtained  after  such  long  intervals  are  not  truly  automatic,  but 
similar  rather  to  the  rhythmical  beats  developed  under  the  influence 
of  pressure  in  the  frog's  apex  preparation  or  by  immersion  in  salt 
solutions  of  tortoise  ventricle  strips. 

In  addition  to  its  marked  power  of  rhythmical  contraction,  the 
cardiac  muscle  is  distinguished  from  ordinary  skeletal  muscle  by 
other  peculiarities.  It  used  to  be  considered  the  most  striking  of 
these  peculiarities  that  '  it  is  everything  or  nothing  with  the  heart  '; 
in  other  words,  that  the  heart  muscle,  when  it  contracts,  makes  the 
best  effort  of  which  it  is  capable  at  the  time;  a  weak  stimulus,  if 
it  can  just  produce  a  beat,  causing  as  great  a  contraction  as  a  strong 
stimulus.     Recent  work,  however,  has  indicated  that  this  property 


THE  HEART-BEAT  IN  ITS  PHYSIOLOCJCAL  RELATIONS      155 

is  also  possessed  by  the  skeletal  muscle-fibre.  When  a  whole  skeletal 
muscle  is  excited  either  directly  or  through  its  motor  nerve,  it  is 
true  that  throughout  a  considerable  range  increase  of  stimulus  is 
accompanied  by  an  apparent  increase  in  the  strength  of  contraction. 
But  there  is  reason  to  believe  that  this  is  because  a  larger  and  larger 
number  of  fibres  become  involved  in  the  excitation  as  the  stimulus 
is  increased,  and  not  because  each  fibre  responds  more  and  more 
strongly  (Lucas).  In  skeletal  muscle  the  fibres  are  completely 
isolated  from  each  other,  and  the  excitation  does  not  spread  from 
fibre  to  fibre,  as  happens  in  the  heart. 

Refractory  Period  and  Extra  Contraction  of  Hear!  Muscle. — A 
more  characteristic  property  of  the  cardiac  muscle  than  the  '  all  or 
nothing  '  law  is  that  a  true  tetanus  of  the  heart  cannot  be  obtained 
at  all,  or  only  under  very  special  conditions.  When  the  ventricle 
of  a  normally  beating  frog's  heart  is  stimulated  by  a  rapid  series  of 
induction  shocks,  its  rate  is  generally  increased,  but  there  is  no 
definite  relation  between  the  number  of  stimuli  and  the  number  of 
beats.  Many  of  the  stimuli  are  ineffective.  In  the  same  way  a 
portion  of  the  heart,  such  as  the  apex  of  the  ventricle,  when  stimu- 
lated in  the  quiescent  condition  by  an  interrupted  current,  responds 
by  a  rhythmical  series  of  beats,  and  not  by  a  tetanus.  It  is  evident 
that  the  cardiac  muscle,  like  ordinary  striped  muscle,  is  for  some 
time  after  excitation  incapable  of  responding  to  a  fresh  stimulus — 
i.e.,  there  is  a  refractory  period.  But  this  is  immensely  longer  in 
cardiac  than  in  skeletal  muscle.  When  the  phenomenon  is  analyzed, 
it  is  found  that  a  stimulus  falling  into  the  heart  muscle  between  the 
moment  at  which  the  contraction  begins  and  the  moment  at  which 
it  reaches  its  maximum  produces  no  effect — is,  so  to  speak,  ignored. 
When  the  stimulus  is  thrown  in  at  any  point  between  the  maximum 
of  the  systole  and  the  beginning  of  the  next  contraction,  it  causes 
what  is  called  an  extra  contraction.  The  extra  contraction  is 
followed  by  a  longer  pause  than  usual — a  so-called  compensatory 
pause — which  just  restores  the  rhythm,  so  that  the  succeeding 
systole  falls  in  the  curve  where  it  would  have  fallen  had  there  been 
no  extra  contraction  (Fig.  68) . 

In  man,  extra  systoles  followed  by  compensatory  pauses  may  occur 
under  pathological  conditions,  giving  rise  to  an  important  group  of 
cardiac  irregularities.  These  extra  systoles  may  be  cither  auricular  or 
ventricular,  the  auricle  or  the  ventricle  contracting  prematurely  without 
wailing  for  the  signal  of  the  sinus  rhythm.  The  analysis  of  pulse - 
tracings  showing  these  irregularities  has  led  to  results  of  great  physio- 
logical and  clinical  interest  (Cushny,  Mackenzie,  etc.),  but  cannot  be 
dwelt  on  here.  When  every  second  beat  is  an  extra  systole,  generally 
weaker  than  the  preceding  and  the  succeeding  normal  beat,  the  condi- 
tion is  called  pulsus  higeminus.  The  weaker  beat  is  always  followed 
by  a  compensatory  pause  of  greater  duration  than  that  preceding  it. 
From  the  pulsus  bigeminus  must  be  distinguished  that  form  of  alterna- 
ting pulse  termed  pulsus  alternans,  in  which  every  second  beat  is  dimin- 
shed  in  size,  but  the  intervals  separating  the  beats  are  of  uniform  length. 


156 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


The  refractory  period  is  shorter  for  strong  than  for  weak  stimuli, 
and  is  markedly  diminished  by  raising  the  temperature  of  the  heart. 
So  that  stimulation  of  the  heated  heart  with  a  series  of  strong 
induction  shocks  may  cause  a  tetaniforni  condition,  if  not  a  typical 

tetanus.  The  con- 
traction of  the 
normally  beating 
heart  is  really  a 
simple  contrac- 
tion, and  not  a 
tetanus.  The 
electrical  changes 
correspond  to  a 
single  contraction 
(P-833) ;  and  when 
the  nerve  of  a 
nerve-muscle  pre- 
paration is  laid 
on  the  heart,  the 
muscle  responds 
to  each  beat  by  a 
simple  twitch, 
and  not  by  tet- 
anus  (p.  20.^). 
That  the  cardiac 
muscle  itself,  apart  from  the  intrinsic  nervous  mechanism,  shows 
the  phenomenon  of  '  refractory  state  '  has  been  shown  in  the 
Limulus  heart  after  extirpation  of  the  ganglion  (Carlson). 

Like  ordinary  skeletal  muscle,  the  cardiac  muscle  is  at  first  bene- 
fited by  contraction,  perhaps  by  an  '  augmenting  '  action  of  fatigue- 
l^roducts  such  as  carbon  dioxide  (Lee),  so  that  when  the  apex  is 
stimulated  at  regular  intervals  each  contraction  is  somewhat 
stronger  than  the  preceding  one.  To  this  phenomenon  the  name  of 
the  staircase  or  '  treppe  '  has  been  given,  from  the  appearance  of  the 
tracings  (p.  749). 


l"ig.  68.  —  Refractory  Period  and  Compensatory  Pause 
(Marey).  A  frog's  lieart  was  stimulated  at  a  point  corre- 
sponding to  the  nick  in  the  horizontal  line  below  each 
curve.  In  i  and  2  there  was  no  response ;  in  3  and  4  there 
was  an  extra  contraction,  succeeded  by  a  compensatory 
pause. 


Section  V. — The  Nervous  Regulation  of  the  Heart 
(Extrinsic  Nervous  Mechanism  of  the  Heart). 

While,  as  we  have  seen,  the  essential  cause  of  the  rhythmical  beat 
of  the  heart  resides  in  the  tissue  of  the  heart  itself,  it  is  constantly 
affected  by  impulses  that  reach  it  from  the  central  nervous  system. 
These  impulses  are  of  two  kinds,  or,  rather,  produce  two  distinct 
effects:  inhibition,  shown  by  a  diminution  in  the  rate  or  force  of  the 
heart-beat,  or  in  the  ease  with  which  the  contraction  is  conducted 
over  the  heart-wall;  and  augmentation,  or  increase  in  the  rate  or 


THE  NliliVOUS  REGULATION  OF  THE  HEART 


157 


force  of  the  beat  or  in  the  conductivity.  Both  the  inhibitory  and 
th  '  augmentor  impulses  arise  in  the  medulla  oblongata,  and  perhaps 
a  narrow  zone  of  the  neighbouring  portion  of  the  cord;  and  they  can 
be  artificially  excited  by  stimulation  in  this  region.  They  pursue 
their  course  to  the  heart  by  fibres  which  may  in  certain  animals  be 
mingled  together,  but  are  anatomically  distinct.  We  may,  there- 
fore, divide  the  extrinsic  or  external  nervous  mechanisnr  of  the 
heart  into  a  cardio-inhibitory  centre  with  its  efferent  inhibitory 
nerve-fibres  and  a  cardio-augmentor  centre  with  its  efferent  acceler- 
ator or  augmentor  fibres.  Both  of  those  centres,  as  we  shall  see, 
have,  in  addition,  extensive  relations 
with  afferent  nerve- fibres  from  all  parts 
of  the  body,  including  the  heart  itself. 

It  was  in  the  vagus  of  the  frog  that 
inhibitory  nerves  were  first  discovered 
by  the  brothers  Weber  seventy  years 
ago,  and  even  now  our  knowledge  of  the 
cardiac  nervous  mechanism  is  more  com- 
plete in  this  animal  than  in  any  other. 
We  shall,  therefore,  first  describe  the 
phenomena  of  inhibition  and  augmen- 
tation as  we  see  them  in  the  heart  of  the 
frog,  and  then  pass  on  to  the  mammal. 

In  the  frog  the  inhibitory  fibres  leave 
the  medulla  oblongata  in  tlie  vagus  nerve. 
Tlie  augmentor  fibres  come  off  from  the 
upper  part  of  the  spinal  cord  by  a  branch 
from  the  third  nerve  to  the  third  sympa- 
thetic gangUon,  and  thence  find  their  way 
along  the  sympathetic  cord  to  its  junction 
with  the  vagus,  in  which  they  run,  mingled 
with  the  inhibitory  fibres,  down  to  the  heart. 

When  the  vago-sympathetic  in  the 
frog  or  toad  is  cut,  and  its  peripheral 
end  stimulated,  the  heart  in  the  vast 
majority  of  cases  is  stopped  or  slowed, 
or  its  beat  is  distinctly  weakened  without,  it  may  be,  any  marked 
slowing.  In  other  w^ords,  the  rate  at  which  the  heart  was 
working  before  the  stimulation  is  greatly  diminished,  or  reduced 
to  zero.  Such  an  effect,  a  diminution  of  the  rate  of  working, 
we  call  Inhibition.  What  precise  form  the  inhibition  shall  take, 
whether  the  stoppage  shall  be  complete  or  partial,  and  if  partial 
whether  the  beats  shall  be  simply  weakened  without  being  slowed 
or  both  slowed  and  weakened,  appears  to  depend  partly  upon  the 
strength  of  the  stimulus  used  and  partly  upon  the  state  of  the 
heart  itself.  Some  hearts  it  may  be  impossible  to  stop  with  weak 
stimulation,  although  other  signs  of  inhibition   may  be  distinct; 


Fig.  69. — Diagram  of  Extrinsic 
Nerves  of  Frog's  Heart  (after 
Foster).  Ill,  3rd  spinal 
nerve;  AV,  annulus  of  Vieus- 
sens;  X,  roots  of  vagus;  IX, 
glosso-pharyngeal  nerve;  VS, 
combined  vagus  and  sympa- 
thetic; I,  2,  and  3,  the  ist. 
2nd,  and  3rd  sympathetic 
ganglia.  The  dark  line  indi- 
cates the  course  of  the  sym- 
pathetic fibres.  The  arrows 
show  the  direction  of  the  aug- 
mentor impulses. 


158  THE  CIRCULATIOS  OF  THE  BLOOD  AND  LYMPH 

while  they  are  readily  stopped  by  stronger  stimulation.  In  other 
cases  the  strongest  stimulation  may  not  produce  complete  standstill. 
Again,  the  inhibitory  effect  produced  on  a  heated  heart  by  a  given 
strength  of  stimulation  of  the  vagus  may  be  greater  than  that  caused 
in  a  heart  at  the  ordinary  temperature  or  a  cooled  heart.  This  is 
especially  e\ndent  on  the  auricular  tracings  when  these  are  recorded 
separately  from  those  of  the  ventricle.  Even  on  the  verge  of  heat 
standstill  of  the  heart  inhibition  is  easily  obtained  (Fig.  71).  Some 
writers  have  assumed  that  the  different  inhibitory  effects  produced 
by  the  vagus  are  due  to  the  existence  in  it  of  separate  groups  of  fibres, 
somr  affecting  only  the  rate  of  the  contraction,  others  its  strength. 


Fig.  70. — Tracing  from  Frog's  Heart.  A,  auricular,  V,  ventricular  tracing.  Sinus 
stimulated  (primary  coil  70  mm.  from  secondary).  Heart  at  temperature 
ii"2°  C.  Complete  standstill.  The  time-tracing  between  the  curves  marks 
intervals  of  two  seconds. 

others  still  the  conductivity  of  the  muscular  tissue  and  its  excita- 
bility. This  theory  has  ennched  the  vocabulary  of  physiology 
with  a  number  of  sonorous  terms  derived  from  the  Greek,  but  has 
not  otherwise  established  itself,  although  it  has  been  useful  in 
emphasizing  the  fact  that  the  inhibitory  nerves  can  influence  the 
heart-beat  in  several  distinct  ways. 

But  there  are  other  points  of  importance  to  be  noted  in  regard  to 
this  inhibition :  (i)  It  does  not  begin  for  a  little  time  after  stimulation 
has  begun.  In  other  words,  there  is  a  distinct  latent  period;  and 
the  length  of  this  latent  period  is  related  to  the  phase  of  the  heart's 


THE  KERV0U6  REC.ULATION  OE  THE  HEART 


150 


contraction  at  whicli  the  stimulus  is  thrown  in,  and  to  the  rate  at 
which  the  heart  is  beating.  As  a  general  rule,  the  heart  makes  at 
least  one  beat  before  it  stops. 

(2)  The  inhibition  does  not  continue  indefinitely,  even  if  stimula- 
tion of  the  nerve  is  kept  up.  Sooner  or  later,  and  usually,  in  fact, 
after  an  interval  of  a  few  seconds,  the  heart  begins  again  to  beat  if  it 
has  been  completely  stopped,  or  to  quicken  its  beat  if  it  has  only  been 
slowed,  or  to  strengthen  it  if  the  inhibition  has  only  weakened  the 
contraction,  and  it  soon  regains  its  old  rate  of  working.  Not  only 
so,  but  very  often  there  follows  a  longer  or  shorter  period  during 
which  the  heart  work.^  at  a  gi-eater  rate  than  it  did  before  the  inhibi- 
tion, and  this  greater  rate  of  working  may  be  manifested  by  increased 


Fig.  71. — Activity  of  Vagus  on  Verge  of  Heat  Standstill.  Auricular  and  ventricular 
contractions  of  toad's  heart  recorded.  Heart  at  34'5*  C,  v  50,  stimulation  of 
vagus  (distance  of  coils  50  mm.).  The  ventricle  was  already  in  heat  standstill; 
the  auricle  was  at  once  inhibited.  Then  follows  secondary  augmentation  (due 
to  the  sympathetic  fibres),  during  which  the  ventricle  also  resumes  beating. 
An  interval  of  a  minute  elapsed  between  the  first  and  second  parts  of  the 
tracing,  during  which  the  heart  remained  at  34'5°  C.  The  auricle  was  almost 
in  standstill  (contractions  can  still  be  seen  on  the  curve  with  a  lens),  when  the 
vagus  was  again  stimulated  at  v  50  with  the  same  distance  between  the  coils. 
Complete  inhibition  followed  by  secondary  augmentation. 

frequency  of  beat,  or  increased  strength  of  beat,  or  by  both.  When 
the  temperature  of  the  heart  is  low,  increased  frequency ;  when  it  is 
high,  increased  strength,  is  generally  seen  during  this  period  of 
secondary  augmentation*  The  cause  of  this  secondary  augmentation, 
and  of  the  primary  augmentation  sometimes  seen  in  fresh  prepara- 
tions and  often  in  hearts  that  have  been  long  exposed  (Fig.  73), 
excited  much  speculation  before  it  was  known  that  sympathetic 
fibres  existed  in  the  vagus.  There  is  no  longer  any  doubt  that  it  is 
due  to  the  stimulation  of  these  accelerator  or,  as  it  is  better  to  call 

*  Augmentation  is  termed  '  secondary  '  when  it  is  preceded  by  inhibition, 
primary  '  when  it  is  not  so  preceded 


i6o  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

them  (since  mere  acceleration  is  not  the  only  consequence  of  their 
stimulation),  augmentor  fibres  in  the  mixed  nerve.  For  (i)  excita- 
tion of  the  roots  of  the  vagus  proper  within  the  skull,  and  therefore 
above  the  junction  of  the  sympathetic  fibres,  causes  no  secondary 
augmentation,  or  very  little,  and  the  inhibition  lasts  far  longer  than 
when  tlie  mixed  trunk  is  stimulated.  (2)  Excitation  of  the  upper 
or  cephalic  end  of  the  sympathetic  cord  before  it  has  joined  the 
vagus  causes,  after  a  relatively  long  latent  period,  marked  augmenta- 
tion. And  if  the  contractions  of  the  heart  are  registered,  the 
tracing  bears  a  close  resemblance  to  the  curve  of  secondary  augmen- 
tation following  excitation  of  the  mixed  nerve  on  the  other  side 
with  an  equally  strong  stimulus  and  for  an  equal  time.  (3)  When 
tlie  vago-sympathetic  is  stimulated  weakly  there  is  little  or  no 


Fig.  72. — Frog's  Heart:  Vagus  stimulated.  Temperature  of  heart  8°  C;  78  mm. 
between  the  coils.  Diminution  in  force  of  auricle  and  ventricle,  but  not  com- 
plete standstill.     Time-tracing  shows  two-second  inter\-als. 

secondary  augmentation.  Now,  it  is  known  that  the  augment  or 
fibres  require  a  comparatively  strong  stimulus  to  cause  any  eftect 
when  they  are  separately  excited,  whereas  a  weak  stimulus  will 
excite  the  inhibitory  fibres. 

The  question  arises  at  this  point,  why  it  is  that,  when  the  inhibitory 
and  augmentor  fibres  are  stimulated  together  in  the  mixed  nerve  (and 
the  same  is  true  when  the  sympathetic  on  one  side  and  the  vagus  on 
the  other  are  stimulated  at  the  same  time),  the  inhibitory  effect  always 
comes  first,  when  there  is  any  inhibitory-  effect,  while  the  augmentation 
always  has  to  follow.  The  answer  has  sometimes  been  given,  that  the 
latent  period  of  the  augmentor  fibres  is  longer  than  that  of  the  inhibitory 
fibres.  But  although  this  is  certainly  the  case,  the  answer  is  insuffi- 
cient.    For  the  period  of  postponement  may  be  much  greater  than  the 


Till'.   ST.RVOUS  REGULATION  OF  THE  HEART 


161 


latent  prriod  of  tlie  sympatlittic  fibres  when  stimulated  by  themselves. 
The  inhibition  apparently  runs  its  course  without  being  affected  by  the 
simultaneous  augmentor  effect,  which,  lying  latent  until  the  end  of  the 
inhibition,  then  bursts  out  and  completes  its  own  curve.  It  is  not  like 
the  passing  of  two  waves  through  each  other,  but  rather  like  the  stopping 
of  one  wave  until  the  other  has  passed  by.  It  seems  as  if  augmentation 
cannot  develop  itself  in  the  presence  of  inhibition — at  least,  until  the 
latter  is  nearly  spent.  Like  a  musical-box  devised  to  play  a  series  of 
melodies  in  a  fixed  order,  and  from  which  a  particular  tune  cannot  be 
obtained  till  those  preceding  it  have  been  run  through,  the  heart,  in 
some  way  or  other,  is  arranged,  in  the  presence  of  competing  impulses 
from  its  extrinsic  iRT\es,  to  play  the  tune  of  inhibition  before  the  tune 


Fig.  7317. — Frog'a  Heart.  A,  auricular,  V,  ventricular  tracing.  Ventricle  beating  very 
feebly.  Vagus  stimulated  (60  mm.  between  coils).  Marked  augmentation  of 
ventricular  beat. 


of  augmentation.  In  the  frog,  at  any  rate,  the  two  processes  can  hardly 
be  considered  as  antagonistic,  in  the  sense  that  a  definite  amount  of 
aiigmcntor  excitation  can  overcome  a  definite  amount  of  inhibitorv 
excitation.  Nor  is  it  the  case  that,  when  tlic  heart  is  played  upon  at 
the  same  time  by  impulses  of  both  kinds,  it  pits  them  against  each  other 
and  strikes  the  balance  accurately  between  them.  It  is  possible,  how- 
ei'er,  that  when  the  inhibitory  fibres  are  ver\'  weakly,  and  the  augmentor 
fibres  ver^'  strongly  stimulated,  the  amount  of  inhibition  may  be  some- 
what diminished.  In  mammals,  on  the  otiicr  hand,  a  true  antagonism 
seems  to  exist;  and  stimulation  of  the  inlii'.^itory  nerves  is  less  effective 
when  the  augmentors  are  excited  at  the  s.'.me  time.  The  cardiac  nerves 
affect  not  only  the  rate  and  force  of  tlie  contraction,  but  also  the  con- 


l62 


THE  {'IRCrLATlOS  OF  THE  BI.nOD  A\D  I.YMPH 


ductivity  of  the  heart.  Thus  in  the  frog's  heart  (hiring  stimulation  of 
the  vaf-iis,  the  contraction  passes  more  slowly,  and  during  stinnilation 
of  the  symiKithetic  more  quickly,  from  auricles  to  ventricle. 

In  mammals  (anil  m  what  follows  wc  shall  restrict  ourselves  chiefly 
to  the  dog.  cat,  and  rabbit,  as  it  is  in  these  animals  that  the  subject 
has  been  most  carefidly  studied)  the  inhibitory  fibres  run  down  the 
vagus  in  the  neck  and  reach  the  heart  by  its  cardiac  branches.  They 
are  derived  from  the  bulbar  roots  ol  the  spinal  accessory,  whose  inner 
branch  joins  the  vagus.  The  nugmcniny  nlires  leave  the  spinal  cord  in 
the  anterior  roots  of  the  second  and  llur>i  thoracic  nerves,  and  possibly 
to  some  extent  bv  the  fourth  and  fifth.      Through  the  corresponding 


Fig.  7.^6.— Miniature  MyocaidioRraph  factual  size) 
(Wiggers).  C,  light  aUimiiiium  segment  capsule 
covered  by  tightly  stretched  rubber  dam,  upon 
wliich  is  cemented  an  aluminium  plate  pivoting 
npiin  tiierliord  side  of  tlic  capsule.  The  plate 
carries  a  light  arm,  A,  with  an  eyelet  at  its  ei>d. 
A  similar  arm,  A^,  is  rigidly  fastened  to  the  body 
of  the  capsule.  The  arms  can  be  bent  so  that 
the  distance  between  the  eyelets  varies  from 
3  to  23  millimetres,  and  are  connected  by 
stitches  through  the  eyelets  to  points  on  the 
auricular  surface.  The  approximation  of  the 
points  causes  a  negative  pressure  in  tht'  cap- 
sule, and  in  the  recording  capsule  (see  descrip- 
tion of  l"ig.  31,  p.  03)  connected  with  it  by  the 
tube  T.  Hence,  the  down-stroke  of  the  curve 
represents  contraction,  the  up-stroke  relaxation. 
The  apparatus  is  supported  by  a  very  light 
spring,  S.  'i"his  enables  it  to  follow  varying 
degrees  of  distension  and  movement  of  the 
auricle  without  affecting  the  curve  of  contrac- 
tion. The  small  mass  (less  than  2  gm.)  and 
high  vibration  frequency  of  the  instrument 
insure  a  more  faithful  record  of  the  con- 
traction than  with  older  forms. 


white  rami  communicantcs  they  reach  the  sympathetic  cord,  and 
running  iip  through  the  stellate  ganglion  (first  thoracic),  and  the 
annuhhi  of  V'icussens,  which  surrounds  the  subclavian  artery,  to  the 
inferior  cervical  ganglion,  thev  pass  off  to  the  heart  by  separate  'acce- 
lerator '  branches,  taking  origin  either  from  the  anindus  or  from  the 
inferior  cervical  ganglion.  Some  augmentor  fibres  are  often,  if  not 
always,  present  in  the  dog's  vago-svmpathctic  in  the  neck.  It  is 
especially  easy  to  demonstrate  their  presence  five  or  six  days  after 
section  of  the  nerve,  when  the  excitability  of  the  inhibitory  fibres  has 
disappeared. 

In  the  dog  the   vagus  and   cervical  sympathetic  are,   in  the  great 
majority  of  cases,  contained   in  a  strong  common   sheath,  and  pass 


77//;  .\i  livous  iriA.ii.A  ri(>\  oh'  i  iii.  iii:  \i<r  k,, 

together  through  the  infcric)r  cervical  gangUon.  I'pon  opening  this 
sheath  thcv  may  with  care  l)c  separated,  the  fibres  running  in  distinct 
strands,  and  not  mixed  together  as  in  the  vago-sympathetic  ot  the  frog. 
For  some  distance  below  the  superior  cervical  ganglion  the  cervical 
sympathetic  is  not  connected  with  the  vagus,  and  here  the  nerves  may 
be  separately  stimulated  without  any  artificial  isolation.  In  the  rabbit 
and  some  other  mammals,  including  man,  the  vagus  and  sympathetic 
nm  a  separate  course  in  the  neck. 

In  the  mammal,  the  inhibitory  fibres  have  a  smaller  direct  action 
on  the  ventricle  than  in  the  frog.  It  indeed  beats  more  slowly  when 
the  auricle  is  slowed,  but  this  is  only  because  in  the  normally  beating 
heart  the  ventricle  takes  the  time  from  the  auricle.  The  strength 
of  the  ventricular  contractions  may  be  not  at  all  diminished,  even 
when  the  auricle  is  beating  very  feebly  during  inhibition.  When  the 
auricle  is  completely  stopped,  which  does  not  occur  so  readily  as  in 
the  frog,  the  ventricle  also  stops  for  a  short  time,  but  soon  begins  to 
beat  again  with  an  independent  rhythm  of  its  own.  In  the  frog  the 
ventricle  is  directly  affected  by  stimulation  of  the  vagus,  and  the 
force  of  its  beats  is  diminished  independently  of  the  inhibitory 
effects  in  the  auricles  (Practical  Exercises,  pp.  198,  203). 

It  has  been  shown  by  delicate  optical  methods  of  recording  the 
contraction  of  small  units  of  the  auricular  musculature  (designated 
as  the  '  fractionate  '  contraction  by  Wiggers)  by  the  method  illus- 
trated in  Fig.  736,  that  the  diminution  in  the  size  of  the  contrac- 
tion produced  by  stimulation  of  the  vagus  is  essentially  due  to 
depression  of  the  contractility  of  the  muscle,  and  not,  or  at  any  rate 
not  primarily,  to  a  diminution  in  its  excitabilit}'.  In  other  words, 
the  strength  of  stimulus  needed  to  elicit  a  contraction  of  the  muscle 
when  under  the  influence  of  vagus  excitation,  in  the  early  part  of 
the  inhibition  at  least,  is  not  increased,  whereas  the  size  of  the 
contraction  evoked  by  a  given  stimulus  is  diminished  (Fig.  74). 

It  is  not  doubted  that  the  excitation  of  the  vagus  does  reduce  the 
excitability  of  the  auricular  muscle,  but  this  reduction  seems  not  to 
occur  so  early  as  the  reduction  in  the  amplitude  of  the  beat,  and 
cannot  therefore  be  responsible  for  it.  The  duration  of  each 
(fractionate)  contraction  is  not  altered  by  vagus  excitation.  It 
can  hkewise  be  shown  that  the  depression  of  contractility  is  not 
secondary  to  the  depression  of  conductivity  produced  by  the  vagus. 
Finally,  it  is  not  dependent  upon  the  slowing  of  the  rhythm  which 
accompanies  the  diminution  in  the  contraction  of  the  naturally 
beating  auricle.  For  when  the  auricle  is  compelled  to  beat  with  an 
artificial  rhythm  by  applying  to  it  a  series  of  regularly  spaced 
electrical  stimuli  at  a  more  rapid  rate  than  the  normal  rh>i:hm, 
stimulation  of  the  vagus  still  causes  reduction  in  the  amplitude  of 
the  contraction  without  change  in  the  rate  (Fig.  74).  One  other 
point  is  worthy  of  note.  Excitation  of  the  vagus  causes  an  increase 
in  the  size  of  the  first,  or  occasionally  of  the  first  two  subsequent 


i64 


THE  CTRCrn.AriON  OF  THE  BLOOD  AND  LYMPH 


contractions  ol  the  auricular  muscle  when  the  rhythm  is  slowed, 
but  not  otherwise.  It  is  probable  that  this  is  due  to  the  beneficial 
influence  of  the  longer  period  of  rest  associated  with  the  diminution 
in  frequency  of  the  beat  before  the  inhibitory  action  has  had  time 
to  cause  depression  in  the  amplitude  (Wiggers). 


vs  W^ 


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I'ig.  74. — -Influence  of  the  Vagus  on  the  Contraclioti  uf  ilic  l>('n'~-  Ki;;in  Auiulr 
The  two  upper  curve?  are  simultaneous  records  of  the  contraction  of  very  short 
portions  of  the  auricle  (bocalled  fractionate  contraction)  taken  from  two 
regions,  one  near  the  sinus  node  P,  and  one  far  from  it,  D.  The  contraction 
begins  and  ends  slightly  sooner  in  the  proximal  than  in  the  distal  region. 
The  losvest  curve  shows  the  depressant  effect  of  the  vagus  excitation  mani- 
fested when  an  artificial  rhythm  (a  series  of  electrical  break  shocks),  which  is 
not  altered  by  sthnulation  of  the  vagus,  is  substituted  for  the  normal  rhythm 
sustained  by  the  '  pacemaker.* 

The  inhibitory  fibres,  then,  influence  the  heart  particularly 
through  the  auricles;  they  are  par  excellence  auricular  nerves.  On 
the  other  hand,  the  accclernntes  in  all  ni.mimals  which  have  been 
investigated  not  only  extend  to  the  \-entricles.  but  are  even  mainlv 
distributed  to  them.    They  are  emphatically  ventricular  fibres,  and 


THE  NERVOUS  REGULATIOS  OE  THE  HEART  165 

in  accordance  with  its  greater  mass  the  left  ventricle  receives  more 
fibres  than  the  right. 

Stimulation  of  the  accelerator  nerves  in  the  dog  causes  an 
increase  in  tlie  force  of  both  the  auricular  and  ventricular  con- 
traction, and  as  a  rule,  in  addition,  some  increase  in  the  rate  of 
the  beat. 

As  to  the  nature  of  the  physiological  linkage  between  the  cardiac 
nerves  and  the  muscular  tissue  of  the  heart  we  know  but  Uttlc. 
(ianglion-colls  lie  on  the  course  of  the  vagus  fibres  after  they 
have  entered  the  lieart,  and  although  the  view  has  been  advocated 
that  they  are  simply  stations  where  the  inhibitory  impulses  pass 
from  medullated  to  non-medullatcd  tibus,  and  where  possibly  other 


Fig-  75- — ^  ood-Presu   ■   Iracings:  Rabbit.     Vagus  stinmlated  at  r.     Stimulus 
biroiigci  m  B  tlian  in  A  (Hiirthlc's  spring  manometer). 

anatomical  changes  and  rearrangements  occuf,  they  may  be  inter- 
mediate mechanisms  which  essentially  modify  the  physiological 
impulses  falHng  into  them.  It  has  been  stated  that  in  the  dog  the 
right  vagus  controls  chiefly  the  rate  of  the  heart,  and  the  left  vagus 
chiefly  the  conduction  from  auricles  to  ventricles,  and  the  suggestion 
has  been  made  that  this  is  because  the  right  vagus  has  a  special 
relation  to  the  sino-auricular  node,  in  which  impulses  are  supposed 
to  arise,  and  the  left  vagus  a  special  relation  to  the  auriculo-ven- 
tricular  node,  the  upper  end  of  the  A-V  bundle,  the  main  conduction 
system  (Cohn  and  Lewis). 

The  nervi  accelerant es  are  already  non-medullated  before  they 


I66  Tlir.   CIRCri  ATWS  01'  THE  BLOOD  ASH  I.YMPH 

reach  the  heart.  The  fact  tliat  tlic  action  of  the  accch'rantes  can 
be  rt'stortd  by  perfusing  the  heart  with  a  nutrient  sohition  at  a 
much  longer  interval  after  somatic  death  than  the  action  of  the 
vagus  strengthens  the  suggestion  that  ganglion-cells  are  interposed 
on  the  inhibitory  though  not  on  the  augmcntor  path,  without, 
however,  proving  of  itself  that  such  a  difference  exist>  In  one 
experiment  the  heart  of  an  anthropoid  ape  was  revived  when  thicc 
successive  periods — viz.,  four  and  a  half,  twenty-eight  and  a  half, 
and  fifty-three  hours  respectively — had  elapsed  after  the  death  of 
the  animal,  although  during  the  last  period  the  heart  had  been 
twice  frozen  hard.  The  vagus  was  shown  to  be  still  capable 
of  causing  some  inhibition  six  hours  after  death,  and  the 
accelerans  some  augmentation  as  late  as  fifty-three  hours  after 
death  (Hering). 

In  the  discussions  over  the  relation  of  the  extrinsic  to  the  intrinsic 
cardiac  nervous  apparatus  appeal  has  frequently  been  made  to  the 
action  of  certain  poisons  on  the  heart.  Thus,  after  vicotine  stimulation 
of  the  vago-sympathctic  causes  no  inhibition  of  the  frog's  heart;  it  may 
cause  augmentation.  But  stimulation  of  the  junction  of  the  sinus  and 
auricle  still  causes  inhibition.  Atropine  not  only  abolishes  the  inhibi- 
tory effect  of  .stimulation  of  the  vagus  trunk,  but  also  that  of  stimula- 
tion of  the  junction  of  sinus  and  auricle.  Muscarine  causes  diastolic 
arrest  in  a  heart  ah-eadv  poisoned  with  nicotine,  but  not  in  a  heart 
under  the  influence  of  atropine.  And  a  heart  brought  to  a  standstill  by 
muscarine  can  be  made  to  beat  again  by  the  application  of  atropine, 
although  not  by  nicotine. 

These  facts  may  be  explained  as  follows:  Nicotine  paralyzes,  not  the 
very  ends  of  the  vagus,  but  the  ganglia  through  which  its  fibres  pass. 
Stimulation  of  the  sinus,  which  is  practically  stimulation  of  the  vagus 
fibres  between  the  ganglion-cells  and  the  muscular  fibres,  is  therefore 
effective,  although  stimulation  of  the  nerve-trunk  is  not  (Langley). 
On  the  other  hand,  the  atropine  group  paralyzes  the  nervc-cndin'gs 
themselves,  or  interferes  with  the  reception  of  the  inhibitory  impulses 
by  acting  on  a  so-called  receptive  substance  in  the  muscle  (p.  182),  so 
that  neither  stimulation  of  the  sinus  nor  of  the  nerve-trunk  can  cause 
inhibition.  Muscarine,  on  the  contrary,  stimulates  the  vagus  fibres 
between  the  nerve-cells  and  the  muscle,  or  the  actual  nerve-endings,  or 
exerts  an  inhibitory  action  on  the  muscle  itself  through  the  appropriate 
receptive  substance,  and  thus  keeps  the  heart  in  a  state  of  permanent 
inhibition,  which  is  removed  when  atropine  cuts  out  the  nerve-endings, 
or  combines  with  the  receptive  substance.  It  is  quite  in  accordance 
with  this  that  muscarine  has  no  effect  on  a  heart  whose  vagus  nerves, 
as  occasionally  happens,  have  no  inhibitory  power.  Pilocarpine  has 
very  much  the  same  action  as  muscarine. 

Stannius'  Experiment. — Another  series  of  phenomena,  intimately 
related  to  our  present  subject,  have  excited,  since  they  were  first  made 
known  by  Stannius,  an  enormous  amount  of  discussion.  The  chief 
facts  of  this  classical  experiment  we  have  already  mentioned  (p.  144), 
and  they  are  also  described  in  the  f^ractical  Exercises  (p.  i<)4).  They 
are  easy  to  verify,  but  difficult  to  interjjret.  The  most  probable  explana- 
tion of  the  standstill  caused  by  the  first  ligature  is  that  the  lower  portion 


Till:  M-in'ors  f^'iA.ri..iri().\  oi'  i iii.  iii.ih'T 


i"7 


<il  tlic  lKa:l.  when  cut  utt  tiom  the  sinus  m  wliicli  Ihc  btat  normally 
originates,  needs  some  lime  for  llie  development  of  its  automatic  power 
to  the  p(Mnt  at  which  an  independent  rhythm  can  be  maintained.  The 
effects  following  the  second  Stannius  ligature  seem  to  depend  upon  the 
power  of  the  ventricle  to  develop  and  maintain  an  independent  rhythm, 
but  the  contractions  are  supposed  by  some  to  be  started  by  stimulation 
of  the  muscular  tissue  in  the  auriculo-vcntricular  groove  by  the  ligature. 
Nature  of  Inhibition  and  Augmentation.  -  So  far  we  have  been  dis- 
cussing the  phenomena  of  iiijiibilion  and  augmentation  as  ultimate 
facts.  We  have  not  attempted  to  go  behind  them,  nor  to  ask  what  it 
is  that  really  happens  when  inhibitory  impulses  fall  into  a  heart,  which 
from  the  first  days  of  embryonic  life  has  gone  on  beating  with  a  regular 
rhythm,  and  in  the  space  of  a  second  or  two  bring  it  to  a  standstill. 
The  question  cannot  fail  to  press  itself  u]on  the  niind  of  anyone  who 
has  ever  witnessed  this  most  beautiful  of  physiological  experiments; 


Fig.  76. — Frog's  Heart.  Sympathetic  stimulated  (30  mm.  between  the  coils). 
Temperature  12°.  Marked  increase  in  force.  Only  auricular  tracing  repro- 
duced.     Time-trace,  two-second  intervals. 


but  as  yet  there  is  no  answ^er  except  ingenious  speculations.  The  most 
plausible  of  these  is  the  trophic  theory  of  Gaskell,  who  sees  in  the  vagus 
a  nerve  which  so  acts  upon  the  chemical  changes  going  on  in  the  heart 
as  to  give  them  a  trophic,  or  anaboUc,  or  constructive  turn,  and  thus  to 
lessen  for  the  time  the  destructive  changes  underlying  the  muscular 
contraction.  The  augmentor  nerves,  on  the  other  hand,  are  supposed 
to  exert  a  katabolic  influence,  and  to  favour  these  destructive  changes. 
And  while,  according  to  Gaskell,  the  natural  consequence  of  inhibition 
is  a  stage  of  increased  efficiency  and  working  power  when  the  inhibition 
has  passed  away,  the  natural  complement  of  augmentation  is  a  tem- 
porary exhaustion.  It  is  very  risky,  however,  to  rely,  as  Gaskell  did, 
upon  a  supposed  change  of  sign  in  the  electrical  effects  during  vagus 
stimulation,  and  the  only  chemical  test  to  which  the  theory  has  been 
subjected,  the  comparison  of  the  oxygen  consumption  of  the  heart  during 
and  in  the  absence  of  inhibition,  is  adverse  to  it.  The  amount  of  oxygen 
used  up  relatively  to  the  functional  activity  of  the  heart  as  measured  by 
the  product  of  the  frequency  of  the  beat  and  the  maximal  increase  of  pres- 
sure caused  bv  it,  is  not  increased  by  stimulation  of  the  vagus  (Rohde). 


I6S 


THE  CI RCVL Alios  OF  THE  BLinU)  AM)  I.VMPU 


Whatexcr  tlic  exact  mcclianisui  of  aiigmcntaliun  inav  Ix-,  there  is 
no  basis  for  the  statement  that  the  cardio-auKnientor  nerves  have 
an  action  on  ihc  heart  so  fundamentally  different  from  the  action  of 
motor  nerves  on  skeletal  muscle  that  they  cannot  originate  contractions 
in  a  heart  entirely  at  rest.  ICxcitation  of  the  cardio-augmentor  nerves 
can  cause  rhythiiucal  contractions  in  the  perfectly  quiescent  heart  of 
molluscs,  and  a  sudden  and  prolonged  outburst  of  beats  of  great 
force  in  the  frog's  heart,  which  has  Ix-cn  brought  to  a  standstill  bv 
cautiously  heating  it  to  40''  to  43"  C.  (Practical  Kxercises,  p.  194)  for 
a  minute  or  two,  or  t(j  a  considerably  lower  temperature,  for  a  longer 
time  (l-'ig.  77).  A  similar  effect  can  be  obtained  on  the  quiescent 
mammalian  heart  b\-  stimuh'tion  of  the  ncrvi  accclerantcs. 


28' 5 
S30 


rTTTTm  I  M  M  1 1  I  11  I  1 1  I  I  I  (  1 1  I  1 1  r  I  rmnni 


/>/•»-,- r^'^^-ry 


].jg.  y-_. — Effect  of  Stiimilalioii  of  I'roj^'s  Cardiac  S\  iiipallictic  during  Lumplcte 
Standstill  of  tlie  Heart  at  28-5"  C.  Upper  tracing,  auricle  ;  lower,  ventricle. 
To  be  read  froui  ri(,'lit  to  left.     Time-trace,  two-second   iuter\-als. 


The  Normal  Excitation  of  the  Cardiac  Nervous  Mechanism. — 
W'c  ha\"c  now  to  intjuirc  how  this  elaborate  nervous  mechanism  is 
normally  set  into  action.  And  we  may  say  at  once,  that  striking  as 
are  the  effects  of  experimental  stimulation  of  the  vagus  trunk  or  the 
ncrvi  accelerantes  in  their  course,  it  is  only  under  exceptional  cir- 
cumstances that  the  efferent  nene-fibres,  at  any  rate  before  they 
have  entered  the  heart,  can  be  directly  excited  in  the  intact  body. 
In  certain  cases  the  pressure  of  a  tumour  or  an  anouinsm  on  the 
nerve-trunks,  or.  in  the  case  of  the  accelerators  the  progress  of  a 
jiathological  change  in  the  sympathetic  ganglia  through  which  the 


THE  SEh'VOVS  RJ.GULA'J  I(h\  OF  THL   11  HART  ib-t 

nerve-trunks,  or,  in  the  case  of  the  accelerators,  the  progress  of  a 
pathological  change  in  the  sympathetic  ganglia  through  which  the 
fibres  pass,  has  been  thought  to  bring  about  by  direct  stimulation 
a  slowing  or  a  quickening  of  the  pulse.  In  some  individuals  the 
vagus  has  been  excited  by  compressing  it  against  a  bony  tumour 
in  the  neck;  and  by  compressing  the  nerve  against  the  vertebral 
column  it  is  possible  to  cause  inhibition  in  many  normal  persons, 
although  it  ought  to  be  stated  that  the  experiment  is  not  free  from 
danger.  But  it  is  from  the  cardio-inhibitory  and  cardio-augmcn'ur 
centres  in  the  medulla  oblongata  that  the  impulses  which  regul'iie 
the  activity  of  the  heart  are  normally  discharged.  Inhibitory  im- 
pulses are  constantly  passing  out  from  the  medulla,  for  section  of 
both  vagi  causes  almost  invariably  an  increase  in  the  rate  of  the 
heart,  at  least  in  mammals,  although  the  increase  is  less  conspicuous 
in  animals  like  the  rabbit,  whose  normal  pulse-rate  is  high,  than  in 
animals  like  the  dog,  whose  pulse-rate  is  comparatively  \o\v.  Section 
of  one  vagus  usually  causes  only  a  comparatively  slight  increase,  for 
the  other  is  able  of  itself  to  control  the  heart.  It  is  not  certainly 
known  whether  the  augmentor  centre  in  like  manner  discharges  a 
continuous  stream  of  impulses,  or  is  only  roused  to  occasional  activity 
by  special  stimuli.  For  the  results  of  section  of  the  nervi  acceler- 
antes,  or  the  extirpation  of  the  inferior  cervdcal  and  stellate  gangha, 
are  dubious  and  conflicting.  But  if  it  does  exert  a  tonic  influence 
on  the  heart,  this  is  feebler  than  the  tone  of  the  inhibitory  centre. 
As  to  the  nature  of  this  inhibitory-  tone,  and  the  manner  in  which  it 
is  maintained,  we  know  but  little.  It  may  be  that  the  chemical 
changes  in  the  nerve-cells  of  the  inhibitory  centre  lead  of  themselves 
to  the  discharge  of  impulses  along  the  inhibitory  nerves.  But  there 
is  some  evidence  that,  in  the  complete  absence  of  stimulation  from 
without,  the  activity  of  the  centre  would  languish,  and  perhaps  be 
ultimately  extinguished.  For  when  the  greater  number  of  the 
afferent  impulses  have  been  cut  off  from  the  medulla  oblongata  by 
a  transverse  section  carried  through  its  lower  border,  division  of  the 
vagi  produces  little  effect  on  the  rate  of  the  heart.  Also,  when  the 
upper  cervical  cord  and  the  brain  are  resuscitated  after  a  period  of 
anaemia,  the  return  of  cardio-inhibitory  tone  is  tardy  in  comparison 
with  the  return  of  the  truly  automatic  function  of  respiration,  and 
does  not  seem  to  precede  the  opening  up  of  the  afferent  paths  to  the 
cardio-inhibitory  centre.  Indeed,  reflex  inhibition  may  be  produced 
at  a  time  when  the  inhibitory  centre  has  regained  none  of  its  tone. 
The  suggestion  is  that  the  normal  tone  of  the  centre  is  largely 
dependent  upon  reflex  impulses.  Be  this  as  it  may,  we  know  that 
the  activity  of  the  inhibitory  centre  is  profoundly  influenced — and 
that  both  in  the  direction  of  an  increase  and  of  a  diminution — by 
impulses  that  fall  into  it  through  afferent  nerves  and  by  stimuli 
directly  applied  to  it.  And  wo  ma^-  assume  that  the  same  is  true 
of  the  augmentor  centre.     The  common  statement  that  stimulation 


17"  7lir.  CtRCUI.ATlOS  OF  THE  nLOOJ)  AXP  LYMPH 

t>f  thr  ct-ntial  end  of  one  \agus,  the  otlier  l;eing  intact,  pnjcluccf. 
distinct  inhibition  docs  not  hold  for  all  mammals.  In  dogs  this  is 
Sometimes  the  case,  but  often  (under  anaesthesia,  at  any  rate)  there 
IS  little  or  no  inhibition,  or  even  augmentation.  In  etherized  cats, 
on  the  other  hand,  some  inhibition  is  always  seen.  Of  all  the  afferent 
fibres  of  the  vagus,  the  pulmonary  fibres  produce  the  most  marke<l 
reflex  inhibition.     The  cardiac  fibres  are  much  less  effective. 

These  pulmonary  nerves  also  influence  the  respiratory  and  vaso- 
motor centres.  The  respiration  is  temporarily  arrested,  and  the 
blood-pressure  falls  through  the  dilatation  of  the  small  arteries  when 
they  are  excited.  It  is  of  interest  in  connection  with  the  subject 
of  death  during  the  administration  of  anaesthetics,  that  the  afferent 
vagus  fibres  coming  from  the  alveoli  of  the  lungs  can  be  chemically 
stinuilated  when  irritant  vapours,  such  as  chloroform,  hydrochloric 
acid,  ammonia,  bromine,  or  formaldehyde  are  inhaled  through  a 
tracheal  cannula,  causing  reflex  arrest  of  the  heart  and  of  the  respira- 
tory movements  and  a  fall  of  blood-pressure  tlurough  vaso-dilatation 
(Brodie).  At  a  certain  stage  in  chloroform  anaesthesia,  before  it 
has  become  very  deep,  comparatively  trifling  cavises  may  bring 
about  great  and  sudden  changes  in  the  pulse-rate,  owing  to  the 
abnormal  mobility  of  the  vagus  centre  (MacWilliam). 

The  depressor  nerve,  a  branch  of  the  vagus,  which  is  easily  found 
in  the  rabbit  as  a  slender  nerve  running  close  to  the  sympathetic 
in  the  neck,  and  a  little  to  its  inner  side,  but  in  the  dog  is  usually 
blended  with  the  vago-sympathetic,  falls  into  the  same  category 
^vith  the  vagus  itself  as  regards  its  reflex  action  on  the  heart,  to 
which  it  bears  an  important  relation.  In  all  mammals  some  of  its 
fibres  end  in  the  wall  of  the  aorta,  but  some  of  them  may  run  down 
over  the  heart  to  the  ventricle.  Stimulation  of  its  peripheral  end 
has  no  effect,  for  the  fibres  in  it  which  influence  the  circulation  are 
afferent,  not  efferent.  But  excitation  of  its  central  end  causes  a 
marked  fall  of  blood-pressure  (p.  185),  accompanied  by,  but  not 
essentially  due  to,  a  distinct  slowing  of  the  heart.  If  the  animal  is 
not  anaesthetized,  there  may  be  signs  of  pain,  and  for  this  reason  the 
depressor  has  sometimes  been  spoken  of,  somewhat  loosely,  as  the 
sensory  nerve  of  the  heart.  The  abdominal  sjnnpathetic  (of  the 
frog)  also  contains  afferent  fibres,  through  which  reflex  inhibition  of 
the  heart  can  be  produced  when  the}'  are  excited  mechanically  by  a 
rapid  succession  of  light  strokes  on  the  abdomen  with  the  handle 
of  a  scalpel. 

On  the  other  hand,  when  the  central  end  of  an  ordinary  peripheral 
ne.  ve  like  the  sciatic  or  brachial  is  excited,  the  common  eifect  is  pure 
augmentation  (Fig.  78),  which  sometimes  develops  itself  with  even 
greater  suddenness  than  when  the  accelerator  nerves  are  directly 
stimulated.  Occasionally,  however,  the  augmentation  is  abruptly 
followed  by  a  typical  vagus  action.  Here  the  reflex  inhibitory  effect 
seems  to  break  in  upon  and  cut  short  the  reflex  augmentor  effect. 


THE  KERVOUS  REi.V I.ATION  Ol-    THE  HEART 


171 


These  examples  show  that  certain  alUrent  nerves  are  especially 
related  to  the  cardio-inhibitory,  and  others  to  the  cardio-aug mentor, 
centre,  or  at  least  that  the  central  connections  of  some  nerves  arc 
such  that  inhibition  is  the  usual  effect  of  their  reflex  excitation, 
while  the  opposite  is  the  case  with  other  nerves.  But  it  is  im- 
probable that  the  effect  of  a  stream  of  afferent  impulses  reaching 
the  cardiac  centres  by  any  given  nerve  is  determined  solely  by 
anatomical  relations.  The  intensity  and  the  nature  of  the  stimulus 
seem  also  to  have  something  to  do  with  the  result.  For  when 
ordinary  sensory  nerves  are  weakly  stimulated,  augmentation  is 
said  to  be  more  common  than  inhibition,  and  the  opposite  when 
they  are  strongly  stimulated.  And  while  a  chemical  stimulus,  like 
the  inhaled  vapour  of  chloroform  or  ammonia,  raiises  in  the  rabbit 


Fig-  78. — Myocardiographic  Tracing  of  Cat's  Ventricle.  The  signal  line  shows  the 
point  at  which  the  central  end  of  the  brachial  nerve  was  stimulated  during 
resuscitation  of  the  animal  after  a  period  of  cerebral  ansmia.  Some  augmenta- 
tion of  the  ventricular  beat  is  seen.  The  notches  in  the  ventricular  tracing  are 
dtie  to  the  artificial  respiration.     Time-trace,  seconds. 


reflex  inhibition  of  the  heart  through  the  fibres  of  the  trigeminus 
that  confer  common  sensation  on  the  mucous  membrane  of  the  nose, 
the  mechanical  excitation  of  the  sensory  nerves  of  the  pharynx 
and  oesophagus  when  water  is  slowly  sipped  causes  acceleration.* 
The  stimulation  of  the  nerves  of  special  sense  is  followed  sometimes 
by  the  one  effect  and  sometimes  by  the  other.  To  complete  the 
catalogue  of  the  nervous  channels  by  which  impulses  may  reach  the 
cardiac  centres  in  the  medulla,  we  may  add  that  there  must  be  an 
extensive  connection  between  them  and  the  cerebral  cortex,  since 
every  passing  emotion  leaves  its  trace  upon  the  curve  of  cardiac 
action.  The  so-called  '  reflex  cardiac  death,'  which  is  an  occasional 
consequence   of  intense  psychical  influences  (anxiety,  fright,  etc.), 

•  In  78  healthy  students  the  average  pulse-rate    (in  the  .sitting  position) 
was  increased  fram  73  to  85  per  minute  by  sipping  water. 


172  THE  CIRCULATIOS'  OF  THE  BLOOD  AND  LYMI'H 

may  be  due  to  the  prolonged  excitation  of  the  cardio-inhibitory 
centre,  as  well  as  to  the  disturbance  of  other  centres  in  the  bulb  by 
the  cortical  storm.  It  is  a  remarkable  fact,  too,  and  one  that  can 
only  be  explained  by  such  a  connection,  that  aithouph  in  the  vast 
majority  of  individuals  the  will  has  no  influence  whatever  on  the 
rate  or  force  of  the  heart,  except,  perhaps,  indirectly  through  the 
respiration,  some  persons  have  the  power,  by  a  voluntary  effort,  of 
markedly  accelerating  the  pulse.  In  ont-  case  of  this  kind  it  was 
noticed  that  perspiration  broke  out  on  the  hands  and  other  parts  of 
the  body  when  the  heart  was  voluntarily  accelerated.  A  rise  of 
blood-pressure  due  to  constriction  of  the  vessels  has  also  been 
observed.  The  effort  cannot  be  kept  up  for  more  than  a  short  time, 
and  the  pulse-rate  quickly  goes  back  to  normal.  It  has  been 
recently  shown  that  this  peculiar  power  is  more  common  than  has 
been  supposed,  and  that  where  it  is  present  in  rudiment  it  can  be 
cultivated,  although  it  is  a  dangerous  acquisition. 

As  an  example  of  the  direct  action  on  a  cardiac  centre  of  a 
changed  chemical  composition  of  the  blood,  we  may  cite  the 
inhibition  produced  by  injection  of  bile  into  a  vein  and  revealed 
in  the  slow  pulse  of  many  cases  of  jaundice  ;  and  as  an  instance 
of  the  direct  action  of  a  physical  change,  the  slovsing  of  the  heart 
as  the  blood-pressure  rises  (p.  i88)  in  asphyxia  or  on  clamping  the 
aorta.  The  variation  in  the  pulse-rate  associated  with  changes 
in  the  position  of  the  body,  to  which  we  have  already  referred 
(p.  107),  is  brought  about  by  direct  stimulation  of  the  in- 
hibitorv  centre  by  the  increase  of  blood-pressure  in  the  medulla 
oblongata  when  a  person  who  has  been  standing  assumes  the  supine, 
or  even  the  sitting,  posture.  But  it  is  also  due  in  part  to  changes  in 
the  amount  of  muscular  contraction,  since  muscular  exercise  cause* 
acceleration  of  the  heart  either  reflexly,  through  afferent  muscular 
nerves,  or  by  a  direct  effect  of  waste  products  of  the  metabolism  of 
the  muscles  on  the  cardiac  centres  in  the  bulb  or  on  the  heart  itself 
(p.  280). 

Theoretically,  quickening  of  the  heart  might  be  caused  either  by 
a  diminution  in  the  inhibitory  tone  or  by  an  increase  in  the  acti\nty 
of  the  augmentor  centre ;  and  slowing  of  the  heart  might  be  due 
either  to  a  diminution  in  the  augmentor  tone,  if  such  exists,  or  to 
an  increase  in  the  activity  of  the  inhibitory  centre.  So  that  it  is 
not  always  easy  to  interpret  such  results  as  we  have  quoted  above. 
But  it  would  appear  that  under  ordinary  conditions  the  rate  of  the 
heart  is  mainly  regulated  by  the  inhibitory  centre,  which,  within  a 
considerable  range,  can  produce  variations  in  either  direction.  The 
augmentor  mechanism  is  perhaps  merely  auxiliary  to  the  inhibitory, 
being  called  into  action  only  in  emergencies. 


THE  MzinoUS  UEGULAliUN  Ob    I  HE  BLOODVESSELS      17; 


Section  VI. — ^The  Nervous  Regulation  of  the  Bloodvessels 
(Vaso-Motor  Nerves). 

Just  as  the  muscular  walls  of  the  heart  are  governed  by  two  sets 
of  nerve-fibres,  a  set  which  keeps  down  the  rate;  of  working  and  a 
set  which  may  increase  it,  the  muscular  walls  of  the  vessels  are  under 
the  control  of  nerves  which  have  the  power  of  diminishing  their 
calibre  {vaso-constrictor),  and  of  nerves  which  have  the  power  of 
increasing  it  (vaso-dilator).  All  nerves  that  affect  the  calibre  of  the 
vessels,  whether  vaso-constrictor  or  vaso-dilator,  are  included  under 
the  general  name  vaso-motor.  These  vaso-motor  nerves,  like  the 
augmentor  and  inhibitory  fibres  of  the  heart,  are  connected  with  a 
centre  or  centres,  which  in  turn  are  in  relation  with  numerous  afferent 
nerves.  It  is  convenient  to  distinguish  the  afferent  nerves  which 
cause  on  the  whole  a  vaso-constriction  and  a  consequent  increase 
of  arterial  pressure  as  pressor  nerves,  and  those  which  cause  on  the 
whole  vaso-dilatation,  with  fall  of  pressure,  as  depressor  nerves, 
reserving  the  terms  vaso-constrictor  and  vaso-dilator  for  the  efferent 
portions  of  the  reflex  arcs.  It  is  through  this  reflex  mechanism 
that  the  bloodvessels  are  mainly  influenced,  although  the  endings 
of  the  vaso-motor  nerves  in  the  smooth  muscular  fibres  or  the 
muscular  fibres  themselves  are  sometimes  directly  affected  by  sub- 
stances circulating  in  the  blood.  Proteoses,  for  instance,  cause  by 
peripheral  action  dilatation  of  the  vessels  and  a  fall  of  blood-pressure 
(p.  215);  suprarenal  extract,  or  its  active  principle,  adrenalin,  or 
epinephrin,  constriction,  with  a  rise  of  pressure  (pp.  216, 655).  Apo- 
codeine  paralyzes  the  vaso-motor  nerve-endings  after  a  preliminary 
stimulation,  and  now  adrenalin  causes  no  constriction.  Chryso- 
toxin,  an  active  principle  of  ergot,  causes  a  marked  rise  of  blood- 
pressure  by  stimulating  the  sympathetic  ganglion-cells  or  the  pre- 
ganglionic fibres  of  the  vaso-constrictor  path,  ^^aso-motor  nerves 
control  chiefly  the  small  arteries.  They  have  no  direct  influence  on 
the  capillaries.*  Nor  has  the  existence  of  an  effective  vaso-motor 
regulation  of  the  calibre  of  the  veins,  except  in  the  portal  system, 
been  proved  up  to  this  time  by  any  clear  and  unambiguous  experi- 
ment, although  there  are  grounds  on  which  it  has  been  surmised 
that  the  nervous  system  does  influence  the  '  tone  '  of  the  whole 
venous  tract.     These  grounds  will  be  mentioned  in  the  proper  place. 

*  It  is  usually  taught  that  the  capillaries,  being  devoid  of  muscular  fibres 
in  their  walls,  are  not  supplied  with  vaso-motor  fibres,  and  that  the  only  kind 
of  active  contraction  of  which  they  axe  capable  is  due  to  a  process  analogous 
to  the  turgescence  of  vegetable  cells,  the  thickness  of  the  wall  being  increased 
at  the  expense  of  the  lumen,  while  the  total  cross-section  of  the  vessel  remains 
unchanged.  It  has  been  asserted,  however,  that  a  true  contraction,  in  which 
both  the  tdtal  section  and  the  lumen  are  diminished,  may  be  caused  in  the 
capillaries  of  the  nictitating  membrane  of  the  frog  either  by  direct  stimulation 
or  by  excitation  of  vaso-motor  fibres  in  the  sympathetic  (Steinach  and  Kahn). 


174  THE  CIRCULATION  OF  Till-    BLOOD  AND  LYMPH 

Meanwhile,  before  describing  the  distribution  of  the  best-known 
tracts  of  vaso-motor  fibres  and  defining  the  position  of  the  vaso- 
motor centres,  we  must  glance  at  the  methods  by  which  our  know- 
ledge has  been  attained. 

(i)  In  translucent  parts  inspection  is  sufficient.  Paling  of  the  part 
indicates  constriction ;  flusliing,  dilatation  of  the  small  vessels.  This 
method  has  been  much  used,  sometimes  in  conjunction  with  (2),  in  such 
parts  as  the  balls  of  the  toes  of  dogs  or  cats,  the  ear  of  the  rabbit,  the 
conjunctiva,  the  mucous  membrane  of  the  mouth  and  gums,  the  web  of 
the  frog,  the  wing  of  the  bat,  the  intestines,  etc. 

(2)  Observation  of  changes  in  the  temperature  of  parts.  This  method 
has  been  chiefly  employed  in  investigating  the  vaso-motor  nerves  of 
the  limbs,  the  thermometer  bulb  being  fixed  between  the  toes.  In  such 
peripheral  parts  the  temperature  of  the  blood  is  normally  less  than  that 
of  the  blood  in  the  internal  organs,  because  the  opportunities  of  cooling 
are  greater.  The  effect  of  a  freer  circulation  of  blood  (dilatation  of  the 
arteries)  is  to  raise  the  temperature ;  of  a  more  restricted  circulation 
(constriction  of  the  arteries),  to  lower  it. 

(3)  Measurement  of  the  blood-pressure.  If  we  measure  the  arterial 
blood-pressure  ct  one  point,  and  find  that  stimulation  of  certain  nerves 
increases  it  without  affecting  the  action  of  the  heart,  we  can  conclude 
that  upon  the  whole  the  tone  of  the  small  vessels  has  been  increased. 
But  we  cannot  tell  in  what  region  or  regions  the  increase  has  taken  place  ; 
nor  can  we  tell  whether  it  has  not  been  accompanied  by  diminution  of 
tone  in  other  tracts. 

But  if  we  measure  simultaneously  the  blood-pressure  in  the  chief 
artery  and  chief  vein  of  a  part  such  as  a  limb,  we  can  tell  from  the 
changes  caused  by  section  or  stimulation  of  nerves  whether,  and  in 
what  sense,  the  tone  of  the  small  vessels  within  this  area  has  been  altered. 
For  example,  if  we  found  that  the  lateral  pressure  in  the  artery  was 
diminished,  while  at  the  same  time  it  was  increased  in  the  vein,  we 
should  know  that  the  '  resistance  '  between  artery  and  vein  had  been 
lessened,  and  that  the  blood  now  found  its  way  more  readily  from  the 
artery  into  the  vein.  If,  on  the  other  hand,  the  venous  pressure  was 
diminished,  and  the  arterial  pressure  simultaneously  increased,  we  should 
have  to  conclude  that  the  vascular  resistance  in  the  p>art  was  greater 
than  before.  If  the  pressure  both  in  artery  and  vein  was  increased,  we 
could  not  come  to  any  conclusion  as  to  local  changes  of  resistance  with- 
out knowing  how  the  general  blood-pressure  had  varied. 

(4)  The  measurement  of  the  velocity  of  the  blood  in  the  vessels  of 
the  part.  This  may  be  done  by  the  stromuhr  or  dromograph,  or  by 
allowing  the  blood  to  escape  from  a  small  vein  and  measuring  the 
outflow  in  a  given  time,  or,  without  opening  the  vessels,  by  estimating 
the  circulation-time  (p.  135).  When  changes  in  the  general  arterial 
pressure  are  eliminated,  slowing  of  the  blood-stream  through  a  part 
corresponds  to  increase  of  vascular  resistance  in  it ;  increase  in  the  rate 
of  flow  implies  diminished  vascular  resistance .  Sometimes  the  red  colour 
of  the  blood  issuing  from  a  cut  vein,  and  the  visible  pulse  in  the  stream, 
indicate  with  certainty  that  the  vessels  of  the  organ  have  been  dilated. 

(5)  Alterations  in  the  volume  of  an  organ  or  limb  are  often  taken  as 
indications  of  changes  in  the  calibre  of  the  small  vessels  in  it.  We 
have  already  seen  how  these  alterations  are  recorded  by  means  of  a 
plethysmograph  (p.  128).  The  brain  is  enclosed  in  the  skull  as  m  a 
natural  plethysmograph,  and  changes  in  its  volume  may  be  registered 
by  connecting  a  recording  apparatus  with  a  trephine  hole. 


THE  NERVOUS  REGULATIOS  OF  THE  BLOODVESSELS      175 

(6)  For  the  separation  of  the  effects  of  stimulation  of  vaso-constrictor 
and  vaso-dilator  fibres  when  they  are  mingled  together,  as  is  the  case 
in  many  nerves,  advantage  is  taken  of  certain  differences  between  them. 
For  example,  the  vaso-constrictors  lose  their  excitability  sooner  than 
the  vaso-dilators  when  cut  off  from  the  nerve-cells  to  which  they  belong. 
So  that  if  a  nerve  is  divided,  and  some  days  allowed  to  elapse  before 
stimulation,  only  the  dilators  will  be  excited.  The  vaso-dilators  are 
more  sensitive  to  weak  stimuli  repeated  at  long  intervals  than  to  strong 
and  frequent  stimuli,  and  the  opposite  is  true  of  the  constrictors.  WTien 
a  nerve  containing  both  kinds  of  fibres  is  heated,  the  excitability  of 
the  vaso-constrictors  is  increased  in  a  greater  degree  than  that  of  the 
dilators:  when  tlie  nerve  is  cooled,  the  dilators  preserve  their  excita- 
bility at  a  temperature  at  which  the  constrictors  have  ceased  to  respond 
to  stimulation  (Fig.  79). 

The  Chief  Vaso-Motor  Nerves. — The  first  discovery  of  vaso-motor 
nerves  was  made  in  the  cervical  sympatlietic.     When  this  nerve  is 


79. — Plethysmograms:  Hind-Limb  ot  Cat  (alter  Bowditch  and  Warren).  To  be 
read  from  right  to  left.  On  the  left  hand  is  shown  the  efifect  of  slow  stimulation 
of  the  sciatic  (i  per  second);  on  the  right  hand  the  effect  of  rapid  stimulation 
(64  per  second).  In  the  first  case  the  limb  swelled  owing  to  excitation  of  the 
vaso-dilators;  in  the  second,  it  shrank  tl^ough  excitation  of  the  vaso-constrictors. 

cut,  the  corresponding  side  of  the  head,  and  especially  the  ear, 
become  greatly  injected  ouing  to  the  dilatation  of  the  vessels.  This 
experiment  can  be  very  readily  performed  on  the  rabbit,  and  the 
changes  are  most  easily  followed  in  an  albino.  The  ear  on  the  side 
of  the  cut  nerve  is  redder  and  hotter  than  the  other;  the  main 
arteries  and  veins  are  swoUen  with  blood,  and  many  vessels  formerly 
in\nsible  come  into  view.  The  slow  rhythmical  changes  of  calibre, 
which  in  the  normal  rabbit  are  very  characteristically  seen  in  the 
middle  artery  of  the  ear,  disappear  for  a  time  after  section  of  the 
sympathetic,  although  they  ultimately  again  become  \'isible. 

Stimulation  of  the  cephaUc  end  of  the  cut  sympathetic  causes  a 
marked  constriction  of  the  vessels  and  a  fall  of  temperature  on  the 
same  side  of  the  head.     From  these  facts  we  know  that  the  cervical 


176  THE  CmCULATiON  OF  Till-:  BLOOD  A  WD   r.YMPH 

synipatlietic  in  inanir.ials  contains  vaso-constrictur  fibres  for  the 
side  of  the  head  and  ear,  and  that  these  fibres  are  constantly  in 
action.  Certain  parts  of  the  eye,  and  the  saHvary  glands,  larynx, 
oesophagus,  and  th\Toid  gland,  are  also  supplied  with  vaso- motor 
(constrictor)  nerves  from  the  cervical  sympathetic. 

It  has  been  asserted  that  the  cervical  sympathetic  contains  some  of 
the  vaso-constrictor  fibres  that  supply  the  corrcspondin;^  half  of  the 
brain  and  its  membranes,  but  this  lias  been  disputed,  and  some  ob- 
servers deny  that  the  vessels  of  the  brain  have  any  vaso-motor  nerves. 
Non-medullated  nervc-fibies,  however,  may  be  seen  in  and  around  the 
walls  of  the  cerebral  and  spinal  bloodvessels,  and  it  is  difficult  to  believe 
that  these  have  not  a  vaso-motor  function,  although  this  has  not  as 
yet  been  clearly  demonstrated  by  experimental  methods. 

It  has  sometimes  been  argued  that  we  ought  not  to  expect  the  brain 
to  be  supplied  with  vaso-motors.  For  it  is  enclosed  in  a  rigid  box,  and 
the  quantity  of  blood  in  it  can  be  increased  or  diminished  only  to  tlie 
slight  extent  to  which  the  ccrebro-spinal  liquid  can  be  displaced  into 
the  vertebral  canal.  Important  changes  in  the  cerebral  blood-supply 
are  therefore  brought  about,  it  is  said,  not  by  a  widening  or  narrowing 
of  the  cerebral  vessels,  but  by  an  alteration  in  the  velocity  of  the  blood 
in  them  as  a  result  of  a  rise  or  fall  of  the  systemic  arterial  pressure. 
This  argument,  however,  leaves  out  of  account  the  consideration  that 
in  general  the  brain  does  not  function  as  a  whole,  but  that  certain 
parts  of  it  may  often  become  active  and  relatively  hypera?mic,  while 
other  parts  are  inactive  and  relatively  anaemic,  and  that  important 
changes  in  the  distribution  of  the  blood  in  the  encephalon  may  be 
effected,  although  the  total  mass  of  blood  in  the  organ  undergoes  little 
or  no  alteration.  It  is,  of  course,  true  that  it  is  not  the  absolute  quantity 
of  blood  in  an  organ  which  is  a  function  of  its  activity,  but  the  rate  at 
which  it  is  renewed.  And  it  is  theoretically  possible  that  an  organ  at 
rest  should  contain  as  much  blood  as  when  it  is  acti\e,  or  even  more. 
But  such  cases,  if  they  exist,  are  certainly  rare.  The  fact  that  adrenalin 
generallv  constricts  the  vessels  of  a  perfused  brain  (Wiggers)  is  in  favour 
of  the  ex  stence  of  vaso-motors.  The  retina,  which  from  the  stand- 
point of  development  is  a  portion  of  tlie  brain,  is  undoubtedly  supplied 
with  vaso-constrictor  fibres  which  run  in  the  cervical  sympathetic. 

That  the  cervical  sympathetic  contains  some  dilator  fibres  is 
proved  by  the  fact  that  stimulation  of  the  cephalic  end  in  the  dog 
causes  flushing  of  the  mucous  membrane  of  the  mouth  on  the  same 
side.  Further,  after  division  of  the  nerve  on  one  side  in  the  rabbit 
it  may  be  observed  that  when  the  animal  is  excited  the  vessels  of  the 
ear  whose  nerve  is  intact  may  become  still  more  dilated  than  those 
whose  constrictor  fibres  have  been  paralyzed.  The  only  explana- 
tion is  that  vaso- dilators  are  being  excited  from  the  central  nervous 
system. 

"  The  vaso-motor  fibres  of  the  head  run  up  in  the  cervical  sympa- 
thetic, and  then  pass  into  various  cerebral  nerves,  of  which  the  fifth 
or  trigeminus  is  the  most  important. 

The  trigeminus  nerve  contains  vaso-constrictor  nerves  for  various 
parts  of  the  eye  (conjunctiva,  sclerotic,  iris),  and  for  the  mucous 


THE  NERVOUS  REGVLATIOS  Of  THE  BLOODVESSELS      ijo 

membrane  of  the  nose  and  gums,  and  section  of  it  is  followed  by 
dilatation  of  the  vessels  of  these  ri.j4ions.  The  lingual  branch  of 
the  trigeminus  supplies  vaso-motor  tibres  to  the  tongue,  and  ap- 
parently l:»oth  vaso-constrictor  and  vaso-dilator. 

In  some  animals — the  rabbit,  for  instance — the  ear  derives  part 
of  its  vaso-motor  supply  through  the  great  auricular  nerve,  a  branch 
of  the  third  'crvical  nerve,  which  they  reach  as  grey  rami  from  the 
stellate  ganglion. 

Another  great  vaso-motor  tract,  the  most  influential  in  the  body, 
is  contained  in  the  splanchnic  nerves,  which  govern  the  vessels  of 
many  of  the  abdominal  organs.  Section  of  these  nerves  causes  an 
immediate  and  sharp  fall  of  arterial  pressure.  The  intestinal  vessels 
are  dilated  and  overfilled  with  blood.  As  a  necessary  consequence 
of  their  immense  capacity,  the  rest  of  the  vascular  system  is  uoder- 
filled,  and  the  blood-pressure  falls  accordingly.  Stimulation  of  the 
peripheral  end  of  the  splanchnic  nerves  causes  a  great  rise  of  blood- 
pressure,  owing  to  the  constriction  of  vessels  in  the  intestinal  area. 
We  therefore  conclude  that  in  the  splanchnics  there  are  vaso-motor 
fibres  of  the  constrictor  type,  and  that  impulses  are  constantly 
passing  down  them  to  maintain  the  normal  tone  of  the  vascular 
tract  which  they  command.  When  the  splanchnic  nerves  are 
stimulated,  the  adrenal  glands  are  so  affected  that  adrenahn  passes 
out  by  the  veins  into  the  blood-stream.  It  is  clear  that  if  the  quan- 
tity thus  liberated  were  sufficiently  large  and  its  liberation  suffi- 
ciently prompt  it  might  play  a  part  in  the  rise  of  pressure  (p.  66i) 
which  follows  stimulation  of  the  nerves,  whether  they  are  excited 
directly  or  in  the  normal  course  of  events  reflexly.  But  it  has  not 
been  demonstrated  that  this  is  an  effective  factor.  Dilator  fibres 
(for  the  intestines  and  the  kidney,  for  example)  have  also  been 
discovered  in  the  splanchnic  nerves,  although  the  constrictors 
predominate,  and  special  methods  have  to  be  employed  for  the 
detection  of  the  dilators. 

The  same  is  true  of  the  nerves  of  the  extremities,  which  certainly 
contain  vaso-dilator  fibres  in  addition  to  vaso-constrictors,  although 
the  difficulty  of  demonstrating  the  presence  of  the  former  is  fully 
as  great  as  it  is  in  the  splanchnics.  For  the  investigation  is  com- 
plicated b}-  the  fact  that  such  nerves  as  the  sciatic  supply  with 
vaso-motor  fibres  two  leading  tissues — skin  and  muscle ;  and  these 
are  not  necessarily  affected  in  the  same  direction  or  to  the  same 
extent  by  stimulation  of  their  vaso-motor  fibres.  The  vaso-con- 
strictors under  ordinary  conditions  preponderate,  so  that  section  of 
the  sciatic  or  the  brachial  is  generally  followed  by  flushing  of  the 
balls  of  the  toes  and  rise  of  temperature  of  the  feet,  stimulation  by 
paling  and  fall  of  temperature.  By  talcing  advantage,  however,  of 
the  unequal  excitability  of  dilators  and  constrictors  in  a  degenerating 
nerve,  and  of  the  differences  between  the  two  kinds  of  fibres  in  their 


t7c  THE  CinCULAllOS  UI-   IHL  BLOOD  AND  LYMPH 

reaction  to  electrical  stimuli  (p.  175),  it  has  been  shown  that  vaso- 
dilators are  also  present,  and  come  to  the  front  when  the  conditions  are 
rendered  favourable  for  them  and  unfavourable  for  the  constrictors. 

Vaso-motor  fibres  for  the  fore-limb  (dog)  issue  from  the  cord  in  the 
anterior  roots  of  the  third  to  the  eleventh  dorsal  nerves,  and  for  the 
hind-limb  in  the  anterior  roots  of  the  eleventh  dorsal  to  the  tliird  lumbar. 
Stimulation  of  most  of  these  roots  causes  constriction  of  the  vessels 
but  stimulation  of  the  eleventh  dorsal  may  cause  dilatation  (Bayliss 
and  Bradford). 

Ihe  I'aso-Molor  Nerves  of  Muscle. — When  the  motor  nerve  of  the  thin 
mylo-hjoid  muscle  of  the  frog,  which  can  be  observed  under  the  micro- 
scope, is  cut,  and  the  peripheral  end  stimulated,  the  vessels  are  seen  to 
dilate  distinctly,  and  this  effect  is  not  abolished  when  contraction  of 
the  muscle  is  prevented  by  a  dose  of  curara  insufficient  to  paralyze  the 
vaso-motor  nerves.  This  indicates  the  existence  in  the  nerve  of  vaso- 
dilator fibres.  But  we  must  be  cautious  in  transferring  this  result  to 
ordinary  skeletal  muscle,  for  the  mylo-hyoid  is  more  closely  allied  to 
the  muscles  of  the  tongue  than,  for  example,  to  the  muscles  of  the  limbs, 
and  in  the  mammal  the  tongue  muscles  are  known  to  be  better  supplied 
with  vaso-dilator  fibres  than  the  limb  muscles.  The  average  flow  of 
blood  through  a  manmialian  muscle  is  indeed  increased  during  volun- 
tary- contraction,  and  during  rhythmically  repeated  artificial  tctaniza- 
tion  of  its  motor  nerve.  The  outflow  of  blood  from  the  main  vein  of 
the  levator  labii  superioris,  one  of  the  muscles  used  in  feeding  in  the 
horse,  was  found  to  be  in  one  experiment  nearly  eight  tinics,  in  another 
about  seven  times,  and  in  a  third  three  and  a  half  times  as  great  during 
vohmtary  work  with  it  (in  chewing)  as  in  rest.  But  as  no  increa.se  in 
the  blood-flow  through  the  skeletal  muscles  of  a  completely  curarized 
mammal  during  excitation  of  their  nerves  has  ever  been  satLsfactorily 
demonstrated,  wc  must  conclude  that  they  are  very  scantily  provided 
with  vaso-dilator  fibres  or  not  at  all.  It  is  uncertain  whether  they  are 
supplied  with  vaso-constrictors.  The  undoubted  increase  in  the  blood- 
flow  in  contraction  may  therefore  be  connected  in  some  way  with  the 
mcichanical  or  chemical  changes  in  the  muscular  fibres  themselves. 

It  has  been  suggested  that  the  muscular  vessels  are  widened  by  the 
direct  action  of  the  acid  products  of  tlie  active  muscle,  since  \er)'  dilute 
acids  (lactic  acid,  e.g.)  cause  general  dilatation  of  the  small  vessels. 
A  similar  explanation  has  been  extended  to  the  dilatation  of  the  vessels 
of  the  brain  during  cerebral  activity  by  some  of  those  who  deny  the 
existence  of  vaso-motor  nerves  for  that  organ,  but  here  the  evidence 
is  by  no  means  satisfactory-.  The  v;:gus  has  been  stated  to  contain 
vaso-constrictor,  and  the  annulus  of  \'icussens  vaso-dilator,  fibres  for 
the  coronary  arteries  of  the  heart.  But  this  question  Ls  far  from  being 
settled.  Adrenalin  causes  dilatation  and  not  constriction  of  the 
coronary  vessels.  There  is  some  reason  to  believe  that  the  metabolic 
products  liberated  in  the  heart-muscle,  e.g.,  carbon  dioxide,  govern  the 
changes  in  the  calibre  of  the  coronary  arterioles.  A  close  relationship 
cxi-sts  between  the  output  of  carbon  dioxide  and  the  rate  of  flow  through 
the  coronary  circulation.  In  asphyxia  the  flow  through  the  coronary 
\esscls  is  notably  increased;  indeed,  it  is  at  its  maximum  just  before 
the  heart  fails  altogether,  as  if  an  effort  were  being  made  to  keep  the 
heart  going  to  the  last  by  maldng  up  to  it  in  the  quantity  of  the  blood 
supplied  what  it  lacks  in  quality.  As  this  increased  flow  is  seen  in  the 
isolated  heart-lung  preparation,  it  has  been  concluded  that  metabolites 
produced  in  the  cardiac  muscle  itself  cause  an  increased  coronary  flow 
when  increased  demands  arc  made  on  the  heart,  a  local  regulative 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      x;9 

mechanism  being  thus  constituted.     There  is  some  evidence  that  carbon 
dioxide  is  not  tlic  most  potent  ol  tlicse  substances. 

Vaso-Moloy  Xcivcs  of  the  Lungs. — There  has  been  much  discussion  as 
to  the  course,  and  even  as  to  the  existence,  of  vaso-motor  fibres  for  the 
lungs.  The  problem  is  perhaps  the  most  difficult  in  the  whole  range  of 
vaso-motor  topography,  for  the  pulmonar\-  circulation  is  so  related  to 
other  vascular  tracts,  that  changes  produced  in  the  \-cssels  of  distant 
organs  by  the  stimulation  or  section  of  nerves  may  affect  the  quantity 
of  blood  received  by  tlu'  right  side  of  the  heart,  and  therefore  the 
quantity  propelled  througli  the  lungs  and  the  pressure  in  the  pulmonary 
artery.  And  changes  in  the  systemic  arterial  pressure  may  favour  or 
hinder  the  discharge  of  the  left  ventricle,  and  therefore  affect  the  pres- 
sure in  the  left  auricle  and  the  pulmonary  veins.  Nevertheless,  evidence 
has  been  obtained  from  a  number  of  sources  that  the  lungs  are  supplied 
with  vaso-constrictor  fibres.  Plumicr,  perfusing  isolated,  '  surviving  ' 
lungs  with  blood  under  constant  pressure  and  measuring  the  outflow, 
showed  that  adrenalin  and  also  stimulation  of  the  annulus  of  Vieussens 
caused  great  diminution  in  the  flow — that  is,  constriction  of  the  vessels. 
Wiggcrs  also  obtained  constriction  with  adrenalin.  Fiihner  and 
Starling,  working  with  a  preparation  including  the  heart  as  well  as  the 
lungs,  found  that  adrenalin  caused  a  rise  of  pressui-c  in  the  pulmonary 
artery  coupled  with  a  fall  of  pressure  in  the  left  auricle,  which  could 
only  be  due  to  constriction  of  the  vessels  of  the  lungs.  It  is  assumed 
that  adrenalin  produces  vaso-constriction  only  in  vessels  supplied  with 
\'aso-constrictor  nerves  (p.  653),  and  that  in  organs  where  this  substance 
does  not  cause  vaso-constriction  no  such  fibres  are  present.  In  mam- 
mals the  vaso-constrictor  fibres  seem  to  pass  out  from  the  upper  half 
of  the  dorsal  spinal  cord,  and  some  of  them  can  be  detected  nearer  their 
destination  in  the  annulus  of  Vieussens.  The  vago -sympathetic  of  the 
tortoise  contains  vaso-constrictors  for  the  lung  of  the  same  side  (Krogh). 

Vaso-Dilator  Fibres. — In  most  of  the  peripheral  nerves  these  are 
mingled  with  vaso-constrictors;  but  in  certain  situations,  for  an 
anatomical  reason  that  will  be  mentioned  presently,  nerves  exist  in 
which  the  only  vaso-motor  fibres  are  of  the  dilator  t5'pe.  Of  these, 
the  most  conspicuous  examples  aje  the  chorda  tympani  and  the 
nervi  crigentes  or  pelvic  nerves;  and,  indeed,  it  was  in  the  chorda 
that  vaso-dilators  were  first  discovered  by  Bernard.  The  chorda 
tympani  contains  vaso-dilator  and  secretory  fibres  for  the  sub- 
maxillary and  subungual  salivary  glands.  With  the  secretory  fibres 
we  have  at  present  nothing  to  do;  and  the  whole  subject  will  have 
to  be  retvirned  to,  and  more  fully  discussed  in  Chapter  VI.  But  a 
most  marked  vascular  change  is  produced  by  stimulation  of  the 
peripheral  end  of  the  divided  chorda  tympani  nerve.  The  glands 
flush  red;  more  blood  is  evidently  passing  through  their  vessels. 
Allowed  to  escape  from  a  divided  vein,  the  blood  is  seen  to  be  of  a 
bright  arterial  colour  and  shows  a  distinct  pulse.  The  small  arteries 
have  been  dilated  by  the  action  of  the  vaso-motor  fibres  in  the  nerve. 
The  resistance  being  thus  reduced,  the  blood  passes  in  a  fuller  and 
more  rapid  stream  through  the  capillaries  into  the  veins,  and  on  the 
way  there  is  not  time  for  it  to  become  completely  venous.  These 
vaso-dilator  fibres  are  not  in  constant  action,  for  section  of  the 


l8o  THE  CUiCrLATIOS  OF  THE  ni.nOD  AST)  LYMPH 

nerve,  as  a  rule,  produces  little  or  no  diangi-.  Vaso-constrictor 
fibres  pass  to  the  salivary  glands  from  the  cervical  sympathrtic 
along  the  arteries,  and  stimulation  of  that  nerve  causes  narrowing  of 
the  vessels  and  diminution  of  the  blood-fiow.  sometimes  almost  to 
complete  stoppage. 

The  nervi  erigentes  are  the  nerves  through  which  erection  of  the 
penis  is  caused.  WTien  they  are  divided  there  is  no  effect,  but 
stimulation  of  the  peripheral  end  causes  dilatation  of  the  vessels  of 
the  erectile  tissue  of  the  organ,  which  becomes  overfilled  with 
blood.  During  stimulation  of  these  nerves,  the  quantity  of  blood 
flowing  from  the  cut  dorsal  vein  of  the  penis  may  be  fifteen  times 
greater  than  in  the  absence  of  stimulation.  It  spurts  out  in  a  strong 
stream,  and  is  bi^^'hter  than  ordinary  venous  blof>d  (Eckhard). 
Stimulation  of  the  peripheral  end  of  the  nervns  pudendus  causes 
constriction  of  the  vessels  of  the  penis,  so  that  it  contains  vaso- 
constrictor fibres  which  are  the  antagonists  of  the  nervi  erigentes. 

Vaso-Motor  Nerves  of  Veins. — Like  arteries,  veins  have  plexuses 
of  nerve-fibres  in  their  walls,  and  contract  in  response  to  various 
stimuU.  In  some  cases — e.g.,  in  the  wing  of  the  bat — rhythmical 
contractions  of  the  veins  are  strikingly  displayed,  but  they  do  not 
depend  on  the  central  nervous  system,  as  they  persist  after  section 
of  the  brachial  nerves.  The  e.xistence  of  vaso-constrictor  fibres  for 
the  venules  given  off  in  the  liver  by  the  portal  vein  is  indicated  by  the 
fact  that  adrenalin  diminishes  the  blood  flow  through  the  organ  even 
when  the  hepatic  artery  has  been  tied  (Burton-Opitz;  Macleod  and 
Pearce,  etc.).  Stimulation  of  the  distal  end  of  the  hepatic  ple.xus 
causes  similar  effects.  The  fibres  issue  from  the  spinal  cord  by  the 
anterior  roots  of  the  third  to  the  eleventh  dorsal  nerves,  but  chiefly 
in  the  fifth  to  the  ninth  dorsal.  The  arterioles  arising  from  the 
hepatic  artery  have  their  own  vaso-motor  supply,  which  is  more  com- 
plete than  that  of  the  portal  vessels.  When  the  liver  is  enclosed  in 
a  plethysmograph,  and  the  central  end  of  an  ordinarv  sensory  nerve, 
like  the  sciatic,  e.xcited,  reflex  vaso-constriction  takes  place  in  the 
portal  area,  the  volume  of  the  organ  diminishes,  and  the  blood-pres- 
sure rises  in  the  portal  vein  (Frangois-Franck). 

The  vena  portae  and  its  branches  are  in  the  physiological  sense 
arteries  rather  than  veins,  since  they  break  up  into  capillaries,  and 
it  was  to  be  expected  that  the  regulation  of  the  blood-flow  in  them 
would  be  carried  out  in  the  same  way  as  in  ordinary  arteries,  namely, 
bv  means  of  vaso-motor  nerves.  But  we  must  not.  without  special 
proof,  extend  the  results  obtained  in  the  portal  system  to  ordinary 
veins.  A  certain  amount  of  evidence,  however,  exists  that  even 
such  veins  as  those  of  the  extremities  are  supplied,  though  scantily, 
with  vaso-constrictor  (veno-motor)  fibres.  After  ligation  of  the 
crural  artery  or  aorta,  stimulation  of  the  peripheral  end  of  the 
sciatic  has  been  seen  to  cause  contraction  of  short  portions  of  the 
superficial  veins  of  the  leg. 


TIIF.   NERVOUS  REGUI.AllON  OF  THE  tSLOODVESSELS      i8i 

Fiiuilly,  acJrriialin  (tjjint'plirin)  causes  constriction  of  rings  of 
'  surviving  '  veins  just  as  of  artery  rings,  although  in  correspondence 
with  the  smaller  amount  of  muscular  tissue  in  the  former  the  con- 
traction is  not  so  strong.  As  adrenalin  is  assumed  to  act  only  upon 
muscle  supplied  by  sympathetic  nerve-fibres  (p.  655),  this  would 
seem  to  indicate  the  existence  of  such  a  supply  for  veins.  The 
question  is  an  important  one  in  connection  with  the  regulation  of 
the  fiUing,  and  therefore  of  the  discharge,  of  the  heart  (Henderson), 
but  the  experimental  data  are  as  yet  too  meagre  to  justify  further 
discussion  of  the  matter  here. 

Course  of  the  Vaso-Motor  Nerves. — In  the  dog  the  vaso -constrictors 
pass  out  as  fine  medullatcd  fibres  (i'8  to  3-6  yu  in  diameter)  in  the 
anterior  roots  of  the  second  dorsal  to  about  the  second  lumbar  nerves. 
They  proceed  by  the  white  rami  communicantes  to  the  lateral  sym- 
pathetic ganglia,  where,  or  in  more  distal  ganglia  such  as  the  inferior 
mesenteric,  they  lose  their  medulla,  and  their  axis-cylinder  processes 
(p.  85 1)  break  up  into  fibrils  that  come  into  close  relation  with 
the  nerve-cells  of  the  ganglia.  These  ganglion-cells  in  their  turn  send 
off  axis-cylinder  processes,  which,  enveloped  by  a  neurilemma,  pass  as 
non-meduUatcd  fibres  by  various  routes  to  their  final  destination,  the 
unstript'd  muscular  fibres  of  the  bloodvessels.  Their  course  to  the  head 
has  been  already  described.  To  the  limbs  they  are  distributed  in  the 
great  nerves  (brachial  plexus,  sciatic,  etc.),  which  they  reach  from  the 
sympathetic  ganglia  by  the  grey  rami  communicantes. 

The  outflow  of  vaso-dilator  fibies  is  not  restricted  to  the  same  portion 
of  the  cord  from  which  the  outflow  of  constrictor  fibres  takes  place. 
Their  existence  is  indeed  most  easily  demonstrated  in  nerves  springing 
from  those  regions  of  the  cerebro-spinal  axis  from  which  vaso-constrictor 
fibres  do  not  arise,  and  where,  therefore,  we  have  not  to  contend  with 
the  difliculty  of  interpreting  mixed  effects.  Vaso-dilators  for  the 
external  generative  organs  and  the  mucous  membrane  of  the  lower  end 
of  the  rectum  pass  out  as  small  medullated  fibres  of  the  anterior  roots, 
of  certain  of  the  sacral  nerves  (mainly  the  second  and  third  in  the  cat) 
into  the  pelvic  nerve  (nervus  erigens).  They  end  in  relation  with 
ganglion-cells  in  the  neighbourhood  of  the  organs  which  they  supply. 
The  seventh  and  ninth  cranial  nerves  carry  vaso-dilator  fibres  which 
are  distributed  by  way  of  the  lingual  and  other  branches  of  the  fiith 
to  the  salivary  glands,  the  tongue,  the  mucous  membrane  of  the  floor 
of  the  mouth,  and  part  of  the  soft  palate.  Those  in  the  lingual,  passing 
through  the  chorda  tympani,  end  in  gangi ion-cells  near  the  submaxillar^' 
and  sublingual  glands,  and  the  axons  of  these  cells  continue  the  path 
to  the  vessels  of  the  glands.  It  is  supposed  that  the  vaso-dilators  dis- 
tributed in  other  branches  of  the  fiith  also  have  ganglion-cells  on  their 
course.  In  fact,  there  is  good  evidence  that  everj'  elferent  vaso-motor 
fibre  is  interrupted  by  one,  and  only  by  one,  ganglion-cell  between  the 
cord  and  the  bloodvessels.  The  statement  has  been  made  that  for 
certain  regions  of  the  body,  especially  the  skin  of  the  limbs,  the  vaso- 
dilator nerves  are  contained,  not  in  the  anterior,  but  in  the  posterior 
roots.  And  these,  it  is  claimed,  are  not  aberrant  efferent  fibres  which 
have  strayed  in  the  course  of  development  into  the  wrong  roots,  but  true 
posterior  root-fibres  whose  cells  of  origin  lie  in  the  spinal  ganglia,  and 
which  conduct  efferent  vaso-dilator  impulses  in  the  wrong  direction,  so 
to  speak,  from  the  cord  to  the  periphery — '  antidromic  '  impulses 
(Bayliss). 


i82  THE  CIRCULATION  OF  THE  BLOOD  AXD  LYMFH 

Effect  of  Nicotine  on  Nerve-Cells. — A  method  which  has  been  found 
most  fruitful  in  studying  the  relations  of  sympathetic  ganglion-cells  to 
the  vaso-motor  fibres,  as  well  as  to  the  pilo-motor*  and  secretory  fibres 
which  in  certain  situations  are  so  intricately  mingled  with  them,  must 
here  be  mentioned.  It  depends  upon  the  fact  that  when  a  suitable 
dose  of  nicotine  (lo  milligrammes  in  a  cat)  is  injected  into  a  vein,  or  a 
solution  is  painted  on  a  ganglion  with  a  brush,  the  passage  of  nerve- 
mipulses  through  the  ganglion  is  blocked  for  a  time  (Langley).  The 
nerve-fibres  peripheral  to  the  ganglion  are  not  affected.  The  question 
whether  efferent  fibres  are  connected  with  ner\e-cells  between  a  given 
point  and  their  peripheral  distribution  can,  therefore,  be  answered  by 
observing  whether  any  effect  of  stimulation  is  abolished  by  nicotine. 
If,  for  instance,  the  excitation  of  a  nerve  caused  constriction  of  certain 
bloodvessels  before,  and  has  no  effect  after,  the  application  of  nicotine 
to  a  ganglion,  its  \aso-constrictor  fibres,  or  some  of  them,  must  be  con- 
nected with  nerve-cells  in  that  ganglion.  Langley  has  brought  forward 
evidence,  that  many  of  the  bodies  which  are  commonly  supposed  to  act 
upon  nerve-endings  (as  nicotine,  curara,  atropine,  pilocarpine,  adrenalin, 
etc.)  really  act  upon  '  receptive  '  sub.stances  of  the  cells  in  connection 
with  which  the  nerve-fibres  end.  These  receptive  substances  are  con- 
ceived to  be  capable  of  being  specificallj-  afiected  by  chemical  bodies 
and  by  nerv'ous  stimuli,  and  in  their  turn  to  be  capable  of  influencing 
the  metabolism  of  the  main  cell  substance  on  which  its  function  depends. 
The  receptive  substances  thus  form  beyond  the  histological  link  of  the 
nerve -ending  a  kind  of  chemical  link  between  the  nerve-fibre  and  the 
cell  which  it  supplies. 

We  have  thus  traced  the  vaso-motor  nerves  from  the  cerebro- 
spinal axis  to  the  bloodvessels  which  they  control ;  it  still  remains 
to  define  the  portion  of  the  central  nervous  system  to  which  these 
scattered  threads  are  related,  which  holds  them  in  its  hand  and  acts 
upon  them  as  the  needs  of  the  organism  may  require. 

Vaso-Motor  Centres. — Now,  experiment  has  shown  that  there  is 
one  very  definite  region  of  the  spinal  bulb  which  has  a  most  intimate 
relation  to  the  vaso-motor  nerves.  If  while  the  blood-pressure  in 
the  carotid  is  being  registered,  say,  in  a  curarized  rabbit,  the  central 
end  of  a  peripheral  nerve  like  the  sciatic  is  stimulated,  the  pressure 
rises  so  long  as  the  bulb  is  intact,  this  rise  being  largely  due  to  the 
reflex  constriction  of  the  vessels  in  the  splanchnic  area.  If  a  series 
of  transverse  sections  be  made  through  the  brain,  the  rise  of  pressure 
caused  by  stimulation  of  the  sciatic  is  not  affected  till  the  upper 
limit  of  the  bulb  is  almost  reached.  If  the  slicing  is  still  carried 
downwards,  the  blood-pressure  sinks,  and  the  rise  following  stimu- 
lation of  the  sciatic  becomes  less  and  less.  When  the  medulla  has 
been  cut  away  to  a  certain  level,  only  an  insignificant  rise  or  none 
at  all  can  be  obtained.  The  portion  of  the  medulla  the  removal  of 
which  exerts  an  influence  on  the  blood-pressure,  and  its  increase  by 
reflex  stimulation,  extends  from  a  level  4  to  5  mm.  above  the  point 
of  the  calamus  scriptorius  to  within  i  to  2  mm.  of  the  corpora 
quadrigemina.     Stimulation  of  the  medulla  causes  a  rise,  destruc- 

*  Pilo-motor  nerves  supply  the  smooth  arrector  pili  muscles,  whose  contrac- 
tion causes  the  hair  to  '  stand  on  end.' 


THE  NERVOUS  REGULATION  01-   THE  BLOODVESSELS      18.I 

tion  of  tliis  portion  of  it  a  severe  fall,  of  general  blood-pressure. 
There  is  evidently  in  this  region  a  nervous  '  centre  '  so  intimately 
related,  if  not  to  all  the  vaso- motor  nerves,  at  least  to  such  very 
important  tracts  as  to  deserve  the  name  of  a  vaso-motor  centre. 
Experiment  has  shown  that  this  is  much  the  most  influential  centre, 
and  it  is  usually  called  the  chief  or  general  vaso-motor  centre.  Some 
writers  prefer  to  speak  of  it  as  the  vaso-constrictor  centre,  since  it 
is  undoubtedly  connected  with  most  or  all  of  the  vaso-constrictor 
paths,  and  has  not  been  shown  to  be  similarly  connected  with  the 
vaso-dilator  paths.  There  is,  indeed,  not  the  same  solid  evidence 
for  the  existence  of  a  general  vaso-dilator  centre  in  the  bulb  as  for 
the  existence  of  the  general  vaso-constrictor  centre.  Yet  there  are 
facts  which  indicate  that  the  bulbar  vaso-motor  centre  or  centres, 
when  reilexly  stimulated,  can,  and  often  do,  respond  not  merely  by 
an  increase  or  a  remission  of  vaso-constrictor  tone,  but  by  a  simul- 
taneous inhibition  of  vaso-constrictor  fibres  and  excitation  of  vase- 
dilators  leading  to  a  fall  of  pressure,  or  by  a  simultaneous  inhibititm 
of  vaso-dilators  and  excitation  of  vaso-constrictors  leading  to  a  rise 
of  pressure. 

The  spinal  cells  of  origin  of  the  pre-ganglionic  segments  of  the 
vaso-constrictor  paths  constitute  subordinate  centres  which  either 
normally  support  a  certain  degree  of  vascular  tone,  or  come  to  do  so 
after  the  chief  vaso-motor  centre  has  been  cut  off. 

Thus,  in  the  frog  it  is  possible  to  go  on  destroying  more  and  more 
of  the  cord  from  above  downwards,  and  still  to  obtain  reflex  vaso- 
motor effects,  as  seen  in  the  vessels  of  the  web,  by  stimulating  the 
central  end  of  the  sciatic  nerve.  Although  these  effects  indeed 
diminish  in  amount  as  the  destruction  of  the  cord  proceeds,  yet  a 
distinct  change  can  be  caused  when  onl}^  a  small  portion  of  the  ccrd 
remains  intact. 

Similarly,  in  the  mammal  evidence  has  been  obtained  of  the 
existence  of  '  centres  '  at  various  levels  of  the  cord,  capable  of  acting 
eventually,  if  not  at  once,  as  vaso-constrictor  centres  after  the  loss 
of  the  controlling  influence  of  the  bulb.  The  best  example  of  a 
vaso-dilator  centre  is  that  situated  in  the  lumbar  cord,  which  controls 
the  erection  of  the  penis.  After  total  section  of  the  cord  at  the  upper 
limit  of  the  lumbar  region,  erection,  which  is  known  to  be  due  to  a 
reflex  dilatation  of  the  arteries  of  the  organ  through  the  ner\'i  eri- 
gentes,  can  still  be  caused  (in  dogs)  by  mechanical  stimulation  of 
the  glans  penis,  so  long  as  the  afferent  fibres  of  the  reflex  arc  con- 
tained in  the  ner  vus  pudendus  are  intact.  Destruction  of  the  lumbar 
cord  abolishes  the  effect.  It  is  impossible  to  avoid  the  conclusion 
that  a  vaso-dilator  or  erection  centre,  which  is  in  relation  on  the 
one  hand  with  the  ner\n  erigentes,  and  on  the  other  with  the  nervus 
pudendus,  exists  in  the  lower  portion  of  the  spinal  cord.  \'aso- 
motor  centres  for  the  hind-limbs  have  also  been  located  in  the 


i84 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


same  region.  When  the  brain,  the  bulb,  and  the  upper  portion  of 
the  cord  have  been  eliminated  by  hgation  of  all  the  arteries  from 
which  blood  can  possibl}'  reach  them,  a  sufficient  vascular  pressure 
persists  to  permit  the  circulation  to  go  on  in  the  lower  portion  of 
the  body  for  hours.  And  while  sectipn — or  freezing  (Fig.  80) — of 
the  cord  in  the  lower  cervical  region  causes  a  marked  fall  of  pressure, 
this  i'.  not  permanent  if  the  animal  is  allowed  to  survive.  Forty-one 
days  after  total  section  of  the  cord  at  the  seventh  cervical  segment 
in  a  dog  an  arterial  pressure  of  130  mm.  of  mercury  was  found.  A 
mechanism  for  the  maintenance  of  vascular  tone  exists  even  beyond 
the  limits  of  the  central  nervous  system.  For  when  the  lower 
portion  of  the  cord  is  completely  destroyed,  the  dilatation  of  the 
vessels  of  the  hind-limbs,  which  is  at  first  so  conspicuous,  passes 
away  after  a  time,  the  functions  of  vaso-motor  centres  having 
perhaps  been  assumed  by  the  sympathetic  ganglia  (Goltz  and 
Ewald).     When  the  lumbo-sacral  sympathetic  chain  is  extirpated, 


^^i^ii/"'^ 


'^^'^^Jh^,^^^;^ 


J'ig.  80. — Effect  on  Blojd-PiL=:jiirc  ui  Freezing  Spinal  Cord  (I'ike).  At  i  the  first 
or  second  dorsal  segment  of  a  dog's  cord  was  frozen  with  liquid  air;  at  2  and  3 
central  end  of  sciatic  stimulated  without  effect  on  pressure  (respectively  one  and 
a  half  and  three  minutes  Jifter  freezing  of  cord).     (Four-fifths  of  original  size.) 

there  is  a  further  loss  of  vascular  tone  in  the  affected  region.  But 
even  this  is  not  irremediable.  After  a  time  recovery  again  occurs, 
although  it  may  be  more  partial  and  tardy  than  before.  This  may 
take  place  either  through  the  intervention  of  still  more  peripheral 
ganglia,  or  through  the  development  of  a  certain  tonus  by  the 
muscular  fibres  of  the  vessels  when  abandoned  to  themselves. 

As  to  the  nature  of  the  tone  of  the  general  vaso-motor  centre,  the 
same  question  may  be  asked  which  has  been  already  discussed  for 
the  cardio-inhibitory  centre.  Is  it  reliex,  or  does  it  depend  upon 
direct  excitation  of  the  centre  by  some  constituent  of  the  blood  or 
lymph,  or  some  substance  produced  in  the  centre  itself  ?  The  best 
answer  which  can  at  present  be  made  is  that  a  constant  central 
excitation  by  the  carbon  dioxide  formed  in  the  centre  or  circulating 
in  the  blood  is  a  not  unimportant  factor  in  the  maintenance  of  the 
vaso-motor  tone.  A  marked  diminution  in  the  carbon  dioxide 
tension  of  the  blood,  a  condition  which  is  termed  '  acapnia,"  may 
indeed  contribute  to  the  severe  fall  of  blood-pressure  associated  with 


77//;  .\7-:A'F^()r.s-  regulatios  or  riu:  ui.ooDVESbELs    185 

surgical  shock  (Henderson).  In  addition  to  the  direct  influence  of 
carbon  dioxide,  and  possibly  of  other  substances,  the  arrival  of 
afferent  impulses  at  the  centre  seems  to  play  a  part  in  maintaining 
that  continual  discharge  of  efferent  impulses  along  the  vaso-motor 
nerves  which  constitutes  its  tone.  In  this  regard,  the  vaso-motor 
centre  occupies  an  intermediate  position  between  the  respiratory 
centre,  the  most  purely  automatic,  and  the  cardio-inhibitory  centre, 
the  most  purely  reflex  of  the  three  great  bulbar  mechanisms. 

Of  the  anatomical  relations  of  the  nerve-cells  that  make  up  the 
b\ilbar  and  spinal  vaso-motor  centres,  little  more  is  knowni  than  may 
be  deduced  from  the  physiological  facts  we  have  been  reciting.  It  has 
been  surmised  on  histological  grounds  that  certain  cells  of  small  size 
scattered  up  and  down  the  thoracic  and  upper  lumbar  regions  of  the 
cord  in  the  lateral  horn  (intermedio -lateral  tract),  and  perhaps  cropping 
out  also  in  the  bulb,  arc  vaso-motor  cells.  There  is  good  evidence  that 
the  prc-g<mglionic  sympathetic  fibres,  including  tlic  vaso-motor  fibres 
wliich  we  have  already  discovered  emerging  from  tlie  cord  in  the  spinal 
roots,  are  connected  with  these  cells.  And,  indeed,  there  is  reason  to 
believe  that  the  connection  is  made  without  the  intervention  of  any 
other  nerve-cells,  and  that  the  axis-cylinders  of  these  vaso-motor  fibres 
arc  the  axis-cylinder  processes  of  the  \'aso-motor  cells.  So  that  the 
simplest  efferent  path  along  which  vaso-motor  impulses  can  pass  may 
be  conEidercd  as  built  up  of  two  neurons,  one  with  its  cell-body  in  the 
cord,  and  the  other  in  a  sympathetic  ganglion.  Less  is  knowTi  of  the 
elements  which  constitute  the  bulbar  centre  and  of  their  connections. 
But  since  it  would  appear  that  the  spinal  \'aso-motor  centres  are  under 
the  control  of  the  chief  centre  in  the  bulb,  it  is  necessary  to  suppose 
that  the  axis-cylinder  processes  of  some  of  the  cells  of  the  bulbar  centre 
come  into  relation  with  the  spinal  vaso-motor  cells,  and  that  impulses 
passing,  let  us  say,  from  the  bulb  to  the  vessels  of  the  leg,  would  have 
to  traverse  three  neurons  (p.  852). 

Vaso-Motor  Reflexes. — We  have  already  seen  that  the  cardiac 
centres  are  constantly  influenced  by  afferent  impulses,  and  that  in 
the  direction  either  of  augmentation  or  inhibition.  The  vaso-motor 
centre  in  the  bulb  is  equally  sensitive  to  such  impulses.  They 
reach  it  for  the  most  part  along  the  same  nerves,  and  by  increasing  or 
diminishing  its  tone  cause  sometimes  constriction  and  sometimes 
dilatation  of  the  vessels,  the  result  depending  partly  upon  the  ana- 
tomical connection  of  the  afferent  fibres,  but  apparently  in  part  also 
upon  the  state  of  the  centre. 

Of  the  afferent  nerves  that  cause  vaso-dilatation,  the  most  im- 
portant is  the  depressor,  whose  reflex  inhibitory  action  on  the  heart 
has  been  already  described.  The  fall  in  the  arterial  pressure  is  due 
chiefl}-,  not  to  the  inhibition  of  the  heart,  but  to  inhibition  of  the 
vaso-constrictor  tone  of  the  bulbar  vaso-motor  centre,  combined 
with  stimulation  of  vaso-dilator  nerves,  and  consequent  general  dila- 
tation of  the  arterioles  throughout  the  body.  That  the  depressor 
action  involves  excitation  of  vaso-dilators  follows  from  the  fact  that 
vaso-dilatation  occurs  in  the  limbs  on  stimulation  of  the  depressor 
after  their  vaso-constrictor  nerves  have  been  cut.  Stimulation  of  the 
central  end  of  the   depressor  may   also  cause  dilatation  of  the 


l86  Tin:  CIRCl'LArWS  01-   THE  BLOOD  ASD  LYMPH 


vessels  of  the  submaxillary  gland  even  on  the  opposite  side,  whether 
the  sympathetic  has  been  divided  or  not!  so  long  as  the  chorda 
tympani  is  intact,  and  this  dilatation  is  not  accompanied  by  a  flow 
of  saUva.  Stimulation  of  the  depressor  produces  its  usual  result  after 
section  of  the  vagi.  It  has  been  suggested  that  the  function  of  the 
nerve  is  to  act  as  an  automatic  clieck  upon  the  blood-pressure  in  the 
interest  both  of  the  heart  and  the  vessels,  its  terminations  in  the 
aorta  or  the  ventricular  wall  bcine  niechanirally  stimulated  whert  the 
pressure  tends  to  rise  towards  the  danger  limit.  In  rare  cases, 
efferent  inhibitory  fibres  for  the  heart  have  been  found  in  the  depres- 
sor of  the  rabbit. 

Many  of  the  peripheral 
nerves  contain  fibr(  s 
whose  stimulation  is  fol- 
lov.ed  by  dib.tation  of  the 


Fig.  8i. — Diagram  of  Deprossor 
in  Rabbit.  X,  vagus  ;  Si,, 
superior  laryngeal  ;  D,  de- 
pressor. Arrows  show  course 
of  impulses. 


/    • 

'  ^. — :.. 

K 

(WvV^^'A'- 

'111  il 

I- 

^HB 

[\ 

■  •; 

■ws^tm 

1 

rig. 82. — ^Blood-Prosure Tracing:  Rabbit.  Central 
end  of  depressor  stimulated  at  i ;  stimulation 
stopped  at  2.     Time-trace,  seconds. 


bloodvessels  in  special  regions,  usually  the  areas  to  which  they  are 
themselves  distributed,  accompanied  by  constriction  of  distant  and, 
it  mav  be,  more  extensive  vascular  tracts.  Thus,  the  usual  local  effect 
of  stimulating  the  afferent  hbres  of  the  lowest  three  thoracic  nerves, 
in  whose  anterior  roots  run  the  vaso-motor  fibres  for  the  kidney,  is 
a  dilatation  of  the  renal  vessels  (Bradford),  and  the  usual  local  effect 
of  stimulating  the  infra-orbital  or  supra-orbital  nerve  a  dilatation 
of  the  external  maxillary  artery.  But  the  general  effect  in  both 
cases  is  vaso-constriction  in  other  regions  of  the  body,  which  more 
than  compensates  the  local  dilatation,  so  that  the  arterial  blood- 
pressure  rises.  It  is  not  difficult  to  see  that  both  of  these  changes 
render  it  easier  for  the  part  to  obtain  an  increased  supply  of  blood. 

Sometirrcs  the  reciprocal  relation  between  vaso-dilatation  in  one  part 
of  the  body  and  vaso-constriction  in  another  is  only  apparent.  For 
example,  sUmulatiou  ul  the  cut  end  of  the  sciatic  causes,  as  we  have 
already  seen,  extensive  va.so-coustriction  and  a  notable  rise  in  the  blood- 
pressure.     The  constriction  certainly  involves  the  splanchnic  area;  but 


77//:  \I-RVOUS  lUlGULATION  OF  THE  BLOODVESSELS      i87 

superficial  parts,  as  the  lips,  may  be  seen  to  be  flushed  with  blood. 
In  asphyxia,  when  the  vaso-motor  centres  arc  directly  stimulated  by 
the  venous  blood,  tliis  apparent  antagonism  is  still  better  marked:  the 
cutaneous  vessels  arc  widely  dilated  and  engorged,  the  face  is  livid, 
but  the  abdominal  organs  arc  pale  and  bloodless  (Heidenhain).  The 
blood-pressure  rises  rapidly,  reaches  a  maximum,  and  then  gradually 
falls  as  the  vaso-motor  centre  becomes  paralyzed  (Figs.  84  and  85).  It 
has  been  shown  that  in  both  cases  vaso-constriction  ot  the  skin  is  really 
produced  as  well  as  vaso-constriction  of  the  internal  organs,  but  the 
increased  blood-pressure  mechanically  overcomes  the  constriction  of 
the  cutaneous  vessels. 

The  kind  of  stimulus  seems  to  have  something  to  do  with  the 
direction  of  the  reflex  vaso-motor  change.  For  while  electrical 
stimulation  of  e\^ery  muscular  nerve,  even  of  the  very  finest  twigs 
that  can  be  isolated  and  laid  on  electrodes,  provokes  always,  whether 
the  shocks  follow  each  other  rapidly  or  slowly,  a  rise  of  general 


Fig.  83. — Pressor  Effect  of  Stimulation  of  Central  End  of  Vagus  in  a  Cat  during 
Resuscitation  after  Cerebral  Anaemia.  The  depressions  in  the  signal  line  ABC 
indicate  the  duration  of  three  successive  excitations  of  equal  strength,  sixty-five, 
seventy-three,  and  seventy-nine  minutes  respectively  after  restoration  of  the 
circulation.  The  pressor  effect  increases  as  resuscitation  proceeds.  Later  on 
the  original  depressor  effect  was  again  obtained.  The  upper  tracing  is  that  of 
the  artificial  respiration.     (Two-thirds  original  size.) 

blood-pressure,  mechanical  stimulation  of  a  muscle,  as  by  kneading 
or  massage,  causes  a  fall.  The  condition  of  the  afferent  fibres  also 
exerts  an  influence.  For  example,  excitation  of  the  central  end  of  a 
sciatic  nerve  that  has  been  cooled  is  followed  by  vaso-dilatation 
and  fall  of  pressure,  the  opposite  of  the  ordinary  result.  These  and 
similar  facts  have  led  to  the  idea  that  most  afferent  nerves  contain 
two  kinds  of  fibres,  whose  stimulation  can  affect  the  actf^ty  of  the 
vaso-motor  centres — '  reflex  vaso-constrictor,'  or  '  pressor  '  fibres, 
and  '  reflex  vaso-dilator,'  or  '  depressor  '  fibres.  The  branch  of  the 
vagus,  however,  to  which  the  name  '  depressor  *  has  been  specially 
given  is  usually  described  as  the  only  peripheral  nerve  the  excitation 
of  which  is  in  all  circumstances  followed  by  a  general  diminution  of 
arterial  pressure.  But  this  is  not  strictly  correct,  for  at  an  early 
period  in  the  resuscitation  of  the  brain  after  anaemia  excitation  of 


J 88  TUIi  CIRCULATION  01-  THE  BLOOD  ASD  LYMPH 

the  rabbit's  '  depressor  '  causes  a  slight  rise  of  pressure  not  followed 
by  any  fall.  This,  perhaps,  indicates  the  presence  in  the  '  depressor  ' 
of  a  small  number  of  pressor  fibres,  which  are  resuscitated  sooner 
than  the  depressor  fibres  proper.  The  same  phenomenon,  only 
more  marked,  may  be  seen  when  the  central  end  of  the  cat's  va]L(us, 
containing  the  depressor  fibres,  is  e.xcited  at  interval>  during  resus- 
citation (Fig.  83).  Or  the  result  may  depend  upon  a  change  in  tht- 
response  of  the  altered  vaso-motor  centres  to  impulses  reaching 
them  along  the  depressor  fibres.  If  specific  '  depressor  '  fibres  exist 
in  other  nerves,  they  are  so  mingled  with  '  pressor  '  fibres  that  their 
action  is  masked  when  both  are  stimulated  together.  The  state  of 
the  vaso-motor  centre  is  unquestionably  a  factor  which  has  some 
importance  in  determining  the  result  of  reflex  vaso-motor  stimula- 
tion. For  instance,  in  an  animal  deeply  anaesthetized  with  chloro- 
form or  chloral,  excitation  of  pressor  fibres  (in  an  ordinary  sensory 


Fig.  84. —  Rise  of  Blood- Pressure  in  Asphy.xia  :  Rabbit.  Respiration  stopped  at  i. 
Interval  bet^veen  2  and  3  (not  reproduced)  44  seconds,  during  which  the  blood- 
pressure  steadily  rose.     At  4,  respiration  resumed.     Time-trace,  seconds. 

nerve)  causes,  not  a  rise,  but  a  fall  of  blood-pressure;  while  in  an 
animal  fully  under  the  influence  of  strychnine  stimulation  of  the 
depressor  nerve  causes  not  a  fall,  but  a  rise. 

The  vaso-motor  reflexes  in  man  can  be  conveniently  studied  by 
the  calori metric  method  described  on  p.  221.  One  of  the  most 
important  of  the  vaso-motor  reactions  is  that  by  which  the  vessels 
of  the  skin  respond  to  the  temperature  of  the  environment  so  as 
to  regulate  the  loss  of  heat  from  the  body  (p.  699).  When  one 
hand,  eg.  the  left,  is  immersed  in  cold  water  (say  at  about  8°  C), 
the  blood-flow  in  the  right  is  at  once  reduced  owing  to  reflex  vaso- 
constriction. Other  parts  of  the  body  are  also  affected,  but  not  so 
readily  as  the  contra-lateral  hand,  since  the  segments  of  the  cord 
into  which  the  afferent  fibres  from  a  given  skin  area  run  are  at  the 
same  time  the  segments  from  which  the  efferent  vaso-motor  fibres 
for  the  symmetrically-placed  area  on  the  opposite  side  of  the  body 
arise.     The  reflex  diminution  in  the  flow  persists  for  a  time  which 


THE  NERVOUS  REGUEATlOK  OF  THE  BLOOD  VESSELS     i8.> 


varies  with  the  iiuHvidual,  tlie  external  temperature,  and  other 
circumstances,  and  then  as  a  rule  rather  suddenly  the  vaso-con- 
strictit)n  gives  way  and  tiie  flow  brgins  again  to  increase,  even  whilr- 
the  left  hand  is  still  kept  in  the  cold  water.  When  the  left  hand  is 
transferred  from  the  cold  to  warm  water  (at  43°  or  44°  C),  the  first 
effect  is  a  transient  diminution  in  the  blood-flow  in  the  right  hand. 
This  soon  gives  place  to  an  increase  (vaso-dilatation).  As  an  ex- 
ample, the  following  table  gives  the  condensed  results  of  three 
experiments  on  two  young  men.  Experiments  II.  and  III.  were  on 
the  same  man  at  an  interval  of  three  days. 


Te 

mperature  o 

f— 

Duration 

Flow  in  Grms. 

Experi-  _ 
ment.    | 

of 
Observation 

per  100  c.c. 
of  Right  Hand 

Left  Hand  in — 

Arterial 
Blood. 

Room. 

Calorim. 

in  Minutes. 

per  Minute. 

' 

, 

'28-9] 
29-0 

r3i-i 

31-7 

16 

12-2 

I.     - 

36-6 

4 

6-9 

Cold  water.             1 

29-0 

31-2 
132-3 

6 

9-9 

Cold  water  still. 

.29-iJ 

II 

II-6 

Warm  water. 

1 

'24-0^ 

f3o-9 

13 

lO-I 

— 

24'2 

31-3 

13 

5-0 

Cold  water. 

II.     - 

23-9 '- 

36-0 

•  31-4 

2 

3-4 

Warm  water. 

1 

23-9 

31-5 

3 

8-4 

Warm  water  still. 

l23-9J 

l3i-7 

7 

15-0 

Warm  water  still. 

'24-81 

('3I-6 

15 

12-4 

— 

■ 

24-4 

32-1 

5 

5-9 

Cold  water. 

111. 

24-4  ■ 

36-5 

-   32-2 

5 

10-7 

Cold  water  still. 

24-4 

32-4 

3 

7-9 

Warm  water. 

' 

124-5. 

132*6 

7 

I7'6 

Warm  water  still. 

Such  facts  enable  us  to  some  extent  to  understand  the  manner  in 
which  the  distribution  of  the  blood  is  adjusted  to  the  requirements 
of  the  different  parts  of  the  body,  so  that  to  a  certain  degree  of 
approximation  no  organ  has  too  much,  and  none  too  little.  The 
blood-supply  of  the  organs  is  always  shifting  with  the  calls  upon 
them.  Now,  it  is  the  actively-digesting  stomach  and  the  activelj'- 
secreting  glands  of  the  alimentarj'  tract  w-hich  must  be  fed  with  a 
full  stream  of  blood,  to  supply  waste  and  to  carry  away  absorbed 
nutriment.  Again,  it  is  the  working  muscles  of  the  legs  or  of  the 
arms  that  need  the  chief  blood-supply.  But  wherever  the  call  may 
be,  the  vaso-motor  mechanism  is  able,  in  health,  to  answer  it  by 
bringing  about  a  widening  of  the  small  arteries  of  the  part  which 
needs  more  blood,  and  a  compensatory  narrowing  of  the  vessels 
of  other  parts  whose  needs  are  not  so  great. 

It  is  also  through  the  vaso-motor  system,  and  especially  by  the 
action  of  that  portion  of  it  which  governs  the  abdominal  vessels,  and 


igo  THE  CJRCULATIOX  OF  THE  BLOOD  ASD  LYMPH 

of  the  netves  that  regulate  the  work  of  the  heart,  that  in  animals 
to  which  the  upright  position  is  normal  (monkey)  and  in  man  the 
influence  of  changes  of  posture  on  the  circulation  is  almost  com- 
pletely compensated.*  The  pressure  in  the  upper  part  of  the 
human  brachial  artery  has  been  measured  with  a  sphygmoman- 
ometer, first  in  the  horizontal  and  then  immediately  afterwards  in 
the  standing  posture,  and  in  health  it  has  been  found  to  remain 
practically  unchanged  (Hill).  But  if  the  person  was  overworked  or 
out  of  sorts,  the  compensation  was  less  complete.  It  is  well  known 
that  in  debilitated  persons,  especially  if  long  confined  to  bed,  the 
sudden  assumption  of  the  upright  position  may  cause  vertigo,  and 
even  syncope,  the  normal  compensatory  mechanism  being  deranged. 
In  such  animals  as  the  rabbit  this  compensation  is  totally  inefficient. 
When  a  domesticated  rabbit,  which  has  been  kept  in  a  hutch,  is 
suspended  vertically  with  the  feet  down,  the  blood  drains  into  the 
abdominal  vessels,  syncope  speedily  ensues,  and  in  a  period  that 
ranges  from  less  than  a  quarter  to  three-quarters  of  an  hour  the 
animal  dies  in  the  convulsions  of  acute  cerebral  anaemia  (Salathe, 
Hill).  The  head-down  position  has  no  ill-effects.  In  wild  rabbits, 
whose  abdominal  wall  is  more  tense  and  elastic,  these  fatal  symp- 
toms are  not  easily  produced,  and  the  same  is  true  of  cats  and  dogs. 
But  in  all  animals,  when  the  compensation  is  destroyed,  as  in 
paralysis  of  the  vaso-motor  centre  by  chloroform,  the  circulation 
may  Ise  profoundly  influenced  by  the  position  of  the  body:  elevation 
of  the  head  may  lead  to  cerebral  auiemia,  syncope,  and  even  death ; 
elevation  of  the  legs,  and  particularly  the  abdomen,  may  restore  the 
sinking  pulse  by  filling  the  heart  and  the  vessels  of  the  brain.  If  a 
chloralized  dog  be  fastened  on  a  board  which  can  be  rotated  about 
a  horizontal  axis  passing  under  the  neck,  the  blood-pressure  in  the 
carotid  artery  falls  greatly  when  the  animal  is  made  to  assume  the 
vertical  position  with  the  head  up,  and  either  rises  a  little  or  remains 
practically  unchanged  when  the  head  is  made  to  hang  down.  So 
great  may  the  fall  of  pressure  be  in  the  former  position  that  death 
may  occur  if  it  be  long  maintained  (Practical  Exercises,  p.  213). 

•  Two  factors  may  be  distinguished  in  the  blood-pressure,  the  hydrostatic 
and  the  hydrodynamic  elements.  The  hydrostatic  portion  of  the  pressure  is 
due  to  the  weight  of  the  column  of  blood  acting  on  the  vessel;  the  hydro- 
dynamic  portion  of  the  pressure  is  due  to  the  work  of  the  heart.  If  a  dog  be 
securely  fastened  to  a  holder  arranged  in  such  a  way  that  the  animal  can  be 
placed  vertically,  with  the  head  up  or  down,  and  the  mean  blood-pressure  in 
the  crural  arterv  be  measured  in  the  two  j)ositions.  there  will  be  a  considerable 
difference.  iVr  when  the  legs  arc  uppermost  the  heart  has  to  overcome  the 
weight  of  the  column  of  blood  rising  above  it  to  the  crural  arten*-;  when  the 
head  is  uppermost  the  action  of  the  heart  is  reinforced  by  the  weight  of  the 
blood.  And  if  no  change  were  produced  in  the  action  of  the  heart,  or  in  the 
general  resistance  of  the  vascular  path,  by  the  change  of  position,  this  differ- 
ence would  be  equal  to  the  pressure  of  a  column  of  blood  twice  as  high  as  the 
straight-line  distance  between  the  cannula  and  the  point  of  the  arterial  system 
at  wiiich  the  pressure  is  the  same  with  head  up  as  with  head  down  (indifferent 
point  J. 


THi:  SEUVOLS  REGVLATIOS  Of-    IHIL  HLOUDVESSI-LS      x<)i 

I'inally,  it  is  in  virtue  of  the  ama/ing  ])Ovvtr  of  accommodation 
possessed  by  the  vascular  system,  as  controlled  by  the  vaso-motor 
and  cardiac  nerves,  that  so  long  as  these  are  not  disabled  the  total 
quantity  of  blood  may  be  greatly  diminished  or  greatly  increased, 
without  endangering  life,  or  even  causing  more  than  a  transient 
alteration  in  the  arterial  pressure.  It  is  not  until  at  least  a  quarter 
of  the  blood  has  been  withdrawn  that  there  is  an\'  notable  effect 
on  the  pressure,  for  the  loss  is  quickly  compensated  bv  an  increase 
in  the  activity  of  the  heart  and  a  constriction  of  the  small  arteries. 
An  animal  may  recover  after  losing  considerably  more  than  half  its 
blood.*  Conversely,  the  volume  of  the  circulating  liquid  may  be 
doubled  by  the  injection  of  blood  or  physiological  salt  solution 
without  causing  death,  and  increased  by  50  per  cent,  without  any 
marked  increase  in  the  pressure.     The  excess  is  promptly  stowed 


..^ 


0^ 


^;00mim^,^^ 


<^-« 


F.u.  S5. — Blood- Pressure  Tracing  from  a  Dog  poisoned  with  Alcohol. 
The  respiratory  centrebeing  paralyzed,  respiration  stopped,  and  f  he 
ty- pical  rise  of  blood-pressure  in  asphyxia  took  place.  The  pressure 
had  again  fallen,  and  total  paral\-sis  of  the  vaso-niotor  centre  was 
near  at  hand,  when  at  A  the  animal  made  a  single  respiratory 
movement.  The  quantity  of  oxgyen  thus  taken  in  was  enough  to 
restore  the  vaso-inotor  centre,  and  the  blood-pressure  again  rose.  This  was 
repeated  five  or  six  times.     (Three-fourths  original  size.) 

awa}'  in  the  dilated  vessels,  especially  those  of  the  splanchnic  area; 
the  water  passes  rapidly  into  the  lymph,  and  is  then  more  gradually 
eliminated  by  the  kidneys. 

From  these  facts  we  can  deduce  the  practical  lesson,  that  blood- 
letting, unless  fairly  copious,  is  useless  as  a  means  of  lowering  the 
general  arterial  pressure,  while  it  need  not  be  feared  that  transfusion 
of  a  considerable  quantity  of  blood,  or  of  salt  solution,  in  cases  of 
severe  haemorrhage,  will  dangerously  increase  the  pressure.  And 
from  the  physiological  point  of  view  the  term  '  haemorrhage  '  includes 
more  than  it  does  in  its  ordinary  sense.  For  as  dirt  to  the  sanir 
tarian  is  '  matter  in  the  wrong  place,'  haemorrhage  to  the  physiolo- 
gist is  blood  in  the  wrong  place.  Not  a  drop  of  blood  may  be  lost 
from  the  body,  and  yet  death  may  occur  from  haemorrhage  into  the 
pleural  or  the  abdominal  cavity,  into  the  stomach  or  intestines. 
Not  only  so,  but  a  man  may  bleed  to  death  into  his  own  blood- 

*  It  is  not  usually  possible  to  obtain  quite  two-thirds  of  the  total  blood  by 
bleeding  a  dog  from  a  large  artery.  In  seven  dogs  bled  from  the  carotid, 
the  ratio  of  the  weight  of  the  blood  obtained  to  the  bodv-weight  was 
I  :  24-7.  I  :  21-7.  I  :  23-7.  i  :  lo-d.  i  :  iS-().  i  :  ib,  i  :  i  V5  In  the  last  case,  the 
blood  clotte  1  wi'.h  abnormal  slo  vnes  •  and  the  animal  died  in  a  few  minutes. 


IQJ  Tin:  CIRLVLATIOS  OP  Tin:  TiLoOb  AM)  LYMPH 

vessels;  in  surgical  (also  sometimes  called  traumatic  or  vascular) 
shock,  it  would  ai)])iar  that  tlu-  blood  wliich  ought  to  be  cinulating 
through  the  brain,  lieart,  and  lungs  may  stagnate  in  the  dilated  \'eins. 
The  essential  nature  of  '  vascular  '  shock,  which  slioujd  be  dis- 
tinguished from  tJie  spinal  shock  d(  .^riibed  in  Chapter  XVI.  is  so 
little  understood,  in  spite  of  the  large  amount  of  work  devoted  to 
the  subject,  that  it  would  not  be  profitable  to  discuss  it  here.  It  may 
be  remarked,  however,  that  there  is  no  reason  to  suppose  that  ex- 
haustion or  loss  of  sensitiveness  of  the  vaso-motor  centre  is  concerned. 
\Miile  an  undue  proportion  of  the  blood  is  accumulated  in  the  great 
\eins,  the  arterioles  and  capillaries  of  the  splanchnic  area,  like  those 
of  the  skin,  are  contracted  and  contain  less  blood  than  normal  (Lyon, 
Janeway  and  Jackson,  etc.). 

Section  VII. — The  Lymph.\tic  Circulation. 

As  has  ah-eady  been  stated,  some  of  the  (.onstitiicnts  of  the  blood, 
instead  of  passing  back  to  the  heart  from  the  capillaries  along  the  veins, 
find  their  wav  by  a  much  more  tedious  route  along  the  lymphatics. 
The  blood  capillaries  are  everywhere  in  very  intimate  relaticMi  with 
Ivmph  capillaries,  which,  completely  lined  with  epithelioid  cells,  lie  in 
irregular  spaces  in  the  connective-tissue  that  everywhere  accompanies 
and  supports  the  bloodvessels.  The  constituents  of  the  blood-plasma 
are  filtered  through,  or  secreted  by  the  capillary  walls  into  these  lymph 
spaces,  and  mingling  there  with  waste  products  discharged  by  the  cells 
of  the  tissues,  form  the  liquid  known  as  tissue  liquid  or  tissue  lymph. 
From  the  tissue  liquid  the  lymph  capillaries  take  up  the  constituents 
of  the  '  lymphatic  '  lymph,  which  then  passes  into  larger  lymphatic 
vessels,  with  lymphatic  glands  at  intervals  on  their  course.  These  fall 
into  still  larger  trunks,  and  finally  the  greater  part  of  the  lymj^h  reaches 
the  blood  again  by  the  thoracic  duct,  which  opens  into  the  venous 
system  at  the  junction  of  the  left  subclavian  and  internal  jugular  veins. 
The  lymph  from  the  right  side  of  the  head  and  neck,  the  right  e.xtremity, 
and  the  right  side  of  the  thorax,  with  its  viscera,  is  collected  by  the 
right  lymphatic  duct,  which  opens  at  the  junction  of  the  right  sub- 
clavian and  internal  jugular  veins.  The  openings  of  both  ducts  are 
guarded  by  semilunar  valves,  which  prevent  the  reflux  of  blood  from 
the  veins.  Serous  cavities  like  the  pleural  sacs,  although  differing 
from  ordinary  lymph  spaces,  are  connected  through  small  opening  , 
called  stomata,  with  lymphatic  vessels. 

The  rate  of  flow  of  the  lymph  in  the  thoracic  duct  is  very  small  com- 
pared with  that  of  the  blood  in  the  arteries — only  about  4  mm.  per 
second,  according  to  one  observer.  Xcvcrthcless,  a  substance  injected 
into  the  blood  can  be  detected  in  the  lymph  of  the  duct  in  four  to  seven 
minutes  (Tschirwinsky).  The  factors  which  contribute  to  the  main- 
tenance of  the  lymph  flow  are : 

(i)  The  pressure  under  wdiich  it  passes  from  the  blood  capillaries  into 
the  lymph  spaces  and  from  the  lymph  spaces  into  the  lymph  capillaries. 
The  pressure  in  the  thoracic  duct  of  a  horse  may  be  as  high  as  i  z  mm. 
of  mercury;  in  the  dog  it  may  be  less  than  1  mm.  The  difference  is 
probably  due,  in  part  at  least,  to  a  difference  in  the  experimental  con- 
ditions, dogs  being  usuallv  anaesthetized  for  such  measurements,  horses 
not.  The  pressure  in  the  lymph  ca))illaries  must,  of  course,  be  higher 
than  in  the  thoracic  duct — how  much  higher  we  do  not  know. 

(2)  The  contraction  of  muscles  increases  the  pressure  of  the  lymph 
by  compressing  the  channels  \n  which  it  is  crmtained,  and  the  valves 


THE  LYMPHATIC  CIRCULATION  I93 

with  which  the  lymphatics  are  even  more  richly  provided  than  the 
veins,  hinder  a  backward  and  favour  an  onward  flow.  The  contractions 
of  the  intestines,  and  especially  of  the  villi,  aitl  the  movement  of 
the  chyle.  By  the  contraction  of  the  diaphraf,Mn,  sub.stances  may 
be  Slicked  from  the  peritoneal  cavity  into  the  lymphatics  of  its 
central  tendon,  throuj^h  the  stomata  in  the  serous  layer  with  which 
its  lower  surface  is  clad.  It  is  even  possible  by  passive  movements  of 
the  diaphragm  in  a  dead  rabbit  to  inject  its  lymphatics  with  a  coloured 
liquid  placed  on  its  peritoneal  surface.  Passive  movements  of  the 
limbs  and  massage  of  the  niuscles  arc  also  known  to  hasten  the  sluggish 
current  of  the  lymph,  and  are  sometimes  employed  with  this  object  in 
the  treatment  of  disease. 

(3)  The  mo\-ements  of  respiration  aid  the  flow.  At  every  inspiration 
the  pressure  in  the  great  veins  near  the  heart  becomes  negative,  and 
IvTnph  is  sucked  into  them  (p.  226). 

(4)  In  some  animals  rhythmically  -  contracting  muscular  sacs  or 
hearts  exist  on  the  course  of  the  lymphatic  circulation.  The  frog  has 
two  pairs,  an  anterior  and  a  posterior,  of  these  lymph  hearts,  which 
pulsate,  although  not  with  any  great  regularity,  at  an  average  rate  ol 
sixty  to  seventy  beats  a  minute,  and  are  governed  by  motor  and  inhibi- 
tory centres  situated  in  the  spinal  cord.  The  beat  is  not  directly  ini- 
tiated from  the  cord,  but  the  tonic  influence  of  the  cord  is  necessary  in 
order  that  the  lymph  hearts  may  continue  to  beat  (Tschermak).  Such 
hearts  are  also  found  in  reptiles.  It  is  possible  that  in  animals  without 
localized  lymph  hearts  the  smooth  muscle,  which  is  so  conspicuous  an 
element  in  the  walls  of  the  lymphatic  vessels,  may  aid  the  flow  by 
rhythmical  contractions. 

PRACTICAL  EXERCISES  ON  CHAPTER  III. 

I.  Microscopic  Examination  of  the  Circulating  Blood. — (i)  Take  a 
tadpole  and  lay  it  on  a  glass  slide.  Cover  the  tail  with  a  large  cover- 
slip,  and  examine  it  with  the  low  power  (I.eitz,  oc.  III.,  obj.  3). 
Generalh'  the  tail  will  stick  so  closely  to  the  slide,  and  the  animal  will 
move  so  little,  that  a  sufficiently  good  view  of  the  circulation  can  be 
obtained.  If  there  is  any  troiiblc,  destroy  the  brain  with  a  needle. 
Observe  the  current  of  the  blood  in  the  arteries,  capillaries  and  veins. 
An  arteiy  may  be  easily  distinguished  from  a  vein  by  looking  for  a 
place  at  which  the  vessel  bifurcates.  In  veins  the  blood  flows  in  the 
two  branches  of  the  fork  towards  the  point  of  bifurcation,  in  afteries 
away  from  it.     Sketch  a  part  of  a  field. 

To  Pith  a  Frog. — Wrap  the  animal  in  a  towel,  bend  the  head  forwards 
with  the  index-finger  of  one  hand,  feel  with  the  other  for  the  depression 
at  the  junction  of  the  head  and  backbone,  and  push  a  narrow-bladed 
knife  right  down  in  the  middle  line.  The  spinal  cord  will  thus  be 
divided  with  little  bleeding.  Now  push  into  the  cavity  of  the  skull  a 
piece  of  pointed  lucifer  match.  The  brain  will  thus  be  destroyed.  The 
spinal  cord  can  be  destroyed  by  passing  a  blunt  needle  down  inside  the 
vertebral  canal. 

(2)  Take  a  frog  and  pith  its  brain  only,  inserting  a  match  to  prevent 
bleeding.  Pin  the  frog  on  a  plate  of  cork  into  one  end  of  which  a 
glass  slide  has  been  fastened  with  sealing-wax.  Lay  the  web  of  one 
of  the  hind-legs  on  the  glass  and  gently  separate  two  of  the  toes,  if 
necessary  by  threads  attached  to  them  and  secured  to  the  cork  plate. 
Put  the  plate  on  the  microscope -stage  and  fasten  by  the  clips  (see 
pp.  15,  118). 

(3)  After  tlie  normal  circulation  has  been  studied  thoroughly  put  a 
very  small  drop  of  tincture  of  cantharides  on  the  p(jrtion  of  the  web 

13 


194        THE  CIRC  LLATIOX  OF  THE  BLOOD  ASD  LYMPH 


which  is  in  the  field  of  the  microscope,  using  a  fine  pipette.     Observe 
the  process  of  inflammation,  including  stasis  and  diapcdcsis  (p.  6i). 

2.  Anatomy  of  the  Frog's  Heart.-  Expose  the  heart  of  a  pithed  frog 
by  pinching  up  ilie  skin  over  the  abdomen  in  the  middle  line,  dividing 
it'  with  scissors  up  to  the  lower  jaw,  and  then  cutting  through  the 
abdominal  muscles  and  the  bony  pectoral  girdle.  The  external  ab- 
dominal vein,  which  will  be  observed  on  reflecting  the  skin,  can  be 
easily  avoided.  The  heart  will  now  be  seen  enclosed  in  a  thin  mem- 
brane, the  pericardium,  which  should  be  grasped  with  fine-pointed 
forceps  and  freely  divided.  Connecting  the  posterior  surface  of  the 
heart  and  the  pericardium  is  a  slender  band  of  connective  tissue,  the 
fra^num.  A  silk  ligature  may  be  passed  roun<l  this  with  a  threaded 
curved  needle,  or  curved  fine-pointed  forceps:  and  tied,  and  then  the 
frjonum  may  be  divided  posterior  to  the  ligature.  The  anatomical 
arrangement  of  the  various  parts  of  the  heart  should  now  be  studied. 
Xote  the  single  ventricle  with  the  bulbus  arteriosus,  the  two  auricles, 
and  the  sinus  venosus,  turning  the  heart  over  to  sec  the  latter  by  means 
of  the  ligature.  Observe  the  whitish  crescent  at  the  junction  of  the 
sinus  venosus  and  the  right  auricle  (Fig.  86). 

.S-  The  Beat  of  the  Heart. — Xote  that  the  auricles  beat  first,  and 
then  the  \entriclc.      The  ventricle  becomes  smaller  and  paler  during 

its  systole,  and  blushes 
red  during  diastole. 
Count  the  number  of 
beats  of  the  heart  in  a 
minute.  Now  excise  the 
heart,  lifting  it  by  means 
of  tlie  ligature,  and  tak- 
ingcare  tocutwide  of  the 
sinus  \enosus.  Place  the 
heart  in  a  small  porce- 
lain capsule  on  a  little 
blotting  -  paper  moist  - 
cned  with  physiological 
salt  solution.*  Observe 
that  it  goes  on  beating. 
Put  a  little  ice  or  snow 
in  contact  with  the  heart 
and  count  the  number  of 
beats  in  a  minute.  The 
rate  is  greatly  dimin- 
ished. Now  remove  the  ice  and  blotting-paper,  cover  the  heart  with 
the  salt  solution,  and  heat,  noting  the  temperature  with  a  thermometer. 
Observe  that  the  heart  beats  faster  and  faster  as  the  temperature  rises. 
At  40°  to  43'  C.  it  stops  beating  in  diastole  (heat  standstill).  Now  at 
once  pour  off  the  heated  liquid,  and  run  in  some  cold  salt  solution.  The 
heart  will  begin  to  beat  again. 

4.  Cut  off  the  apex  of  the  ventricle  a  little  below  the  auriculo- 
ventricular  groove.  The  auricles,  with  the  attached  portions  of  the 
ventricle,  go  on  beating.  The  apex  does  not  contract  spontaneously, 
but  can  be  made  to  beat  by  stimulating  it  mechanically  (by  pricking 
it  with  a  needle)  or  electrically.  Divide  the  still  contracting  portion 
of  the  heart  by  a  longitudinal  incision.     The  two  halves  go  on  beating. 

5.  Heart  Tracings. — (1)  Fasten  a  myograph-plate  (Fig.  87)  on  a 
stand.     Take  a  long  light  lever,  consisting  of  a  straw  or  a  piece  of 

•  For  frog's  tissues  this  should  be  0-7  to  0-75  per  cent,  sodium  chloride 
solution,  for  mammalian  tissues  a  little  stronger  (about  0-9  per  acnt.). 


rig.  86. — Frog's  Hfart  with  Stanuius'  Ligatures  in 
Position  (Cyon).  .\ntPiior  surface  of  heart  shown 
on  the  left,  posterior  surface  on  the  right,  a,  right 
auricle;  h,  left  auricle;  c,  ventricle;  </,  bulbus  arte- 
riosus; e,f,  aorta-;  g,  sinus  venosus. 


PRACTICAL  EXERCISES 


195 


^ « "wjui  '""^^Mlfc^ 


Fia 


87. — Arrangement  for  obtaining  a 
Heart  Tracing  from  a  Frog. 


thin  chip,  armed  at  one  end  \vilh  a  writing-point  of  parchment-paper, 
supported  near  the  other  end  by  a  horizontal  axis,  and  pierced  not 
far  from  the  axis  by  a  needle  carrying  on  its  point  a  small  piece  of 
cork  or  a  ball  of  sealing-wax. 

A  coimtcrpoise  is  adjusted  on  the  short  arm  of  the  lever  in  the  form 
of  a  small  leaden  weight.  Cover  a  drum  with  glazed  paper  and  smoke 
it.  The  paper  must  be  i)ut  on  so  tightly  that  it  will  not  slip. 
To  smoke  the  drum,  hold  it  by  the  spindle  in  both  hands  over 
a  fish-tail  burner,  depress  the  drum  in  the  fiame,  and  rotate 
rapidly.  The  speed  of  the  drum  can  be  varied  by  putting  in 
or  taking  out  a  small  vane.  Arrange  an  electro-magnetic  time- 
marker  for  writing  seconds  (Fig. 
88).  Pith  a  frog  (brain  only). 
expose  the  heart,  and  put  under 
it  a  cover-slip  to  give  it  support. 
Pin  the  frog  on  the  myograph- 
plate,  and  adjust  the  foot  of  the 
lever  so  that  it  rests  on  the  ven- 
tricle or  the  auriculo-ventricular 
junction.  Bring  the  writing-point 
of  the  lever  and  that  of  the  time- 
marker  vcrticalh-  under  each  other 
on  the  surface  of  the  drum.  Set  off 
the  drum  at  the  slow  speed  (say, 
a  centimetre  a  second) .  When  the 
lever  rests  on  the  auriculo-ventricular  junction,  the  part  of  the  tracing 
corresponding  to  the  contraction  of  the  heart  will  be  broken  into  two 

portions,  representing 
the  systole  of  the  auri- 
cles and  ventricle  re- 
spectively. Cut  the 
paper  off  the  drum 
with  a  knife  (keeping 
the  back  of  the  knife 
to  the  drum  to  avoid 
scoring  it)  and  carry 
it  to  the  varnishing- 
trough,  holding  the 
tracing  bv  the  ends 
with  both  hands, 
smoked  side  up.  Im- 
merse the  middle  of  it 
in  the  varnish,  draw 
first  one  end  and  then 
the  other  through  the 
varnish,  let  it  drip 
for  a  minute  into  the 
trough,  and  fasten  it 
up  with  a  pin  to  dn.-. 
(2)  Heart  Tracing, 
with  Simultaneous  Re- 
cord of  Auricular  and  Ventricular  Contractions. — (a)  For  this  purpose  two 
levers  may  be  arranged,  '  nc  resting  on  the  auricle,  the  other  on  the  ven- 
tricle, the  writing-points  being  placed  in  the  same  vertical  straight  line 
on  the  drum.     A  convenient  form  of  apparatus  is  shown  in  Fig.  Sq. 

[b)  Gaskell's  Method  {a  modification  of). — Attach  a   silk  ligature  to 
the  very  apex  of  the  ventricle.     Divide  the  frs>num,  cut  the  aorta 


Fig.  88. — Electro  -  Magnetic  Time  -  Marker  connected 
with  Metronome.  The  pendulum  of  the  metro- 
nome carries  a  wire  which  closes  the  circuit  when 
it  dips  into  either  of  the  mercury  cups,  Hg. 


t96 


THE  CIRCULATION  OF  THE  BLOOD  ASD  LYMPH 


across  close  to  the  bulbiis,  piiuh  up  a  tiny  portion  of  the  auricle  and 
ligature  it.  Remove  the  intestines,  liver,  lungs,  etc..  care  being  taken 
in  cutting  away  the  liver  not  to  injure  the  sinus.  Then  rcmo\e  tlic 
lower  jaw,  and  cut  awAy  the  whole  of  the  body  except  the  head,  part 
of  the  oesophagus,  and  the  tissue  connecting  it  with  the  heart.  Fix 
the  head  in  a  clamp  sliding  on  an  ordinar^'^  stand.  The  heart  is  held 
at  the  auriculo-vcntricular  junction  in  a  Gaskell's  clamp  supported  on 
a  separate  btand.  The  thread  connected  with  the  ventricle  is  brought 
round  a  pulley  and  attached  to  a  lever  above  the  heart.  The  auricle 
is  connected  with  another  lever.  The  writing-points  of  the  two  levers 
arc  arranged  in  a  vertical  line  on  the  drum.  The  small  pulley  must 
be  oiled  from  time  to  time  to  lessen  the  friction  (Fig.  90). 

If  tortoises  or  turtles  are  available,  the  much  larger  heart  of  these 
animals  may  be  used  for  Experiments  5  (2)  (a)  and  (6).  The  animal 
having  been  killed  by  cutting  oft  its  head,  the  ventral  portion  of  the 
carapace  is  detach<:  d  by  the  saw.  The  pericardium  can  now  be  slit 
open,  and  the  pads  of  the  levers  arranged  on  auricles  and  ventricle 


Fig.  89. —  Apparatus  for  obtaining  a  Simultaneous  Tracing  of  AuricuUr  and 
Ventricular  Contractions. 


respectively,  as  in  Experiment  5  (2)  (a),  without  further  disturbing 
the  heart.  Or  the  heart  may  be  removed,  together  with  the  upj^er 
portion  of  the  body,  the  pericardium  opmcd,  and  the  liver  cut  away. 
The  aortic  tnmk  is  then  divided,  and  the  portion  of  it  attached  to 
the  heart  grasped  by  a  small  forceps  clamp.  Fine  silk  ligatures  are 
attached  to  the  apex  of  the  ventricle  and  the  top  of  the  right  auricle. 
The  vagus  nerves  are  exposed  in  the  neck,  ligatcd.  and  divided.  The 
upper  portion  of  the  body  is  supported  on  a  stand.  The  forceps  grasp- 
ing the  aorta  is  fixed  in  an  ordinary  holder,  and  the  threads  are  attached 
to  the  levers,  as  in  Experiment  3  (2)  (b). 

With  the  vagi.  Experiment  7  may  be  perfonned.  It  must  be  remem- 
bered that  the  actiMty  of  the  two  vagi  is  unequal  in  the  tortoise,  the 
right  being  the  more  active. 

6.  Dissection  of  the  Vagus  and  Cardiac  Sympathetic  Nerves  in  the 
Frog. —  (i)  Put  the  tissues  in  the  region  of  the  neck  on  the  stretch  by 
passing  into  the  gullet  a  narrow  test-tube  or  a  thic  k  glass  rod  nioistened 
with  water,  and  by  pinning  apart  the  anterior  limbs.     Expose  the  heart 


PRACTICAL  EXERCISES 


^V 


UK] 


by  «utting  througli  the  pectoral  girdle  in  the  way  drscribcd  in  2  (p.  194). 
On  eleaiiiig  away  a  little  connective  tissue  and  ninscle  witli  a  seeker, 
three  large  nerves  will  come  into  view.  The  upper  is  the  glosso- 
pharvngeal,  the  lower  the  hypoglossal;  the  vagus  crosses  diagonally 
between  them  (Fig.  91).  Above  the  v;'gus  trunk,  running  parallel  to 
it,  and  separated  from  it 
by  a  thin  muscle  and  a 
bloodvessel  (the  carotid 
artery),  lies  its  lar5Tigcal 
branch.  The  vagus  should 
be  traced  up  to  the  gang- 
lion situated  on  it  near  its 
exit  from  the  skull. 

(2)  Then  cut  away  the 
lower  jaw,  dividing  and 
reflecting  the  membrane 
covering  the  roof  of  the 
mouth.  At  the  junction 
of  the  skull  and  the  back- 
bone will  be  seen  on  each 
side  the  levator  anguli 
scapulae  muscle  (Fig.  9^). 
Remove  this  muscle  care- 
fully with  fine  forceps. 
Clear  away  a  little  con- 
nective tissue  lying  just 
over  tlie  upper  cervical 
vertebnc,  and  the  s^tu- 
pathetic  chain,  with  its 
ganglia,  will  be  seen.  Pass 
a  fine  silk  thread  beneath 
the  sympathetic  alx)ut  the 
level  of  the  large  brachial 
nerve,  by  means  of  a 
sewing-needle  which  has 
been  slightly  bent  in  a 
flame  and  fastened  in  a 
handle.  Tie  the  ligature, 
divide  the  sympathetic  be- 
low it,  and  isolate  it  care- 
fully with  fine  scissors  up 
to  its  junction  with  the 
vagus  ganglion. 

Batteries — To  set  np  a 
Daniell  Cell. — Fill  the  por- 
ous pot  (Fig.  230,  p.  724), 
previously  well  soaked  in 
water,  with  dilute  sulph- 
uric acid  (I  part  of  com- 
mercial acid  to  10  or  15 
parts  of  water)  to  within 
\\  inches  of  the  brim,  and  place  in  it  the  piece  of  amalgamated  zinc.  If 
the  zinc  is  not  properly  amalgamated,  leave  it  in  the  pot  for  a  minute  or 
two  to  clean  its  surface.  Then  lift  it  out,  pour  over  it  a  little  mcrcurv, 
and  rub  the  mercury  thoroughly  over  it  with  a  cloth.  Put  tlie  pot 
into  the  outer  vessel,  which  contains  the  copper  plate,  and  is  filled 
with  a  saturated  solution  of  sulphate  of  copper,  with  some  undissolved 


Fig.  90.— Arrangement  for  recording  Auricular 
and  Ventricular  Contractions  (and  studying  the 
Influence  of  Temperature  of  the  Heart).  C, 
clamp  holding  the  heart  at  the  auriculo-ven- 
tricular  groove;  P,  pulley  round  which  a  thread 
attached  to  the  apex  of  the  ventricle  passes  to 
the  lever  L';  L,  lever  connected  with  auricle. 
(The  rest  of  the  arrangement  is  for  studying  the 
influence  of  temperature  on  the  heart  and  its 
neri-es,  G  being  a  vessel  filled  with  physiological 
salt  solution  in  which  the  heart  is  immersed;  R. 
an  inflow  tube  from  a  reservoir  containing  salt 
solution  at  the  temperature  required;  O',  an  out- 
flow tube  by  which  G  may  be  emptied  into  the 
beaker  B';  O,  a  tube  passing  to  the  beaker  B  to 
prevent  overflow  from  G;  T,  a  thermometer.) 


198  THE  CIRCVLATIUS  Ob    THE  BLOOD  A\D  lA  MFH 

crj'stals  to  keep  it  saturated.  After  using  the  Daniell,  it  must  always 
be  taken  down.  The  outer  pot  is  left  with  the  copper  plate  and  the 
sulphate  solution  in  it.  The  zinc  is  washed  and  brushed  bright.  The 
sulphuric  acid  is  poured  into  the  stock  bottle,  and  the  porous  jx)t  put 
into  a  large  jar  of  water  to  soak. 

The  Bichromate  Cell  contains  only  one  liquid — a  mixture  of  i  part 
of  sulphuric  acid  with  4  parts  of  a  10  per  cent,  solution  of  potassium 
bicliromate.  In  this  is  placed  one,  or  in  some  forms  two.  carbon 
plates  and  a  plate  of  amalgamated  zinc,  .\fter  using  the  battery,  take 
the  zinc  out  of  the  liquid. 

The  Leclanche  battery  consists  of  a  porous  pot  filled  with  a  mixture 

of  manganese  dioxide  and  carbon  packed  around  a  carbon  plate,  which 

forms  the  positive  pole.     The  pot  stands  in  an  outer  jar  of  glass  filled 

with  a  saturated  solution  of  ammonium  chloride,  into  which  dips  an 

amalgamated  zinc  rod,  which  constitutes  the  negative  pole.     Various 

forms  of  dry  batteries  can  be  conveniently  used  for  running  induction- 

.  coils  or  time-markers,  but  are  not 

'V '.•>.<  /.-•v     |i .  iJH  adapted  for  yielding  constant  cur- 

'I''  f^H  rents  of  long  duratio'.i. 

>,A       ^^V  '     Wi  7-  Stimulation  of  the  Vagus  in 

/^'y^9««^'^1^_J».  the  Frog.— -Make  the  same  arrange- 

\J/^^^    ^\\  ment.s  as  in  5  (i)  (p.  195),  but  in 

f\^  i9      M  /  /    ^^idition     set     up    an    induction 

7  .^      ^Lqfyo^eaL    machine    arranged    for   an    inter- 

/  /^^^    \\  branch  0/    rupted    current   (Fig.  93),  with  a 

(~""~'T'  ^^C    H  ^^'^^'^     Daniell,  abichromate,  a  Leclanche, 

>!,      I''    ^^^^v~-^  or  a  dr^' cell  in  the  primary  circuit, 

/"^^J  i       ^^^       ^\        which  should  also  include  a  simple 

//^/io^«i<i/-^A^^^^^    y^  \  V       key.     Insert  a  short-circuiting  key 

\/ijat/^.^ — ^w'^^kX.       \  ^  *^®  secondary'  circuit.     Attach 

^^  /    "     //HL^B^^^^'^X    \         *^®  electrodes  to  the  short-circmt- 

'If     v^  )M    V--      "^S  key,  push  the  secondary  coil 

^  '  //f   -f^rW        /J      \       "P  'towards  the  primary  imtil  the 

I  (1   ^    ^^^\(/y  I       shocks  are  distinctly  felt   on  the 

A\  \  B     H^rl    y^       /  \       tongue  when  the  Neef 's  hammer  is 
\J  I     p     /        set  going  and  the  short-circuiting 

■  Lv{i^         '      /  key  opened.     Pith  the  brain  of  a 

Fig.  91. -The  Relations  of  the  Vagus        f^g,  expose  the  hearl,  dissect  out 
in  the  Frog.  ^^^  vagus  on  one  side,  ligature  it 

as  high  up  as  possible,  and  divide 
above  th^  ligature.  Fasten  the  electrodes  on  the  cork  plate  by  means 
of  an  indiarubber  band,  and  lay  the  vagus  on  them.  Set  the  drum 
off  (at  slow  speed).  After  a  dozen  heart-beats  have  been  recorded, 
stimulate  the  vagus  for  two  or  three  seconds  by  opening  the  short- 
circuiting  key.  If  the  nerve  is  active,  the  heart  will  be  slowed, 
weakened,  or  stopped.  In  the  last  case  the  lever  will  trace  an  unbroken 
straight  line ;  but  even  if  the  stimulation  is  continued  the  beats  will 
again  begin. 

8.  Stimulation  of  the  Junction  of  the  Sinus  and  Auricles. — After  a 
sufficient  number  of  the  observations  described  in  7  have  been  taken 
with  varying  time  and  strength  of  stimulation,  lake  the  writing-points 
off  the  drum,  apply  the  electrodes  directly  to  the  crescent  at  the  junc- 
tion of  the  sinus  venosus  with  the  right  auricle,  and  stimulate.  The 
heart  will  be  affected  ven,-  much  in  the  same  way  cis  by  stimulation  of 
the  vagus,  except  that  during  the  actual  stimulation  its  beats  may  be 
quickened  and  the  inhibition  may  only  begin  after  the  electrodes  have 
been  removed  (Fig.  70,  p.  158). 


PRACTICAL  EXERCISES 


IJfV 


£AS 


g.  Effect  of  Muscarine  (or  Pilocarpine)  and  Atropine. — Paint  on  tlie 
sinus  venosus  with  a  small  camcl's-hair  brush  a  very  dilute  solution  oi 
muscarine  (or  of  pilocarpine).  The  heart  will  soon  be  seen  to  beat 
more  slowly,  and  will  ultinuitdy  stop  in  diastole.  Now  apply  a  dilute 
solution  of  sulphate  of  atropine  to  the  sinus.  The  heart  will  again 
begin  to  beat.  Stimulation  of  the  vagus  \vill  now  cause  no  inhibition 
of  the  heart,  because  its  endings  have  been  paralyzed  by  atropine. 
(Muscarine  or  pilocarpine  has  also  been  applied  to  the  heart,  but  it 
could  be  shown  by  a  separate  experiment  that  atropine  by  itself  has 
the  same  effect  on  the  vagus  endings — p.  i6   .) 

10.  Stannius'  Experiment. — Pith  a  frog.  Expose  the  heart  in  the 
way  described  under  2  ip.  194).  Ligature  the  fraenum  with  a  fine  sillt 
thread,  and  use  the  thread  to  manipulate  the  heart.  With  a  curved 
needle  pass  a  moistened  silk  thread  between  the  aorta  and  the  superior 
\ena,  cava,  and  tie  it  round  the 
junction  of  the  sinus  and  right 
auricle  (Fig.  86).  The  auricles 
and  ventricle  stop  beating  as 
soon  as  the  ligature  is  tightened. 
The  sinus  venosus  goes  on  beat- 
ing. Now  separate  the  ven- 
tricle from  the  rest  of  the  heart 
by  an  incision  through  tlie 
auriculo-ventricular  groove,  or 
tie  a  second  ligature  in  the 
groove.  The  ventricle  begins 
to  beat  again,  the  auricle  re- 
maining quiescent  in  diastole 
(p.  i6d).  Occasionally  both 
auricle  and  ventricle,  or  only 
the  auricle,  may  begin  to  beat. 

11.  Stimulation  of  Cardiac 
Sympathetic  Fibres  in  the  Frog 
— (i)  In  the  vagosympathetic 
after  the  inhibitory  fibres  have 
been  cut  out  by  atropine. — 
Arrange  ever\-tliing  as  in  7 
(p.  198).  Assure  yourself,  by 
stimulating  the  vagus,  that  it 
inhibits  the  heart,  and  take 
a  tracing  during  stimulation. 
Then  paint  a  dilute  solution 
of  atropine  on  the  sinus. 
Stimulation  of  the  vagus,  which  is  really  the  vago-sxTupathetic  (see 
Fig.  92),  will  now  cause,  not  inhibition,  but  augmentation  (increase 
in  rate  or  force,  or  both),  since  the  endings  of  the  inhibitor^'  fibres  have 
been  paralyzed  by  atropine.  The  strength  of  the  stimulating  current 
required  to  bring  out  a  typical  augmentor  effect  is  greater  than  that 
needed  to  stimulate  the  inhibiton,-  fibres.  Take  a  tracing  to  show 
augmentation  produced  by  stimulating  the  nerve. 

(2)  By  direct  stimulation  of  the  cervical  sympathetic. — Make  the  same 
arrangements  as  in  11  (i),  but,  instead  of  isolating  the  vagus,  dissect 
out  the  s^Tnpathetic  on  one  side  in  the  manner  described  in  6  (2)  (p.  197). 
and  do  not  apply  atropine  to  the  heart.  Lay  the  upper  (cephalic)  end 
of  the  sympathetic  on  very  fine  and  well-insulated  electrodes,  and 
stimulate  (Fig.  76,  p.  167).  (To  insulate  electrodes  the  points  may  be 
covered  with  melted  paraffin.     When  the  paraf&n  has  cooled,  a  narrow 


Fig.  92.  —  Relation  of  the  Sympathetic  to 
the  Vagus  in  the  Frog  (after  Gaskell). 
Sym,  sympathetic  chain ;  G,  ganglion  of 
the  vagus;  VS,  vago  -  sympathetic  ;  GP, 
glosso-pharj-ngeal  nerve;  LAS,  levator 
anguli  scapulae  muscle ;  SA,  subclavian 
artery;  A,  descending  aorta;  V,  vertebral 
column;  OC,  occipital  part  of  skull;  1-4, 
spinal  nerves. 


200 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


groove,  just  siiffn  itiit  to  lay  l>arc  tlio  wires  on  tlic  upper  side,  is  made 
in  it,  and  the  nerve  is  laid  in  this  groove.) 

Experiments  7,  11  (i)  and  11  (_»)  will  be  rendered  more  exact  by 
connecting  a  second  electro-magnetic  signal  with  a  Fold's  commutator 
without  cross-wires  (Fig.  i).}),  in  such  a  way  that  the  circuit  is  inter- 
rupted at  the  instant  when  stimulation  begins. 

12.  The  Action  of  Inorganic  Salts  on  Heart-Muscle. — Expose  and 
remove  the  heart  of  a  tortoise  or  turtle  (p.  nj6).  Cut  off  the  apical  two- 
thirds  of  the  ventricle  by  an  incision  parallel  to  the  auriculo-ventricular 
groove.  By  a  second  parallel  cut  remove  a  ring  of  tissue  2  or  3  milli- 
metres wide  from  the  upper  end  of  this  portion  of  the  ventricle.  Divide 
the  ring  at  opposite  ends  of  a  dianacter,  so  as  to  form  two  strips.  Tie 
a  fine  silk  thread  to  each  end  of  one  strip.  Attach  one  of  the  threads 
to  the  short  limb  of  a  glass  rod  bent  at  right  angles,  so  that  it  can  be 
immersed  at  will  in  a  beaker.  The  other  end  of  the  rod  is  fixed  in  a 
holder  sliding  on  a  stand.     Attach  the  second  thread  to  the  short  arm 


Fig.  js. — Arrangement  of  Induction  Machine  for  Tetanus.  B,  battery;  K,  simple 
key;  P,  primary  coil;  S.  secondary  coil:  A,  C,  binding  screws  to  be  connected 
with  battery  for  single  shocks;  F.  G,  binding  screws  for  tetanizing  current;  N, 
Neef's  hammer;  D,  short-circuiting  key  in  secondary;  E,  electrodes.  D  and  E 
are  drawn  to  a  much  larger  scale  than  the  rest  of  the  figure. 


of  a  counterpoised  lever  arranged  to  write  on  a  slowly-moving  drum. 
If  the  strip  is  still  beating,  wait  till  the  contractions  have  ceased ;  then 
(i)  Immerse  the  strip  in  a  beaker  filled  with  07  per  cent,  solution  of 
sodium  chloride.  After  a  time  it  begins  to  beat  rhythmically.  The 
contractions  become  rapidly  stronger,  and  then  after  a  while  diminish, 
and  gradually  cease.  The  tone  or  tonus  of  the  strip  is  diminished  by 
the  solution. 

(2)  Arrange  the  other  strip  in  the  same  way,  and  immerse  it  in  a 
solution  of  calcium  chloride  (about  i  per  cent.)  isotonic  with  the  sodium 
chloride  solution  used  in  (i).  If  the  strip  is  contracting,  the  contrac- 
tions will  cease.  Rhythmical  contractions  will  not  appear  as  in  the 
sodium  cliloride  solution.     The  tone  of  the  strip  may  be  increased. 

(3)  Remove  most  of  the  calcium  chloride  solution  from  the  beaker, 
and  fill  it  up  with  07  per  cent,  sodium  chloride  solution.  The  rhythmi- 
cal  contractions  will  appear  after  a  longer  or  shorter  latent  period,  and 
will  be  stronger  and  last  for  a  longer  time  than  in  the  sodium  chloride 
solution  alone. 

(4)  Immerse  a  fresh  strip  in  a  solution  containing  sodium   chloride 


PRACTICAL   F.XHRCfSES 


2or 


(07  por  cent),  calriuin  i  hlorido  (ooiT  per  cent.),  and  potassium 
chloride  (003  per  cent.)  (a  modified  Ringer's  solution).  A  longer 
series  of  rhythmical  contractions  will  be  ol)t;uned  than  in  either  (i) 
or  (3).  That  this  is  not  due  to  the  potassium  chloride  acting  alone 
can  be  shown  by  immersing  a  strip  in  a  solution  of  potassium  chloride 
(about  09  per  cent.)  isotonic  with  the  sodium  chloride  solution  used 
in  (i).     No  contractions  will  be  caused. 

13.  The  Action  of  the  Mammalian  Heart. — Inject  under  the  skin  of  a 
dog  (preferably  a  small  one)  i  c.c.  of  a  2  per  cent,  solution  of  morphine 
hydrochlorate  for  e\cr\'  kilo  of  body-weight.  .\s  soon  as  the  morphine 
has  taken  effect  (in  15  to  30  minutes,  but  better  after  an  hour),  fasten 
the  animal  back  down  on  a  holder  (as  in  Fig.  i35.  P-  301).  pushing  the 
mouth-pin  behind  the  canine  teeth  and  screwing  the  nut  liome.*  In 
the  meantime  select  a  tracheal  cannulaf  of  suitable  size,  and  get  ready 
instruments  for  dissection — one  or  two  pairs  of  artery-forceps,  a  pair 
of   artery-clamps    (bulldog  pattern),   two  or  three   glass   cannulcc  of 


Pig  g^_ — Arrangement  for  recording  the  Beginning  and  End  of  Stimulation.  C. 
Pohl's  commutator  without  cross-wires;  B,  battery  in  circuit  of  primary  coil  P; 
B',  battery  in  circuit  of  electro-magnetic  signal  T;  K,  simple  key  in  primary 
circuit;  S,  secondary  coil.  When  the  bridge  of  the  commutator  is  tilted  into 
the  position  shown  in  the  figure,  the  primary  circuit  is  closed  and  the  circuit  of 
the  signal  broken. 

various  sizes  for  bloodvessels,  ten  strong  waxed  ligatures,  sponges, 
hot  water,  a  towel  or  two,  and  a  pair  of  bellows  to  be  connected  with 
the  tracheal  cannula  when  the  chest  is  opened.     Arrange  an  induction- 

*  A  simple  but  efticient  and  convenient  holder  for  a  dog  may  be  easily 
constructed  as  follows:  Take  a  board  of  the  length  required  (2I  to  5  feet, 
according  to  the  size  of  the  dog) .  At  one  end  fasten  two  short  upright  wooden 
pins,  with  a  clear  space  of  4  to  6  inches  between  them.  These  are  pierced 
from  side  to  side  with  four  or  five  holes  at  different  heights.  An  iron  p:a  passes 
behind  the  canine  teeth  of  the  animal  through  two  corresponding  holes  in  the 
uprights,  and  the  muzzle  is  tied  over  this  by  a  cord  which  secures  the  head. 
For  a  large  dog  an  upper  pair  of  holes  is  used,  for  a  small  dog  a  lower  pair. 
The  feet  are  fastened  by  cords  to  saaples  inserted  into  the  sides  of  the  board, 
the  fore-legs  being  drawn  tailwards  for  all  operations  on  the  neck  or  head, 
headwards  for  operations  on  the  thorax.  A  rabbit-holder  can  be  made  in 
exactly  the  same  way. 

t  A  tracheal  cannula  is  easily  made  by  heating  a  piece  of  glass  tubing, 
about  6  inches  long,  a  short  distance  from  one  end,  and  drawing  it  out  slightly 
so  as  to  form  a  '  neck.'  The  tubing  is  then  bent  about  its  middle  to  an  obtuse 
angle,  and  the  end  next  the  neck  is  ground  obliquely  on  a  stone.  The  diameter 
of  the  cannula  should  be  about  the  same  as  that  of  the  trachea,  into  which  it 
is  to  be  inserted  by  its  oblique  end. 


202  THE  CIRCULATION  OF  THE  BLOOD  ASD  LYMPH 

coil  and  elcctnxlcs  for  a  tt  tanizing  current  (Fig.  93,  p.  200).  With 
scissors  curved  on  the  flat  cHj)  away  the  hair  from  the  front  of  the 
neck.  Put  tlie  hair  carefully  away,  and  remove  all  the  loose  hairs 
with  a  wet  sjKinge  so  that  tluy  may  not  get  into  the  wounds.  Give  ether, 
or  pour  into  the  stomach  by  a  tube  3  c.c.  of  a  05  per  cent,  solution 
of  chloroform  in  10  per  cent,  alcohol  per  kilo  of  body-weight,  diluted 
before  administration  with  3  or  4  volumes  of  water  (Grehant's  method). 
To  put  a  Cannula  in  the  Trachea. — The  hair  having  been  clipped  in 
the  middle  line  of  the  neck  and  the  skin  shaved,  a  mesial  incision  is 
to  be  made,  beginning  a  little  below  the  cricoid  cartilage,  which  can 
be  felt  with  the  finger.  The  trachea  is  then  cleared  from  its  attach- 
ments by  forceps  or  a  blunt  needle,  and  two  strong  ligatures  are  passed 
beneath  it.  A  single  loop  is  placed  on  each  of  these,  but  is  not  drawn 
tight.  Raiding  the  trachea  by  means  of  the  upper  ligature,  the  student 
makes  a  longitudinal  incision  through  two  or  three  of  llie  cartilaginous 
rings,  inserts  the  cannula,  and  ties  the  lower  ligature  firmly  around  its 
neck.     The  upper  ligature  can  now  be  withdrawn. 

Clip  off  the  hair  on  each  side  of  the  sternum.  Make  an  incision  on 
each  side  through  the  skin  and  down  to  the  co.stal  cartilages  about 
2  inches  from  the  edge  of  the  breast-bone,  and  long  enough  to  expose 
about  four  costal  cartilages  (say,  3rd  to  6th).  With  a  curved  needle 
pass  waxed  ligatures  round  the  cartilages,  and  tie  firmly  to  compress 
the  intercostal  vessels.  The  bellows  should  now,  or  earlier  if  any 
symptoms  of  impeded  respiration  have  appeared,  be  connected  with 
one  end  of  the  horizontal  limb  of  a  glass  T-piece,  the  other  end  of 
which  is  similarly  connected  with  the  tracheal  cannula.  The  stem  of 
the  T-piece  is  provided  with  a  short  piece  of  rubber  tubing,  which, 
when  artificial  respiration  is  being  carried  on,  is  to  be  alternately  closed 
and  opened — closed  during  inflation  of  the  lungs,  and  opened  when 
the  air  is  to  be  allowed  to  escape  from  them.  Or  a  screw-clamp  may 
be  adjusted  on  the  piece  of  tubing  so  that  the  opening  is  sufficiently 
narrow  to  permit  the  lungs  to  be  properly  inflated  when  the  bellows 
are  compressed,  and  yet  sufficiently  wide  to  permit  easy  escape  of  the 
air  and  collapse  of  the  lungs  at  the  end  of  each  inflation.  Etner  may, 
when  necessary,  be  administered,  by  inserting  between  the  T-piece  and 
the  tube  from  the  bellows  an  ether  bottle  \\  ith  two  tubes  passing  through 
the  cork  to  within  an  inch  or  two  of  the  ether.  If  the  cannula  has  a 
side-opening,  as  is  usually  the  case  v/ith  metal  cannulae,  the  T-piece 
may  be  dispensed  with.  One  student  should  take  sole  charge  of  the 
artificial  respiration,  v.hich  ought  to  be  begun  as  soon  as  the  chest  has 
been  opened,  and  continued  at  the  rate  of  about  twenty  inflations 
per  minute.  The  costal  cartilages  are  rapidly  cut  through  with  strong 
scissors  just  on  the  sternal  side  of  the  ligatures,  the  artificial  respira- 
tion being  suspended  for  an  instant,  as  each  cut  is  made,  to  avoid 
wounding  the  lungs.  The  sternum  is  divided  at  its  lower  end  and 
turned  up.  If  there  is  much  bleeding  a  ligature  should  be  tied  round 
its  upper  end.  With  a  curved  needle  a  ligature  is  passed  below  the 
internal  mammarj'  arteries  as  they  approach  the  sternum.  That  bone 
may  now  be  removed,  and  the  heart,  enclosed  in  the  pericardium,  come? 
into  view.  A  thread  is  passed  with  a  suture-needle  through  each  side  ol 
tlie  pericardium,  which  is  then  stitched  to  the  chest-wall  and  opened. 

{a)  Note  the  various  portions  of  the  heart,  right  and  left  ventricles, 
right  and  left  auricles,  with  the  auricular  app.ndices.  Feel  the  heait 
with  the  hand,  and  observe  that  the  right  ventricle  is  softer  and  has 
thinner  walls  than  the  left,  and  that  the  auricles  are  softer  than  the 
ventricles.  Note  how  all  the  parts  of  the  heart  harden  in  the  hand 
during  systole  and  soften  during  diastole  (pp.  86,  90). 


PRACTICAL  EXERCISrS 


203 


(b)  Dissect  out  the  vago-sympathetic  on  one  side  in  the  neck  of  the 
<log.  The  guide  to  the  nerve  is  the  carotid  artery.  These  two  struc- 
tures and  the  internal  jugu- 
lar vein  lie  side  by  side  in 
a  common  sheath.  Feel 
for  the  artery  a  little  ex- 
ternal to  the  trachea,  ci.t 
down  on  it,  open  the  sheath , 
isolate  the  vago-sympa- 
thetic for  about  an  inch, 
pass  two  ligatures  under  it, 
tie  them,  and  divide  be- 
tween the  ligatures.  The 
peripheral  and  central  ends 
of  the  nerve  may  now 
be  successively  stimulated. 
Stimulation  of  the  peri- 
pheral end  causes  slowing 
of  the  heart,  or  stoppage 
in  diastole.  Feel  that  it 
softens  when  it  stops.  It 
soon  begins  to  beat  again. 
Stimulation  of  the  central 
end  of  the  vago-sympa- 
thetic may  or  may  not 
cause  inhibition .  If  it  does, 
expose  the  other  vago- 
sjTnpathetic .  divide  it,  and 
repeat  the  stimulation  of 
the  central  end .  There  will 
now  be  no  inhibition  of  the 
heart.  Incidentally  it  may 
be  seen  that  stimulation 
of  the  central  end  of  the 
vago  -  sjTnpathetic  causes 
strong,  though,  of  course, 
withopened  chest, abortive, 
respiratory  movements. 

{c)  Pith  a  frog  (brain 
and  cord),  dissect  out  the 
sciatic  nerve  on  one  side  up 
to  the  sacral  plexus.  Cut 
off  the  whole  leg.  Drop  the 
cut  end  of  the  nerve  on  the 
heart,  and  hold  the  prep- 
aration so  that  the  nerve 
touches  the  heart  also  by 
its  longitudinal  surface.  At 
each  cardiac  beat  the  nerve 
is  stimulated  by  the  action 
current  (p.  833),  and  the 
muscles  of  the  leg  contract. 

[d)  Raise  the  board  so 
that  the  head  of  the  animal 
is  down  and  the  hind-feet 
up,  and  note  whether  there 
is  any  effect  on  the  action 


Fig.  95- — Myocardiograph  of  Adami  and  Roy 
(modified  by  Cushny  and  Matthews).  AB,  a 
perpendicular  rod  descending  from  a  universal 
joint,  which  is  not  shown  in  the  figure;  CD,  a 
brass  sheath,  moving  easily  on  the  rod,  and 
bearing  on  its  upper  end  an  ivory  pulley,  and  at 
its  lower  end  a  horizontal  bar,  which  is  inter- 
rupted by  a  plate  of  hard  rubber,  I.  The  per 
pendicular  rod  EF  moves  on  the  horizontal  bai 
by  the  hinge-joint,  J.  EF  is  hooked  at  one  end 
for  attachment  to  the  heart,  and  bored  at  the 
other  for  a  thread  which,  passing  over  the  pulley 
at  C,  passes  through  the  universal  joint  and 
moves  a  writing  lever  not  shown  in  the  figure. 
CD  is  prevented  from  moving  up  AB  by  a  ring  of 
brass,  G,  which  is  screwed  to  AB,  but  is  not 
attached  to  CD ;  the  hook  F  can  therefore  move 
to  and  from  AB,  and  can  rotate  round  it,  while 
it  cannot  move  up  or  down.  The  hooks  F  and  B 
are  insulated  from  each  other  by  the  hard  rubber. 
I.  H  is  a  binding  post  through  which,  and 
through  another  connected  with  A,  induction 
shocks  may  be  sent  at  will  into  the  portion 
of  the  heart  lying  between  the  hooks. 


204 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


and    filling  of  the  lirart.      Hrprat  the  observation  witli  iu-ad  up  and 

feet  clown. 

{e)  C(jniprcss  the  aoiia  with  the  fnigcrs,  and  observe  the  effect  on 

tlie  degiee  of  dilatation  of  the  various  cavities  of  the  heart.      Repeat 

the  experiment  with  the  inferior  vena  cava,  and  compare  the  results. 

~  if)   Smoke    a    drum.     Insert    the 

hooks  of  the  myocardiograph  (Fig.  95) 
into  the  ventricle,  taking  care  not 
to  penetrate  deeply  into  the  wall. 
Arrange  the  lever  to  write  on  the 
drum.  While  a  tracing  is  being 
taken  stimulate  the  peripheral  end  of 
the  vagus.  Unhook  the  cardiograph. 
{g)  Stop  the  artificial  respiration, 
and  observe  the  changes  which  take 
place  in  the  auricles  and  ventricles, 
comparing  particularly  the  right  side 
of  the  heart  with  the  left.  Before 
the  heart  has  stopped  beating,  re- 
commence the  artificial  respiration. 

(A)  Connect  a  cylinder  of  oxygen 
with  a  good-sized   rubber  catheter. 


D  .'C 

Fig.  96.— Arrangement  to  illustrate  Action  of  Cardiac  Valves  in  the  Heart  o£  an  0\ 
(Gad).  C,  glass  window  in  left  auricle;  D,  window  in  aorta;  E.  tube  inserted 
through  apex  of  heart  into  left  ventricle  and  connected  with  pump  P;  A.  side 
tube  on  E,  through  which  wires  are  connected  with  a  tiny  incandescent  lamp  in 
the  ventricle ;  W.  water  in  bottle  B ;  T.  T',  tubes. 

and  pass  the  catheter  down  the  tracheal  cannula  or  through  a  separate 
opening  in  the  trachea.  Allow  a  small  stream  of  oxygen  to  flow  into 
the  lungs.  Artificial  respiration  is  now  unnecessary.  The  lungs 
remain  at  rest,  yet  the  blood  is  sufficiently  oxygenated,  and  the  heart 
goes  on  beating.  The  myocardiographic  tracing  thus  goes  on  undis- 
turbed by  respiratory  movements. 

(»■)  Stop  the  oxygen,  and  resume  the  artificial  respiration.     Make  a 


PRACTICAL  EXERCISES 


205 


Small  penetrating  wound  with  a  scalpel  in  the  left  ventricle.  Observe 
the  course  of  the  lucinorrhagc,  and  note  especially  the  difference  in 
systole  and  diastole. 

(/)  Lay  the  electrodes  on  the  heart,  and  stimulate  it  with  a  strong 
interrupted  current.  The  character  of  the  contraction  soon  becomes 
profoundly  altered.  Shallow,  irregular 
contractions  flicker  over  the  surface,  with 
a  kind  of  simmering  movement  sugges- 
tive of  a  boiling  pot  (delirium  cordis, 
fibrillar  contraction).  Now  kill  the  ani- 
mal by  stopping  the  artificial  respiration. 
Observe  how  long  the  heart  continues  to 
beat,  and  which  of  its  divisions  stops 
last. 

{k)  Make  a  dissection  of  the  cervical 
sympathetic  up  to  the  superior  cervical 
ganglion,  and  (hnvn  through  the  inferior 
cervical  ganglion  to  the  stellate  or  hrst 
thoracic  ganglion.  Make  out  the  annuhis 
of  Vieusscns  and  the  cardiac  sympa- 
thetic (accelerator)  branches  going  off 
from  the  annulus  or  the  inferior  cei'vical 
ganglion  to  the  cardiac  plexus. 

14.  Perfusion  of  the  Isolated  Mam- 
malian Heart, — -The  heart  of  a  dog  em- 
ployed for  some  other  experiment  may 
be  used.  Or  a  rabbit  may  be  killed  by 
a  blow  on  the  back  of  the  head,  and 
the  heart  at  once  removed.  The  aorta 
should  not  be  cut  off  too  short.  Tie  a 
cannula  into  the  aorta  and  attach  it  to 
a  T-picce  connected  by  rubber  tubes, 
which  must  be  perfectly  clean,  with  two 
bottles,  one  containing  Ringer's  solution 
(pp.  66,  201),  preferably  that  made  with 
dextrose,  the  other  containing  defibrin- 
ated  blood  diluted  with  Ringer's  solu- 
tion. The  dcfibrinated  blood  should  be 
strained  so  as  to  remove  any  small  pieces 
of  fibrin.  The  bottles  are  supported  on  a 
high  stand,  so  that  the  level  of  the  bottles 
above  the  heart  can  be  altered,  and  the 
pressure  of  the  perfusion  liquid  thus 
varied.  Perfusion  may  be  begun  with 
Ringer,  to  wash  out  any  remaining  blood 
and  obviate  the  possible  formation  of 
clots  in  tlie  small  vessels.  Oxygen  is 
allowed  to  bubble  through  the  Ringer's 
solution,  but  this  is  not  necessarj^  for  the 
blood,  since,  if  shaken  up,  it  will  retain 
far  more  oxygen  than  the  Ringer's  solu- 
tion. The  temperature  of  the  liquids 
should  be  at  about  40°  C.  when  nearing  the  heart 
easily  insured  by  interposing  a  worm  immersed  m  a  heated  bath  or 
other  heating  arrangement  between  the  cannula  and  the  T-tube.  and  tor 
the  studv  of  its  movements  by  inspection  the  heart  itself  can  be  placed 
m  a  glass"  vessel  immersed  in  the  bath.     When  records  of  the  contractions 


Fig.  97. — Mammalian  Heart  Per- 
fusion Apparatus  (Gunn).  a, 
Liebig  condenser,  cut  off  as 
shown  ;  b,  inlet  for  the  warm 
water ;  d,  thermometer  ahnost 
filling  up  the  lumen  of  the  thin 
glass  tube  c  ;  e,  cork  ;  /.  cannula 
for  aorta  fitted  with  a  collar  of 
rubber  tubing,  g,  in  the  end  of 
the  tube  c  ;  h,  Y-tube  connected 
with  two  reservoirs,  one  contain- 
ing Ringer's  solution,  the  other 
any  other  liquid  which  is  to  be 
perfused. 

This  can  be  most 


THE  CIRCULA'JtO^  OF  THE  JSLOOt)  A XI)  LYMPH 


arc  to  be  obtained,  threads  are  attaclud  to  the  auricle  and  to  the  apex 
of  the  ventricl  ■.  The  heart  is  suspended  by  fastening  the  cannula  in  a 
holder  on  a  stand,  and  the  threads,  after  passing  over  pulleys  to  give 
them  a  convenient  direction,  are  attached  to  writing-levers. 

As  the  heart  cannot  now  be  easily  kept  immersed  in  the  bath,  it  is 
suspended  in  the  air,  and  can  be  kept  warm  by  the  following  simple 
arrangement:  A  copper  pipe  about  4  inches  long  is  slit  on  one  side,  and 
on  the  opposite  side  is  screwed  or  riveted  to  a  copper  rod,  under  wliicli 
is  hung  a  spirit-lamp.  The  lamp  is  adjuslcd  at  such  a  point  on  the  rod 
that  when  the  copper  tube  is  placed  around  the  heart  the  heat  conducted 
along  the  rod  keeps  the  air  around  the  heart  at  about  body-temperature. 
The  perfusion  liquid  before  it  enters  the  heart  may  be  heated  thus: 
A  Liebig's  condenser  is  cut  through  the  middle,  and  the  large  end 
closed  by  a  paraffined  cork.  A  glass  tube  is  run  down  from  the  toj) 
through  this  cork,  and  the  aorta  is  attached  directly  to  this,  so  that 
the  heart  is  very  near  the  condenser.  This  tube  is  mostly  filled  up  by 
a  thermometer,  so  that  the  perfusion  liquid  passes  through  it  in  a  thin 
stream  which  is  easily  heated   by  the  water  in  the  condenser,  which 

contains  a  second  ther- 
mometer. This  water  is 
kept  constantly  flowing 
through  the  condenser 
from  a  heated  bath.  The 
T-piece  connecting  with 
the  perfusion  bottles  is 
attached  to  the  upper 
end  of  the  glass  tube 
to  which  the  heart  is 
attached  (Gunn  and 
Cushnv). 

15.  Action  of  the 
Valves  of  the  Heart.— ^ 
(i)  Study  the  action  ul 
the  Aalves  of  the  o.x- 
licart,  connected  with 
the  pump  P  and  bottle  B 
in  the  artificial  scheme, 
as  shown  in  Fig.  96.  The 
cavity  of  the  heart  is 
illuminated  by  means  of 
a  small  electric  lamp,  the 
wires  of  which  pass  in  at 
A.  When  the  j)iston  of  the  pump  is  })ushed  down,  water  is  forced 
through  the  aorta  D  along  the  tulie  1'  into  the  bottle,  and  flows  back 
again  into  the  left  auricle  by  tho  tube  T'.  During  each  stroke  of  the 
pump  the  auriculo-ventricular  valve  is  seen  through  the  glass  disc 
mserted  into  C"  to  close,  and  the  semilunar  v;ilve  is  seen  through  the 
glass  in  D  to  open.  When  the  piston  is  raised,  the  semilunar  valve  is 
seen  to  be  closed  and  the  auriculo-ventricular  \ai\e  to  be  opened. 
For  comparison,  a  human  heart  with  a  valvular  lesion  might  be  u.sed. 

{2)  With  the  sheep's  or  dog's  heart  i)rovided,  pci-form  the  follow^ing 
experiments : 

(a)  Open  the  peric;udium  and  notice  how  it  is  reflected  around  the 
great  vessels  at  the  base  of  the  heart.  Distinguish  the  pulmonary 
arterj-,  the  aorta,  the  superior  and  inferior  vena-  cav.e.  and  the  pul- 
monar\-  veins.  The  trachea  and  portions  of  the  lungs  mav  also  be 
attached.     If  so,  remove  them  carefully  without  injuring  the  heart. 


o 
F"ig.  98. — Diagram  of  Valves  of  the  Heart.  Tlie 
valves  are  supposed  to  be  viewed  from  above,  the 
auricles  having  been  partially  removed.  A,  a'»rta 
with  semilunar  valve;  B,  pulmonary  artery  and 
valve;  C,  tricuspid,  and  D,  mitral  valve;  E,  right, 
andF,  left  coronary  artery;  (1,  wall  of  right,  and  H, 
of  left  auricle.  I,  wall')f  right,  andj,  of  1 -ft  ventricle. 


PRACTICAL  LXLliCISES  207 

{b)  Take  two  wide  glass  tubes,  drawn  slightly  into  a  nork  at  one  end. 
One  of  the  tubes  slioukl  be  about  10  cm.  long,  and  tlv:  other  about 
50  cni.  Tic  the  short  tube  A  firmly  by  its  neck  into  liie  superior  \'ena 
cava,  the  long  tube  B  into  the  pulmonaiy  arterJ^  Ligature  the  inferior 
vena  cava.  Connect  .A  by  a  small  piece  of  rubber  tubing  with  a  funnel 
supported  in  a  ring  on  a  stand.  Pour  water  into  the  funnel  till  the 
riglit  side  of  the  heart  is  full.  It  will  escape  from  the  left  azygos  vein, 
which  must  be  tied.  Put  on  any  additional  ligatures  that  may  be 
needed  to  render  the  heart  water-tight.  Support  B  in  the  vertical 
position  by  a  clamp.  Fill  the-  funnel  with  water,  and  it  will  rise  in  B 
to  the  same  le\'cl  as  in  the  funnel.  Now  compress  the  right  ventricle 
with  the  hand,  and  the  water  will  rise  higher  in  B.  Relax  the  pressure 
and  notice  that  the  water  remains  at  the  higher  level  in  B,  being  pre- 
vented by  the  semilunar  valves  from  flowing  back  into  the  ventricle. 
By  alternately  compressing  the  ventricle  and  allowing  it  to  relax,  water 
can  be  pumped  into  B  till  it  escapes  from  its  upper  end,  and  if  this  is 
so  curved  that  the  water  falls  into  the  funnel,  a  '  circukition  '  which 
imitates  that  of  the  blood  tan  be  established.  Note  that  during  the 
pumping  the  sinuses  of  Valsalva,  behind  the  semilunar  valves  at  the 
origin  of  the  pulmonary  artery,  become  prominent. 

(c)  Take  out  B  and  tear  out  one  of  the  segments  of  the  semilunar 
valve.  Replace  B,  and  notice  that,  while  compression  of  the  ventricle 
has  the  same  effect  as  before,  the  water  no  longer  keeps  its  level  on 
relaxation,  but  regurgitates  into  tlic  ventricle.  This  illustrates  the 
condition  kno\vn  as  insufficiency  or  incompetence  of  the  valves.  But 
if  the  injury  is  not  too  extensive,  it  is  still  possible,  by  more  vigorously 
and  more  rapidly  compressing  the  heart,  to  pump  water  into  the  fumiel. 
This  illustrates  the  establishment  of  compensation  in  cases  of  valvular 
lesion. 

(d)  Now  remove  both  tubes.  Tic  the  pulmonary  artery.  Cut  away 
the  greater  part  of  the  right  auricle.  Pour  water  into  the  auriculo- 
ventricular  orifice,  and  notice  that  the  segments  of  the  tricuspid  valve 
are  floated  up  so  as  to  close  the  orifice.  Invert  the  heart,  and  the 
ventricle  will  remain  full  of  water.  Open  the  right  ventricle  carefully, 
and  study  the  papillary  muscles  and  the  chordae  tendineie,  noting  that 
the  latter  are  inserted  into  the  lower  surface  of  the  ■segments  of  the 
tricuspid  valve,  as  well  as  into  their  free  edges. 

(e)  Repeat  {b),  [c),  and  {d)  on  the  left  side  of  the  heart,  tying  tube  B 
into  the  aorta  as  far  from  th?  heart  as  possible,  and  A  into  the  left  auricle. 

(/)  Separate  the  aorta  from  the  left  ventricle,  cutting  wide  of  its 
origin  so  as  not  to  injure  the  semilunar  valves,  and  tie  a  short  wide 
tube  into  its  distal  end.  Pill  the  tube  with  water,  and  notice  that  the 
vahes  support  it.  Cut  open  the  aorta  just  between  two  adjacent  segments 
of  the  valve,  and  notice  the  pockets  behind  the  segments,  and  how  they 
are  related  to  each  other,  and  connected  to  the  wall  of  the  vessel. 

16.  Sounds  of  the  Heart. — (a)  In  a  fellow-student  notice  the  position 
of  the  cardiac  impulse,  the  chest  being  well  exposed.  Use  both  a 
l:)inaural  and  a  single-tube  stethoscope.  Place  the  chest-piece  of  the 
stethoscope  over  the  impulse,  and  make  out  the  two  sounds  and  the 
pause,  {b)  With  the  hand  over  the  radial  or  brachial  artery,  try  to 
determine  whether  the  beat  of  the  pulse  is  felt  in  the  period  of  the 
sounds  or  of  the  pause,  (c)  Listen  with  the  stethoscope  over  the 
junction  of  the  second  right  costal  cartilage  with  the  sternum,  and 
compare  the  relative  intensity  of  the  two  sounds  as  heard  here  with 
their  ;elative  intensity  as  heard  over  the  cardiac  impulse. 

17.  Cardiogram. — Smoke  a  drum,  and  arrange  a  recording  tambour 
and  a  time-marker  beating  half  or  quarter  seconds  to  write  on  it  (Fig.  88, 


2oS         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


p.  195).  Apply  the  button  of  a  cardiograph  (Fig.  -'7.  p.  90)  over  your 
own  cardiac  inipuls'\  and  fasten  it  round  the  body  by  the  bands  attached 
to  the  instrument.  Connect  the  cardiograph  by  an  indiarubber  tube 
with  a  recording  tainlx)ur  (Fig.  99).  Set  the  drum  off  at  a  fast  speed, 
take  a  tracing,  and  vaniish  it.  Compare  with  Fig.  28  (p.  91),  and  if 
the  tracing  is  sufficiently  typical,  as  is  often  not  the  case  with  human 
cardiograms,  measure  oiit  the  time-value  of  the  various  events  in  the 
cardiac  revolution. 


^■*&-  -■'■"■■■■' 


Fig.  99. — Marey's  Tambour. 

For  the  cardiograph,  a  small  glass  funnel,  or  thistle-tube,  the  stem 
of  which  is  connected  with  the  recording  tambour,  may  be  substituted, 
the  broad  end  of  the  funnel  being  pressed  over  the  apex-beat. 

18.  Sphygmographic  Tracings.— Attach  a  Marey's  sphygmograph 
(Fig.  37,  p.  103)  to  the  arm.  Fasten  a  smoked  paper  on  the  plate  D. 
Apply  the  pad  C  of  the  sphygmograph  to  the  wrist  over  the  point 

where  the  pulse  of  the  radial 
artcn,-  can  be  most  distinctly 
felt.  Adjust  the  pressure  by 
moving  the  screw  G.  The 
writing-point  of  the  lever  E 
will  rise  and  fall  with  ever\- 
pulsc-bcat.  When  cverjiihing 
is  sat ibfactorily  arranged,  set 
off     the     clockwork     which 


Dudgeon's  Sphygmograph. 


moves  the  plate  D.  and  a  pulse  tracing  will  be  obtained.  Study  the 
changes  which  can  be  produced  in  the  pulse  curve — \a)  by  altering  the 
position  of  the  bodv  (sitting  standing,  and  lying  down) ;  (6)  by  exercise 
(Fig.  101);  (c)  by  inhalation  of  1  drops  of  amyl  nitrite  poured  on  a  hand- 
kerchief by  the  demonstrator  (Fig.  102);  {d)  by  raising  the  arm  above 
the  head  and  letting  it  hang  at  the  side  ;  [e]  by  compression  of  the  brachial 
artery  at  the  bend  of  the  elbow;  (/)  by  altering  the  pressure  of  the  pad 
\'amish  the  tracings  after  marking  on'them  the  conditions  under  which 
they  were  obtained. 

A  Dudgeon's  sphygmograph  (Fig.   100)  may  also  be  employed.      In 
this  the  clockwork  carries  the  strip  of  blackened  paper  along  beneath 


PJiA  C TI CA L  EXERCISES 


200 


/X.fV.'^^.l 


'U\JiJV.!UUUUUUV 


Fig.  loi. — Effect  of  Exercise  oa  the 
Pulse  (Marey).  Upper  tracing, 
normal;  lower,  cifter  running. 


the  needle  which  records  the  movements  of  the  artery.  Or  a  small 
glass  funnel  or  thistlc-tubc  connected  with  a  recording  tambour  may 
be  pressed  over  the  carotid  artcr\-.  The  lever  of  the  tambour  writes 
on  a  drum,  on  which  at  the  same  time  lialf  or  quarter  seconds  arc 
marked  by  an  ele*  tro-niagnctic  signal. 
i<).  Venous  Pulse  Tracing  from  the 
Jugular  Vein. — Arrange  a  rcconlir.g 
tambour  to  write  on  a  drum.  Con- 
nect the  tambour  with  the  stem  of  a 
small  glass  thistle-tube  or  funnel  tor 
with  a  small  metal  cup)  by  a  piece  of 
narrow  rubber  tubing,  and  apply  the 
cup-shaped  end  of  the  thistlo-tubc 
over  the  right  jugular  bulb  of  a 
fellow-student.  This  liesabout  i  inch 
external  to  the  right  stemo-clavicular 
articulation,  and  a  little  above  it.  The 
receiver  may  have  to  be  moved  about 
a  little  until  the  best  pulsation  is 
obtained.     The    '  patient  '  should  be 

lying  down,  the  shoulders  slightly  raised,  the  head  on  a  pillow  and  turned 
slightly  to  the  right,  in  order  to  relax  the  right  stemo-mastoid  muscle 
(Mackenzie). 

20.  Polygraph  Tracings.— Arrang;  the  polygraph  over  the  radial 
artery,  as  with  an  ordinary-  sphvg  nograph.  so  that  the  lever  will  record 
the  radial  pulse  when  the  strip' of  paper  is  set  moving.     If  the  mstru- 

ment  has  only  one  tambour,  con- 
nect the  tambour  to  a  receiver 
or  thistle-tube  o\-er  the  jugular 
bulb.  The  writing-point  of  the 
tambour  is  arranged  so  as  to  be 
immediately  below  the  writing- 
point  connected  with  the  radial. 
If  the  polygraph  is  pro\'ided 
with  clockwork  to  record  time, 
set  oft  the  time-marker  writing 
fifths  of  a  second.  When  it  is 
seen  that  the  writing-points  are 
marking  properly,  start  the 
clockwork  which  moves  the 
strip  of  smoked  paper.  Repeat 
the  observation  with  the  tam- 
bour connected  with  the  apex- 
beat.  Letter  the  cur\-es  as  far 
as  possible  as  in  Figs.  65  and 
66  (p.  149)  without  at  present 
attempting  their  exact  analysis. 
If  the  polygraph  has  two  tam- 
bours, simultaneous  tracing  of  the  radial  pulse,  the  jugular  pulse,  and  the 
cardiac  impulse,  or  of  the  carotid  pulse,  the  jugular  pulse,  and  the  apex- 
beat,  may  be  taken,  and  other  combinations  as  well.  If  no  polygraph 
is  available,  a  drum  may  be  employed,  the  tracings  being  all  taken  with 
thistle-tubes  connected  With  recording  tambours.  The  levers  of  the 
tambours  must  be  arranged  to  write  on  the  drum  in  the  same  vertical 
straight  line,  or,  without  making  the  adjustment  quite  exact,  vertical  lines 
of  reference  may  be  drawn  through,  each  curve,  with  the  drum  at  rest, 
indicating  the  relative  positions  of  the  writing-points. 


Fig.  102. — Effect  of  .\rnyl  Nitrite  on  the 
Pulse  (Marey).  Upper  tracing,  normal; 
lower,  after  inhalation  of  amyl  nitrite. 


210  TJJI-:  CJRCLJ.AIIO.S    Ut    lllh   liJ.OOD  ASD  J.VMPH 

21.  Plethysmographic  Tracings.— Connect  the  vessel  D  (Fig.  36. 
p.  128),  uiiiciiy  Willi  ;i  recording  lamb(,ur  by  tlie  lube  F,  omitting  for 
simp'.icily  the"  recording  arrangimcnt  in  the  figure.  Place  the  arm 
in  the  plcthysmogn'ph,  and  adjust  the  indiarubbcr  band  to  make 
a  watertight  connection.  Support  D  so  that  the  arm  rests  easily 
within  it.  and  fill  it  with  water  at  body  temperature.  No  water  must  get 
into  the  tambour,  and  it  is  well  to  insert  a  piece  of  glass  tubing  in  the 
connection  between  it  and  the  plctliysmograph.  so  that  it  may  be  seen 
when  the  water  is  rising  too  high.  A  T-piece  with  a  short  piece  of 
rubber  tubing  on  the  stem  should  be  inserted  in  the  course  of  the  tube 
leading  to  the  tambour.  All  adjustments  are  made  with  the  T-picce 
open,  and  when  a  tracing  is  to  be  taken  the  short  rubber  tube  is  closed 
by  a  clip.  Arrange  a  time-marker  to  wTite  half  or  quarter  seconds 
(Fig.  88,  p.  n»5).  Adjust  the  writing-point  to  write  on  a  druni,  and 
close  the  upper  tubulurc  C  with  a  cork.  The  quantity  of  blood  in  the 
arm  is  increased  with  cver>'  sy.stole  of  the  left  ventricle,  diminished  in 
diahtole.  The  lever  will  therefore  rise  when  the  ventricle  contracts, 
and  sink  when  it  relaxes. 

(i)  Take  tracings  with  the  arm  (a)  horizontal,  [b)  hanging  down. 

(2)  With  the  arm  horizontal,  take  tracings  to  show  the  effect  {a)  of 
closing  and  opening  the  fist  inside  the  plethysmograph;*  (fc)  of  apply- 
ing a  light  bandago  round  the  arm  a  little  way  above  the  indiarubber 
band;  (c)  of  inhaling  2  drops  of  amyl  nitrite. 

Instead  of  the  arm  plethysmograph,  a  small  plethysmograph  to  hold 
a  finger  may  be  employed.  It  consists  of  a  glass  tube  drawn  out  at 
one  end.  The  wide  end  is  provided  with  a  rubber  collar.  The  narrow 
end  is  connected  by  a  small  rubber  tube  with  a  ver\-  small  and  sensitive 
recording  tambour,  a  T-picce  being  inserted  on  the  connection  as  b<  fore. 
With  the  T-piece  closed  fill  the  tuoe  with  water.  Then,  holding  up  the 
wide  end  of  the  tube,  the  tip  of  the  finger  is  put  in  so  as  just  to  close 
the  tube.  The  T-piece  is  then  raised  and  opened,  and  the  finger  pushed 
in  as  far  as  it  will  go.  The  collar  must  fit  the  finger  so  as  to  form  a 
watertight  joint.  Now  get  the  proper  pressure  in  the  tambour  by 
blowing  into  the  T-piece,  and  close  the  clamp.  A  time-tracing  can  l>e 
taken  as  before. 

22.  Pulse-Rate. — (i)  Count  the  radial  pulse  for  a  minute  in  the 
sitting,  supine,  and  standing  positions.  Use  a  stop-watch,  setting  it 
off  on  a  pulse-beat  and  counting  the  next  beat  as  one.  Make  three 
observations  in  each  position. 

(2)  Count  the  pulse  in  a  person  sitting  at  rest,  and  then  again  in  the 
sitting  position  immediately  after  active  muscular  exertion.  Note  how 
long  it  takes  before  the  pulse-rate  comes  back  to  normal. 

(3)  Count  the  pulse  in  a  person  sitting  at  rest.  Repeat  the  observa- 
tion while  water  is  being  slowly  sipped,  and  note  any  change. 

(4)  With  one  hand  over  the  thorax  of  a  rabbit,  count  its  pulse.  Then 
notice  the  effect  (a)  of  suddenly  closing  its  nostrils,  [b)  of  bringing  a 
small  piece  of  cotton-wool  sprinkled  with  ammonia  or  chloroform  in 
front  of  the  no.se  {reflex  inhibition  of  the  heart). 

23.  Blood-Pressure  Tracing. — (a)  Put  a  dog  under  morphine  (p.  63). 
Sot  up  an  induction  machine  arranged  for  an  interrupted  current 
(Fig.  93,  p.  200).  Fill  the  U-shaped  manometer  tube  lif  this  has 
not  already  been  done)  with  clean  mercury-  to  the  height  of  10  to 
12  cm.  in  each  limb.  If  the  float  tends  to  stick,  half  an  inch  of  oil 
may  be  put  above  the  mercury-  in  the  distal  (straight)  limb  before 
putting  in  the  float.     But  where  the  mercury  is  clean  and  dr^-,  and  the 

•  Closing  the  fist  causes  a  tall  in  the  curve — i.e..  a  diminution  in  the  volume 
ot  the  arm.     On  opening  the  hand,  the  curve  regains  its  level. 


PRACTICAL   EXERCISES  2ii 

size  of  tliL'  tloat  proix^rly  adjusted  to  that  of  the  tube,  this  is  no!  neces- 
sary, and  is  to  L>e  avoided.  Then,  tilting  the  tube  <  arefully,  hll  the 
proximal  limb  (i.e.,  the  limb  which  is  to  be  connected  with  the  blood- 
vessel) with  a  saturated  solution  of  sodium  carbonate  or  a  half-saturated 
solution  of  magnesium  sulphate,  or,  what  is  better  for  most  purposes, 
a  z  per  cent,  solution  of  sodium  citrate.  This  is  easily  done  by  means 
of  a  pipette  furnished  with  a  long  point.  Now  attach  a  .strong  rubber 
tube  to  the  proximal  end  of  the  manometer,  and  fill  it  also  with  the 
solution.  All  air  must  be  got  out  of  the  manometer  and  its  connecting- 
tube.  Raise  the  end  of  the  rubber  tube  and  blow  into  it,  so  as  to  cause 
a  difference  of  about  lo  cm.  in  the  height  of  the  mercury  in  the  two 
limbs  of  the  manometer,  and,  without  releasing  the  pressure,  clamp  the 
tube  with  a  pinchcock  or  screw  clamp  (Fig.  4   ,  p.  1 10). 

Now  smoke  a  druni,  and  arrange  the  writing-point  of  the  manometer- 
float  so  that  it  will  write  on  it.  Suspend  a  small  weight  by  a  piece  of 
silk  thread  from  a  support  attached  to  the  stand  of  the  drum,  so  that 
it  hangs  down  outside  of  the  writing-po-nt  of  the  manometer-float  and 
always  keeps  it  in  contact  with  the  smoked  surface  without  undue 
friction.  Or  a  piece  of  glass  rod  drawn  out  to  a  fine  thread  in  the 
blowpipe  flame  answers  ver^'  well.  Below  the  writing-point  of  the 
float,  and  in  the  same  vertical  line  with  it,  adjust  the  writing-point 
of  a  time-marker  beating  seconds  (Fig.  88,  p.  193). 

Next  fasten  the  animal  on  a  holder,  back  down.  Give  ether  and 
insert  a  tracheal  cannula  (p.  202).  (The  tracheal  cannula  is  not  abso- 
lutely required  for  the  experiment,  but  it  is  convenient,  as  the  animal 
is  more  under  control,  and  artificial  respiration  can  be  begun  at  any 
moment,  should  this  be  necessary-.)  Insert  a  glass  cannula,  armed 
with  a  short  piece  of  rubber  tubing,  into  the  central  (cardiac)  end  of 
the  carotid  artery  (p.  63).  Leaving  the  bulldog  forceps  on  the  arterv', 
fill  the  cannula  and  tube  with  the  sodium  citrate  or  one  of  the  other 
solutions.  Slip  the  rubber  tube  over  a  short  glass  connecting-tube.  Fill 
this  also  with  the  solution,  and  connect  it  with  the  manometer-tube, 
seeing  that  both  are  quite  full  of  liquid,  so  that  no  air  may  be  enclosed. 

Where  a  permanent  working  place  is  provided  for  blood-pressure 
experiments  it  is  convenient  to  connect  the  cannula  and  manometer 
with  a  pressure-bottle  containing  the  sodium  citrate  solution,  and  to 
use  a  three-way  cannula  for  the  bloodvessels  (Fig.  103).  The  cannula 
has  a  bulbous  enlargement,  which  hinders  clotting.  The  end  of  the 
cannula  is  connected  with  the  tube  from  the  pressure-bottle,  which  is 
closed  by  a  clip,  and  the  side-tube  is  connected  with  one  limb,  E,  of 
the  manometer  showm  in  Fig.  104.  E  is  itself  provided  with  a  side- 
tube,  F,  armed  with  a  short  piece  of  rubber  tubing.  The  cannula  does 
not  require  to  be  fiJled  with  liquid  before  being  inserted  into  the  aiter^-. 
By  opening  F  and  releasing  the  clip  on  the  tube  from  the  pressure- 
bottle  the  cannula  and  the  tube  connecting  it  with  the  manometer  can 
be  filled,  and  any  blood-clots  can  be  easily  washed  out  in  the  course  of 
an  experiment.  Before  the  bulldog  forceps  is  taken  off  the  artery  to 
obtain  a  blood-pressure  tracing,  F  must  be  closed,  and  the  clip  on"  the 
tube  from  the  pressure-bottle  opened.  The  bottle  is  attached  to  a 
strong  cord  passing  over  a  pulley,  by  which  it  is  raised  to  a  height 
sufficient  to  balance  approximately  the  pressure  in  the  artery.  The 
tube  to  the  pressure-bottle  is  then  clipped.  If  no  manometer  with 
side-tube  is  available,  a  T-piece  can  be  inserted  in  the  connection 
between  the  cannula  and  the  manometer,  and  the  cannula  can  be 
washed  out  through  this. 

Now  take  the  bulldog  forceps  oft  the  artery-,  and  allow  the  drum  to 
revolve  at  slow  speed.     The  writing-point  of  the  manometer-float  will 


THE  CIRCULATION  Oh   THE  BLOOD  ASI>  LYMPH 


trace  a  (  uvvc  showing  an  ckvalion    for   ta-.h    heart-beat,  and 
waves  due  to  the  movements  of  respiration. 

(6)  lst)late  the  vago-synipathetic  nerve  D 
in  the  neck.  Lig.iture  doubly,  and  cut 
between  the  ligatures.  Stimulate  the  peri- 
pheral (lower)  end ;  the  heart  will  be  slowed 
or  stopped,  and  the  blood-pressure  will  fall. 
Stimulate  the  central  (upper)  end;  there 
may  bo  inhibition  of  the  heart  or  accelera- 
tion, and  the  pressure  may  fall  or  ri.se 
(p.  170). 

(c)  Expose  and  di\ide  the  other  vago- 
sympathetic while  a  tracing  is  being  taken. 

\gain  stimulate  the  central  end  of  the 
nerve  and  observe  whether  there  is  any 
effect. 

(d)  Expose  the  sciatic  nerve  in  one  leg, 
as  follows :  The  leg  having  been  loosened 
from  the  holder,  the  foot  is  seized  by  one 
hand  and  lifted  straight  up,  so  as  to  put 


longci 


Thrce-wav  Cannula. 


the  skin  of  the  thigh  on  the  stretch.  An 
incision  is  now  made  in  the  middle  line  on 
the  posterior  aspect  of  the  thigh,  through 
the  skin  and  subcutaneous  tissue.  The 
muscles  are  separated  in  the  line  of  the 
incision  with  the  fingers,  and  the  sciatic 
nerve  comes  into  \iew  lying  deeply  be- 
tween them.  Place  a  double  ligature  on  it, 
and  divide  between  the  hgatures.  Stimu- 
late the  upper  (central  end);  the  blood- 
pressure  proljably  rises,  and  the  heart  may 
be  accelerated.  Stimulate  the  peripheral 
end  of  the  nerve ;  there  is  little  change  in 
the  blood-pressure  and  none  in  the  rate  of 
the  heart. 

{e)  Note,  incidentally,  that  stimulation 
of  the  central  end  of  the  sciatic  or  the  upper 


I'JK-  i"J4-  —  Manometer  with 
Side-tube  (Guthrie).  A, float; 
B,  collar  through  which  the 
wire  C  of  the  float  moves;  D, 
vertical  wire  fixed  to  mano- 
meter-holder, which  keeps  the 
writing-point  on  the  drum; 
E,  limb  of  manometer  con- 
nected with  cannula,  with  its 
side-piece,  F. 


icephaUc)    end   of   the   vago-sympathctic 

mav  cause  increase  in  the  rate  and  depth  of  the  respiratory  movements^ 

Dilatation  of  the  pupil  is  also  caused  by  stimulation  of  the  upper  end  ol 


PRACTICAL  EXERCISES 


axj 


the  vago-sym pathetic  through  the  sympathetic  (pupillo-dilator)  fibres 
that  supply  the  iris. 

(/)  Again  stimulate  the  peripheral  end  of  one  vagus,  or  of  both  at 
the  same  time,  wliile  a  tracing  is  being  taken,  and  see  how  long  it  is 
possible  to  keep  the  heart  from  beating.  Sometimes,  but  rarely  in  the 
dog.  inhibition  can  be  kept  up  so  long  that  the  animal  dies. 

[g)  Close  the  tracheal  cannula  so  that  air  can  no  longer  enter  the 
lungs.  In  a  very  short  time  the  blood-pressure  curve  begins  to  rise 
(rise  of  asphyxia).  After  some  minutes  the  pressure  falls,  and  finally, 
when  the  circulation  has  stopped  completely  and  the  pressure  has 
become  equalized  throughout  the  whole  vascular  system,  a  residual 
pressure  of  only  a  few  mm.  (usually  about  lo  mm.  Hg)  is  indicated. 
In  order  to-'get  the  true  zero  pressure,  disconnect  the  arterial  cannula 


oti-m'-ilbiion-  of ' 

c ent ral.  end  stopped 


Peripheral  er>ci  yrf' 


-,v/^^ 


e.  ■n_ol 
.SiMTnu.lcited 


Fig.  105. — Blood- Pi essuxe  Tracing  from  a  Dog:  Stimulation  ot  Central  and  Peripheral 
Ends  of  Vagus.  The  other  vagus  was  intact.  Stimulation  of  the  peripheral  end 
caused  stoppage  of  the  heart  and  a  marked  fall  of  pressure.  Stimulation  of  the 
central  end  produced  a  great  rise  of  pressure,  with,  perhaps,  a  slight  acceleration 
of  the  heart. 


from  the  manometer,  and  allow  the  writing-point  to  trace  a  horizontal 
straight  line  (line  of  zero  pressure)  on  the  drum  (Figs.  84  and  85). 

24.  Estimation  of  the  Arterial  Blood-Pressure  in  Man. — Use  the  Riva- 
Rocci  apparatus,  as  described  on  p.  113.  Beghi  with  the  subject  in  the 
sitting  position.  The  observer's  left  hand  maj-  be  used  for  palpating 
the  pulse,  and  the  right  for  working  the  bulb.  Employ  the  ausculta- 
tory method  as  well  as  palpation,  and  determine  the  systohc  and  dias- 
tolic pressures.  Repeat  the  observations  with  the  person  standing  up 
and  lying  down.  Investigate  the  effect  of  muscular  exercise  on  the 
blood-pressure. 

25.  The  Influence  of  the  Position  of  the  Body  on  the  Blood-Pressure. 
— Inject  into  the  rectum  of  a  dog  3  to  4  grm.  of  chloral  hydrate  dis- 
solved in  a  little  water.     See  chat  it  does  not  run  out  again  immediately 


214  THn  CIRCULATION  OF  THE  BLOOD  AND  LYMTII 

after  injection.  In  ten  minutes  anicbthclizc  the  animal  fully  with  a 
mixture  of  equal  parts  of  alcohol,  chloroform,  and  ether  (one  of  the 
so-called  A.C.1£.  mixtures),  or  with  chloroform,  and  tic  it  very  securely, 
back  downward,  on  a  board,  which  can  be  rotated  around  a  liorizontal 
axis,  corresponding  in  position  to  the  point  at  which  the  cannula  is  to 
be  inserted.*  Set  up  a  drum  and  manometer  as  in  23  (p.  2  10),  but  with 
a  rubber  connecting-tube  of  such  length  as  will  allow  free  rotation  of 
the  board.  Put  a  cannula  in  the  trachea.  Insert  a  cannula  into  the 
central  end  of  the  carotid  artery  at  a  point  immediately  above  the  axis 
of  rotation  of  the  board,  and  connect  it  with  the  manometer. 

(a)  Take  a  blood-pressure  tracing  with  the  board  horizontal. 

(b)  Whilst  the  tracing  is  being  taken,  rotate  the  board  so  that  the 
position  of  the  animal  becomes  vertical,  with  the  feet  down.  Mark 
on  the  tracing  the  moment  when  the  change  of  position  takes  place. 
The  pressure  falls.  Replace  the  dog  in  the  horizontal  position.  The 
manometer  regains  its  former  level.  Now  rotate  the  board,  till  the 
animal  is  again  vertical,  but  with  feet  up  and  head  down,  and  observe 
tlie  effect  on  the  blood-pressure.  The  respiratory  variations  in  the 
prer^sure  are  usually  greater  with  feet  down  than  with  head  down. 
Notice  in  both  cases  whether  there  is  any  change  in  the  rate  of  the  heart. 

(c)  Take  the  board  off  the  stands,  lay  it  on  a  table,  expose  the  femoral 
artery,  and  insert  a  cannula  into  it.  Shift  the  axis  so  that  it  now  lies 
below  this  cannula.  Replace  the  board  on  the  stands,  and  repeat  (a) 
and  (6).  The  fall  of  pressure  will  now  take  place  in  the  head-down 
position.!  In  the  feet-down  position  (with  the  cannula  in  the  femoral 
artery)  a  rise  of  pressure  in  general  takes  place.  But  sometimes  this 
is  very  small,  and  lasts  only  a  few  seconds,  being  succeeded  by  a  fall, 
during  which  the  heart-beats  on  the  tracing  are  much  weaker  than 
before,  since  enough  blood  is  not  reaching  the  heart  to  enable  it  to 
maintain  the  pressure.  In  the  feet-down  position  see  whether  the 
corneal  reflex  can  be  got.  If  not,  as  is  likely,  turn  the  animal  into  the 
head-down  position.  The  reflex  may  now  soon  be  obtained,  and  it 
may  again  disappear  on  putting  the  animal  in  the  feet-down  position. 
If  the  chloroform  anaesthesia  is  light  the  reflex  may  not  be  abolished 
in  the  feet-down  position,  although  .strong  respiratory  movements  may 
occur,  owing  to  an;cniia  of  tlie  medulla  oblongata. 

26.  Effects  of  Haemorrhage  and  Transfusion  on  the  Blood-Pressure. 
— Anaesthetize  a  dog  with  morphine  and  ether,  and  insert  a  cannula 
into  the  trachea.  Put  a  cannula  into  the  central  end  of  the  carotid 
artery  and  another  into  the  central  end  of  the  femoral  artery.  Then 
insert  a  cannula,  which  should  have  a  piece  of  indiarubber  tubing  2  to 
3  inches  in  length  on  its  w-ide  end,  into  the  central  end  of  the  femoral 
vein  on  the  opposite  side.     In  doing  this  more  care  is  necessary  than 

*  A  simple  arrangement  for  this  purpose  is  a  board  with  a  number  of  staples 
fastened  in  pairs  into  its  lower  surface,  so  that  an  iron  rod  can  be  pushed 
through  any  pair,  and  form  a  horizontal  axis  at  right  angles  to  the  length  of 
the  board.  The  dog  having  been  tied  down,  the  rod  is  pushed  iluough  the 
pair  of  staples  corresponding  to  the  position  of  the  cannula  in  the  artery  that 
is  to  be  connected  with  the  manometer.  The  projecting  ends  of  the  rod  rest 
in  two  ordinary  clamp-holders,  fastened  at  a  convenient  height  on  two  strong 
stands,  whose  bases  are  clamped  to  tlic  end  of  a  table.  The  other  end  of  the 
board  is  supported  by  a  jiiece  of  wood  that  rests  on  the  floor,  and  can  be  re- 
moved when  the  board  is  to  be  rotated. 

•f  In  16  dogs  the  fall  of  pressure  in  the  carotid  in  the  feet-down  position 
varied  from  12  to  luo  mm.  of  mercury;  average  fall,  44-4  mm.  In  12  out  of 
the  i6  animals  the  rise  of  pressure  in  the  head-down  position  varied  from 
2  to  36  mm. ;  in  i  there  was  no  change;  in  3  there  was  a  fall  of  5  to  24  mm. 


PRACTICAL  EXERClSliS  215 

ill  putting  a  ciinnuhi  into  an  artery.  Feel  for  the  femoral  artery,  cut 
down  over  it,  and  with  forceps  or  a  blunt  needle  separate  the  femoral 
vein  from  it  for  about  an  inch.  Pass  two  ligatures  under  the  vein,  and 
tic  a  loose  loop  on  each.  Put  a  pair  of  bulldog  forceps  on  the  vein 
between  the  ligatures  and  the  heart.  Now  tic  the  lower  (distal)  liga- 
ture, and  cut  one  end  short.  The  piece  of  vein  between  it  and  the 
bulldog  forceps  is  thus  distended  with  blood,  and  this  facilitates  the 
next  step.  With  fine-pointed  scissors  make  a  snip  in  the  wall  of  the 
vein.  The  cannula  is  now  pushed  through  the  slit  in  the  vein,  and 
the  upper  ligature  tied  firmly  round  its  neck.  By  the  aid  of  a  pipette, 
made  by  drawing  a  piece  of  glass  tubing  out  to  a  long  point,  the  cannula 
and  rubber  tube  arc  then  completely  filled  with  09  per  cent,  salt 
solution.  Be  sure  to  pass  the  point  of  the  piprtte  right  down  to  the 
point  of  the  cannula,  so  as  to  dislodge  any  bubble  of  air  that  may  tend 
to  cling  there.  Then,  holding  up  the  open  end  of  the  rubber  tube, 
close  it,  without  allowing  any  air  to  enter,  by  means  of  a  screw  clamp 
or  bulldog  forceps,  or  a  small  piece  of  glass  rod.  Connect  the  cannula 
in  the  carotid  with  a  manometer,  arranged  to  write  on  a  drum  as  in 
experiment  23  (p.  iio).  Take  the  bulldog  off  the  carotid,  and  measure 
the  difteronce  in  the  level  of  the  mercury  in  the  two  limbs  of  the  man- 
ometer with  a  millimetre  scale. 

(i)  («)  Wliilc  a  tracing  is  being  taken,  draw  off  about  10  c.c.  of  blood 
from  the  femoral  artery,  and  observe  whether  there  is  any  effect  on 
the  tracing.  Mark  on  the  tracing  the  moment  when  the  removal  of 
the  blood  begins  and  ends. 

(6)  Repeat  (a),  but  run  off  about  100  c.c*  of  blood,  and  let  this  be 
immediately  delibrinatcd.  Then  draw  off  portions  of  100  c.c*  at  short 
intervals  until  a  distinct  fall  of  blood-pressure  has  been  produced.  All 
the  samples  of  blood  should  be  defibrinatcd  and  strained  through 
cheese-cloth. 

(2)  (a)  Now,  while  a  tracing  is  being  taken,  inject  the  whole  of  the 
defibrinatcd  blood  slowly  through  the  cannula  in  the  femoral  vein  by 
means  of  a  funnel  supported  by  a  stand  at  such  a  height  that  the  blood 
runs  in  easily.  A  pinchcock  should  be  put  on  the  tube  connecting  the 
funnel  and  the  cannula,  and  this  should  be  closed  before  the  funnel  is 
quite  empty,  so  as  to  obviate  any  risk  of  air  getting  into  the  vein .  Of 
course,  the  cannula  and  connecting-tubes  must  all  be  freed  from  air 
before  injection  is  begun.  Again  measure  the  difference  in  the  level 
of  the  mercury  and  compare  the  pressure  with  that  observed  before 
the  first  haemorrhage. 

(6)  Inject  into  the  vein,  while  a  tracing  is  being  obtained,  about 
100  c.c*  of  o'9  per  cent,  salt  solution  heated  to  40°  C,  and  go  on 
injecting  portions  of  100  c.c.  until  a  distinct  rise  of  pressure  has  taken 
place,  keeping  a  record  of  the  total  amount  injected,  and  marking  the 
time  of  each  injection  on  the  curve. 

(c)  After  an  interval  of  thirty  minutes,  again  measure  the  height  of 
the  mercury  in  the  manometer.  Then  bleed  the  dog  to  death  while  a 
tracing  is  being  recorded. 

27.  The  Influence  of  Proteoses  (and  Peptones)  on  the  Blood-Pressure. 
— Set  up  the  apparatus  for  taking  a  blood-pressure  tracing  as  in  experi- 
ment 23  (p.  216),  but  omit  the  induction-coil.  Weigh  a  dog.  Weigh 
out  a  quantity  of  Witte's  peptone  equivalent  to  05  grm.  for  every  kilo 
of  body-weight.  Dissolve  the  peptone  in  about  ten  times  its  weight 
of-  o"9  per  cent,  salt  solution.  Anaesthetize  the  dog  with  morphine  and 
ether  or  A.C.E.  mixture.  Insert  a  cannula  into  the  trachea.  Put 
cannulae  into  the  central  end  of  one  carotid  and  of  one  femoral  vein 

*  200  c.c.  for  a  large  dog. 


2I(. 


Tin-:  ctncui.ATioN  of  the  blood  and  lymph 


(p.  214).  Connect  the  carotid  with  the  manometer,  and  tlic  femoral 
vein  with  a  bnrette  or  large  syringe  containing  the  peptone  solution. 
Take  care  that  the  connecting-tube  and  cannula  are  free  from  air. 
Now  commence  to  take  a  blood-pressure  tracing  and  while  it  is  going 
on  inject  the  peptone  solution.  Tlie  ]iressure  fails  owing  largely  to 
a  dilatation  of  the  small  arteries  through  the  direct  action  of  the  pep- 
tone on  llicir  nius(  idartissur  or  on  1 1ircndiiiqs  of  the  vaso-motor  nerves.* 
28.  Effect  of  Suprarenal  Extract  on  the  Blood-Pressure. — Make  the 
arrangements  for  a  blood-prcssurc  tracing  from  a  dog  as  in  23  (p.  210). 
Put  a  ramiula  in  the  carotid  and  another  in  the  femoral  vein  or  one  of 
its  branches  (p.  214).  Expose  both  vagi  in  the  neck,  and  pass  threads 
loosely  under  them.  Connect  the  carotid  with  the  manometer  and 
take  a  tracing.  Then,  while  the  tracing  is  continued,  inject  slowly 
into  the  femoral  vein  an  amount  of  watery  extract  corresponding  to 
about  o'2  grm.  of  suprarenal,  or,  wdiat  is  more  convenient,  a  few  c.c. 
of  a  solution  of  adrenalin  chloride  of  the  strength  of  i  to  50,000  in 
o'9  per  cent.'^  sodium'  chloride  solution,  the  dose  depending,  of  course, 
on   the  size  of  the  animal.     The  blood-pressure  risesf  owing  to  con- 


.1  PeJDtone'  irijej''.  ri  . 


.^t'^ 


..UAI^'^*^'' 


Fig.   106. — Effect  of  Injection  of  l^eptone  on  the  Blood- Pressure  in  a  Hog. 
(To  be  read  from  right  to  left.) 

striction  of  the  arterioles  by  direct  excitation  of  the  junction  between 
their  vaso-constrictor  nerves  pud  their  muscular  tissue.  The  heart  is 
slowed,  but  its  beat  is  strengthened.  At  once  cut  both  vagi  while  a 
tracing  is  being  taken;  the  blood-pressure  ri.ses  still  more  (p.  655). 
The  rise  of  pressure  is  sometimes  so  great  that  to  prevent  the  mercury 
from  being  forced  out  of  the  manometer  the  tube  must  be  clipped. 
The  rise  is  not  long  maintained,  but  a  second  injection  causes  a  renewed 
increase  of  pressure. 

29.  Action  of  Epinephrin  (Adrenalin)  on  Artery  Rings. — The  experi- 
ment (8)  described  on  p.  (>(>  in  coimeclion  with  the  constrictor  action 
of  serum  may  equally  well  be  performed  here. 

*  In  12  (logs  the  blood-pressure  always  fell,  the  amount  of  the  fall  varying 
from  81  to  21  mm.  of  mercury  (average,  60  mm.).  It  sometimes  returned  to 
normal  in  twenty  to  thirty  minutes,  but  usually  required  a  longer  time.  In 
some  dogs,  after  the  injection  of  the  whole  of  this  amount  of  peptone,  death 
occurs  before  there  has  been  any  considerable  recovery  of  the  pressure. 

f  The  amount  of  the  initial  rise  of  pressure  is  very  variable,  since  tlie  slow- 
ing of  the  heart  tends  to  diminish  the  pressure,  while  the  constriction  of  the 
arterioles  tends  to  increase  it.  Thus,  in  one  experiment  the  increase  of  pres- 
sure on  injection  of  the  extract  was  only  6  mm.  of  mercury,  while  in  another 
it  was  36  mm.  On  section  of  the  vagi  in  this  second  experiment,  there  was 
an  additional  rise  of  64  nun.,  and  after  a  second  injection  a  further  rise  oi 
70  mm.,  making  an  increase  of  190  mm.  in  all  above  the  original  pressure. 


PR  ACT  IC  A  I.  HXhliClSES 


2J7 


30.  Determination  of  the  Circulation-Time. —  (kj  bi  yiu  uith  an  arii- 
ticial  sclicnu-  (I'ig.  107).  l'"ill  the  syringe  with  a  (r2  per  cent,  sohitioa 
of  methylene  blue.  Allow  the  water  to  flow  from  the  bottle  by  loosen- 
ing the  clamp.  Inject  a  definite  quantity  of  the  methylene-bluc  solu- 
tion, and  with  a  stop-watch  observe  how  long  it  takes  to  pass  from 
■the  point  of  injection  to  the  end  of  the  glass  tube  filled  with  beads 
Make  ten  readings  of  this  kind,  and  take  the  mean.  Then  raise  the 
bottle  so  as  to  increase  the  ra  c  of  flow  of  the  water,  and  repeat  the 
observations.     The  '  circulation-lime  '  will  be  found  to  be  diminished. 

This  corresponds  to  an  increase  of 
blood- pressure  due  to  increased  act 
tivity  of  the  heart,  without  change 
in  the  calibre  of  the  bloodvessels. 
Next,  leaving  the  bottle  in  its  present 
position,  diminish  the  outflow  by 
tightening  (he  clamp;  the  circulation- 
time  will  be  increased.  This  corre^- 
})onds  to  an  increase  of  blood-pressure 
due  to  diminution  in  the  calibre  of 
the  small  arteries. 

(b)   Fill    the    syringe*    with    methy- 
lene-blue    solution    (o'2    per   cent,    in 


Fig.  107. — Artificial  Scheme  tj  illustrate  a  Method  of  measuring  the  Circulation- 
Time.  B,  bottle  Containing  water,  the  rate  of  outflow  of  which  is  regulated  by 
screw-clanip  a;  S,  syringe  filled  with  methyleue-blue  solution,  connected  with 
T-piece  A;  M,  beaker  containing  methylene-blue  solution;  b,  c,  screw-clamps; 
C,  T-piece,  inserted  in  the  course  of  the  flexible  tube  E,  and  connected  with  the 
glass  tube  T,  which  is  filled  with  beads;  I',  outflow  tube.  The  clamp  c  having 
been  closed  and  b  opened,  the  syringe  is  filled  with  the  methylene-blue  solution; 
b  is  then  closed,  c  opened,  and  a  definite  quantity  of  the  solution  injected  into  the 
system.  The  time  from  the  beginning  of  injection  till  the  appearance  of  the  blue 
at  G  is  measured  with  the  stop-watch. 

0-9  per  cent,  salt  solution),  as  in  [a).  Keep  the  solution  warmed  to 
40^  C.  by  immersing  the  small  beaker  containing  it  in  a  water-bath,  or 
heating  it  over  a  Bunsen  with  a  small  flame.  Weigh  a  rabbit  or  cat. 
In  the  case  of  the  rabbit,  inject  |  grm.  chloral  hydrate  into  the  rectum, 
and  later  on  give  ether  if  nece"ssar3\  If  a  cat,  give  ether  alone,  or 
urethane  (1-5  grm.  per  kilo  by  stomach  tube  1  to  2  hours  before). 
Fasten  it  on  a  holder,  back  downwards  (Fig.  Or,  p.  136).  Cover  it  with 
a  towel  to  keep  it  warm.  Clip  off  the  hair  on  the  front  of  the  neck,  and 
make  an  incision  i  J    inches  long  in  the  middle  line,  beginning  a  little 

*  A  burette,  slo))ed  so  as  to  make  a  small  angle  with  the  horizontal,  may 
be  substituted  for  the  syringe.  The  burette  is  supported  on  a  stand  at  such 
a  height  (say  10-15  cm.  above  the  level  of  the  cannula)  that  the  methylene- 
blue  solution  runs  without  great  force  into  the  jugular.  The  danger  of  pro- 
ducing an  abnormal  result  by  suddenly  raising  the  pressure  in  the  right  side 
of  the  heart  is  thus  avoided. 


2iS  THE  CIRCULATION  OF  THli  BLUOlJ  ASU  LYMPH 

way  below  the  cricoid  cartilage.  Relk-ct  the  skin  and  isolate  the 
external  jugular  vein,  which  is  quite  superficial.  Carefully  separate 
about  f  inch  of  the  vein  from  the  surrounding  tissue,  and  pass  two 
ligatures  luidcr  it,  but  do  not  tic  thcni.  Compress  the  vein  with  a  pair 
of  bulldog  forceps  between  the  heart  and  the  ligatures.  Now  tie  the 
uppermost  of  the  two  ligatures  (that  next  the  head),  but  only  put  a 
single  loose  loop  on  the  other.  The  piece  of  vein  between  the  upper 
ligature  and  the  bulldog  is  now  distended  with  blood.  With  fine- 
pointed  scissors  make  a  small  slit  in  the  vein,  taking  great  care  not  to 
divide  it  completely,  insert  the  cannula,  and  tie  the  loose  ligature  firmly 
over  its  neck.  Fill  the  cannula  and  the  small  piece  of  rubber  tubing 
attached  to  it  with  09  per  cent,  salt  solution  by  means  of  a  pipette 
with  a  long  point.  Expose  the  carotid  on  the  other  side,  isolate  it  tor 
J  inch,  clear  it  carefully  from  its  sheath,  slip  under  it  a  strip  of  thin 
sheet  indiarubber,  and  between  this  and  the  artery  a  little  piece  of  white 
glazed  paper.  Connect  the  cannula  in  the  jugular  with  the  T-piece 
attached  to  the  syringe.  Care  must  be  taken  that  no  air  remains  in 
the  cannula  or  its  connecting-tube,  as  a  rabbit  not  unfrequcntly  dies 
instantaneously  when  a  bubble  of  air  is  injected  into  the  right  heart, 
although  a  considerable  quantity  of  air  can  generally  be  injected  into 
the  jugular  of  a  dog  without  killing  it. 

Now  take  off  the  bulldog  from  the  vein,  and  make  a  series  of  observa- 
tions on  the  pulmonary  circulation-time.  The  animal  must  be  so 
placed  that  a  good  light  falls  on  the  carotid.  If  necessary,  the  light 
of  a  gas-flame  may  be  concentrated  on  it  by  a  lens.  The  student  holds 
the  stop-watch  in  one  hand,  and  injects  a  measured  quantity  of  the 
methylene-blue  solution  with  the  other.  Uniformity  in  the  quantity 
injected  is  secured  by  fastening  on  the  piston  of  the  syringe  a  screv/- 
clamp,  which  stops  the  piston  at  the  desired  point.  The  observation 
consists  in  setting  off  the  watch  at  the  moment  when  injection  begins 
and  stopping  it  when  the  blue  appears  in  the  carotid.  After  each 
injection  the  screw-clamp  or  pinchcock  on  the  tube  connected  with  the 
cannula  must  be  tightened,  the  other  opened,  and  the  syringe  refilled. 
Great  care  must  be  taken  never  to  open  the  two  clamps  at  the  same 
time,  as  in  that  case  blood  may  regurgitate  through  the  jugular  and 
fill  the  syringe,  or  methylene  blue  may  be  sucked  into  the  circulation. 
As  many  observations  as  possible  should  be  taken,  and  the  mean 
determined.  The  circulation-time  observed  is  approximately  that  of 
the  lesser  circulation,  the  time  taken  by  the  blood  to  pass  from  the 
left  ventricle  to  the  carotid  being  negligible  for  the  purposes  of  the 
student. 

The  specific  gravity  of  the  blood  may  also  be  tested  at  the  beginning 
and  end  of  the  experiment  by  Hammcrschlag's  method  (p.  (^2).  If 
a  large  number  of  injections  have  been  made  in  quick  succession,  the 
specific  gra\ity  will  be  less  than  normal ;  but  if  a  considerable  interval 
has  been  allowed  to  elapse  after  the  last  injection,  little  or  no  differ- 
ence may  be  found,  as  the  surplus  liquid  readily  passes  out  of  the 
bloodvessels. 

Necropsy. — Obserxe  particularly  the  state  of  the  lungs,  whether  the 
bladder  is  distended  or  not,  and  whether  any  of  the  serous  cavities  or 
the  intestines  contain  much  liquid;  so  as  to  determine,  if  possible,  by 
what  channel  the  water  injected  into  the  blood  may  have  been  elimin- 
ated. Study  the  distribution  of  the  methylene  blue  in  such  organ?  as 
the  kidneys  and  the  muscles  immediately  after  death,  and  notice  that 
the  blue  colour  becomes  more  pronounced  after  exposure  for  a  time  to 
the  air.  Make  a  longitudinal  section  through  a  kidn?y,  and  observe 
that  the  pigment  is  found  especially  in  the  cortex  and  around  the 


PRACTICAI.   EXERi  ISES 


219 


pelvis  at  the  apices  of  the  jjyrainids,  or  it  may  be  only  in  the  cortex. 
The  urine  is  greenish.  If  some  methylene  blue  has  been  injected  after 
the  heart  ceased  to  beat,  the  lilood vessels,  particularly  in  the  mesentery, 
may  be  beautifully  maj^ped  out  by  the  pigment.  This  is  not  the 
case  if  the  last  injection  took  place  before  death,  since  the  methylene 
blue  is  rapidly  reduced  by  living  tissues  to  a  colourless  substance, 
Icuco-methylene  blue. 

31.  Measurement  of  the  Blood-Flow  in  the  Hands. — Arrange  the 
calorimeters  as  in  Fig.  knS.  The  thermometers  in  the  calorimeters 
should  be  graduated  in  tenths  of  a  degree,  so  that  by  means  of  the  small 
lenses  or  '  readers  '  which  slide  on  the  stems  hundredths  of  a  degree 
can  be  estimated.  Where  it  is  desirable  that  a  number  of  students 
should  make  observations  in  as  short  a  time  as  possible,  one  calorimeter 
can  be  allotted  to  each  subject,  the  other  hand  being  kept  in  the  pocket 
or  covered  with  a  glove  if  the  room  is  cool,  so  as  to  avoid  rellex  vaso- 
motor interference.  A  felt  collar  is  chosen  which  fits  the  wrist  closely. 
A  liorizontal  pencil-mark  is  made  at  the  lower  edge  of  the  styloid 
process  of  the  ulna,  and  another  parallel  mark  at  a  distance  above  this 
slightly  greater  than  the  thickness  of  the  collar.  When  this  second 
mark  is  just  kept  in  view  above  the  collar  with  the  hand  in  the 
calorimeter,  the  first  (lower)  mark  will  be  ju^t  l)eIow  the  level  of  the 
lid.  A  large  bath  holding  20  or  30  litres  or  more  (a  clean  '  garbage  ' 
or  '  offal  '  can  is  suitable)  is  filled  with  water  at  about  32°  C.  The 
exact  temperature  is  not  important,  but  it  should  be  about  the  same 
in  all  measurements  which  are  to  be  compared.  An  ordinary'  ther- 
mometer graduated  in  degrees  is  all  that  is  necessary  for  reading  the 
temperature  of  the  bath.  The  calorimeters  are  now  filled  from  the 
bath.  They  are  conveniently  made  of  such  a  size  that  3  litres  of  water 
and  the  hand  can  be  contained  in  them  without  any  slopping  over 
when  the  water  is  stirred.  Time  is  saved  by  having  a  metal  flask 
which  just  holds  the  quantity  of  water  that  goes  into  each  calorimeter. 
'J'he  orifices  of  the  calorimeters  are  closed  by  felt  discs.  The  subject, 
sitting  in  a  high  chair  placed  between  the  calorimeters,  now  immerses 
his  hands  in  the  bath  to  a  point  between  the  two  marks.  The  fingers 
are  kept  spread.  The  bath  is  occasionally  stirred.  An  ordinary  ther- 
mometer suspended  at  the  back  of  the  chair  gives  the  room  tempera- 
ture. After  ten  minutes  the  hands  are  withdrawn  from  the  bath,  the 
wrists  rapidly  dried  with  a  towel,  the  hands  at  once  introduced  into  the 
calorimeters,  and  the  felt  collars  adjusted  round  the  wrists.  The  sub- 
ject leans  back  comfortably  in  the  chair,  allowing  the  arms  to  hang 
down  without  effort.  The  fingers  are  kept  slightly  spread.  The  ob- 
server sits  on  a  low  seat  behind  the  subject,  and  reads  the  thermometers 
from  time  to  time,  always  after  stirring  the  water  well  with  goose- 
feathers  passing  through  the  stirring-holes  in  the  lid.  The  readings 
can  be  made  at  intervals  of  a  minute,  two  minutes,  or  any  interval 
which  is  convenient.  At  the  end  the  hands  are  quickly  withdrawn, 
the  felt  discs  put  over  the  orifices,  and  the  water  vigorously  stirred  for 
ten  or  fifteen  seconds  before  the  thermometers  are  read.  In  this  way 
any  errors  due  to  imperfect  stirring  or  to  accidental  contact  of  the 
hands  with  the  thermometers  are  eliminated. 

The  volume  of  each  hand  is  now  measured  by  immersing  it  exactly 
to  the  lower  mark  in  water  contained  in  a  glass  douche-can  connected 
by  a  short  rubber  tube  with  a  pipette  furnished  with  a  side-tube  at  its 
lower  end.  The  lowest  graduation  on  the  burette  (50  on  a  50  c.c. 
burette)  is  brought  level  with  the  water  before  the  hand  is  immersed. 
While  the  hand  is  being  held  steadily  and  vertically  in  the  water  by 
an  assistant,  the  level  of  the  water  in  the  burette  is  read  off.     All  that 


220         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

is  necessary  to  get  the  volume  of  the  hand  is  to  pour  water  into  the 
can  from  a  graduated  measure  after  withdrawal  of  the  hand  until  the 
same  level  is  reached.  Or  the  value  of  a  division  of  tlie  burette  can 
be  determined  ouce  for  all.  The  burette  is  simply  used  as  a  transparent 
scale.  Wlien  the  two  hands  are  successively  measured,  the  small 
amount  of  water  removed  by  the  first  is  automatically  restored  by 
dipping  the  second  into  a  separate  vessel  of  water,  and  putting  it  wet 
into  tlie  douche-can.  The  rectal  i  mpcrature  should  now  be  obtained. 
The  temperature  of  the  arterial  blood  entering  the  hand  is  taken  as 
o'5''  C.  below  that  of  the  rectum.  If  only  the  mouth  temperature  can 
be  got,  the  thermometer  should  be  put  in  a  second  time  without  shaking 


Fig.   io8. — Calorimetric  Method  of  measuring  Blood-Flow   in   Hands. 


down  to  see  if  it  rises  any  more.  The  mouth  temperature  is  taken  as 
equal  to  the  arterial  blood  temperature. 

After  thorough  stirring,  the  calorimeter  temperatures  can  now  be 
read  again.  The  two  being  noted,  the  amoimt  of  cooling  of  the  calor- 
imeters can  be  determined.  This  has  to  be  added  to  the  actually 
obser\'ed  rise  of  the  thermometers  during  immersion  of  the  hands. 

Suppose  an  experiment  yielded  the  following  data:  Rise  of  ther- 
mometer in  a  calorimeter  in  twenty  minutes  during  immersion  of  a  hand 
in  it,  io°  C;  temperature  of  calorimeter  at  beginning  of  the  twenty 
minutes.  310°  C. ;  at  end  of  twenty  minutes,  320°  C;  cooling  of  calor- 
imeter in  twenty  minutes,   01°  C;   water  in  calorimeter,   3,000  c.c; 


PRACTICAL  EXERCISES  221 

volume  of  liaml,  450  c.c. ;  rectal  teinpLnitiire,  370°  C. ;  water  e(|uival<.iit 
of  calorimeter,  100  c.c. 

The  water  equivalent  of  the  hand  is  450  x  08*  -  360  c.c. 
The  water  equivalent  of  tlie  calorimeter  is  -  100  c.c. 
Water  ------     3,000  c.c. 


Total  -  .  .  _     3,460  c.c. 

3,460  X  I." I  =  3,806  .small  calories  given  oft  by  the  hand  in  twenty 
minutes. 

Temperature  of  arterial  blood  (36" 5°)  minus  temperature  of  venous 
blood  Gi'o",  the  mean  temperature  of  the  calorimeter)  =^5"o. 

Flow  per  minute  through  hand  =  ^^^ x  — '  =  42-3  grm. 

Flow  per  loo  c.c.  of  hand  per  minute  ^94  grm. 

The  readings  of  the  calorimeter  thermometers  for  the  first  one  or  two 
minutes  may  not  be  usable,  owing  to  disturbance  caused  by  the  intro- 
duction of  the  hands.  As  soon  as  they  begin  to  rise  steadily  and 
imiformly,  the  readings  can  be  utilized  for  the  calculation  of  the  flow. 

32.  Vasomotor  Reflexes. — Begin  as  in  31.  Then,  after  the  hands 
have  been  in  the  calorimeters  for  a  sufficient  period  (say  ten  minutes)  to 
allow  satisfactory  readings  for  the  determination  of  the  blood-flow  to 
be  obtained,  rapidly  transfer  one  hand  to  cold  water  (at  about  8°  C), 
while  the  other  remains  in  the  calorimeter.  Continue  reading  the 
calorimeter  thermometer.  Its  rise  will  be  checked  by  reflex  vaso- 
constriction. If  the  hand  is  kept  for  a  few  minutes  in  the  calorimeter, 
the  reflex  vaso-constriction  of  the  hand  in  the  calorimeter  will  probably 
disappear,  and  the  thermometer  will  rise  faster.  When  a  sufficient 
number  of  readings  have  been  obtained  for  calculating  the  alteration 
in  the  flow,  which  will  usually  be  the  case  in  eight  or  ten  minutes, 
transfer  the  hand  from  the  cold  water  to  warm  water  (at  about  43°  C), 
and  continue  reading  the  calorimeter  thermometer.  There  is  usually 
a  reflex  vaso-constriction  followed  by  vaso-dilatation. 

*  This  factor  is  the  product  of  the  specific  gravity  and  the  specific  heat  of 
the  hand.  The  volume  multiplied  by  the  specific  gravity  gives  the  mass  of 
the  hand,  which  multiplied  by  the  specific  heat,  gives  the  water  equivalent  of 
the  hand . 

t  The  reciprocal  of  the  specific  heat  of  blood  (see  formula,  p.  122). 


CHAPTER  IV 

RESPIRATION 

Respiration  in  its  widest  sense  is  the  sum  total  of  the  processes  by 
which  the  ultimate  elements  of  the  body  gain  the  oxygen  they 
require,  and  get  rid  of  the  carbon  dioxide  they  produce. 

Section  I. — Preliminary  Anatomical  Data. 

Comparative. — In  a  unicellular  organism  no  special  mechanism  of 
respiration  is  needed;  the  oxygen  diffuses  in,  and  the  carbon  dioxide 
diffuses  out,  through  the  general  surface.  The  simple  wants  of  such 
multicellular  animals  as  the  coelenterates,  the  group  to  which  the  sea- 
anemone  belongs,  are  also  supplied  by  diffusion  through  the  ectoderm 
from  and  into  the  surrounding  water,  and  through  the  endodcrm  from 
and  into  the  contents  of  the  body-cavity  and  its  ramifications. 

But  in  animals  of  more  complex  structure  special  arrangements 
become  necessary,  and  respiration  is  divided  into  two  stages:  (i)  Ex- 
ternal respiration,  an  interchange  between  the  air  or  water  and  a  cir- 
culating medium  or  blood  as  it  passes  through  richly  vascular  skin, 
gills,  tracheae,  or  lungs;  and  (2)  internal  respiration,  an  interchange 
between  the  blood,  or  lymph,  and  the  cells. 

Jn  the  lower  kinds  of  worms  respiration  goes  on  solely  through  the 
skin,  under  which  plexuses  of  bloodvessels  often  exist,  but  in  some 
higher  worms  there  are  special  vascular  appendages  that  play  the  part 
of  gills.  The  Crustacea  also  possess  gills,  while  in  the  other  arthropoda 
respiration  is  carried  on  either  by  the  general  surface  of  the  body  (in 
some  low  forms),  or  more  commonly  by  means  of  trachea;,  or  branched 
tubes  surrounded  by  blood  spaces  and  communicating  externally  with 
the  air  and  internally  by  their  finest  twigs  with  the  individual  cells. 
Most  of  the  moUusca  breathe  by  gills,  but  a  few  only  by  the  skin. 

Among  vertebrates  the  fishes  and  larval  amphibians  breathe  by  gills, 
but  most  adult  amphibians  have  lungs.  The  skin,  too,  in  such  animals 
as  the  frog  has  a  very  important  respiratory  function,  more  of  the 
gaseous  exchange  taking  place  through  it  in  some  conditions  than 
through  the  lungs. 

One  small  group  of  fishes,  the  dipnoi,  has  the  peculiarity  of  possessing 
both  gills  and  a  kind  of  lungs,  the  swim-bladder  being  surrounded  with 
a  plexus  of  bloodvessels  and  taking  on  a  respiratory  function. 

In  all  the  higher  vertebrates  the  respiration  is  carried  on  by  lungs; 
the  trifling  amount  of  gaseous  interchange  which  can  possibly  take 
place  through  the  skin  is  not  worth  takiag  into  account.  The  lungs 
arc  to  be  regarded  as  developed  from  outgrowths  of  the  alimentary 
canal,  beginning  near  the  mouth. 

2(23 


j'h'i:r.n/i.\.U\'Y  AW-troMicAf.  data  223 

The  object  oi  all  special  respiratory  arrangements  being,  in  (ho  first 
instance,  to  facilitate  the  gaseous  exchange  Ix'twcen  the  surrounding 
medium  (air  or  water)  and  the  blood,  a  prime  necessity  of  a  respiratt^ry 
organ,  be  it  skin,  gill,  trachea,  or  lung,  is  a  free  supply  of  bi(Jod,  in 
vessels  so  tine  and  thin  that  diffusion  readily  takes  place  into  them 
and  out  of  them.  But  a  free  supply  of  blood  would  be  of  no  avail  if  the 
n'edium  to  which  tlie  blood  ga\c  up  its  carbon  dioxide  and  from  which 
it  drew  its  oxygen  was  not  being  constantly  and  sufficiently  renewed. 

Sometimes  the  natural  currents  of  the  water  or  the  air  are  of  them- 
selves sufficient  to  secure  this  renewal;  in  other  cases,  artificial  currents 
are  set  up  by  cilia,  or  special  bailing  organs,  like  the  scaphognathites 
of  the  lobster.  In  all  the  higher  animals,  active  movements  by  which 
air  or  water  is  brought  into  contact  with  the  respiratory  surfaces,  are 
necessary;  and  it  is  possible  that  such  movements  take  place  even  in 
(he  trachea'  of  insects  and  other  air-breathing  arthropoda.  Fishes,  by 
rhvthmical  swallowing  movements,  take  in  water  through  the  mouth 
anfl  pass  it  over  the  gills  and  out  by  the  gill-slits,  while  the  frog  distends 
its  lungs  by  swallowing  air. 

Physiological  Anatomy  of  the  Respiratory  Apparatus. — In  man  the 
respiratory  apparatus  consists  of  a  tube  (the  trachea)  widened  at  its 
upper  part  into  the  larynx,  which  contains  the  special  mechanism  of 
voice,  and  communicates  through  the  nose  or  mouth  with  the  external 
air.  Below,  the  trachea  divides  dendritically  into  innumerable 
branches,  the  ultimate  divisions  of  which  are  called  bronchioles.  Each 
bronchiole  ends  in  several  openings  or  vestibula,  each  of  which  in  turn 
leads  into  a  dilatation  called  an  atrium.  I-rom  each  atrium  are  given 
off  two,  or  more,  often  funnel-shaped  diverticula,  the  infundibula,  the 
walls  of  which  are  everywhere  pitted  with  recesses  or  alcoves,  called 
alveoli.  The  atria  are  also  lined  with  alveoli.  The  infundibula  (with 
the  atria)  constitute  the  essential  distensible  elements  of  the  lung,  by 
the  alternate  stretching  and  relaxation  of  which  the  respiratory  changes 
in  the  volume  of  the  organ  are  mainly  brought  about.  The  trachea  and 
bronchi  are  strengthened  by  hyaline  cartilage  which  renders  them  rela- 
tively rigid.  But  the  fact  that  the  cartilage  does  not  form  complete 
rings  permits  small  changes  of  calibre  to  take  place. 

In  the  bronchioles,  no  cartilage  is  present,  but  the  circularly-arranged 
muscular  fibres  still  persist,  and  also  form  a  thin  layer  in  the  infundi- 
bula. In  the  air-cells,  or  alveoli,  however,  there  are  no  muscular  fibres. 
Their  walls  consist  essentially  of  a  network  of  elastic  fibres,  continuous 
with  a  similar  layer  in  the  infundibula  and  bronchioles,  and  covered  on 
the  side  next  the  lumen  by  a  single  layer  of  large,  clear  epithelial  scales, 
with  here  and  there  a  few  smaller  and  more  granular  polyhedral  cells. 
From  the  larynx  to  the  bronchioles  the  mucous  membrane  is  ciliated 
on  its  free  surface,  the  cilia  lashing  upwards  so  as  to  move  the  secre- 
tion towards  the  larynx  and  mouth.  In  the  infundibula  the  ciliated 
epithelium  begins  to  disappear,  and  is  absent  from  the  alveoli.  Part 
of  the  nasal  cavity  and  the  upper  part  of  the  pharynx  are  also  lined  with 
ciliated  epithelium.  Mucous  glands  are  present  in  abundance  in  the 
upper  portic  n  ;  of  the  respiratory  passages,  but  disappear  in  the  smaller 
bronchi. 

Blood-Supply  of  the  Lungs. — The  quantity  of  blood  traversing  the 
lungs  bears  no  proportion  to  the  amount  required  for  their  actual 
nourishment.  Small,  however,  as  this  latter  quantity  is,  it  cannot 
apparently  be  derived  from  the  vitiated  blood  of  the  right  ventricle, 
but  is  obtained  directly  from  the  aortic  system  by  the  bronchial  arteries. 
These  are  distributed  with  the  bronchi,  which  they  supply  as  well  as 
the  connective  tissue  of  the  interlobular  septa  running  through  the 


224  RESPIHATIO^J 

substance  of  the  lung,  llif  pleura  lining  it  and  the  walls  of  the  large 
bloodvessels.  Most  of  the  blood  from  the  bronchial  arteries  is  returned 
by  the  bronchial  veins  into  the  systemic  venous  system,  but  some  of  it 
finds  its  way  by  anastomoses  into  the  pulmonary  veins. 

The  branches  of  the  pulmonary  artery  arc  also  distributed  with  the 
bronchi,  and  break  up  into  a  dense  capillary  network  around  the  alveoli. 
From  the  capillaries  veins  arise  which,  gradually  uniting,  form  the  large 
pulmonary  veins  that  pour  their  blood  into  the  left  auricle. 

The  same  quantity  of  blood  must,  on  the  whole,  pass  per  unit  of 
time  through  the  lesser  as  tlirough  the  greater  circulation,  otherwise 
equilibrium  could  not  exist,  and  blood  would  accumulate  either  in  the 
lungs  or  in  the  systemic  vessels.  But  it  does  not  follow  that  at  each 
heart-beat  the  output  of  the  two  ventricles  is  exactly  equal.  If,  indeed, 
the  capacity  of  the  lesser  circulation  were  constant,  the  quantity- 
driven  out  at  one  systole  by  the  right  ventricle  would  be  the  same  as 
that  ejected  at  the  next  by  the  left  ventricle.  But  it  is  known  that 
the  capacity  of  the  pulmonary  vessels  is  altered  by  the  movements 
of  respiration  and  probably  in  other  ways,  so  that  it  is  only  on  the 
average  of  a  number  of  beats  that  the  output  of  the  two  ventricles  can 
be  supposed  equal. 

The  time  required  by  a  given  small  portion  of  blood — e.g.,  by  a  single 
corpuscle — to  complete  the  round  of  the  lesser  circulation,  is,  as  we 
have  seen  (p.  137),  much  less  than  the  average  time  needed  to  complete 
the  systemic  circulation.  In  man  the  ratio  is  probably  about  i  :  5. 
Since  all  the  blood  in  a  vascular  tract  must  pass  out  of  it  in  a  period 
equal  to  the  circulation  time,  the  average  quantity  of  blood  in  the 
lungs  and  right  heart  of  a  man  would  thus  be  about  one-fifth  of  that  in 
the  systemic  vessels.  That  is  to  say,  not  less  than  700  grm.  out  of  the 
4^^  kilos*  of  blood  in  a  70-kilo  man  would  be  contained  in  the  lesser  cir- 
culation, and  about  3 J  kilos  in  the  greater.  This  corresponds  sufficiently 
well  with  calculations  from  other  data. 

For  example,  the  average  weight  of  the  lungs  in  three  persons  exe- 
cuted by  beheading,  was  457  grm.  (Gluge).  The  average  weight  of 
the  lungs  in  a  great  number  of  persons  who  had  died  a  natural  death 
was  1,024  g-if^-  (Juncker).  The  weight  of  the  pulmonary  tissue  alone 
in  the  first  set  of  cases  must  be  less  than  457  grm..  for  the  lungs  of  a 
person  who  has  bled  to  death  are  never  bloodless.  In  a  dog  killed  by 
bleeding  from  the  carotid,  one-quarter  of  the  weight  of  the  lungs  con- 
sisted of  blood.  Assuming  the  same  proportion  for  the  decapitated 
individuals,  we  get  343  grm.  as  the  net  weight  of  the  blood-free  lungs. 
Deducting  this  from  1,024  grm.,  we  arrive  at  681  grm.  as  the  average 
quantity  of  blood  in  the  lungs.  Adding  to  this  the  quantity  in  the 
right  side  of  the  heart  (p.  140),  we  get,  in  round  numb:rs,  750  grm. 
as  the  amount  in  the  lesser  circulation.  It  is  true  that  in  the  living 
body  the  conditions  are  not  the  same  as  after  death;  but  it  is  probable 
that  in  a  laige  number  of  cases  taken  at  random  the  differences  would 
be  approximately  equalized. 

It  has  been  further  calculated  that  the  total  area  of  the  alveolar 
surface  of  the  lungs  of  a  man  is  about  100  square  metres  (sixty  times 
greater  than  the  area  of  the  skin),  of  which,  perhaps,  75  square  metres 
are  occupied  by  capillaries.  The  average  thickness  of  this  immense 
sheet  of  blood  has  been  reckoned  to  be  equal  to  the  diameter  of  a  red 
blood-corpuscle,  or,  say,  8  u.  This  would  give  600  c.c.  (630  grm.)  as 
the  quantity  of  blood  in  the  lungs,  which  is  probably  somewhat  too 
low  an  estimate. 

♦  See  footnote  on  p.  139 


MECHASICAI.   PIIESOMENA   OF  EXTERXAI.   RES/'/RATmX    325 

]f    we  take  the  pulmoiiiiry  circuhition-liiue  us   13  seconds  (p.   137). 

07  X  60  X  6t) 
and  the  quantity  of  blood  in  the  hings  as  700  grni.,  then  ~7o~ 

—  194  kilos  of  blood  will  pass  througli  the  lungs  in  an  iiour,  or  4,050 
kilos  (say,  4,400  litres)  in  twenty-four  hours.  1  his  would  fill  a  cubical 
tank  in  which  the  man  could  almost  stand  upright  with  the  lid  closed. 

Section  II. ^Mechanical  Phenomena  of  Extkknal 
Respiration. 

The  lungs  are  enclosed  in  an  air-tight  box,  the  thorax;  or  it  may 
be  said  with  e(iual  truth  that  they  form  part  of  the  wall  of  the 
thoracic  cavit}-,  and  the  part  which  has  by  far  the  greatest  capacity 
of  adjustment.  The  alveolar  surface  of  the  lungs  is  in  contact  with 
the  air.  The  pleura,  which  covers  their  internal  surface,  is  reflected 
over  the  chest-walls  and  diaphragm,  so  as  to  form  two  lateral  sacs, 
the  pleural  cavities.  In  health  these  are  almost  obliterated,  and  the 
visceral  and  parietal  pleurae,  separated  and  lubricated  by  a  few 
drops  of  lymph,  glide  on  each  other  with  every  movement  of 
respiration.  But  in  disease  the  pleural  cavities  may  be  filled  and 
their  walls  widely  separated  by  exudation,  as  in  pleurisy,  or  by 
blood,  as  in  rupture  of  an  aneurism,  or  by  air  in  the  condition 
known  as  pneumo-thorax.  Between  the  two  pleural  sacs  lies  a  mesial 
space,  the  mediastinum,  commonly  divided  into  an  anterior  medias- 
tinum in  front  of  the  heart,  and  a  posterior  mediastinum  behind  it. 
The  pleural  and  pericardial  sacs  and  the  mediastinum  constitute 
together  the  thoracic  cavity.  The  external  surface  of  the  chest- 
wall  and  the  alveolar  surface  of  the  lungs  are  subjected  to  the 
pressure  of  the  atmosphere,  to  which  the  pressure  in  the  thoracic 
cavity  (intra-thoracic  pressure)  w  ould  be  exactly  equal  if  its  bound- 
aries were  perfectly  ^delding.  But  in  reality  the  intra-thoracic 
pressure  is  always  normally  something  less  than  this.  For  even 
the  lungs,  the  least  rigid  part  of  the  boundary,  oppose  a  certain 
resistance  to  distension,  and  so  hold  off,  as  it  were,  from  the  thoracic 
cavity  a  portion  of  the  alveolar  pressure;  and  in  any  given  position 
of  the  chest  the  intra-thoracic  pressure  is  equal  to  the  atmospheric 
pressure  minus  this  elastic  tension  of  the  lungs. 

The  object  of  the  respiratory  movements  is  the  renewal  of  the  air 
in  contact  with  the  alveolar  membrane — in  other  words,  the  ventila- 
tion of  the  lungs.  Two  main  methods  are  followed  by  sanitary 
engineers  in  the  ventilation  of  buildings:  they  force  air  in,  or  they 
draw  it  in.  In  both  cases  the  movement  of  the  air  depends  on  the 
establishment  of  a  slope  of  pressure  from  the  inlet  to  the  interior. 
In  the  first  method,  this  is  done  b}^  increasing  the  pressure  at  the 
inlet;  in  the  second,  by  diminishing  the  pressure  at  the  outlet.  In 
certain  animals  Nature,  in  solving  its  problem  of  ventilation,  has 
made  use  of  the  first  principle.     Thus,  the  frog  forces  air  into  its 

15 


226 


Uh.Sl'IHATION 


lungs  by  a  swallowing  movement.  In  aitiliciai  respiration,  as 
practised  in  physiological  experiments,  the  same  method  is  usually 
employed:  air  is  driven  into  the  lungs  under  pressure.  But  in  the 
vast  majority  of  air-breathing  animals,  including  man,  the  opposite 
principle  has  been  adopted;  and  the  '  indraught  '  of  air  from  nose 
and  pliarynx  to  alveoli  is  not  set  up  by  increasing  the  pressure  in 
the  former,  but  by  diminishing  it  in  the  latter.  This  '  indraught,' 
or  inspiration,  is  brought  about  by  certain  movements  of  the  chest- 
wall,  which  increase  the  capacity  of  the 
thoracic  cage  and  lower  the  pressure  in  the 
thoracic  cavity.  The  expansion  of  the 
highly-distensible  lungs  keeps  pace  with 
the  diminution  of  pressure  in  tlie  pleural 
sacs,  and  they  follow  at  every  point  tin- 
retreating  chest  -  wall  and  diaphragm, 
although  they  do  not  expand  equally  in 
all  directions.  The  dorsal  surface  in  con- 
tact with  the  vertebral  column,  the 
mediastinal  surface  in  contact  with  the 
pericardium  and  the  contents  of  the 
mediastinum,  and  the  surface  of  the  apex, 
move  but  little.  The  surfaces  in  contact 
with  the  diaphragm,  ribs,  and  sternum 
have  the  greatest  range  of  movement. 
Intermediate  portions  of  the  parenchyma 
of  the  hmgs  expand  in  a  degree  determined 
by  their  distance  from  the  relatively 
stationary  and  mobile  surfaces.  The  pres- 
sure of  the  air  in  the  alveoli  during  the 
rapid  expansion  of  the  lungs  necessarily 
sinks  below  that  of  the  at;nospliere,  and 
air  rushes  in  through  the  trachea  and 
bronchi  till  the  difference  is  equalized. 
Then  commences  the  movement  of  ex- 
piration. The  expanded  chest  falls  back 
to  its  original  limits;  the  pressure  in  the 
thoracic  cavity  increases;  the  distended 
lungs,  in  virtue  of  their  elasticity,  shrink  to  their  former  volume; 
the  pressure  of  the  air  in  the  al\-eoli  rises  above  that  of  the  atmo- 
sphere, and  with  this  reversal  of  the  slope  of  pressure  air  streams 
out  of  the  bronchi  and  trachea. 

In  inspiration  the  chest  dilates  in  all  its  diameters.  Its  vertical 
diameter  is  increased  by  the  contraction  of  the  diaphragm,  which, 
composed  of  a  central  tendon,  a  peripheral  ring  of  muscular  tissue, 
and  the  two  muscular  crura,  bulges  up  into  the  thorax  in  the  form 
of  two  flattened  domes,  one  on  each  side,  and  thus  closes  its  lower 


Fig.  .109.  —  Scheme  to  illus- 
trate the  Movements  of  the 
Lungs  in  the  Chest.  T  is 
a  buttle  from  which  the 
bottom  has  been  removed: 
1),  a  flexible  and  elastic 
iiienibrane  tied  on  the 
bottle,  and  capable  of  being 
pulled  out  by  the  string  S 
so  as  to  increase  the  ca- 
pacity of  the  bottle.  L  is 
a  thin  elastic  bag  repre- 
senting the  lungs.  It  coin- 
municateswith  the  external 
air  by  a  glass  tube  fitted 
airtight  through  a  cork  in 
the  neck  of  the  bottle. 
When  D  is  drawn  down,  the 
pressure  of  the  e.xternal  air 
causes  L  to  expand.  When 
the  string  is  let  go.  L  con- 
tracts again,  in  virtue  of 
its  elasticity. 


Mr.arAMc.u.  phenomena  or  r:.\TEh\\.u.  hTsri ration   227 

aperture.  When  the  diaphragm  contracts,  even  in  ordinary  quiet 
breathing,  the  central  tendon  descends  distinctly  (about  half  an 
inch)  after  the  manner  of  a  piston.  The  acute  angle  which  the 
muscular  ring  makes  during  relaxation  with  the  thoracic  wall  opens 
out  around  its  whole  circumference,  so  as  to  form  a  groove  of  trian- 
gular section.  But  the  most  peripheral  portion  of  the  ring  is  alwaj's 
kept  in  close  apposition  to  the  chest- wall  by  the  negative  intra- 
thoracic pressure.  The  lungs  follow  the  descending  diaphragm, 
their  lower  borders  keeping  accurately  in  contact  with  it.  The 
descent  of  the  diaphragm  is  not  directly  downwards,  but  downwards 
and  forwards.  For  it  is  compounded  of  two  movements,  the  spinal 
segment  of  the  muscle  (the  crura)  causing  a  vertical  elongation  of 
the  thorax,  while  the  sterno-costal  part  (the  muscular  ring)  pushes 
the  abdominal  viscera  downwards  and  forwards  (Keith).  Since 
the  diaphragm  is  attached  to  the  lower  ribs,  there  is  a  tendency 
during  its  contraction  for  these  to  be  drawn  inwards  and  upwards; 
but  this  is  opposed  by  the  pressure  of  the  abdominal  viscera,  and  by 
the  action  of  the  qnadratiis  litmbormn,  which  fixes  the  twelfth  rib, 
and  of  the  serratus  posticus  inferior,  which  draws  the  lower  four 
ribs  backward.  When  these  and  the  other  inspiratory  muscles 
that  act  especially  upon  the  ribs  are  paralyzed  by  injuW  to  the 
spinal  cord,  and  respiration  is  carried  on  by  the  diaphragm  alone, 
the  hne  of  its  attachment  to  the  ribs  is  distinctly  marked  during 
inspiration  by  a  shallow  circular  groove. 

The  thorax  is  also  enlarged  by  the  action  of  certain  muscles  that 
act  upon  the  ribs.  Among  the  elevators  of  the  ribs,  as  their  name 
indicates,  are  usually  reckoned,  although  erroneously,  the  levatores 
costanim — twelve  in  number  on  each  side.  They  arise  from  the 
transverse  processes  of  the  last  cervical  and  first  eleven  dorsal 
vertebrae,  and  passing  obliquely  downwards  and  outwards,  are  in- 
serted between  the  tubercle  and  the  angle  into  the  first  or  second  rib 
below  their  origin.  They  do  not  elevate  the  ribs,  but  take  part  in 
lateral  movements  of  the  spinal  column.  The  scalene  muscles, 
which  may  in  a  lean  person  be  felt  to  be  tense  during  inspiration, 
fix  the  first  and  second  ribs  (scalenus  anticus  and  medius,  the  first ; 
scalenus  posticus,  the  second  rib),  and  so  aft'ord  a  fixed  line  for  the 
intercostal  muscles  to  work  from  on  the  lower  ribs. 

The  most  important  elevators  of  the  ribs  are  the  external  inter- 
costals.  The  intercartilaginous  portions  of  the  internal  inter- 
costals  (the  intercartilaginei  muscles,  as  they  are  sometimes  called) 
also  contract  simultaneously  with  the  diaphragm,  and  may  there- 
fore be  included  in  the  list  of  inspiratory  muscles;  but  instead  of 
elevating  the  ribs  they  depress  the  costal  cartilages,  and  thus  help 
to  widen  the  angles  between  them  and  the  ribs.  In  addition  to 
increasing  the  capacity  of  the  chest,  the  contraction  of  the  external 
intercostals  and  the  intercartilaginous  muscles  aids  in  inspiration 


:28  RESPIRATION 


by  augniLnting  tlie  rigidity  of  the  intercostal  spaces,  and  so  pre- 
venting them  from  being  drawn  in  as  easily  as  would  otherwise  be 
the  case  when  the  thorax  is  expanded  by  the  action  of  the  dia- 
phragm and  the  other  inspiratory  muscles. 

Leaving  out  of  account  the  floating  ribs,  which  functionally  form 
a  part  of  the  abdominal  wall,  the  ribs  in  relation  to  their  respiratory 
functions  may  be  divided  into  the  following  groups:  (i)  The  first 
rib,  which,  moving  itself  very  httle,  provides  a  fixed  line  towards 
which  the  next  set  of  ribs  may  be  raised. 

(2)  An.  upper  costal  series  consisting  of  the  ribs  from  the  second 
to  the  fifth.  These  are  raised  in  inspiration  towards  the  fixed  first 
rib  by  the  contraction  of  the  intercostal  muscles.  The  movement 
of  these  ribs  is,  mainly  at  any  rate,  a  rotation  around  a  transverse 
axis,  the  axes  on  which  they  move  corresponding  to  their  necks. 
The  manner  in  which  they  are  articulated  to  the  vertebrae  prevents 
any  sensible  rotation  around  an  antero-posterior  axis  or  '  bucket- 
handle  '  movement.  Since  these  ribs  slant  downwards  and  forwards 
to  their  sternal  attachments,  the  sternum  is  raised  when  they  are 
elevated;  or,  rather,  since  the  manubrium  is  practically  immovable 
in  ordinary  breathing,  the  body  of  that  bone  is  bent  on  the  manu- 
brium at  the  manubrio-sternal  joint.  This  causes  an  increase  in 
the  antero-posterior  diameter  of  the  thorax.  Further,  since  the 
arches  formed  by  the  ribs  widen  in  regular  progression  from  above 
downwards  in  the  upper  portion  of  the  thoracic  cage,  so  that  the 
second  rib  is  a  segment  of  a  larger  circle  than  the  first,  and  the 
third  than  the  second,  it  is  clear  that  a  general  elevation  of  the  chest 
will  tend  to  increase  the  transverse  diameter  at  any  given  level. 
Such  an  increase  is  also  favoured  by  the  opening  out  of  the  angles 
between  the  bony  ribs  and  the  costal  cartilages  under  the  influence 
of  the  couple  (or  pair  of  oppositely  directed  forces)  that  acts  on  them 

viz.,  the  upward  pull  of  the  external  intercostals  exerted  on  the 

ribs,  and  the  downward  pull  of  the  intercartilaginei  and  the  resist- 
ance of  the  sternum  to  further  displacement  exerted  on  the  carti- 
lages. The  whole  arrangement  is  perfectly  adapted  to  permit  the 
expansion  of  the  roughly  conical  upper  lobes  of  the  lungs. 

(3)  The  lower  costal  series,  consisting  of  the  ribs  from  the  sixth 
to  the  tenth.  These  ribs,  with  their  muscles,  form  a  mechanism 
which  normally  acts  along  with  the  diaphragm  (Keith).  They  are 
so  arranged  that  in  inspiration  the  lateral  and  anterior  part  of 
each  moves  outwards  to  a  greater  extent  than  the  one  above  it. 
There  is  not  only  a  rotation  around  a  transverse  axis,  by  which  the 
lower  end  of  the  sternum,  connected  to  these  ribs  by  the  combined 
cartilages  of  the  sixth  to  the  ninth,  is  elevated,  but  also  a  rotation 
around  an  antero-posterior  axis.  The  movement  of  the  lower  ribs 
results,  therefore,  in  increasing  both  the  back-to-front  diameter  and 
the  transverse  diameter  of  the  lower  portion  of  the  thorax.     The 


MECHANICAL  PHl.XOMKXA   Ol'  hXTHRSAr.  PF.SPI h\lTlO\     z>., 

widening  of  the  thorax  from  side  to  side  may  also  be  in  a  sHght 
degree  ascribed  to  a  twisting  movement  of  the  ribs,  which  tends  to 
evert  their  lower  borders.  With  the  diaphragm,  these  lower  ribs 
arranged  in  a  vertical  series  of  not  very  different  curvature  con- 
stitute a  mechanism  for  the  inspiratory  expansion  of  the  roughly 
cylindrical  lower  lobes  of  the  lungs. 

Expiration  in  perfectly  tranquil  breathing  is  brought  about  with 
less  aid  from  active  muscular  contraction.  The  sense  of  effort 
disappears  as  soon  as  the  chest  ceases  to  expand.  The  diaphragm 
and  the  elevators  of  the  ribs  relax.  The  structures  that  have  been 
stretched  or  twisted  recoil  into  their  original  positions;  the  struc- 
tures that  have  been  raised  against  the  force  of  gra\'ity  fall  back 
by  their  weight,  and  in  the  measure  in  which  the  pressure  increases 
in  the  thoracic  cavity  the  elasticity  of  the  lungs  causes  them  to 
slirink.  The  pressure  in  the  alveoli,  which  at  the  end  of  inspiration 
was  just  equal  to  that  of  the  atmosphere,  is  thus  increased,  and  the 
air  expelled.  It  is  probable  that,  even  in  man  and  in  quiet  respira- 
tion, the  interosseous  portions  of  the  internal  intercostals  help  b}' 
their  contraction  in  depressing  the  ribs,  and  that  a  slight  contrac- 
tion of  the  abdominal  muscles  hastens  the  return  of  the  diaphragm 
to  its  position  of  rest.  In  reptiles  and  birds,  expiration  is  normally 
effected  by  an  active  muscular  contraction.  This  is  also  true  in 
some  mammals — the  rabbit,  for  instance,  in  which  the  external 
obhque  muscles  of  the  abdominal  wall  take  an  important  share  in 
the  expiratory  act 

Types  of  Respiration. — Differences  exist  also,  not  only  between 
different  groups  of  animals,  but  even  between  women  and  men,  in 
the  relative  importance  in  inspiration  of  the  diaphragm  and  the 
muscles  that  raise  the  lower  ribs  on  the  one  hand,  and  the  muscles 
that  elevate  the  upper  ribs  on  the  other.  When  the  movements  of 
the  diaphragm  predominate,  the  respiration  is  said  to  be  of  the 
abdominal  or  diaphragmatic  type  ;  when  the  movemenus  of  the  upper 
ribs  and  sternum  are  most  conspicuous,  of  the  costal  or  thoracic  type. 
In  abdominal  respiration,  the  inspiratory  movement  commences  at 
the  diaphragm,  and  then  involves  the  lower  ribs  and  the  tip  of  the 
sternum.  In  costal  respiration,  the  upper  ribs  initiate  the  move- 
ment, and  are  followed  by  the  abdomen.  In  the  rabbit,  during 
quiet  breathing,  the  respiration  is  purely  diaphragmatic,  the  ribs 
remain  motionless;  and  herbivorous  animals  in  general  conform 
more  or  less  closely  to  this  type.  In  the  carnivora,  on  the  contrarj', 
the  costal  t\'pe  prevails.  Man  allies  himself  as  regards  his  respira- 
tion with  the  rabbit  and  the  sheep ;  he  uses  his  diaphragm  more  than 
his  upper  ribs.  Ci\'ilized  woman  falls  into  the  class  of  the  wolf  and 
the  tiger;  she  uses  her  upper  ribs  more  than  her  diaphragm.  The 
cause  of  the  difference  between  men  and  women  has  been  much 
discussed.     It  is  not  a  primitive  sexual  difference,  for  it  is  far  from 


230  RESPIRATION 

being  universal;  in  the  uncivilized  and  semi-civilized  races  that 
have  been  investigated,  the  women  breathe  like  the  men.  It  is 
therefore  probable  that  the  predominance  of  the  costal  type  among 
women  of  European  race  is  a  peculiarity  developed  by  a  mode  of 
dressing  which  hampers  the  movements  of  the  diaphragm  while 
permitting  the  elevation  of  the  ribs.  This  conclusion  is  strengthened 
by  the  fact  that  in  children  no  difference  exists;  both  boys  and  girls 
show  the  abdominal  type  of  respiration. 

All  this  refers  to  ordinary  breathing.  In  forced  respiration,  when 
the  need  for  air  becomes  urgent,  costal  breathing  always  becomes 
prominent  alike  in  men,  in  women,  and  in  animals,  for  by  elevation 
of  the  ribs  the  capacity  of  the  chest  can  be  increased  to  a  greater 
degree  than  by  any  contraction  of  the  diaphragm. 

In  forced  inspiration,  indeed,  all  the  muscles  that  can  elevate  the 
ribs  may  be  thrown  into  contraction,  as  well  as  other  muscles  which 
give  these  fixed  points  to  act  from.  During  a  paroxysm  of  asthma, 
for  example,  the  patient  may  grasp  the  back  of  a  chair  with  his 
hands,  so  as  to  fix  the  arm?  and  shoulders  and  allow  the  pertorals 
and  serratus  magnus  to  raise  the  ribs.  Similarly  in  forced  expiration 
all  the  muscles  are  used  which  can  depress  the  ribs,  or  increase  the 
intra-abdominal  pressure  and  push  up  the  diaphragm. 

Artificial  Respiration. — An  efficient  pulmonary  \entilation can  be 
obtained  by  various  methods  when  the  natural  breathing  is  in  abey- 
ance. In  animals  the  method  most  commonly  employed  for  ex- 
perimental purposes  is  the  rhythmical  inflation  of  the  hings  by  a 
pump  or  bellows,  or  by  a  stream  of  compressed  air  which  is  regularly 
interrupted,  the  chest  being  allowed  to  collapse  after  each  inflation. 
Wlien  the  animal  is  to  be  kept  alive  after  the  experiment  the  inflation 
is  produced  through  a  tube  introduced  through  the  glottis.  If  the 
animai  is  not  to  be  kept  alive,  the  apparatus  is  generally  connected 
with  a  cannula  in  the  trachea.  When  it  is  desired  to  avoid  move- 
ments of  the  lungs,  respiration  may  be  maintained  by  a  stream  of 
oxygen  through  a  catheter  passed  down  the  trachea  (method  of 
insufflation).  In  man  the  exchange  of  air  between  the  atmosphere 
and  the  lungs  may  be  most  readily  accomplished  by  strong  rhythmi- 
cal compression  of  the  lower  part  of  the  chest.  This  forces  out 
some  of  the  air  from  the  lungs;  on  relaxing  the  pressure  the  chest 
expands  again  and  air  is  drawn  in.  Schafer  has  shown  that  this  is 
the  most  efficient  method  of  respiration  in  resuscitation  of  the  ap- 
parently drowned.  '  The  patient  is  placed  face  downwards  on  the 
ground,  with  a  f(jlded  coat  under  the  lower  part  of  the  chest.  The 
operator  puts  himself  athwart  or  at  the  side  of  the  patient,  facing  his 
head  and  kneeling  upon  one  or  both  knees  (Fig.  no),  and  places  his 
hands  on  each  side  over  the  lower  part  of  the  back  (lowest  ribs).  He 
then  slowly  throws  the  weight  of  his  bodv  forward  to  bear  upon  his 
own  arms,  and  thus  presses  upon  the  thorax  and  forces  air  out  of 
the  lungs.     He  then  gradually  relaxes  the  pressure  by  bringing  his 


MIA  IIAMC.IL   l'lli:\(>Mh.\.l   OJ-   ]:.\  llhW.lL   UESl'IKAl  luS   i^i 


own  body  iij)  a^ain  tt»  a  more  I'lcd  i><»siti()ii,  hut  witlujut  moving 
the  hands.'  Air  is  tliu>  diawn  into  \\\v  limys.  The  process  is 
repeated  tvehe  to  filleeii  tiine.-^  a  minute. 

Certain  accessory  phenomena  (movements  and  sounds)  are  asso- 
ciared  with  tlie  proper  movements  of  respiration.  The  larynx  rises 
in  expiration,  and  sinks  in  inspiration.  The  glottis  (and  particu- 
larly its  posterior  portion,  the  glottis  respiratoria)  is  widened  during 
deep  inspiration  and  narrowed  during  deep  expiration.  The  same 
is  the  case  with  the  nostrils,  and,  indeed,  in  some  persons  the  alae 
nasi  move  even  in  ordinary  breathing.  It  has  long  been  known 
that  in  deep  respiration  changes  in  the  calibre  of  the  bronchi  syn- 
chronous with  the  respiratory  movements  may  occur.  In  young 
persons  it  may  be  directly  observed  with  the  bronchoscope,  an 
instrument  used  by  laryngologists  for  exploring  the  larger  bronchi, 

that  these  dilate 
in  inspiration 
and  constrict  in 
expiration  (In- 
galls).  In  part 
at  least  these 
movements  are 
passively  pro- 
duced by  the 
changes  of  intra- 
thoracic  pres- 
sure, but  it  has 
not  been  defi- 
nitely deter- 
mined whether 
they  are  not  in 
])art   caused  by 

alternate  contraction  and  relaxation  of  the  circular  bronchial 
muscles.  To  these  muscles  has  sometimes  been  attributed  the 
function  of  regulating  the  flow  of  air  into  and  out  of  the  infundib- 
ula,  as  the  muscle  of  the  arterioles  regulates  the  distribution  of  the 
blood  in  the  organs. 

As  regards  the  respiratory  sounds,  all  that  is  necessary  to  be  said 
here  is  that  when  we  Ustcn  over  the  greater  portion  of  the  kings  with 
the  ear,  or,  much  better,  with  a  stethoscope,  a  soft  breezy  murmur, 
that  has  been  compared  to  the  rustUng  of  the  wind  through  distant 
trees,  is  heard.  This  has  been  called  the  vesicular  murmur.  It  is  only 
heard  in  health  during  inspiration  and  the  very  beginning  of  expira- 
tion, and  is  louder  in  children  than  in  adults.  Around  the  larger 
bronchi  and  the  trachea  a  blowing  sound  is  heard,  which  certainly 
originates  at  the  glottis,  and  is  strengthened  by  the  resonance  of  the 
air-tubes.  In  health  this  is  not  recognized  over  the  greater  portion  of 
the  lung.  But  in  certain  diseases  in  which  the  alveoli  are  devoid  of 
air,  whether  from  compression  or  because  they  are  filled  up  with 
exudation,  and  in  other  conditions,  this  bronchial  or  tubular  breathing 


Fig.  no. — Artificial  Respiration  in  Cases  of  Drowning  (after 
Schafer). 


^Ji  TiF.SPI  RATION 

may  be  I)card  over  tlic  affected  area.  The  bronclii  themselves,  how- 
ever, must  still  be  patent  and  contain  air.  i'hc  most  commonly 
accepted  explanation  is  tliat  the  laryngeal  sound  is  better  conducted 
through  the  smaller  bronchi  towards  the  surface  of  the  lungs  when 
their  walls  have  been  rendered  more  rigid  bv  the  solidification  of  the 
parenchyma,  in  spite  of  the  fact  that  the  consolidated  tissue  as  such 
does  not  conduct  the  sound  so  well  as  the  air-containing  alveoli.  It 
seems  probable  that,  in  addition,  the  columns  of  air  in  the  bronchi, 
which  arc  encased  in  solid  tissue,  may  actually  increase  the  intensity 
of  the  transmitted  laryngeal  murmur  by  resonance. 

It  has  been  much  debated  whether  the  vesicular  murmur  also  arises 
at  the  glottis,  and  is  modified  by  transmission  through  the  pulmonary 
tissue,  or  whether  it  arises  somewhere  in  the  terminal  bronchi,  the 
infundibula  or  the  alveoli.  Both  views  may  be  supported  by  certain 
arguments,  and  to  both  some  objections  maj'  be  raised.  The  fact 
appears  to  be  that  tliere  are  two  elements  in  the  inspiratory  murmur — 
a  true  vesicular  sound,  produced  about  the  place  where  the  terminal 
bronchioles  give  off  the  infundibula.  and  a  resonance  sound  set  up  in 
the  trachea  and  bronchi  by  the  glottic  murnmr.  This  resonance  sound 
as  heard  over  portions  of  the  lung  containing  onh'  snxall  bronchi  has 
a  different  character  from  that  heard  over  large  bronclii,  inasmuch  as 
the  fundamental  note,  and  to  a  still  greater  extent  the  overtones 
Jp.  310),  are  much  weakened  in  those  small  and  easily-distensible 
tubes.  The  true  vesicular  element  is  heard  all  over  the  lungs,  but 
the  resonant  laryngeal  element  in  large  animals,  like  the  horse  and  ox, 
dies  out  as  an  audible  murmur  before  it  reaches  the  reTnotest  lobules, 
and  can  only  be  distinguished  over  a  portion  of  the  pulmonary-  area. 
When  the  glottic  sound  is  eliminated  by  causing  an  anJrmil  to  breathe 
through  a  tracheal  fistula,  the  vesicular  murmur  is  still  heard,  and  in 
the  horse  is  even  somewhtit  sharper  than  normal,  although  in  the  dog 
it  is  softer  and  weaker.  The  expiratory'  murmur  does  not  seem  to 
contain  a  true  vesicular  element,  but  is  exclusively  due  to  the  resonance 
of  the  expiratory  glottic  sound  (Marek).  It  is  generally  admitted,  and 
this  is  of  great  importance  in  practical  medicine,  that  when  the  normal 
vesicular  sound  is  heard  over  any  portion  of  the  lung  tissue,  it  may  be 
inferred  that  this  portion  is  being  properly  distended,  and  that  air  is 
freely  entering  its  alveoli. 

Up  to  this  point  we  liave  contented  ourselves  with  a  purely 
([ualitative  description  of  the  mechanical  phenomena  of  respiration. 
We  have  now  to  consider  their  quantitative  relations,  and  the 
methods  by  which  these  have  been  studied. 

The  expansion  of  the  lungs  in  inspiration  may  be  easily  demonstrated 
in  man,  and  even  a  rough  estimate  of  its  amount  obtained,  by  the  clinical 
method  of  percussion.  For  example,  the  resonant  note  tliat  is  elicited 
when  a  finger  laid  on  the  chest  at  a  part  where  it  overlies  the  right 
lung  is  smartly  struck  can  be  followed  down  until  it  is  lost  in  the  '  liver 
duhiess.'  If  the  lower  limit  of  the  resonant  area  be  marked  on  the 
chest-wall  first  in  full  inspiration,  and  then  in  full  expiration,  the  mark 
will  be  lower  in  the  former  than  in  the  latter,  and  the  difference  will 
represent  the  difference  in  the  vertical  length  of  the  shrunken  and  dis- 
tended lung.  A  similar  enlargement  in  the  transverse  direction  ma\ 
bo  demonstrated  in  the  same  way,  the  inner  borders  of  the  lungs  coming 
nearer  to  the  middle  line  in  inspiration,  and  receding  from  it  in  expira- 
tion.    The  examination   of  the  chest   by  the   Rontgen   rays  has  also 


MECMAMCAL  IVlhXUMLXA   Ol-    /•.VV/l /I'.V.IL  UILSPIRATIO^    233 


yielded  results  of  importance  in  the  study  of  nornuil  respiratory  con- 
ditions, and  still  more  important  results  in  pulmonary  disease. 

For  most  physiological  purposes,  however,  a  faithful  graphic  record 
of  the  respiratory  movements  is  indispensable.     This  may  be  obtained — 

(i)  13y  registering  the  movements 
of  a  single  point,  or  the  variations  in 
a  single  circumference,  of  the  bound- 
ary of  the  thoracic  cavity.  In  man, 
changes  in  the  circumference  of  the 
thorax  at  any  level  can  be  recorded 
by  means  of  a  tambour  adjusted  to 
the  chest  (Figs.  1 1 1  and  13.4),  and  in 
communication  with  another,  which 
is  provided  with  a  writing  lever 
(Figs.  99  and  137).  Or  an  elastic 
tube,  with  a  spiral  spring  in  its 
lumen,  may  be  fastened  around  the 
tliorax  or  abdomen  and  connected 
with  a  piston-recorder  (a  small  cylin- 
der in  which  works  a  piston  carrying 
a  writing-point)  (Fitz). 

(2)  By  recording  the  changes  of 
pressure  produced  in  the  air-passages 
by  the  respiratory  movements.  This 
can  be  done  by  connecting  a  cannula 
in  the  trachea  of  an  animal  with  a 
recording  tambour  in  the  manner 
described  in  the  Practical  Exercises 
(p  300).  The  variations  of  pressure 
may  be  measured  by  connecting  a 
manometer  with  the  trachea,  or  in 
man  with  the  noiJtril. 

(3)  By  writing  off  the  changes  of  pressure  which  occur  in  the  thoracic 
cavity  during  respiration.  For  this  purpose  a  trocar  (Fig.  113)  is  intro- 
duced through  an  intercostal  space  into  one  of  the  pleural  sacs,  without 
the  admission  of  air,  or  into  the  pericardium,  and  then  connected  with 
a  manometer  or  other  recording  apparatus.  Or  a  tube,  similar  in  con- 
struction to  a  car- 
diac sound  (p.  96), 
may  be  pushed 
down  the  oesopha- 
gus. The  varia- 
tions in  the  intra- 
thorrxlc  pressure 
are  transmitted  to 
the  air  in  the  elas- 
tic bag.  and  thence 
to  a  tambour. 

(4)  In  the  rabbit 
the  part  of  the  dia- 
phragm attached  to  the  ensiform  cartilage  may  be  isolated  from  the 
rest  and  its  contractions  recorded  by  a  lever  (Head) .  For  some  purposes 
this  is  the  best  method. 

When  the  respiratory  movements  are  studied  in  any  of  these  ways, 
it  is  found  that  there  is  practically  no  pause  between  the  end  of 


I-'ig.  III. — Scheme  of  Tambour  for 
recording  Respiratory  Movements. 
C.  a  metal  capsule  connected  airtight 
with  B,  A.  two  caoutchouc  mem- 
branes, the  chamber  formed  by  which 
can  be  inflated  by  means  of  the  tube 
and  stopcock  E.  The  tube  D  con- 
nects the  space  H  with  a  registering 
tambour  provided  with  a  lever.  The 
membrane  .\  is  applied  to  the  chest, 
round  which  the  inextensible  strings 
F  are  tied.  At  every  expansion  of  the 
chest  the  pressure  in  H  is  increased, 
and  the  increase  of  pressure  is  trans- 
mitted to  the  registering  tambour. 


Fig.   112. — ^Respiratory  Tracing  from  Man  (Marey). 
stroke,  inspiration;  up  stroke,  expiration. 


Down 


■!34 


RESPlUAriDS 


d 


\_fa 


Fig.    US- 


inspiration  and  till'  bcj^inninf,'  of  expiration.  Xor,  although  the 
chest  collapses  more  gradually  than  it  expands,  is  there  any  distinct 
interval  in  ordinary  breathing  between  the  end  of  expiration  and 
the  beginning  of  the  sucxeeding  inspiration.  When,  however,  the 
respiration  is  unusually  slow,  an  actual  pause  (expiratory  pausej 
may  occur  at  this  point.  Expiration  takes 
somewhat  longer  time  than  inspiration,  the 
ratio  varying  from  7  :  6  to  3  :  2,  according  to 
age,  sex,  and  other  circumstances. 

The  frequency  of  respiration  is  by  no  means 
constant  even  in  health.  All  kinds  of  in- 
fluences affect  it.  It  is  dif^cult  even  to  direct 
the  attention  to  the  respiratory  act  without 
bringing  about  a  modification  in  its  rhythm. 
In  the  adult  15  to  20  respirations  per  minute 
may  be  taken  as  about  the  normal.  In  young 
children  the  frequency  may  be  twice  as  great 
(new-born  child,  50  to  70;  child  from  i  to  5 
years  old,  20  to  30  per  minute).  It  is  greater 
in  a  female  than  in  a  male  of  the  same  age.  A 
rise  of  temperature  increases  it;  150  respira- 
tions per  minute  have  been  seen  in  a  dog  with 
a  high  temperature.  Sudden  coohng  of  the  skin, 
exercise,  and  various  emotional  states,  increase 
the  rate,  and  sleep  diminishes  it.  The  will  can 
alter  the  frequency  and  depth  of  respiration 
for  a  time,  and  even  stop  it  altogether,  but  in 
less  than  a  minute,  in  ordinary  individuals,  the 
desire  to  breathe  becomes  imperative.  Cato's 
assertion  that  he  could  kill  himself  at  any  time 
'  merely  by  holding  his  breath  '  is  only  a  proof 
that  he  was  a  better  philosopher  than  physi- 
ologist. After  a  period  of  forced  respiration 
the  breath  can  be  held  for  a  much  longer  time. 
This  is  due  to  the  '  washing  out  '  of  the  carbon 
dioxide,  the  normal  stimulus  to  the  respiratory 
centre  (p.  281).  After  six  minutes  of  forced 
breathing  the  interval  of  voluntary  inhibition  can  be  extended  be- 
yond four  minutes.  A  profes>ional  diver  has  remained  under  water 
in  a  tank  for  about  four  and  three-quarter  minutes.  When  oxygen 
is  inhaled  instead  of  air  during  the  last  few  breaths  of  the  forced 
respiration,  the  interval  during  which  the  breath  can  be  held  may 
be  much  increased  (up  to  nine  or  ten  minutes).  In  animals  the  rate 
of  respiration  can  be  greatly  affected  by  drugs  and  by  the  section 
and  stimulation  of  certain  nerves;  but  to  this  we  shall  return  when 
we  come  to  consider  the  nervous  mechanism  of  respiration. 


Simple 
Pleural  Cannula.  B. 
a  line  of  small  spurs 
which,  after  the  can- 
nula C  has  been 
pushed  without  ad- 
mission of  air  through 
an  intercostal  space 
into  the  pleural 
cavity,  stick  in  the 
parietal  pleura  and 
securely  fasten  the 
cannula.  Traction 
being  made  on  the 
cannula,  a  ligature  is 
tied  at  L  around  the 
protruding  tissue  for 
greater  security.  S, 
side-tube  by  whichthe 
cannula  is  connected 
with  a  manometer  or 
tambour. 


MIXHASICAL  I'in.SDMENA   Of  I:.\TI:RSAL  in:Sl'lh'ATIO\'     235 


It  cannot  tail  to  be  observed  that  to  a  great  extent  the  rate  of 
respiration  is  affected  by  the  same  circumstances  as  the  frequency 
of  the  heart  (p.  107),  and  in  the  same  direction.  And,  indeed,  in 
health,  these  two  physiological  quantities,  amid  all  their  absolute 
variations,  maintain  to  each  other  a  fairly  constant  ratio  (i  to  4  or 

I  to  5  in  man).  Even  in  many  diseases 
this  proportion  remains  tolerably 
stable,  although  in  others  it  is  dis- 
turbed. 

The  total  quantity  of  air  expired,  or, 
what  comes  to  the  same  thing,  the 
alteration  in  the  capacity  of  the  chest 
during  expiration,  can  be  measured  by 
means  of  a  gas-meter  or  of  a  spiro- 
meter (Fig.  114),  which  consists  of  an 
inverted  graduated  glass  cyhnder  dip- 
ping by  its  open  mouth  into  water 
and  balanced  by  weights.  The  vessel 
is  sunk  till  it  is  full  of  water,  the  air 
being  allowed  to  escape  by  a  cock. 
The  expired  air  is  now  permitted  to 
enter  it  through  a  tube,  and  displaces 
some  of  the  water.  The  spirometer 
is  adjusted  so  that  the  level  of  the 
water  inside  and  outside  is  the  same, 
and  then  the  volume  of  air  contained  in  it  is  read  off.  This  gives 
the  volume  of  the  expired  air  at  atmospheric  pressure.  Similarly, 
by  breathing  air  from  the  spirometer  the  amount  inspired  can  be 
measured  (p.  303). 

From  400  to  500  c.c.  of  air*  are  taken  in  and  given  out  at  each 
respiration  in  quiet  breathing.  This  is  called  tidal  air.  It  amounts 
to  35  pounds  by  weight 
in  twenty-four  hours, 
or  enough  to  fill,  at 
atmospheric  pressure, 
a  cubical  box  with  a 
side  of  8  feet.  With 
the  deepest  possible  in- 
spiration room  can  be 
made  for  2,000  c.c.  more ;  this  is  called  complemental  air.  By  a  forced 
expiration  1,500  c.c.  can  be  expelled  besides  the  tidal  air ;  and  to  this 

♦  The  average  for  81  healthy  students,  with  an  average  body-weight  of 
66  kilos,  was  460  c.c,  or  7  c.c.  per  kilo.  In  4  new-born  children  the  tidal  air 
varied  from  20  to  30  c.c,  and  from  76  to  7' 3  c.c.  per  kilo,  which  is  not  very 
different  from  the  amount  in  the  adult.  The  pulmonary  ventilation  must 
therefore  be  far  more  rapid  in  the  child,  since  its  respiratory  frequency  is  so 
much  greater. 


Fig.  114. — Diagram  of  Spirometer. 
A.  vessel  filled  with  water.  B, 
glass  cylinder  with  scale  C, 
swung  on  pulleys  and  counter- 
poised by  weights  W.  D,  tube 
for  breathing  through. 


y^tal    I M///M//M  Compkmntal  air 

.)mm.  \Rp.str7un?  Oip 


Fig.  115. — Diagram  to  illustrate  the  Relative  Amoimt 
of  Complemental,  Tidal,  Supplemental,  and  Residual 
Air. 


2j6  PKSPIRATIOK 

quantity  tne  nami'  •>{  supplemental  or  reserve  air  has  ht-en  given. 
After  the  deepest  expiratiun  tlitrr  always  remains  i.ooo  to  1.200  c.c. 
of  air  in  the  lungs  (Durig),  and  this  is  railed  the  residual  air.  After 
a  normal  expiration  following  a  normal  inspiration  the  lungs  still 
contain  stationary  air  to  the  amount  of  about  2.500  c.c. 

The  term  vital  or  respiratory  capacity  is  ap])lied  to  the  quantitx' 
of  air  which  can  be  expelled  by  the  deepest  expiration  following  the 
deepest  inspiration,  and  amounts  in  an  adult  of  average  height  to 
3,500  or  4.000  c.c.  The  maximum  quantity  of  air  which  the  lungs 
can  contain  is  evidently  equal  to  vital  capacity  plus  residual  air. 
At  one  time  the  vital  capacity  was  thought  to  be  capable  of  affording 
valuable  information  in  the  diagnosis  of  chest  diseases;  but  little 
stress  is  now  laid  upon  it,  as  it  varies  from  so  many  causes.  For 
instance,  it  can  be  increased  by  practice  with  the  spirometer.  It  is 
greater  in  mountaineers  than  in  the  inhabitants  of  lowland  plains. 

The  Dead  Space. — It  is  clear  from  the  figures  we  have  given  that  in 
ordinary  breathing  only  a  small  proportion  of  the  air  in  the  lungs 
comes  in  direct  at  each  inspiration  from  the  atmosphere,  and  only  a 
small  proportion  escapes  into  the  atmosphere  at  each  expiration. 
The  greater  part  of  the  air  in  the  lungs  is  simply  moved  a  little  farther 
from  the  upper  respiratory  passages,  or  a  little  nearer  them;  and 
fresh  oxygen  reaches  the  alveoli,  as  carbon  dioxide  leaves  them, 
mainly  by  diffasion,  aided  by  convection  currents  due  to  inequali- 
ties of  temperature,  and  to  the  churning  which  the  alternate  expan- 
sion and  shrinking  of  the  lungs,  and  the  pulsations  of  their  arteries 
must  produce.  But  that  some  of  the  tidal  air  strikes  right  down 
to  the  alveoli  is  evident  enough.  For  the  respiratory  '  dead  space  ' 
— that  is,  the  capacity  of  the  upper  air-passages  and  the  bronchial 
tree  down  to  the  infundibula — -is  only  140  c.c,  or  one-third  of  the 
amount  of  the  tidal  air  (Zuntz,  Loewy).  There  is  no  direct  way  of 
determining  whether  any  respiratory  exchange  goes  on  through  the 
walls  of  the  upper  air-passages.  But  by  indirect  methods  it  has 
been  estimated  that  about  30  per  cent,  of  the  volume  of  the  tidal  air 
is  pure  air  (Haldane  and  Priestley).  This,  of  course,  corresponds 
to  the  '  effective  '  dead  space.  Taking  the  average  tidal  air  at 
4O0  c.c.  (p.  235),  it  is  clear  that  the  effective  corresponds  very  closely 
with  the  anatomical  dead  space— that  is  to  say,  the  respiratory 
function  of  the  air-passages  above  the  point  where  the  infundibula 
are  given  off  is  negligible.  Although  such  calculations  can  only  b2 
approximately  correct,  the  agreement  is  of  intere;ft.  Some  observers 
have  stated  that  great  variations  occur  in  the  size  of  the  dead  space 
with  changes  in  the  depth  of  respiration,  its  volume  being  increased 
four  or  even  eight  times  by  very  deep  breathing.  This,  however, 
is  incorrect,  although  with  maximum  expansion  of  the  lungs  the 
increase  may  amount  to  100  c.c.  (Krogh  and  Lindhard,  Pearce). 

The  Amount  and  Variations  of  the  Intrathoracic  Pressure. — In 
the  deepi'St  expiration  the  lung>  are  ncxcr  con^pKlely  ( <illaj)-ed:  their 


MECHANICAL  I'Ur.NOMnNA   OI-   EXTLRNAL  hliSHl RAT l()\      j^ 

clastic  fibres  are  still  stretched;  and  the  tension  of  these  acts  in  th<: 
opposite  direction  to  the  external  atmospheric  pressure,  and  dimin 
ishes  by  its  amount  the  pressure  inside  the  thoracic  cavity.  In  tin 
dead  body  Donders  measured  the  value  of  this  tension,  and  there- 
fore of  the  negative  pressure  of  the  thorax,  by  tying  a  manometer 
into  the  trachea,  and  then  causing  the  lungs  to  collapse  by  opening 
the  chest.  It  varied  from  7-5  mm.  of  mercury  in  the  expiratory 
position  to  9  mm.  in  the  inspiratory.  So  far  as  can  be  judged  from 
observations  made  on  persons  suffering  from  various  diseases  of  the 
respirator\'  organs,  the  alterations  during  ordinary  broathyig  do  not 


Fig.  116. — Variations  of  Intrathoracic  Pressure.  Upper  curve,  carotid  blood-pres- 
sure (dog)  lower  curve,  intrapleural  pressure.  At  4::  the  trachea  was  closed  ; 
the  blood-pressure  curve  shows  the  rise  of  asphyxia,  and  the  intrapleural  curve, 
greatly  exaggerated  pressure  variations  due  to  the  strong  and  slow  but  abortive 
respirations. 

amount  to  more  than  3  or  4  mm.  of  mercury.  But  when  an  attempt 
is  made  in  the  dead  body  to  imitate  a  deep  inspiration  by  making 
traction  on  the  chest  walls  so  as  to  expand  the  lungs,  the  intra- 
thoracic pressure  may  fall  to  —30  mm.  of  mercury;  and  in  a  living 
rabbit,  during  a  deep  natural  inspiration,  a  pressure  of  —20  mm. 
has  been  seen. 

The  reason  why  the  lungs  collapse  when  the  chest  is  opened  is 
that  the  pressure  is  now  equal  on  the  pleural  and  alveolar  surfaces, 
being  in  both  cases  that  of  the  atmosphere.  There  is  therefore 
nothing  to  oppose  the  elasticity  of  the  lungs,  which  tends  to  con- 
tract them.  So  long  as  the  chest  is  unopened,  the  pressure  on  the 
pleural  surface  of  the  lungs  is  less  than  that  on  the  alveolar  surface 


238  RESPIRATION 

and  the  elastic  tension  can  only  cause  them  to  shrink  until  it  just 
balances  this  difference. 

In  intra-uterine  hfe,  and  in  stillborn  cliildren  who  have  never 
breathed,  the  lungs  arc  completely  collapsed  (atelectatic),  and  there 
is  no  negative  intrathoracic  pressure.  They  are  kept  in  this  con- 
dition b}-  adhesion  of  the  walls  of  the  bronchioles  and  alveoli.  If 
the  lungs  have  been  once  inflated,  this  adhesion  ceases  to  act,  and 
they  never  completely  collapse  again. 

Amount  and  Variations  of  the  Respiratory  or  Intrapulmonary 
Pressure. — As  we  have  already  remarked,  the  pressure  in  the  alveoli 
and  air-passages  is  less  than  that  of  the  atmosphere  while  the  in- 
spiratory movement  is  going  on,  greater  than  that  of  the  atmosphere 
during  the  expiratory  movement,  and  equal  to  that  of  the  atmo- 
sphere when  the  chest-walls  are  at  rest.  When  the  external  air- 
passages  are  closed— e.g.,  by  connecting  a  manometer  with  the 
mouth  and  pinching  the  nostrils — the  greatest  possible  variations 
of  pressure  are  produced.  In  the  deepest  inspiration  under  these 
conditions  a  negative  pressure  of  about  75  mm.  of  mercury  {i.e.,  a 
pressure  less  than  that  of  the  atmosphere  by  this  amount)  has  been 
found,  and  in  deep  expiration  a  somewhat  greater  positive  pressure* 
(Practical  Exercises,  p.  304). 

But  with  ordinary  breathing,  the  variations  of  pressure  as 
measured  by  this  method  do  not  exceed  5  to  10  mm.  of  mercury 
above  or  below  the  pressure  of  the  atmosphere. 

When  the  external  openings  are  not  obstructed,  as,  for  example, 
when  the  lateral  pressure  is  taken  in  the  trachea  of  an  animal  by 
means  of  a  cannula  with  a  side-tube  connected  with  a  manometer, 
still  smaller,  and  doubtless  truer,  values  have  been  found  (2-3  mm. 
of  mercury  as  the  positive  expiratory  pressure  and  i  mm.  as  the 
negative  inspiratory  pressure  in  dogs).  But  since  the  respiratory 
passages  are  abruptly  narrowed  at  the  glottis,  the  variations  of 
pressure  muit  be  greater  below  than  above  it,  and  in  general  they 
must  increase  with  the  distance  from  that  orifice,  being  greater,  for 
instance,  in  the  alveoli  than  in  the  bronchi. 

The  mechanical  phenomena  of  respiration  having  been  described, 
it  might  seem  logical  to  consider  next  the  nervous  mechanism  by 
which  the  respiratory  movements  are  controlled;  but  the  regulation 
of  these  movements  through  the  nervous  system  is  in  so  important 
a  degree  a  chemical  regulation  that  it  cannot  be  properly  understood 
without  some  knowledge  of  the  chemical  changes  in  the  blood 
associated  with  external  and  internal  respiration.  We  therefore 
pass  to  the  consideration  of — 

*  The  maximum  negative  pressure  in  deepest  inspiration  averaged  for  ^g 
students  -73  mm.  (highest  observation  -  137  mm.)  of  mercury;  the  maxi- 
mum positive  pressure  in  deepest  expiration,  -f-  So  mm.  (highest  observation 
-f  140  mm.). 


Tiir.  cnr.Mis] u'i  or  esti:u\'aj.  ri.spi ration        230 

Section  III. — The  Chemistry  of  External  Respiration. 

Our  knowledge  of  this  subject  has  been  entirely  acquired  in  the 
last  200  years,  and  chiefly  in  the  last  century. 

Boyle  showed  by  means  of  the  air-pump  that  animals  die  in  a 
Va;(!:uhm,  and  Bernouilli  that  fish  cannot  live  in  water  from  whirh 
the  air  has  been  driven  out  by  boiling. 

Mayow,  of  Oxford,  seems  to  a  considerable  extent  to  have  antici- 
pated Black,  who  in  1757  demonstrated  the  presence  of  carbonic 
acid  (carbon  dioxide)  in  expired  air  by  the  turbidity  which  it  causes 
in  lime-water. 

A  fundamental  step  was  the  discovery  of  oxygen  by  Priestley  in 
1771,  and  his  proof  that  the  venous  blood  could  be  made  crimson, 
like  arterial,  by  being  shaken  up  with  oxygen. 

Lavoisier  discovered  the  composition  of  carbonic  acid,  and  applied 
his  discovery  to  the  explanation  of  the  respiratory  processes  in 
animals,  the  heat  of  which  he  showed  to  be  generated,  like  that  of  a 
candle,  by  the  union  of  carbon  and  oxygen.  He  made  many  further 
important  experiments  on  respiration,  publishing  some  of  h:^  results 
in  1789,  when  the  French  Revolution,  in  which  he  was  to  be  one  of 
the  most  distinguished  victims,  was  breaking  out.  He  made  the 
mistake,  however,  of  supposing  that  the  oxidation  of  the  carbon 
takes  place  in  the  blood  as  it  passes  through  the  lesser  circulation. 

That  some  carbon  dioxide  is  formed  in  the  lungs  there  is  no  reason 
to  doubt,  and  the  quantity  may  even  be  considerable.  But  that 
they  are  not  the  chief  seat  of  oxidation  was  sufficiently  proved  as 
soon  as  it  was  known  that  the  blood  which  comes  to  them  from  the 
right  heart  is  rich  in  carbon  dioxide,  while  the  blood  which  leaves 
them  through  the  pulmonary  veins  is  comparatively  poor. 

There  are  two  main  lines  on  which  research  has  gone  in  trying  to 
solve  the  chemical  problems  of  respiration:  (i)  The  analysis  and 
comparison  of  the  inspired  and  expired  air,  or,  in  general,  the  in- 
vestigation of  the  gaseous  exchange  between  the  blood  and  tlis  air 
in  the  lungs.  (2)  The  analysis  and  comparison  of  the  gases  of 
arterial  and  venous  blood,  of  the  other  liquids,  and  of  the  solid 
tissues  of  the  body,  with  a  view  to  the  determination  of  the  gaseous 
exchange  between  the  tissues  and  the  blood.  We  shall  take  these 
up  as  far  as  possible  in  their  order. 

The  methods  which  have  been  used  for  comparing  the  composi- 
tion of  inspired  and  expired  air  and  estimating  the  respiratory  ex- 
change are  very  various 

(i)  Breathing  into  one  spirometer  and  out  of  another,  the  inspired 
and  expired  air  being  directed  by  valves.  The  contents  of  the  spiro- 
meters are  analyzed  at  the  end  of  the  experiment  (Speck).  In  the 
arrangement  of  Zuntz  and  Geppert,  instead  of  the  whole  of  the  expired 
air,  a  sample  is  collected  for  analysis  during  the  entire  duration  of  the 
experiment,  while  the  total  volume  expired  is  measured  by  a  gas-meter. 
This  is  a  very  convenient  method  for  observations  on  man,  especially 


2^o  nr.spin.iTroN 

ill  (liscMMV  but  cacli  (.xpciiment  can  only  be  airried  on  at  most  for 
tilteen  to  twenty  mmutcs. 

(2)  A  small  apparatus,  much  on  the  same  principle,  was  used  for 
rabbits  by  Pfliigcr  and  his  pupils.  A  cannula  in  the  trachea  was  con- 
nected with  a  balanced  and  self-adjusting  spirometer  containing  oxygen, 
and  the  inspired  and  expired  air  separated  by  potassium  hydroxide 
valves,  which  absorbed  the  carbon  dioxide.  The  amount  of  oxygen 
used  could  be  read  oft  on  the  spirometer,  and  the  amount  of  carbon 
dioxide  produced  estimated  in  the  liquid  of  the  valves. 

(3)  Elaborate  arrangements,  such  as  Pettenkofer's  great  respiration 
apparatus,  and  the  still  larger  and  more  efficient  modifications  of  it 
constructed  since  his  time,  in  which  a  man,  or  even  several  men,  can 
remain  for  an  indefinite  period,  working,  eating,  and  sleeping.  Air  is 
drawn  out  of  the  chamber  by  an  engine,  its  volume  being  measured 
by  a  gas-meter.  But  as  it  would  be  far  too  troublesome  to  analyze 
the  whole  of  the  air,  a  sample  stream  of  it  is  constantly  drawn  off,  which 
also  passes  through  a  gas-meter,  through  drying-tubes  containing 
sulphuric  acid,  and  through  tubes  filled  with  baryta  water.  The  baryta 
solution  is  titrated  to  determine  the  quantity  of  carbon  dioxide ;  the 
increase  in  weight  of  the  drydng  tubes  gives  the  quantity  of  aqueous 
vapour.  A  similar  sample  stream  of  the  air  before  it  passes  into  the 
chamber  is  treated  exactly  in  the  same  way,  and  from  the  data  thus  got 
the  quantity  of  carbon  dioxide  and  aqueous  vapour  given  off  can  readily 
be  ascertained.  The  oxygen  can  be  calculated,  as  the  difference  be- 
tween the  fijial  body-weight  and  the  original  body-weight  plus  the 
weight  of  the  carbon  dioxide  and  water  eliminated,  but  may  also  be 
directly  estimated  by  special  methods. 

(4)  Haldane  and  Pembrey  have  elaborated  a  gravimetric  method, 
which  is  very  suitable  for  small  animals.  It  depends  upon  the  absorp- 
tion of  carbon  dioxide  by  soda  lime.  (See  Practical  l-lxercises,  p.  3^;.) 
In  Atwater's  so-called  respiration  calorimeter,  which  will  be  referred  to 
again  under  '  Animal  Heat.'  and  by  which,  not  only  the  gaseous  metab- 
olism, but  the  heat  production  can  be  measured  in  man,  the  carbon 
dioxide  is  estimated  in  the  same  way. 

Inspired  and  Expired  Air. — The  expired  air  is  at  or  near  the  body 
temperature,  and  is  saturated  witli  \\atcr\-  \apour.  In  ordinary 
breathing  it  contains  about  4  per  cent,  of  carbon  dioxide,  while  the 
inspired  air  only  contains  a  trace.  The  expired  air  contains  lO  or 
17  per  cent,  of  oxygen,  the  inspired  air  about  21  per  cent.  There  arc 
in  addition  in  expired  air  small  quantities  of  hydrogen  and  marsh- 
gas  derived  from  the  alimentary  canal,  either  directly  from  eructa- 
tion or  after  absorption  into  the  blood.  Sometimes  a  trace  of 
ammonia  can  be  detected  in  the  air  of  expiration,  but  this  is  due  to 
decomposition  of  proteins  taking  place  in  the  mouth,  especially  in 
carious  +eeth,  or  in  the  air-passages  and  lungs  in  disease  of  these 
organs.  It  has  indeed  been  shown  that  the  lungs  are  practically 
impermeable  for  ammonia.  Expired  air  is  entirely  free  from  float- 
ing matter  (dust),  which  is  always  present  in  the  inspired  air.  The 
volume  of  the  expired  air,  owing  to  its  higher  temperature  and  ex- 
cess of  watery  vapour,  is  somewhat  greater  than  that  of  the  inspired 
air,  but  if  it  be  measured  at  the  temperature  and  degree  of  satura- 
tion of  the  latter,  the  \olumc  is  somewhat  less.  Since  the  oxygen 
of  a  given  quantity  of  carbon  dioxide  would  have  exactly  the  same 


THE  CHEMISTRY  OE  EXTERNAL  EESPlR.lT lOK  i.,i 

volume  as  the  carbon  dioxide  itself  :\i  a  gi\en  temperature  and 
pressure,  it  is  clear  that  the  deficienc}'  is  due  to  the  fact  that  all  th(; 
oxygen  which  is  taken  up  in  the  lungs  is  not  given  oft"  as  carbon 
dioxide.     Some  of  it,  going  to  oxidize  hydrogen,  reappears  as  water. 

Alveolar  Air.  — The  percentage  of  carbon  dioxide  in  the  air  of  the 
alveoli  is  of  course  greater  and  that  of  oxygen  less  than  in  the 
ordinary  expired  air.  lM)r  the  relatively  pure  air  of  the  dead-space 
makes  up  a  substantial  fraction  of  the  tidal  air.  The  mean  of  the 
oxygen  or  carbon  dioxide  percentages  in  samples  taken  from  the 
last  portions  of  the  air  of  two  deep  expirations,  one  following  an 
ordinary  inspiration  and  the  other  following  an  ordinary  expiration, 
corresponds  fairly  well  with  the  mean  percentage  in  the  alveoli 
during  ordinary  breathing.  This  method  becomes  untrustworthy 
duiing  muscular  work.  The  average  percentage  of  oxygen  may 
be  taken  as  I4'5,  corresponding  to  a  partial  pressure  (p.  248) 
of  109  mm,  of  mercury.  The  percentage  of  carbon  dioxide  in 
the  alveolar  air  with  the  body  at  rest  is  remarkably  constant  in  one 
and  the  same  individual  at  constant  atmospheric  pressure.  It 
varies  in  different  men  from  4-6  to  6*2  (mean  5'5)  per  cent,  of  the  dry 
alveolar  air.  In  women  and  in  children  of  both  sexes  it  is  less  than 
in  men.  From  this  we  conclude  that  in  men  the  partial  pressure 
of  carbon  dioxide  in  the  alveoli  may  be  at  least  one-eighteenth  of 
an  atmosphere,  or  42  mm.  of  mercury  (Fitzgerald  and  Haldane). 

Respiratory  Quotient. — The  quotient  of  the  volume  of  oxygen 
given  out  as  carbon  dioxide  by  the  volume  of  oxygen  taken  in  is 
the  respiratory  quotient.  It  shows  what  proportion  of  the  oxygen 
is  used  to  oxidize  carbon.  It  may  approach  unity  on  a  carbo-hydrate 
diet  which  contains  enough  oxgyen  to  oxidize  all  its  own  hydrogen 
to  water.  With  a  diet  rich  in  fat  it  is  least  of  all;  with  a  diet  of 
lean  meat  it  is  intermediate  in  amount.  For  ordinary  fat  contains 
no  more  than  one-sixth,  and  proteins  not  one-half,  of  the  oxygen 
needed  to  oxidize  their  hydrogen  (p.  620).  In  man  on  a  mixed  diet 
the  respiratory  quotient  may  be  taken  as  0*8  or  O'Q.  So  long  as  the 
type  of  respiration  is  not  changed,  the  respiratory  quotient  may 
remain  constant  for  a  wide  range  of  metabolism.  In  hibernating 
animals,  however,  the  respiratory  quotient  may  become  very  small 
during  winter  sleep  (as  low  as  0-25),  both  the  output  of  carbon 
dioxide  and  the  c(jnsumption  of  oxygen  falling  enormously,  but 
the  former  in  general  more  than  the  latter.  This  has  been  explained 
on  the  assumption  that  oxygen  is  stored  away  in  winter  sleep  in  the 
form  of  incompletely  oxidized  substances.  On  the  other  hand,  in 
dyspnoea  accompanying  muscular  exertion  the  respiratory  quotient 
has  been  found  as  high  as  1-2.  It  must  be  remembered  that  even 
a  voluntary  increase  in  the  respiratory  movements  causes  an  imme- 
diate temporary  increase  in  the  respiratory  quotient,  owing  to  the 
'  washing  out  '  of  carbon  dioxide  from  the  blood  and  tissues.  This 
change  has  no  metabolic  significance.     Indeed,  the  determination 

i6 


-,i  AV;.S7'/AM //O.V 

of  tlu"  'csijiratorv  quotient  for  short  periods  has  onl\  a  limitrfl 
\  ahic,  and  such  ohscrvations  must  hv  int('r])rctod  with  great  can-. 
Ill  starvation  the  respiratory  quotient  diminislies,  the  production 
of  carbon  dioxide  falhiip;  off  at  a  greater  rate  than  the  consumption 
of  oxygen,  for  the  starving  organism  hves  on  its  own  fat  and  pro- 
teins, and  has  only  a  trifling  carbo-hydrate  stock  to  draw  upon. 
In  a  diabetic  patient,  fed  on  a  diet  of  fat  and  protein  alone,  the 
respinitory  quotient  was  only  o-6  to  07,  just  as  in  a  starving  man. 
Total  Respiratory  Exchange. — The  amount  of  oxygen  absorbed  in 
a  man  at  rest  lias  been  determined  under  certain  conditions  as  about 
0-29  gramme  per  hour,  and  the  discharge  of  carbon  dioxide  as  about 
0-33  gramme  per  hour  per  kilogramme  of  body- weight.  In  an 
average  man  weighing  70  kilos  the  mean  production  of  carbon 
dioxide  is  about  800  grammes  (400  litres)  in  twenty- four  hours,  and 
the  mean  consumption  of  oxygen  about  700  grammes  (490  litres). 
But  there  are  very  great  variations  depending  upon  the  state  of  the 
body  as  regards  rest  or  muscular  activity  and  on  other  circum- 
stances. In  hard  work  the  production  of  carbon  dioxide  was  foimd 
to  rise  to  nearly  1,300  grammes,  and  in  rest  to  sink  to  less  than 
700  grammes,  the  consumption  of  oxygen  in  the  same  circumstances 
increasing  to  nearly  1,100  grammes  and  diminishing  to  600  grammes. 
In  rest,  in  moderate  exertion,  and  in  hard  work,  the  production  of 
carbon  dioxide  was  found  to  be  nearly  proportionate  to  the  numbers 
2,  3,  and  6  respectively.  When  unaccustomed  work  is  performed, 
the  increase  in  the  carbon  dioxide  output  (and  oxygen  intake)  may 
be  much  greater.  With  training  it  diminishes.  In  a  case  of  diabetes 
the  consumption  of  oxygen  was  50  per  cent,  greater  than  in  a  healthy 
man,  corresponding  to  the  higher  heat-equivalent  of  the  food  of 
the  diabetic  patient. 

Ventilation. — Taking  400  litres  per  twenty-four  hours,  or  17  litres 
per  hour,  as  the  m-an  production  of  carbon  dioxide  by  an  average  male 
adult  at  rest  or  doing  only  light  work,  we  can  calculate  the  quantity  of 
fresh  air  which  must  be  supplied  to  a  room  in  order  to  keep  it  properly 
ventilated. 

It  has  been  found  that  when  the  carbon  dioxide  given  off  in  respiration 
amounts  to  no  more  than  2  parts  in  10,000  in  tTie  air  of  an  ordinary 
room,  the  air  remains  sweet.  When  the  carbon  dioxide  given  off  reaches 
4  parts  in  10,000,  the  room  feels  distinctly,  and  at  6  in  10,000  disagree- 
ably, close,  while  at  9  parts  in  10,000  it  is  oppressive  and  almost  in- 
tolerable. This  is  not  due  to  the  carbon  dioxide  as  such,  for  pure 
carbon  dioxide  added  alone  in  similar  proportions  to  the  air  of  a  room 
has  not  the  same  bad  effect,  and  the  amount  of  this  gas  is  onlv  taken 
as  an  index  of  the  extent  to  which  the  air  has  been  vitiated  by  some 
other  products  or  processes  connected  with  the  occupation  of  the 
room.  Very  often  the  mere  rise  of  temperature  in  a  crowded  and  ill- 
ventilated  space  is  sufficient  to  induce  dis.igroeablc  symptoms,  especially 
as  it  is  inevitably  associated  with  an  ijicrcase  in  the  humidity  of  the 
air,  which  reduces  the  capacity  of  the  body  to  cool  itself  by  increasing 
the  secretion  of  sweat.  Thus  it  has  been  found  that  persons  in  a 
respirator)'  chamber  feel  quite  comfortable  with  only  moderate  ventila- 
tion when  the  carbon  dioxide  has  risen  to  i  per  cent.,  if  care  is  taken 


THt-  Ctn:.\flSTRY  OF  EXThUKAL  RESP]UATIOS  243 

that  the  temperature  and  the  proportion  of  water\'  vapour  do  not  rise 
too  high.  In  aildition,  however,  it  has  been  supposed  by  some  that  a 
volatile  poison  exhaled  from  the  lungs  is  j>eculiarly  responsible  for  the 
evil  effects.  Certain  observers,  indeed,  alleged  that  the  condensed 
vapour  of  the  breath,  when  injected  into  rabbits,  produced  fatal  symp- 
toms. But  this  has  been  shown  to  be  erroneous;  and  the  most  careful 
experiments  have  failed  to  detect  in  the  air  expired  by  healthy  persons 
any  trace  of  such  a  poison.  It  has  therefore  been  suggested  that  the 
odour  and  some  of  the  other  ill-effects  of  a  close  room  are  due  to  sub- 
stances given  off  in  the  sweat  and  the  sebum,  and  allowed  by  persons 
of  uncleanly  habits  to  accumulate  on  the  skin,  and  also  to  the  products 
of  slow  putrefactive  processes  constantly  going  on,  under  favourable 
conditions,  on  the  walls,  fioor,  or  furniture,  but  only  becoming  per- 
ceptible to  the  sense  of  smell  when  ventilation  is  insufficient.  In  a 
small,  newly-painted  chamber,  presumably  free  from  such  impurities, 
it  was  not  until  the  carbon  dioxide  reached  3  to  4  per  cent.,  an  immensely 
greater  proportion  than  occurs  even  in  very  badly  ventilated  rooms, 
that  marked  discomfort,  with  dyspnoea,  began  to  be  felt.  No  close 
odour  could  be  detected. 

Nevertheless,  experience  has  shown  that  it  is  a  good  working  rule  for 
ventilation  to  take  the  limit  of  permissible  respiratory  impurity  at 
2  parts  of  carbon  dioxide  per  10,000;  and  the  17  litres  of  carbon  dioxide 
given  off  in  tke  hour  will  require  85.000  Litres  (or  3,000  cubic  feet)  of 
air  to  dilute  it  to  this  extent.  This  is  the  average  quantity  required 
for  the  male  adult  per  hour.  For  men  engaged  in  active  labour,  as  in 
factories  or  mines,  twice  this  amount  may  not  be  too  much.  For 
women  and  children  less  is  required  than  for  men.  If  a  room  smells 
close,  it  needs  ventilation,  whatever  be  the  proportion  of  carbon  dioxide 
in  the  air.  It  must  be  remembered  that  in  permanently  occupied 
rooms  mere  increase  in  the  size  will  not  compensate  for  incomplete 
renewal  of  the  air,  although  it  may  be  easier  to  ventilate  a  large  room 
than  a  small  one  ■without  causing  draughts  and  other  inconveniences. 
But  as  few  apartments  are  occupied  during  the  whole  twenty-four  hoiirs, 
a  large  room  which  can  be  thoroughly  ventilated  in  the  absence  of  its 
inmates  has  a  distinct  advantage  over  a  small  one  in  its  great  initial 
stock  of  fresh  air.  The  cubic  space  per  head  in  an  ordinan-  dwelling- 
house  should  be  not  less  than  28  cubic  metres  or  1,000  cubic  feet. 

The  quantity  of  carbon  dioxide  given  off  (and  of  oxygen  consumed) 
is  not  onl}'  affected  by  muscular  work,  but  also  by  everything  which 
influences  the  general  metabolism.  In  males  it  is  greater  on  the 
average  than  in  females  (in  the  latter  there  is  a  temporary  increase 
during  pregnancy),  but  for  the  same  body- weight  and  under  similar 
external  conditions  there  is  no  difference  between  the  sexes.  The 
gaseous  exchange  is  greater  in  proportion  to  the  body-weight  in  the 
child  than  in  the  adult.  This  depends  largely  on  the  fact  that, 
other  things  being  equal,  the  metabolism  is  relatively  to  the  body- 
weight  more  active  in  a  small  than  in  a  large  organism,  since 
the  surface  (and  therefore  the  heat  loss)  is  relatively  greater  in  the 
former.  But  it  has  been  shown  that  even  in  proportion  to  the 
surface  the  metabolism  is  greater  in  youth  than  in  adult  life,  and 
greater  in  the  vigorous  adult  than  in  the  old  man.  So  that  the  age 
of  the  organism  has  an  influence  apart  from  the  extent  of  surface. 
The  taking  of  food  increases  the  gaseous  exchange,  partly  from  the 


244 


RESPinATION 


increased  mechanical  and  chemical  work  performed  by  the  aU- 
mentary  canal  and  the  cHj^'estive  glands.  But  that  this  is  not  the 
sole  cause  of  the  increase  is  shown  by  the  fact  that  it  varies  with 
different  kinds  of  food  to  a  greater  extent  than  can  be  explained 
by  differences  in  the  ease  with  which  they  are  digested.  For  in- 
stance, maize  produces  a  much  greater  increase  than  oats  when 
given  in  equal  amount,  and  a  protein  diet  a  greater  increase  than  a 
diet  of  carbo-hydrate  or  fat.  Sleep  diminishes  the  production  of 
carbon  dioxide  partly  because  the  muscles  are  at  rest,  but  also  to 
.some  extent  because  the  external  stimuli  that  in  waking  life  excite 
the  nerves  of  special  sense  are  absent  or  ineffective.  Even  a  bright 
light  is  said  to  cause  an  increase  in  the  aonount  of  carbon  dioxide 
produced  and  of  ox3-gen  consumed;  but  probably  only  by  increasing 
muscular  movements,  including  the  movements  of  respiration. 
The  external  temperature  also  has  an  influence.  In  poikilothermal 
animals  (such  as  the  frog),  the  temperature  of  which  varies  with 
that  of  the  surrounding  medium,  the  production  of  carbon  dioxide, 
on  the  whole,  diminishes  as  the  external  temperature  falls,  and 
increases  as  it  rises.  In  homoiothertnal  animals,  that  is,  animals 
with  constant  blood  temperature,  external  cold  increases  the  pro- 
duction of  carbon  dioxide  and  the  consumption  of  oxygen.  But  if 
the  connection  of  the  nervous  system  with  the  striated  muscles  has 
been  cut  out  by  curara,  the  warm-blooded  animal  behaves  like  the 
cold-blooded  (Pfliiger  and  his  pupils  in  guinea-pig  and  rabbit). 
These  interesting  facts  will  be  returned  to  under  '  Animal  Heat.' 

Cold-blooded  animals  produce  far  less  carbon  dioxide,  and  con- 
sume far  less  oxygen,  per  kilo  of  body-weight  than  warm-blooded. 

The  following  table  shows  the  relation  between  the  body-weight 
and  the  excretion  of  carbon  dioxide  in  man : 


Age. 

1 

MI-  •   u.  •     VI                  COo  excreted  per  Kilo 
Weight  in  K.los.                         per  Hour. 

Male 

f58 

44 

35 

^8 

i6 
I  9-6 

84'6                   0'4i  gramme 
76'5                   0-48 
65  "                    0-51 
82                      0-49 

577                   0-59        .. 
22                      0*92 

r66 

Female  a  ^ 

iio 

66-9 

53-9 
557 
23 

0-39 
0-54 
0-45 
083        .. 

The  next  table  illustrates  the  difference  in  the  intensity  of  metab- 
olism in  different  kinds  of  animals,  a  difference,  however,  largely 
dependent  upon  relative  size: 


Tin:  Cin-MISTRY  OF  F.XTERNAL  RESPIRATION 


245 


Oxygen  absorbed  per 
kilo  per  Hour. 

Carbon  Dioxide  given  off 
per  Kilo  per  Hour. 

Respiratory  Quotient 

Animal. 

CO2      Oj  (in  CO2) 

Id  Grms. 

In  C.C. 

In  Grms. 

In  C.C. 

Ol°'      ~02~- 

Greenfincli    - 

I  V<JOO 

9091 

13-590 

6909 

0-76 

Hen       - 

1-058 

740 

1-327 

675 

0-91 

Dog      - 

1-303 

911 

1-325 

674 

074 

Rabbit 

o-()87 

690 

1-244 

632 

0-91 

Sheep   - 

0-490 

343 

0-671 

.341 

0-99 

Boar     - 

0-39I 

^73 

0-443 

2-25 

0-82 

Frog     - 

0-105 

73-4 

0-II3 

57-7 

0-78 

Crayfish 

0-054 

38 

0-0O4 

32-7 

0-86 

Forced  respiration,  although  it  will  temporarily  increase  the 
quantity  of  carbon  dioxide  given  off  by  the  lungs,  and  thus  raise 
for  a  short  time  the  respiratory  quotient,  does  not  sensibly  affect 
the  production ;  it  is  only  the  store  of  already  formed  carbon  dioxide 
in  the  body  which  is  drawn  upon.  The  amount  of  oxygen  taken 
up  is  little  altered  by  changes  in  the  movements  of  respiration. 
Within  wide  limits  the  oxygen  consumption  of  the  organism  is  in- 
dependent of  the  supply  of  oxygen  offered  to  it. 

How  it  is  that  the  depth  of  the  respiration  may  affect  the  rate  at 
which  carbon  dioxide  is  eliminated,  we  can  only  understand  when 
we  have  examined  the  process  by  which  the  gaseous  interchange 
between  the  blood  and  the  air  of  the  alveoli  is  accomplished;  and 
before  doing  this  it  is  necessary  to  consider  the  condition  of  the 
oxygen  and  carbon  dioxide  in  the  blood. 


Section  IV. — ^The  Gases  of  the  Blood. 

Physical  Introduction. — Matter  may  be  assumed  to  be  made  up  of 
molecules  beyond  which  it  cannot  be  divided  without  altering  its  essen- 
tial character.  A  molecule  may  consist  of  two  or  more  particles  of 
matter  (atoms)  bound  to  each  other  by  chemical  links.  The  kinetic 
theory  of  matter  supposes  the  molecules  of  a  substance  to  be  in  constant 
motion,  frequently  colliding  with  each  other,  and  thus  having  the  direc- 
tion of  their  motion  changed. 

In  a  gas  the  mean  free  path,  that  is,  the  average  distance  which  a 
molecule  travels  without  striking  another,  is  comparatively  long,  and 
far  more  time  is  passed  by  any  molecule  without  an  encounter  than  is 
taken  up  with  collisions.  Although  the  average  velocity  of  the  mole- 
cules is  very  great,  these  collisions  will  produce  all  sorts  of  differences 
in  the  actual  velocity  of  different  molecules  at  any  given  time.  Some 
will  be  moving  at  a  greater,  some  at  a  slower  rate,  than  the  average; 
while  some  may  be  for  a  moment  at  rest.  If  the  gas  is  in  a  closed 
vessel,  the  molecules  will  be  constantly  striking  its  sides  and  rebounding 
from  them.  If  a  ver}'  small  opening  is  made  in  the  vessel,  some  mole- 
cules will  occasionally  hit  on  the  opening  and  escape  altogether.  If  the 
opening  is  made  larger,  or  the  experiment  continued  for  a  longer  time 


24<5  prspiRATTny  < 

with  the  small  opening,  all  the  molecules  will  in  course  of  time  have 
passed  out  of  the  vessel  into  the  air,  while  molecules  of  the  oxygen, 
nitrogen,  and  argon  of  the  air  will  have  passed  in.  In  a  gas,  then,  not 
enclosed  by  impenetrable  boundaries,  there  is  no  restriction  on  the  path 
which  a  molecule  may  take,  no  tendency  for  it  to  keep  within  any  limits. 

When  two  chemically  indifferent  gases  are  placed  in  contact  with  each 
other,  diffusion  will  go  on  till  they  are  uniformly  mixed.  The  diffusion 
of  gases  may  be  illustrated  thus.  Suppose  we  have  a  perfectly  level 
and  in  every  way  uniform  field  di\idcd  into  two  equal  parts  by  a  visible 
but  intangible  line,  the  well-known  whitewash  line,  for  instance.  On 
one  side  of  the  line  place  500  blind  men  in  green,  and  on  the  other  500 
blind  men  in  red.  At  a  given  signal  let  them  begin  to  move  about  in 
the  field.  Some  of  the  men  in  green  will  pass  over  the  line  to  the  '  red  ' 
side;  some  of  the  men  in  red  will  wander  to  the  '  green  '  side.  Some 
of  the  men  may  pass  over  the  line  and  again  come  back  to  the  side 
they  started  from.  But,  upon  the  whole,  after  a  given  interval  has 
elapsed,  as  many  green  coats  will  be  seen  on  the  red  side  as  red  coats 
on  the  green.  And  if  the  interval  is  long  enough  there  will  be  at  length 
about  250  men  in  red  and  250  in  green  on  each  side  of  the  boundary- 
line.  WTien  this  state  of  equilibrium  has  once  been  reached,  it  will 
henceforth  be  maintained,  for,  upon  the  whole,  as  many  red  uniforms 
will  pass  across  the  line  in  one  direction,  as  will  recross  it  in  the  other. 

In  a  liquid  it  is  very  different ;  the  molecule  has  no  free  path.  In  the 
depth  of  the  liquid  no  molecule  ever  gets  out  of  the  reach  of  other 
molecules,  although  after  an  encounter  there  is  no  tendency  to  return  on 
the  old  path  rather  than  to  choose  any  other;  so  that  any  molecule 
may  wander  through  the  whole  liquid.  Although  the  average  velocity 
of  the  molecules  is  much  less  in  the  liquid  state  than  it  would  be  for 
the  same  substance  in  the  state  of  gas  or  vapour  (gas  in  presence  of  its 
liquid),  some  of  them  may  have  velocities  much  above  the  average. 
If  any  of  these  happen  to  be  moving  near  the  surface  and  towards  it, 
they  may  overcome  the  attraction  of  the  neighbouring  molecules  and 
escape  as  vapour.  But  if  in  their  further  wanderings  they  strike  the 
liquid  again,  they  may  again  become  bound  down  as  liquid  molecules. 
And  so  a  constant  interchange  may  take  place  between  a  liquid  and  its 
vapour,  or  between  a  liquid  and  any  other  gas,  until  the  btate  of  equi- 
librium is  reached,  in  which  on  the  average  as  many  molecules  leave  the 
liquid  to  become  vapour  as  are  restored  by  the  vapour  to  the  liquid,  or  as 
many  molecules  of  the  dissolved  gas  escape  from  solution  as  enter  into  it. 

For  the  sake  of  a  simple  illustration,  let  us  take  the  case  of  a  shallow 
vessel  of  water  originally  gas-free,  standing  exposed  to  the  air.  It  will 
be  found  after  a  time  that  the  water  contains  the  atmospheric  gases  in 
certain  proportions — in  round  numbers,  about  yjjj  of  its  volume  of 
oxygen  and  -^q  of  its  volume  of  nitrogen  (measured  at  760  mm.  mercury 
and  0°  C). 

Now,  let  a  similar  vessel  of  gas-free  water  be  placed  in  a  large  airtight 
box  filled  with  air  at  atmospheric  pressure,  and  let  the  oxygen  be  all 
absorbed  before  the  water  is  exposed  to  the  atmosphere  of  the  box. 
The  latter  now  consists  practically  only  of  the  nitrogen  of  the  air,  and 
its  pressure  will  be  only  about  four-fiiths  that  of  the  external  atmo- 
sphere. Nevertheless,  the  quantity  of  nitrogen  absorbed  by  the  water 
will  be  exactly  the  same  as  was  absorbed  from  the  air.  If  the  box 
was  completely  exhausted,  and  then  a  quantity  of  oxj'gen,  equal  to  that 
in  it  at  first,  introduced  before  the  water  was  exposed  to  it,  the  pressure 
would  be  found  to  be  only  about  one-fifth  that  of  the  external  atmo- 
sphere ;  but  the  quantity  of  oxygen  taken  up  by  the  water  would  be 
exactly  equal  to  that  taken  up  in  the  first  experiment. 


Till'.  GASFs  Of  Tin:  isr.OOD 


2.17 


Two  well-known  physical  laws  are  illustrated  by  our  supposed  ex- 
periments: (i)  In  a  mixture  of  gases  which  do  not  act  chemically  on  each 
other  the  pressure  exerted  by  each  gas  {called  the  partial  presstire  of  the 
gas)  is  the  same  as  it  ivould  exert  if  the  others  were  absent.  (2)  The  quan- 
tity {mass)  of  a  gas  absorbed  by  a  liquid  which  does  not  act  chemically  upon 
it  is  proportional  to  the  partial  pressure  of  the  gas.  It  also  depends  upon 
the  nature  of  the  gas  and  of  the  liquid,  anil  on  the  temperature,  increase 
of  temperature  in  general  diminishing  the  quantity  of  gas  absorbed. 
It  is  to  be  noted  that  when  the  volume  of  the  absorbed  gas  is  measured 
at  a  pressure  equal  to  the  partial  pressure  under  which  ii  was  absorbed, 
the  same  volume  of  gas  is  taken  up  at  every  pressure. 

The  volume  of  a  gas  (reduced  to  0°  C.  and  760  mm.  pressure)  physi- 
cally' absorbed  or  dissolved  in  i  c.c.  of  a  liquid  exposed  to  the  gas  at 
760  mm.  pressure  is  called  the  absorption  coefficient  of  the  gas  in  that 
liquid.  The  following  table  from  Bohr  shows  the  absorption  coefficients 
of  the  three  gases  of  physiological  interest— oxygen,  nitrogen,  and 
carbon  dioxide  in  water,  blood-plasma,  whole  blood  and  blood-corpuscles 
at  the  body  temperature  (38°  C.) : 


Water 

Blood-plasma 
Blood  - 
Blood-cells   - 


Oxygen. 


0-0237 
0-023 
0-022 
0-019 


Nitrogen. 


0-0122 
O-0I2 
O-OII 
O-OIO 


Carbon  Dioxide. 


o'555 
0-541 
0-511 

0-450 


Suppose,  now,  that  a  vessel  of  water,  saturated  with  oxygen  and 
nitrogen  for  the  partial  pressures  under  which  these  gases  exist  in  the 
air,  is  placed  in  a  box  filled  with  pure  nitrog<-n  at  full  atmospheric  pres- 
sure. As  we  have  seen,  there  is  a  constant  interchange  going  on  between 
a  liquid  which  contains  gas  in  solution  and  the  atmosphere  to  which  it 
is  exposed.  Oxygen  and  nitrogen  molecules  will  therefore  continue  to 
leave  the  water;  but  if  the  box  is  large,  few  oxygen  molecules  will  find 
their  way  back  to  the  water,  and  ultimately  little  oxygen  will  remain 
in  it.  In  other  words,  the  quantity  of  oxygen  absorbed  by  the  water 
will  become  again  proportional  to  the  partial  pressure  of  oxygen,  which 
is  not  now  much  above  zero.  On  the  other  hand,  molecules  of  nitrogen 
will  at  first  enter  the  water  in  larger  number  than  they  escape  from  it, 
for  the  pressure  of  the  nitrogen  is  now  that  of  the  external  atmosphere, 
of  which  its  partial  pressure  was  formerly  only  four-fifths.  In  unit 
volume  of  the  gas  above  the  water  there  will  be  5  molecules  of  nitrogen 
for  every  4  molecules  in  the  same  volume  of  atmospheric  air.  There- 
fore, on  the  average  5  nitrogen  molecules  will  in  a  given  time  get  en- 
tangled by  liquid  molecules  for  every  4  which  came  within  their  sphere 
of  attraction  before.  On  the  whole,  then,  the  water  will  lose  oxygen 
and  gain  nitrogen,  while  the  atmosphere  of  the  airtight  box  will  gain 
oxygen  and  lose  nitrogen. 

In  the  case  of  water,  in  which  oxygon  and  nitrogen  are  absorbed 
solely  in  solution,  the  partial  pressures  of  these  gases  under  which  the 
water  was  originally  saturated  could,  of  course,  be  easily  calculated 
from  the  amount  dissolved  and  the  ccefficient  of  absorption.  But 
supposing  that  these  partial  pressures  were  unkno^\^l,  it  is  evident  that 
by  exposing  it  to  an  atmosphere  of  known  composition,  and  afterwards 
determining  the  changes  produced  m  the  composition  of  that  atmo- 


248 


RKSPIRA  TION 


w^    w^ 


sphere  by  loss  to.  or  gain  from,  the  gases  of  the  water,  wc  could  find  out 
something  about  the  original  partial  pressures.  If,  for  example,  the 
quantity  of  oxygen  in  the  atmospliere  or  the 
chamber  was  increased,  we  could  conclude  that 
the  jiartial  pn  ssure  of  oxygen  under  which  the 
water  had  been  saturated  was  greater  than 
that  in  the  chamber  at  the  beginning  of  the 
expcrmient.  And  if  we  found  that  with  a 
certain  partial  pressure  of  oxygen  in  the  atmo- 
sphere of  the  chamber  there  was  neither  gain 
nor  loss  of  this  gas,  we  might  be  sure  that  the 
partial  pressure  (the  temperature  l)cing  sup- 
posed not  to  vary)  was  the  same  when  the 
water  was  saturated.  We  shall  see  later  on 
how  this  principle  has  been  applied  to  deter- 
mine the  partial  ])ressure  of  oxygen  or  carbon 
dioxiile  which  just  suffices  to  prevent  blood,  or 
any  other  of  the  liquids  of  the  body,  from 
losing  or  gaining  these  gases  when  they  are  not 
merely  dissolved,  but  also  combined  in  the 
form  of  dissociable  compounds.  This  pressure 
is  evidently  equal  to  that  exerted  by  the  gases 
of  the  licjuid  at  its  surface,  which  is  sometimes 
called  their  '  tension  ' ;  for  if  it  were  greater, 
gas  would,  upon  the  whole,  pass  into  the  blood  ; 
and  if  it  were  less,  gas  would  escape  from  the 
blood.  Thus,  the  tension  of  a  gas  in  solution  in 
a  liquid  is  equal  to  the  partial  pressure  of  that 
gas  in  an  atmosphere  to  which  the  liquid  is  ex- 
posed, which  is  just  sufficient  to  prevent  gain  or 
loss  of  the  gas  by  the  liquid  (p.  258). 

The  following  imaginary  experiment  may 
further  illustrate  the  meaning  of  the  term  '  ten- 
sion '  of  a  gas  in  a  lic[uid  in  this  connection. 

Suppose  a  cylinder  filled  with  a  liquid  con- 
taining a  gas  in  solution,  and  closed  above  by 
a  piston  moving  airtight  and  without  friction, 
in  contact  with  the  surface  of  the  liquid  (Fig. 
117).  Let  the  weight  of  the  pi.ston  be  balanced 
by  a  counterpoise.  The  pressure  at  the  sur- 
face of  the  liquid  is  evidently  that  of  the 
atmosphere.  Now,  let  the  whole  be  put  into 
the  receiver  of  an  air-pump,  and  the  air 
gradually  exhausted.  Let  exhaustion  proceed 
until  gas  begins  to  escape  from  the  licpiid  and 
lies  in  a  thin  Uiycr  between  its  surface  and  the 
piston,  the  quantity  of  gas  whicli  has  become 
free  being  very  small  in  proportion  to  that 
still  in  solution.  At  this  point  the  piston  is 
acted  upon  by  two  forces  which  balance  each 
other,  the  pressure  of  the  air  in  the  receiver 
acting  downwards,  and  the  pressure  of  the  gas 
escaping  from  the  liquid  acting  upwards.  If 
the  pressure  in  the  receiver  is  now  slightly 
increased,  the  gas  is  again  absorbed.  The  pressure  at  which  this  ju.st 
happens,  and  against  which  the  pi.ston  is  still  supported  by  the  impacts 
of  gaseous  molecules  flying  out  of  the  liquid    while  no  pressure  is  as  yet 


Fig.  ii/- — Imaginary  Ex- 
periment to  illustrate 
'  Tension  '  of  a  Gas  in  a 
Liquid.  P,  frictionless 
piston;  L,  liquid  in  cy- 
linder; G,  gas  beginning 
to  escape  from  litjuid. 
P  is  exactly  counter- 
poised. In  addition  to 
the  manner  described  in 
the  text,  the  experiment 
may  be  supposed  to  be 
j)ertormed  thus:  Let  the 
weight,  \V,  be  deter- 
mined which,  when  the 
receiver  is  completely 
exhausted,  suffices  just  to 
keep  the  pi"  on  in  contact 
with  the  litpiid.  The 
pressure  of  the  gas  is 
then  just  counter- 
I)alanced  by  W;  and  if 
S  is  the  area  of  the  cross- 
section  of  the  piston,  the 
jiressure  of  the  gas  per 

W 

unit  of  area  is  j^.     Or,  if 

the  piston  is  hollow,  and 
mercury  is  poured  into 
it  so  as  just  to  keep  it  in 
contact  with  the  liquid, 
the  height  of  the  column 
of  mercury  required  is 
also  equal  to  the  pressure 
or  tension  of  the  gas. 


TIIF  GASES  or  THE  BI.OOD 


249 


exerted  dirci  tly  Ixtwicii  the  liquid  and  the  piston,  is  obviously  equal 
to  the  pressure  or  tension  of  the  gas  in  the  Uquid. 

From  the  above  principles  it  follows  that  a  gas  held  in  solution  may 
be  extracted  by  exposure  to  an  atmosphere  in  which  the  partial  pressure 
of  the  gas  is  niade  as  small  as  possible.  Thus,  oxygen  can  be  obtained 
from  liquids  in  which  it  is  simply  dissolved  by  putting  them  in  an 
atmosphere  of  hydrogen  or  nitrogen,  in  which  the  partial  pressure  of 
oxygen  is  zero,  or  in  the  vacuum  01  an  air-pump,  in  which  it  is  extremely 
small.  Heat  also  aids  the  expulsion  of  dissolved  gases.  Some  gases 
held  in  weak  chemical  union,  like  the  loosely-combined  oxygen  of 
oxyluemoglobin,  can  be  obtained  by  dissociation  of  their  compounds 

Fig.  118.— Scheme  of  Gas-Pump.  \.  the  blood 
bulb;  B.  the  froth  chamber;  C,  the  drying  tube; 
U.  fixed  mercury  bulb  ;  E.  movable  mercury 
bulb  connected  by  a  flexible  tube  with  D;  F, 
eudiometer;  G,  a  narrow  delivery  tube;  i.  2,  3,  4. 
taps,  4  being  a  three-way  tap.  A  is  filled  with 
blood  by  connecting  the  tap  i  by  means  of  a 
tube  with  a  bloodvessel.  Taps  i  and  2  are  then 
closed.  The  rest  of  the  apparatus  from  B  to  D  is 
now  exhausted  by  raising  E,  with  tap  4  turned 
so  as  to  place  D  only  in  communication  with  G, 
till  the  mercury  fills  D.  Tap  4  is  now  turned  so  as 
to  connect  C  with  D,  and  cut  off  G  from  D,  and  E 
is  lowered.  The  mercury  passes  out  of  D,  and  air 
passes  into  it  from  B  and  C.  Tap  4  is  again  turned 
so  as  to  cut  off  C  from  D  and  connect  G  and  D.  E 
is  raised  and  the  mercury  passes  into  D  and  forces 
the  air  out  through  G,  the  end  of  which  has  not 
hitherto  been  placed  under  F.  This  alternate 
raising  and  lowering  of  E  is  continued  till  a  man- 
ometer  connected  between  C  and  4  indicates  that 
the  pressure  has  been  sufficiently  reduced.  The 
tap  2  is  now  opened;  the  gases  of  the  blood  bubble  up  into  the  froth  chamber,  pass 
through  the  drying-tube  C,  which  is  filled  with  pumice-stone  and  sulphuric  acid,  and 
enter  D.  The  end  of  G  is  placed  under  the  eudiometer  F,  and  by  raising  E.  with 
tap  4  turned  so  as  to  cut  off  C,  the  gases  are  forced  out  through  G  and  collected 
m  F.  The  movements  required  for  exhaustion  can  be  repeated  several  times  till 
no  more  gas  comes  off.  The  escape  of  gas  from  the  blood  is  facilitated  by  immersing 
the  bulb  A  in  water  at  40"  to  50°  C. 

when  the  partial  piessure  is  reduced.  More  stable  combinations  may 
require  to  be  broken  up  by  chemical  agents — carbonates,  for  instance, 
by  acids. 

Extraction  of  the  Blood-Gases. — This  is  best  accomplished  by  ex- 
posing blood  to  a  nearly  perfect  vacuum.  The  gas-pumps  which  have 
hztn  most  largely  used  in  blood  analysis  are  constructed  on  the  principle 
of  the  Torricellian  vacuum.  A  diagram  of  a  simple  form  of  Pfliiger's 
gas-pump  is  given  in  Fig.  118.  The  gases  obtained  are  ultimately  dried 
and  collected  in  a  eudiometer,  which  is  a  graduated  glass  tube  with  i.^s 
mouth  dipping  into  mercury.  The  carbon  dioxide  is  estimated  by 
introducing  a  little  potassium  hydroxide  to  absorb  it.  The  diminution 
in  the  volume  of  the  gas  contained  in  the  eudiometer  gives  the  volume 
of  the  carbon  dioxide.  The  oxygen  may  be  estimated  by  putting  into 
the  eudiometer  more  than  enough  hydrogen  to  unite  with  all  the  oxygen 
so  as  to  form  water,  and  then,  after  reading  ofif  the  volume,  exploding 
the  mixture  by  means  of  an  electric  spark  passed  through  two  platinum 
wires  fused  into  the  glass.  One-third  of  the  diminution  of  volume 
represents  the  quantity  of  oxygen  present.     It  can  also  be  estimated 


250  ruspiration 

by  absorption  \vith  a  solution  of  pyrogallic  acid  anil  potassium  hyiliox- 
ide,  or  an  alkaline  solution  of  sodium  hydrosulplute,  which  is  more 
cleanly.  The  remainder  of  the  original  mixture  of  blood-gases,  after 
deduction  of  the  carbon  dioxide  and  oxygen,  is  put  down  as  nitrogen 
(with,  no  doubt,  a  small  proportion  of  argon).  l"or  the  sake  of  easy 
comparison,  the  observed  volume  of  gas  is  always  stated  in  terms  of  its 
equivalent  at  a  standard  pressure  and  temperature  (7()o  mm.,  or  some- 
times on  the  C(jntinent  i  metre  of  mercury,  and  o    C). 

It  is  also  possible  in  various  ways  to  estimate  the  amount  of  oxygen 
in  blood  without  the  use  of  the  pump.  Thus,  since  a  definite  volume  of 
oxygen  (1338  c.c.  at  0°  C.  and  760  mm.  pressure)  combines  with  a 
gramme  of  h?cmoglobin,  we  can  calculate  the  total  volume  of  oxygen 
present  if  we  know  how  much  of  the  blood-pigment  is  in  the  form  of 
oxyha>moglobin ;  and  this  can  be  determined  by  means  of  the  spectro- 
photometer. Or  potassium  fcrricyanidc  may  be  added  to  the  blood. 
This  expels  the  oxygen  from  its  combination  witii  the  hanioglobin, 
which  then  unities  with  an  exactly  equal  amount  of  oxygen  obtained 
from  the  ferricyanide  to  form  methiemoglobin  (Haldane)  (p.  75). 

In  the  hands  of  Barcroft  and  his  pupils  this  method  has  been  highly 
developed,  so  that  accurate  results  can  be  obtained  with  small  quantities 
of  blood  (i  c.c,  and  with  the  smaller  apparatus  even  o-i  c.c.).  Bar- 
croft's  differential  apparatus  consists  essentially  of  two  small  bottles, 
as  nearly  alike  as  possible,  connected  by  a  manometer  filled  with  oil  (of 
cloves).  The  amount  of  oxygen  liberated  in  one  of  the  bottles  by 
potassium  ferricyanide  from  a  measured  amount  of  blood  can  be  est-t- 
mated  from  the  displacement  of  the  liquid  in  the  manometer.  Tlie 
function  of  the  second  bottle  is  to  automatically  eliminate  effects  due 
to  changes  in  the  temperature  of  the  bath  in  which  the  apparatus  is 
immersed,  etc.,  since  bf)th  bottles  are  affected  alike. 

The  Quantity  of  the  Blood-Gases. — In  arterial  and  in  venous  blood 
oxygen,  carbon  dioxide,  nitrogen,  and  argon  are  constantly  found. 
Both  the  oxygen  and  the  carbon  dioxide  vary  considerably  in 
amount  in  the  arterial  blood,  even  of  individuals  of  the  same  animal 
group,  and,  of  course,  much  more  in  the  venous  blood,  as  might 
naturally  be  expected,  since  even  to  the  eye  it  varies  greatly  accord- 
ing to  the  vein  it  is  obtained  from,  the  rapidity  of  the  circulation, 
and  the  activity  of  the  tissues  whicli  it  has  just  left.  In  one 
observation  on  blood  obtained  directly  from  a  human  artery,  2i'6c.c. 
of  oxygen,  40*3  c.c.  of  carbon  dioxide,  and  !•()  c.c  of  nitrogen  were 
found  in  100  c.c.  of  blood.  Tlie  quantity  of  oxygen  taken  up  outside 
of  the  body  by  specimens  of  human  blood  drawn  from  six  normal 
persons,  when  shaken  up  with  atmospheric  air,  varied  from  1 7-6  c.c. 
to  22-5  c.c.  per  100  c.c.  of  blood,  the  variations  depending  mainly 
on  the  hgemoglobin  content.  The  arterial  blood  as  it  actually  left 
the  lungs  of  those  persons  must  have  contained  somewhat  less  oxygen 
(about  I  c.c.  less  per  100  c.c.  of  blood),  since  the  partial  pressure  of 
oxygen  in  the  alveolar  air  is  decidedly  below  that  in  atmospheric 
air.  In  dogs  the  amount  of  carbon  dioxide  in  arterial  blood  has 
been  found  to  vary  from  35  to  45  c.c.  per  100  c.c.  of  blood,  the 
differences  being  due  to  variations  in  the  extent  of  the  pulmonary 
ventilation  and  to  other  factors. 


TIIIl  gases  Ol-    iHE  IIUJOD  231 

In  a  scries  of  observations  on  the  venous  blood  of  dogs  the  oxygen 
content  ranged  from  5-5  to  i6-6c.c. (average  ii-gc.c),  and  the  carbon 
dioxide  content  from  38-8  c.c.  to  47-5  (average  44-3  c.c.)  per  100  c.c. 
of  blood  (Schoffer).  It  will  be  sufficiently  accurate  to  assume  that 
on  the  average, 

Volumes  of 


O2.  COi;.  N2. 

too  volumes  of  arterial  blood  yield      -         -        20  40  1-2 

„  ,,  mixed  venous  blood  (from 

right  heart)  yield 10-12       45-50       1-2 

(reduced  to  0°  C.  antl  -Oo  mm.  of  mercury). 

Average  venous  blood  contains  7  or  8  per  cent,  by  volume  less 
oxygen,  and  7  or  8  per  cent,  more  carbon  dioxide,  than  arterial 
blood.  Thus,  in  the  lungs  the  blood  gains  about  twice  as  many 
volumes  of  oxygen  per  cent,  as  the  air  loses,  and  the  air  gains  about 
half  as  many  volumes  of  carbon  dioxide  per  cent,  as  the  blood  loses. 
It  is  easy  to  see  that  this  must  be  so,  for  the  volume  of  air  inspired 
in  a  given  time  is  about  twice  as  great  as  that  of  the  blood  which 
passes  through  the  pulmonary  circulation  (pp.  223,  236).  Even 
arterial  blood  is  not  quite  saturated  with  oxygen;  it  can  still  take 
up  a  variable  small  amount.  The  percentage  saturation  with 
oxygen  of  the  arterial  blood  of  a  normal  woman  from  whom 
blood  was  being  transfused  into  a  patient  was  directly  determined. 
The  blood  proved  to  be  94  per  cent,  saturated — i.e.,  it  could  still 
have  taken  up  about  one-sixteenth  of  the  quantity  contained  in 
it.  Nor  is  venous  blood  nearly  saturated  with  carbon  dioxide; 
when  shaken  with  the  gas  it  can  take  up  about  150  volumes  per  cent. 

The  total  oxygen  capacity  of  the  blood  in  any  individual  can  be 
determined,  if  the  volume  of  the  blood  is  known  (p.  56),  by  estimating 
the  amount  of  oxygen  needed  to  saturate  a  sample  of  the  blood. 
This  is  most  conveniently  done  by  the  ferricyanide  method  mth 
Barcroft's  apparatus.  Suppose,  for  example,  that  i  c.c.  of  blood, 
after  being  thoroughly  shaken  up  with  air  or  oxygen,  gives  off 
0-2  c.c.  of  oxygen  when  acted  upon  by  ferricyanide,  and  that  the 
total  volume  of  the  blood  has  been  determined  to  be  5  litres,  then 
the  total  oxygen  capacity  of  the  blood  will  be  1,000  c.c.  This 
quantity,  it  is  clear,  is  a  measure  of  the  power  of  the  blood  to  trans- 
port oxygen.  The  oxygen  capacity  of  a  sample  of  blood  is  propor- 
tional to  the  amount  of  haemoglobin  in  it,  so  that  the  estimation  of 
the  percentage  amount  of  haemoglobin  by  a  properly  standardized 
hsemoglobinometer  is  really  an  estimation  of  the  oxgyen  capacity  of 
the  quantity  of  blood  used  for  the  determination.  The  total  oxygen 
capacity  of  the  body  cannot,  of  course,  be  derived  from  such  an 
observation,  any  more  than  the  total  quantity  of  haemoglobin,  unless 
the  amount  of  blood  in  the  body  is  known. 

When  the  gases  are  not  removed  from  blood  immediately  after 


252  RESPIRATION 

it  is  drawn,  it  yields  more  carbon  dioxide  and  less  oxygen  than  if  it 
is  evacuated  at  once  (Pfliigcr).  From  this  it  is  concluded  that 
oxidation  g(X's  on  in  the  blood  for  some  time  after  it  is  shed.  The 
oxidizable  substances  are,  however,  confined  to  the  corpuscles, 
which  suggests  that  ordinary  metabolism  simply  continues  for 
some  time  in  the  formed  elements  of  the  shed  blood,  and  that  the 
disappearance  of  oxygen  is  not  due  to  the  oxidation  of  substances 
which  have  reached  the  blood  from  the  tissues.  It  is  an  interesting 
fact  that  the  rate  of  oxygen  consumption  of  nucleated  (bird's)  ery- 
throcytes is  much  greater  than  that  of  non-nucleated  mammalian 
corpuscles.  The  young  non-nucleated  erythrocytes,  which  in  experi- 
mental aniemia  in  manmials  [e.g.,  after  hiemorrhage)  find  their  way 
in  large  numbers  into  the  circulation,  have  a  relatively  intense 
metabolism,  and  therefore  consume  a  relatively  large  amount  of 
oxygen. 

The  Distribution  and  Condition  of  the  Oxygen  in  the  Blood. — ^The 
oxygen  is  nearly  all  contained  in  the  corpuscles.  A  little  oxygen 
can  be  pumped  out  of  serum  (o-2  or  o«3  per  cent,  by  volume),  but  this 
follows  the  Henry-Dalton  law  of  pressures — that  is,  it  comes  off  in 
proportion  to  the  reduction  of  the  partial  pressure  of  the  oxygen  in 
the  pump,  and  is  simply  in  solution. 

\\lien  blood  at  body  temperature  is  shaken  up  with  air  at  the 
ordinary  pressure,  corresponding  to  a  partial  pressure  of  oxygen 
of  a  little  over  one-fifth  of  an  atmosphere  (in  round  numbers  i6o  mm. 
of  mercury),  the  blood-pigment  becomes  saturated  with  oxygen  or 
nearly  so.  When  the  blood  is  now  pumped  out,  very  little  oxygen 
( omes  off  till  the  pressure  has  been  reduced  to  about  half  an  atmo- 
sphere, corresponding  to  a  pressure  of  oxygen  of  about  80  mm. 
At  about  70  mm.  partial  pressure  the  dissociation  is  somewhat 
greater.  At  a  third  to  a  quarter  of  an  atmosphere  (50  to  40  mm.'; 
the  amount  of  oxygen  liberated  is  markedly  increased,  and  the  dis- 
sociation becomes  more  and  more  rapid  as  the  pressure  falls  to- 
wards zero.  This  behaviour  shows  that  the  oxygen  is  not  simply 
absorbed,  but  is  united,  as  a  dissociable  compound,  to  some  con- 
stituent of  the  blood.  The  same  thing  is,  of  course,  seen  when 
defibrinated  blood  is  saturated  at  body  temperature  with  oxygen  at 
different  pressures.  As  the  partial  pressure  of  the  gas  is  increased 
from  z.ero  the  first  increments  of  pressure  correspond  to  a  much 
greater  absorption  of  oxygen  than  further  equal  increments.  Thus 
as  is  seen  in  Fig.  120,  with  an  oxygen  pressure  of  10  mm.  100  c.c. 
of  blood  took  up  6  c.c.  of  oxygen,  or  30  per  cent,  of  the  amount 
required  to  saturate  it.  When  the  pressure  of  oxygen  was  30  mm. 
over  16  c.c.  of  oxygen  was  absorbed,  the  blood  being  80  per  cent, 
saturated.  A  further  increase  of  the  oxygen  pressure  to  40  mm. 
increased  the  quantity  of  the  gas  taken  up  by  only  2  c.c.  (to  90  per 
cent,  saturation).      TL^  uext  increment  of  10  mm.  in  the  oxygen 


THE  GASES  01'    THE  BLUOD 


253 


pressure  only  produced  an  additional  absorption  of  i  c.c,  and  above 
this  increasing  the  pressure  had  very  little  effect. 

We  may  suppose  that  at  the  ordinary  tcnipcralurc  and  pressiire 
some  oxygen  is  rontinually  escaping  from  the  bonds  bv  which  it  is  tied 
to  the  haemoglobin:  but,  on  the  whole,  an  equal  number  of  free  mole- 
cules of  oxygen,  coming  within  the  range  of  the  haemoglobin  molecules, 
are  entangled  by  them,  an  1  thus  ecpiiiibriuni  is  kept  up.  If  now  the 
atmospheric  pressure,  ard  therefore  the  partial  pressure  of  oxygen 
is  reduced,    the    tendency 


of  the  oxygen  to  break 
off  from  the  haemoglobin 
will  be  unchanged,  and  as 
many  molecules  on  the 
whole  will  escape  as  before ; 
but  even  after  a  consider- 
able reduction  of  pressure 
the  haemoglobin,  such  is  its 
avidity  for  oxygen,  will  still 
be  able  to  seize  as  much 
oxygen  as  it  loses.  The 
more,  however,  the  partial 
pressure  of  the  oxygen  is 
diminished — that  is  to  say, 
the  fewer  oxygen  molecules 
there  are  in  a  given  space 
above  the  haemoglobin — • 
the  smaller  will  be  the 
chance  of  the  loss  being 
made  up  by  accidental  cap- 
tures. At  a  certain  pressure 
the  escapes  will  become 
conspicuously  more  numer- 
ous than  the  captures ;  and 
the  gas-pvimp  will  giv-e  evi- 
dence of  this.  The  higher 
the  temperature  of  the 
haemoglobin  is,  the  greater 
will  be  the  average  yelocitj' 
of  the  molecules,  and  the 


■•e-cc'^tage  of  Oxvac 


1  J         2 

6         3  9        5  ?        C 

•.      ;  8     9  J     10  s     nt     * 

r 

'ie'c 

i — 

-^ 

*■      " 

38^ 

/ 

/ 

/ 

/ 

/ 

Partial   Pressure  of  Oxygen 

Fig.  119- — Curves  of  Dissociation  of  Oxyhtemo- 
globin  freed  from  salts  by  dialysis  (after  Bar- 
croft).  .\long  the  horizontal  axis  are  plotted 
the  partial  pressures  (numbers  below  the  curve) 
of  oxvgen  in  air,  to  which  a  solution  (jt  hcemo- 
globin  was  exposed.  The  corresponding  per- 
centages of  oxygen  are  given  above  the  curve. 
Along  the  vertical  axis  is  plotted  the  percentage 
saturation  of  the  haemoglobin  with  oxygen. 

greater  the  chance  of  escape  of  molecules  of  oxygen. 

It  is  easily  proved  that  the  substance  in  the  corpuscles  which 
unites  with  oxygen  is  the  blood-pigment.  Although  a  solution  of 
oxyhasmoglobin  crystals  behaves  towards  oxvgen  somewhat  differ- 
ently from  blood  containing  the  same  proportion  of  the  native  pig- 
ment, the  maximum  amount  of  oxygen  taken  up  is  the  same  for 
each.  Much  labour  has  been  spent  in  determining  curves  \yhich 
express  the  relation  between  the  partial  pressure  of  oxygen  to  which 
blood  or  a  haemoglobin  solution  is  exposed,  and  the  proportion  to 
which  the  blood  pigment  becomes  saturated  with  oxygen  under 
each  pressure.  The  differences  in  the  results  of  the  various  in- 
vestigators who  have  worked  out  the  curves  of  dissociation  for 
haemoglobin  and  for  blood  (Figs.  119.  120,  121)  have  been  largely 
cleared  up  by  the  researches  of  Barcroft  and  his  co-workers.     One 


^5A 


IfnSPlRATION 


factor   wliith   was  overlooked   ui   the  e;irlier  uljservations  is   the 
influence  of  salts. 

The  form  o{  curve  (a  rectangular  luperbohi.  I'ig.  i  iq)  which  Hiifncr 
put  forward  by  an  unjustifiable  generalization,  as  the  curve  of  dis- 
sociation of  oxyhacmoglobin  is  only  found  when  the  hscnioglobin  solu- 
tion is  thoroughly  freed  from  salts,  as  by  prolonged  dialysis.  When 
this  condition  is  'fulfilled  it  can  be  shown  that  the  curve  is  always  a 
rectangular  hyperbola,  but  a  different  one  for  each  temperature  at 
which  the  observations  are  made.  I"or  ha-moglobin  solutions  not  freed 
from  salts  or  for  blood  or  dilutions  ftf  blood  the  curve  is  of  a  different 
order  altogether,  a  curve  with  a  double  contour  (S-shaped).  (Figs.  120, 
121).  If  to  a  solution  of  haemoglobin  freed  from  salts  and  yielding  a 
rectangular  hyperbola  as  its  dissociation  curve,  salts  be  added  in  the 
quantities  and  uf  the  kiml  known  to  exist  in  dog's  blood,  the  curve  of 

«0r 1 1 1 r=-i ■        I  iTtri 


•0 
•0 

B^ 

— ^ 

-1 

^ 

i 

/ 

> 

^ 

/ 

/ 

/ 

y 

f 

/ 

Vt 

/ 

/ 

40 
SO 
ZO 

to 

1  i 

f 

'/ 

1/ 

jj 

/.  -- 

_. 

._, 

„_ 

_ 

__ 

._ 

i. 

._ 

_, 

._ 

._ 

,_. 

18  UC 

leoc 

I4CjC 

lacjQ 

lOCC 

•  ce. 

6CC 

4CC 

2  C.C 
0  3CC 


1-ig 


0         10     to     JO     40      t«      M     70      «0     10     100    HO    120    130     140    ISO 

ijo. — (JuiV'~  (jf  l>i?'?')Ciation  of  Oxygen  for  Horse's  Blood  (Bj  and  L'og's  Haemo- 
globin solution  (H)  at  38^  C.  (Boiir).  The  figures  along  the  base-line  are  th? 
partial  pressures  of  oxygen  to  which  the  blood  aud  haemoglobin  solution  were 
exposed.  Those  along  the  vertical  axis  on  the  left  are  the  percentage  saturations 
with  oxygen.  The  figures  along  the  vertical  at  the  right  give  the  actual  number 
of  C.C  of  oxygen  chemically  combined  by  100  c.c.  of  the  blood  for  each  pressure 
of  oxygen.  The  interrupted  line  P  indicates  the  amount  of  oxygen  dissolved  in 
the  plasma  of  the  blood  at  each  partial  pressure  on  the  assumption  that  the 
plasma  is  two-thirds  of  the  volume  of  the  blood.  Thus,  at  150  mm.  oxygen 
pressure  the  plasma  of  100  c.c.  of  blood  took  up  0-3  c.c.  oxygen. 

dissociation  given  by  dog's  blood  is  obtained.  The  addition  of  the 
salts  appropriate  to  human  blood  in  the  proper  amounts  causes  the 
hvperbolic  curve  of  the  pure  haemoglobin  solution  to  change  into  an 
S-shaped  curve,  such  as  is  given  by  human  blood,  and  so  on. 

The  foundation  has  thus  been  removed  from  the  theor\'  that 
different  animals  possess  h?emoglobins  differing  in  their  capacity 
to  take  up  oxy.gen.  The  salts  are  su])]^i)sed  to  alter  the  dissociation 
curve,  by  changing  the  degree  of  aggregation  of  the  hsmoglobin 
molecules- — i.e.,  by  causing  them  to  adhere  to  each  other  to  a  greater 
or  less  extent  according  to  the  quantity  and  kind  of  salts  present. 

Another  factor  which  greatly  influences  the  binding  power  of 
hremoglobin  for  o.xygen,  and  therefore  the  dissociation  curve,  is 
the  reaction  of  the  blood  (p.  24).     When  the  hydrogen-ion  concen- 


THE  GASES  or  THE  HLoOD 


t ration  is  incioasod.  as  by  addition  of  carbon  dioxitio  (I'ig.  1 211  or 
lactic  acid,  the  effect  is  to  increase  the  dissociation  tension  of 
oxyhitmoglobin.  or  what  is  a  different  way  of  expressing  the  same 
thing,  to  diminish  the  amount  of  oxygen  taken  up  under  a  given 
oxygen  partial  pressure.  So  that  to  obtain  a  given  percentage 
saturation  oi  the  inemoglobin,  a  greater  partial  pressure  of  oxygen 
mvist  be  employed  than  in  the  absence  of  the  acid. 

So  sensitive  is  the  dissociation  curve  to  changes  in  the  hvdrogen-ion 
concentration,  that  a  metliod  (if  detecting  and  estiinatinp;  alterations  in 
the  acidity  of  the  blood  has  boon  ba^cd  upon  the  (Ictcrniination  of  the 
percentage  saturation  of  tlie  blood 
with  oxygen,  at  a  detinile  partial 
pressure.  The  influence  of  the 
carbon  dioxide  in  the  patient's 
blood  is  eliminated  by  adding  to 
the  gaseous  mixture  with  which 
the  blood  is  shaken  up  a  per- 
centage of  carbon  dioxide,  corre- 
sponding to  the  partial  pressure 
of  that  gas  in  the  blood,  that  is 
to  say,  a  percentage  equal  to  the 
percentage  of  carbon  dioxide  in 
his  alveolar  air  (p.  241'!. 

In  blood  haemoglobin,  of 
course,  exists  in  the  presence 
of  salts  and  of  carbon  dioxide 
and  other  acid  metabohtes,  and 
tlierefore  such  curves  as  are 
given  in  Figs.  120  and  121, 
more  nearly  represent  the  dis- 
sociation ciu'ves  of  the  blood 
pigment  under  physiological  conditions,  than  those  reproduced  in 
Fig.  119. 

The  Distribution  and  Condition  of  the  Carbon  Dioxide  in  the 
Blood. — The  question  is  much  more  complicated  than  for  the 
oxvgen,  which  is  practically  confined  to  one  of  the  morphological 
elements  of  the  blood  (the  erythroc^'tes),  and  exists  in  the  form  of  a 
single  compound.  Carbon  dioxide  is  distributed  over  the  entire 
blood  in  important  amounts,  and  is  present  in  several  forms.  The 
serum  vields  a  larger  percentage  of  carbon  dioxide  than  the  cloc, 
but  this  percentage  is  not  great  enough  to  allow  us  to  assume  that 
the  whole  of  the  carbon  dioxide  is  contained  in  the  plasma.  Some- 
what more  than  a  third  of  it  belongs  to  the  corpuscles. 

As  regards  the  condition  of  the  carbon  dioxide,  it  is  known  that 
some  of  it  is  simply  dissolved  in  the  plasma  and  corpuscles;  but 
although  this  fraction,  on  account  of  the  relatively  high  cdefificient  of 
absorption  of  the  gas  (p.  245),  is  much  greater  than  the  corresponding 
oxygen  fraction,  it  is  insignificant  in  comparison  with  the  quantity 
chemicallv    combined.     Carbon    dioxide    is    united    in    dissociable 


Fig. 


0      'i^      30      «0      is      00      Id      eo      90     (OS 

121. — Dissociation  Curves  of  Blood, 
with  Different  Tensions  of  CO3  (o,  ;,, 
20,  40,  and  90  mm.).  Ordiaates  = 
percentage  saturation.  Abscissa?  = 
oxygen  pressure.     (After  Barcroft.) 


2S6  RESPIRATION 

combinations  with  a  number  of  the  constituents  of  the  blotKl,  both 
inorganic  and  organic,  and  our  knowledge  of  these  combinations, 
especially  of  the  compounds  formed  with  organic  substances,  is  far 
Irom  complete.  The  inquiry  is  complicated  by  the  circumstance 
that  the  proportion  of  the  total  combined  carbon  dioxide  united 
with  a  given  constituent  or  bound  by  plasma  and  corpuscles  respec- 
tively is  not  constant,  but  varies  with  the  varying  tension  of  the  gas, 
while  the  total  amount  of  carbon  dioxide  is  itself  dependent  upon 
the  varying  '  titratable  alkalinity  '  (p.  25).  There  is  no  doubt  that 
some  of  the  carbon  dioxide  in  blood  is  combined  with  alkali,  but 
the  amount  of  alkali  available  is  not  nearly  suthcient  to  unite  with 
all  the  carbon  dioxide  even  in  the  form  of  bicarbonate.  Some  of 
the  dissociable  carbon  dio  ide  must  therefore  be  combined  with 
organic  substances.  The  relations,  even  of  that  portion  which 
exists  as  bicarbonate,  are  peculiar.  This  is  sufficiently  indicated  by 
the  fact  that  from  defibrinated  blood  the  whole  of  the  carbon 
dioxide  can  in  time  be  pumped  out  without  the  addition  of  an  acid 
to  displace  it  from  the  bases  with  which  it  is  united.  On  the  other 
hand,  from  a  bicarbonate  solution  whose  concentration  corresponds 
to  that  of  the  blood,  not  much  more  than  half  of  the  loosely  bound 
carbon  dioxide  (that  is,  the  carbon  dioxide  which  comes  off  accord- 
ing to  the  equation  2HXaC03=  Na^COg +COj  +  HgO)  can  be  ob- 
tained even  when  the  evacuation  is  kept  up  for  days.  This  is  only 
about  one-fourth  of  the  total  carbon  dioxide  in  the  bicarbonate; 
yet,  when  sodium  bicarbonate  is  added  to  blood,  even  in  consider- 
able amount,  all  the  carbon  dioxide  in  it  can  be  obtained  by  the 
pump.  From  serum  a  great  deal,  but  not  the  whole,  of  the  carbon 
dioxide  can  be  likewise  pumped  out,  and  the  liberation  of  the  gas 
does  not  stop,  as  in  the  case  of  the  bicarbonate  solution,  when  all 
the  bicarbonate  has  been  cliiinged  into  carbonate.  The-  residue 
(from  10  to  18  per  cent,  of  the  whole)  is  set  free  on  the  addition  of 
an  acid — e.g.,  phosphoric  acid. 

The  most  satisfactory  explanation  is  that  in  tlic  serum  there  exist 
substances  which  can  act  as  weak  acids  in  gradually  driving  out  the 
carbon  dioxide,  when  its  escape  is  rendered  easier  by  tlie  vacuum. 
The  quantitv  of  these,  however,  is  not  so  large  but  that  a  jiortion  of 
the  carbon  dioxide  remains  in  the  scrum.  Tlio  proteins  of  the  serum, 
such  as  scrum-globulin,  behave  in  certahi  r.spccts  like  weak  acids, 
and  may  contribute  to  tlie  driving  out  of  the  carbon  dioxide.  When 
defibrinated  blood  is  pumped  out,  the  whole  of  the  carbon  dioxide  can 
be  removed,  apparently  because  substances  of  acid  nature  pass  from 
the  corpuscles  into  the  serum  and  help  to  break  up  the  carbonates. 
The  liajmoglobin  in  tlie  corpuscles  acts  as  a  weak  acid,  and  as  some 
corpuscles  arc  ha^molyzed  during  the  evacuation,  the  haemoglobin  may 
exert  this  action  in  the  scrum  as  well  as  in  the  interior  of  the  corpuscles. 

The  quantity  of  carbon  dioxide  combined  with  alkali  (as  bicar- 
bonate) has  not  been  exactly  determined.  Bohr  estimated  it  by 
shaking  blood  with  atmospheric  air,  which  was  supposed  to  leave 


THE  GASES  OF  THE  BLOOD 


257 


the  bicarbonate  intact,  while  removing  nearly  all  the  rest  of  the 
carbon  dioxide,  the  compounds  of  the  gas  with  organic  constituents 
of  the  blood  being  more  easily  dissociated  than  the  bicarbonate. 
The  best  known  of  these  compounds  is  that  which  carbon  dioxide 
seems  to  form  with  haemoglobin.  A  solution  of  haemoglobin  absorbs 
more  of  the  gas  than  water,  and  the  quantity  taken  up  is  not  pro- 
portional to  the  pressure.  There  is  also  evidence  of  the  existence 
of  dissociable  combinations  between  carbon  dioxide  and  the  proteins 
of  the  plasma,  by  which  considerable  amounts  of  the  gas  can  be 
bound  at  such  carbon  dioxide  tensions  as  normalh^  exist  in  blood. 

In  the  red  corpuscles  a  portion  of  the  carbon  dioxide  is  in  com- 
Ignition  with  alkalies.  We  know  that  the  corpuscles  contain  more 
alkali  than  the  serum,  and  the  titratable  alkalinity  of  '  laked  ' 
blood  (pp.  25,  28)  is  greater  than  that  of  unlaked  blood,  unless 
a  long  time  is  allowed  in  the  case  of  the  latter  for  the  alkalies  of  the 
corpuscles  to  reach  the  acid  used  in  titration.  The  haemoglobin  of 
the  corpuscles  holds  a  portion  of  the  carbon  dioxide  in  weak  com- 
bination. 

Although  the  student  is  warned  not  to  give  too  much  weight  to 
the  actual  numbers,  the  present  position  of  our  knowledge  in  regard 
to  the  distribution  and  condition  of  the  carbon  dioxide  of  the  blood 
may  be  summed  up  by  quoting  the  calculation  of  Loewy,  that  in 
100  c.c.  of  arterial  blood  containing  (with  a  carbon  dioxide  tension 
of  30  mm.  of  mercury)  40  c.c.  of  carbon  dioxide,  there  are — 


In  Plasma. 

In  Corpuscles. 

1 

In  ]{lood. 

Physically  absorbed      -         -         - 
Combined  as  bicarbonate 
In  organic  combinations 

1-2  C.C. 
I2-0      ,, 
II-8     ,, 

07  C.C. 
6-8     ,, 
7-5    .. 

1-9  C.C. 
i8-8    ,. 
19-3    ,. 

When  blood  is  saturated  with  carbon  dioxide  and  then  sepai-ated  into 
serum  and  clot,  the  serum  is  found  to  yield  more  gas  than  the  clot;  but 
if  the  serum  and  clot  are  separately  saturated,  the  latter  takes  up  more 
carbon  dioxide  than  the  former.  From  this  it  is  argued  that  a  substance 
combined  with  carbon  dioxide  must  in  blood  saturated  with  the  gas  pass 
out  of  the  corpuscles  into  the  scrum.  The  corpuscles  at  the  same  time 
gain  water  and  become  larger.  The  molecular  concentration  (p.  .|2'j) 
of  the  serum  of  defibrinated  blood,  as  measured  by  the  lowering  of  the 
freezing-point,  increases  when  it  is  saturated  with  carbon  dioxide.  On 
the  other  hand,  when  blood  is  saturated  with  oxygen,  the  corpuscles 
lose  water  and  shrink  in  volume,  while  the  molecular  concentration  of 
the  serum  is  diminished.  Hamburger  has  extended  these  observations 
to  the  circulating  blood,  and  has  shown  that  the  plasma  of  venous 
blood  has  a  higher  percentage  of  alkali,  protein,  sugar,  and  fat  than 
the  plasma  of  arterial  blood,  and  that  the  corpuscles  have  a  greater 
volume,  though  not  a  greater  diameter.  He  therefore  supposes  that  in 
the  pulmonary  capillaries,  under  the  influence  of  oxygen,  water  passes 
into  the  plasma  from  the  corpuscles.  In  the  systemic  capillaries  the 
blood  becomes  loaded  with  carbon  dioxide,  and  therefore  the  corpuscles 

17 


23  S  RESPIRATION 

take  up  water  from  the  plasma,  which  accordingly  has  a  more  concen- 
trated supply  of  food-substances  to  offer  to  the  tissues  than  the  plasma 
of  arterial  blood  itself.  Some  writers  see  in  this  interchange  an  auto- 
matic arrang.^ment  by  which  oxidation  is  favoured.  \Vhitcver  may  be 
thought  of  this  view — and  objections  to  it  aro  not  wanting— the  current 
theory,  that  the  corpuscles  are  simply  passive  carriers  of  oxygen,  and 
exercise  no  further  influence  on  the  plasma,  breaks  down  in  face  of  the 
facts.  We  must  admit  that  an  active  and  many-sided  commerce  exists 
between  them  and  the  liquid  in  which  they  float. 

The  nitrogen  of  the  blood  is  siniph'  absorbed.* 

The  Tension  of  the  Blood-Gases. — If  the  gases  of  the  blood  existed 
in  simple  solution,  their  tension  or  partial  pressure  could  be  deduced 
from  the  amount  dissolved  and  the  coefficient  of  absorption.  We 
have  seen  that  they  are  mainly  combined,  and  it  is  characteristic 
of  dissociable  compounds  of  this  kind  that  the  relation  between  the 
partial  pressure  of  the  gas  in  contact  with  the  liquid  and  the  quantity 
of  gas  taken  up  is  much  more  compHcated  than  in  the  case  of  pure 
physical  absorption.  It  is  therefore  necessary  to  determine  the 
tension  directly. 

This  can  be  done  by  means  of  arrangements  called  aerotonometers. 
There  are  various  forms  of  aerotonometer,  but  the  object  of  all  is  to 
bring  the  blood  into  contact  with  an  atmosphere  or  gaseous  mixture 
into  which  the  gases  of  the  blood  can  diffuse  and  from  which  gases  can 
enter  the  blood.  When  the  composition  of  the  mixture  has  ceased  to 
change,  the  gases  in  it  are  under  the  same  partial  pressure  as  the  corre- 
sponding gases  in  the  blood,  and  all  that  is  necessary  in  order  to  arrive 
at  the  tension  of  the  blood-gases  is  to  determine  the  final  composition 
of  the  gaseous  mixture  by  analysis.  The  speed  with  which  equilibrium 
is  attained  depends  essentially  upon  the  magnitude  of  the  surface  of 
contact  between  the  blood  and  the  g<is  mixture  in  proportion  to  the 
volume  of  the  gas  space.  In  the  earlier  observations  with  the  aerotono- 
meter it  was  found  tf»  be  very  difficult  to  get  complete  equilibrium,  and 
therefore  the  gas  space  was  filled  at  the  beginning  with  a  mixture  whose 
gases  had  partial  pressures  as  nearly  equal  as  possible  to  those  expected 
in  the  blood.  In  one  form  of  the  apparatus  the  blood  is  made  to  pass 
directly  from  the  vessel  to  glass  tubes,  which  it  traverses  at  the  same 
time,  the  stream  being  divided  between  them;  it  then  passes  out  again. 
The  tubes  are  warmed  by  means  of  a  water-jacket  to  the  body-tem- 
perature. Some  of  them  are  filled  with  gaseous  mixtures  having  a 
greater,  and  the  others  with  mixtures  having  a  smaller,  partial  pressure, 
say  of  carbon  dioxide,  than  is  expected  to  be  found  in  the  blood.  As 
the  latter  runs  in  a  thin  sheet  over  the  walls  of  the  tubes,  it  loses  carbon 
dioxide  to  some  of  them  and  takes  up  carbon  dioxide  from  others. 
From  the  alteration  in  the  proportion  of  the  carbon  dioxide  in  the  tubes, 
the  partial  pressure  of  that  gas  in  the  blood  is  calculated — that  is,  the 
partial  pressure  which  would  be  necessary  in  the  tubes  in  order  that 
the  blood  might  pass  through  them  without  losing  or  gaining  carbon 
dioxide  (p.  248). 

Bohr's  aerotonometer,  constructed  and  worked  much  in  the  same 
way  as  a  stromuhr  (p.  121),  permits  the  blood  after  passing  through  the 
gas  space  to  return  to  the  circulation.     A  stream  of  blood  can  thus  be 

*  But  according  to  Buckmaster  and  Gardner,  the  volume  of  nitrogen  in 
blood  does  not  foUow  the  ordinary  physical  laws  of  absorption  with  vaxyiag 
nitroge;!  pressures  in  the  alveolar  air. 


THE  GASES  OF  THE  BLOOD 


259 


kept  in  coiitiict  with  the  gas  for  a  quarter  of  an  hour  or  longer,  so  as 
to  insure  equihbrium.     Finally,  in  Krogh's  microtovomcier  tlij  gas  space 


kt 

to  uisure  equilibrium,  x-iiiaiiy,  in  rvrogn  s  microionome'er  tiij  gas  space 
is  reduced  to  the  smallest  possible  dimensions,  being  composed  merely 
of  an  air-bubble  1  mm.  in  diameter,  which  is  exposed  to  the  contact  of 
a  stream  of  blood  from  an  artery  or  vein.  Equilibrium  is  established 
so  quickly  that  it  is  indilferent  whether  a  bubble  of  air  or  of  pure 
nitrogen  is  employed.  The  bubble  is  analyzed  at  the  end  of  the  obser- 
vation, and  its  composition  gives  the  tension  of  the  blood  gases. 

Suppose  that  the  gaseous  mixture  which  is  in  equilibrium  with  the 
blood  contains  10  per  cent,  of  oxygen  and  5  per  cent,  of  carbon  dioxide, 

Fig.  122.  —  Krogh's  Micro  to- 
nometer. The  apparatus, 
which  is  filled  with  salt  solu- 
tion, consists  of  a  graduated 
capillary  tube,  3,  the  lower 
part  of  which,  with  its  ex- 
panded lower  end,  is  shown 
on  a  much  enlarged  scale  in 
A.  The  rest  of  the  capillary 
tube,  surrounded  by  a  water- 
jacket  to  control  the  tempera- 
ture, is  shown  on  a  smaller 
scale  in  B.  2  is  a  gas-bubble, 
against  which  blood  flowing 
from  the  very  narrow  mouth 
of  the  tube  i  plays,  i  is  con- 
nected by  a  rubber  tube  with 
a  cannula  in  a  bloodvessel. 
The  blood  forces  its  way  up 
above  the  gas-bubble,  which 
is  pressed  a  little  down  by  the 
current,  and  kept  oscillating 
rapidly.  The  blood  flows  off 
through  the  tube  5,  and  is 
collected  drop  by  drop  and 
measured.  By  means  of  the 
screw  4,  shown  in  B,  which 
moves  in  mercury,  the  gas- 
bubble  can  be  drawn  into  the 
capillary  for  measurement. 
The  upper  end  of  the  capil- 
lary tube  also  expands  into  a 
funnel-shaped  cavity,  which 
is  closed  by  a  stopper,  and 
is  only  used  for  cleaning  the 
apparatus. 

the  tension  of  oxvgen  in  the  blood  would  be  one-tenth  of  an  atmosphere 
[i.e.,  of  760  mm.  of  mercurj').  or  76  mm  ,  and  the  tension  of  the  carbon 
dioxide  in  the  blood  one-twentieth  of  an  atmosphere,  or  38  mm.  of 
mercunv". 

Another  method  hy  which  the  tensio;i  of  the  gases  in  the  venous 
blood  passing  from  the  right  heart  through  the  lungs  has  been  estimated 
depends  upon  the  use  of  the  pulmonary  catheter.  This  consists  of  two 
tubes,  one  within  the  other.  The  inner  tube,  which  is  a  fine  elastic 
catheter,  projects  free  from  the  other  for  a  little  distance  at  its  lower 
end.  The  outer  tube  terminates  in  a  thin  india-rufjber  balloon,  through 
which  the  inner  tube  passes  without  communicating  with  the  balloon. 


26o  RESPIRA  TION 

The  balloon  can  be  inflated  so  as  to  block  the  bronchus  into  which  it 
is  passed,  and  cut  off  the  corresponding  portion  of  the  hing  from  com- 
munication with  the  outer  air.  A  sample  of  the  air  below  the  block  can 
be  drawn  off  through  the  inner  tube,  which  opens  free  in  the  bronchus. 

This  method  has  been  applied  both  to  animals  and  to  man.  In 
observations  on  man  the  catheter  was  passed  into  the  right  bronchus 
so  as  to  occlude  at  will  any  one  of  the  lobes  of  the  right  lung.  On  the 
assumption  that  the  ga.seous  exchange  in  the  lungs  depends  essentially 
on  the  physical  process  of  diffusion,  the  occluded  alveoli  will  correspond 
to  the  gas  space  of  an  aerotonometer.  When  the  occlusion  has  lasted 
long  enough  for  the  gases  in  the  alveoli  and  the  blood  ga^es  to  come 
completely  into  equilibrium — say  half  an  hour — all  that  is  necessary  is 
to  draw  off  the  air,  and  from  its  composition  to  deduce  the  tensions  in 
the  blood.  Since  the  respiratory  function  of  the  occluded  lobe  is  in 
abeyance,  the  blood  circulating  in  it  is  all  unaltered  venous  blood,  as  it 
comes  from  the  right  ventricle,  so  that  the  gas  tensions  found  can  be 
considered  those  of  the  mixed  venous  blood. 

For  estimating  the  oxygen  tension  in  the  arterial  blood  a  method 
was  introduced  by  Haldane  and  Smith,  which  differs  fundamentally 
from  those  described  above,  in  that  it  docs  not  depend  upon  the  use  of 
aerotonometers.  They  applied  it  not  only  to  animals  but  also  to  man. 
The  subject  of  the  experiment  breathes  air  containing  a  definitely 
known  verA-  small  percentage  of  carbon  monoxide  until  the  haemoglobin 
has  united  with  as  much  of  that  gas  as  it  will  take  up  for  the  given 
concentration  of  it  in  the  air.  Then  the  percentage  amount  to  which 
the  haemoglobin  has  become  saturated  with  carbon  monoxide  is  deter- 
mined in  a  sample  of  blood  taken,  say,  from  the  finger.  Xow,  the  final 
saturation  with  carbon  monoxide  of  a  haemoglobin  solution  brought 
into  contact  with  a  gaseous  mixture  containing  carbon  monoxide  and 
oxygen,  depends  on  the  relative  tensions  of  the  two  gases  in  the  liquid. 
But  the  tension  of  carbon  monoxide  in  the  blood  leaving  the  lungs  will 
(after  absorption  has  ceased"*  be  the  same  as  that  in  the  inspired  air. 
Knowing  this  tension  and  the  degree  of  saturation  of  the  haemoglobin 
w^ith  carbon  monoxide,  the  oxygen  tension  in  the  blood  leaving  the 
lungs — i.e.,  in  the  arterial  blood — ii^  known. 

Before  proceeding  to  the  consideration  oi  the  results  obtained  by 
these  di^■cr^-  methods,  it  may  be  well  to  point  out  that  when  a  gas 
is  stated  to  be  under  such  and  such  a  tension  in  the  blood,  no  direct 
information  is  given  as  to  the  quantify  of  gas  present .  For  instance, 
the  oxygen  tension  in  blood  exposed  to  atmospheric  air  will  be  the 
same  for  the  erythrocytes  as  for  the  serimi — namely,  about  ibo  mm. 
of  mercury;  but  lOO  c.c.  of  serum  will  scarcely  'ontain  i  c.c.  of 
oxygen,  while  too  c.c.  of  corpuscles  will  have  absorbed  about  60  c.c. 
of  the  gas. 

\\Tien  we  now  turn  to  the  actual  blood-gas  tension.s  obtained  by 
different  observers  and  by  different  methods,  these,  as  displayed  in 
such  a  table  as  appears  on  p.  261,  seem  to  present,  at  first  sight, 
nothing  but  a  welter  of  widely  diverging  and  contradictory  figiu-es. 

This  table,  at  the  time  it  was  drawn  up  a  few  \ear?  ago,  represented 
the  outcome  of  a  vast  amount  of  work  by  physiologists  of  the  greatest 
ability,  and  specially  skilled  in  such  studies.  To-day,  the  absolute 
numbers  possess  little  value,  especially  in  \4ew  of  the  fact  that  most 


THE  GASES  OF  THE  BLOOD 


261 


of  them  could  not  be  accurately  compared  with  the  corresponding 
gas  tensions  in  the  alveolar  air.  The  discussion  of  the  table  is 
none  the  less  instructive  to  the  student  who  desires  to  learn  how 
knowledge  is  won,  and  how  frequently  an  advance  in  knowledge  is 
dependent  upon  an  advance  in  technique. 

As  regards  the  venous  blood,  we  have  already  learnt  that  very 
considerable  variations  in  the  content  of  oxygen  and  of  carbon 
dioxide  are  associated  with  the  varying  functional  activity  of  the 
tissues  from  wliich  the  blood  comes.  This  factor,  of  course,  is  also 
not  without  influence  upon  the  gas  tensions  of  the  venors  blood. 
The  carbon  dioxide  tension  of  arterial  blood  is  affected  by  variations 
in  the  amount  of  the  pulmonary  ventilation,  which  affect  the  partial 
pressure  of  the  carbon  dioxide  in  the  alveolar  air  and  thus  alter  the 
steepness  of  the  slope  of  pressure  between  the  two  sides  of  the  pul- 
monary membrane. 


Arterial  Blood  : 

Venous  Blood : 

Tension  in 

Mm.  He. 

Tension  in  Mm.  Hg. 

riK.-                       or,^     Vl      .K.™1 

^OSCTTOf  BllQ   irlCtOOQ. 

Oxygen. 

Carbon 
Dioxide. 

Oxygen. 

Carbon 
Dioxide. 

9. 

Strassburg     -         -         -         - 

21-43 

16-29 

10-35 

38-49 

0 

(29-6)* 

(20) 

(20-6) 

(41) 

6 

Herter 

39-79 

17-31 

— 

c  ■ 

Bohr 

101-144 

20-32 

— 



0 

Bohr  (later  series) 

— 

9-27 

— 

26-43 

E 

Fredericq       -         -         -         - 

91-105 

17-19 

0 

< 

Falloise          .         -         .         . 

■ — 



17-37 

32-54 

t'u 

(42-5) 

g  0  rWolflfberg      .         -        .        . 

— 



(26) 

18-37 

0  JJ  _  Nussbaum     -         -         -         - 

— 



(27) 

24-33 

J  ^  1  Loewy  and  Schrotter  \    p. 

(  ~ 

— 

(37-7) 

34-59 

^        Haldane  and  Smith     J  "^^^ 

U00  + 

"" 

— 

(45) 

It  is  chiefly  the  enormous  differences  in  the  recorded  oxygen 
tensions  of  the  arterial  blood  which  excite  surprise.  To  some  ex- 
tent, indeed,  these  also  may  depend  upon  differences  in  the  partial 
pressure  of  the  oxygen  in  the  alveoli,  and  it  has  been  shown  experi- 
mentally (by  the  aerotono meter)  that  with  increasing  oxygen  tension 
of  the  inspired  air  the  oxygen  tension  of  the  arterial  blood  increases 
(Fredericq).  Still,  the  differences  which  can  possibly  have  existed 
in  the  partial  pressure  of  the  oxygen  in  the  alveoh  in  the  various 
series  of  observations  can  onlj^  to  a  small  extent  account  for  the 
differences  in  th^  results.  The  main  reason  for  the  great  range  of 
values  lies  unquestionably  in  the  different  experimental  procedures 
•  The  numbers  in  brackets  are  averages. 


2t^2  RESPIRATION 

by  which  they  were  obtained.  There  is  no  doubt  that  in  the  earHcr 
observations  with  the  uerotonometer  (Strassburgj  tiic  oxygen  of 
tlie  blood  could  not  have  come  into  equilibrium  with  the  mixture 
in  the  gas  space,  in  which  the  oxygen  pressure  was  at  the  beginning 
much  lower  than  that  in  the  blood ;  the  results  are  therefore  too  low. 
The  same  is  true  for  the  oxygen  tension  of  the  venous  blood,  but  as 
this  is  in  any  case  considerably  smaller  than  that  of  the  arterial 
blood,  the  proportional  error  is  not  so  great.  The  later  experiments 
(of  Herter),  given  in  the  second  line  of  the  table,  yield  much  higher 
values,  owing  to  improved  technique,  but  the  findings  are  still  to  be 
regarded  as  minimal  and  not  average  results.  At  the  other  end  of 
the  scale  stand  the  results  oi  Haklanc  and  Smith,  who  lound  m  man 
an  oxygen  tension  in  the  arterial  blood  of  over  200  mm.  of  mercury 
equal  to  more  than  26  per  cent,  of  an  atmosphere.  This  exceeds 
the  partial  pressure  of  oxygen  in  the  external  air,  and  is  about  twice 
as  great  as  that  of  the  air  of  the  alveoli.  In  the  bird  they  found 
an  oxygen  tension  of  between  300  and  400  mm.,  equal  to  45  per 
cent,  of  an  atmosphere. 

The  chief  interest  of  this  discussion  of  the  blood-gas  tensions  Hes 
in  their  fundamental  importance  in  the  problem  of  the  gaseous 
exchange  in  the  lungs,  on  the  one  hand,  and  between  the  blood  and 
tissues  on  the  other.  In  the  presence  of  such  results  Haldane  and 
Smith  necessarily  adopted  a  secretion  theory  of  gaseous  exchange 
in  the  lungs.  For  it  was  manifestly  impossible  for  oxygen  to  diffuse 
from  the  alveoli  into  the  blood  against  the  slope  of  pressure. 

Their  findings,  however,  differed  so  vastly  from  those  of  all  observers 
who  had  used  tonometric  methods,  and  it  seemed  so  difficult  to  assign 
an  adequate  physiological  value  to  the  slight  increase  in  the  percentage 
saturation  of  the  ha?moglobin  with  oxygen  (see  Figs.  119-121),  which 
could  be  brought  about  by  even  a  great  excess  of  ox^'gen  tension  above 
that  of  atmospheric  air,  that  there  was  a  general  disposition  to  distrust 
the  accuracy  of  their  method.  At  the  same  time  the  ordinary  tono- 
metric techiiiquc  left  so  much  to  be  desired  that  there  seemed  little 
hope  of  bringing  the  matter  to  a  decisive  test.  The  introduction  a 
few  years  ago  by  Krogh,  of  better  aerotonometric  methods,  and  the 
remarkable  series  of  researches  carried  out  by  their  aid,  have  changed 
the  whole  aspect  of  the  question.  He  showed  that  in  tlie  arterial  blood 
of  rabbits  the  oxygen  tension  was  in  all  cases  somewhat  (usually  2  to 
3  per  cent,  of  the  atmospheric  pressure,  or  15  to  23  mm.  of  mercury) 
lower  than  the  oxygen  tension  in  air  from  the  bifurcation  of  the  trachea. 
In  animals  it  is  not  possible  to  obtain  the  actual  alveolar  air.  These 
results  agree  very  well  with  those  of  Fredericq,  who  found  in  dogs 
oxygen  tensions  of  13  to  14  per  cent,  of  an  atmosphere-  -i.e.,  something 
like  100  mm.  of  mercury,  when  the  animals  breathed  atmospheric  air. 
Krogh  proved  that  the  amount  of  oxygen  lost  by  self-reduction  of 
the  blood  (see  p.  2G1)  in  his  aerotonometer  wan  negligible,  even  in 
rabbits,  although  it  is  known  that  rabbit's  blood  uses  up  more  oxygen 
than  that  of  higher  mammals.  He  also  pointed  ou^some  sources  of 
error  in  the  Haldane-Smith  method.  About  the  same  time  Haldane. 
after  a  careful  re-examination  of  the  question,  came  to  the  con- 
clusion that    his   previous    results    were    much    too    high;    and    that 


77/ L  (,ASLS  Ol-    Till::  BLOOD  263 

during  rest  nul  when  normal  air  is  breathed  the  oxygen  tension  in 
arterial  blood  never  exceeds  the  tension  in  the  alveolar  air.  He  still 
beheves,  and  brings  forward  evidence  for  liis  belief,  that  even  the  best 
aerotonometric  methods  yield  with  arterial  blood  oxygen  pressures 
lower  than  the  true  oxygen  pressure  in  the  blood  leaving  the  pulmonary 
capillaries.  But  he  no  longer  doubts  that  a  sufhcicnt  slope  of  pressure 
exists  between  the  alveoli  and  the  blood  to  explain  the  absorption  of 
oxygen  under  ordinary  conditions. 

To  all  intents  and  purposes,  then,  we  may  look  upon  the  contro- 
versy as  closed,  and  with  the  happy  result,  too  rare  in  physiological 
disputes,  that  a  practically  unanimous  conchision  has  been  arri\ed 
at.  While  the  oxygen  tension  in  arterial  blood  may  jail  only  slightly 
below  that  in  alveolar  air,  the  difference  perhaps  being  even  less  than 
that  found  by  Krogh,  the  slope  of  pressure  is  always,  under  ordinary 
conditions  at  least,  from  the  alveoli  to  the  blood. 

Mechanism  of  the  Gaseous  Exchange  in  the  Lungs. — Granting 
that  this  is  so,  it  must  still  be  asked  whether  the  diffusion  of  oxygen 
from  the  lungs  into  the  blood  can  take  place  rapidly  enough  to 
account  for  the  quantities  actually  absorbed. 

Calculations  made  on  the  basis  of  such  anatomical  and  physical  data 
as  are  available  (total  surface  of  the  lungs,  thickness  of  the  membrane 
which  separates  the  air  of  the  alveoli  and  the  blood  in  the  capillaries, 
rate  of  '  invasion,'  or  entrance  of  the  gases  into  water;  velocity  of 
diffusion  of  oxygen  and  carbon  dioxide),  indicate  that  even  with  differ- 
ences of  oxygen  tension  between  the  blood  and  the  alveolar  air,  which 
would  lie  within  the  limits  of  error  of  our  present  methods  of  measure- 
ment, enough  oxygen  covUd  diffuse  across  the  pulmonary  membrane  to 
cover  the  whole  normal  intake. 

For  example,  it  has  been  shown  from  determinations  of  the  '  invasion- 
coefficient  '  of  oxygen  that  300  c.c.  of  oxygen,  the  amount  ordinarily 
absorbed  in  a  minute,  in  an  average  man,  can  be  carried  from  the  alveo- 
lar air  into  the  wet  surface  of  the  pulmonary  epithelium  with  a  difference 
of  oxygen  pressure  of  a  little  over  3  mm.  of  mercury.  If  during  mus- 
cular exercise  six  or  seven  times  as  miich  oxygen  were  absorbed,  the 
necessary  difference  of  oxygen  pressure  would  still  be  only  about  20  mm. 
of  mercury,  less  than  3  per  cent,  of  an  atmosphere. 

It  is  one  thing,  however,  to  know  that  the  necessary  oxygen  can  be 
taken  up  into  the  surface  of  the  pulmonary  membrane  by  a  purely 
physical  process,  but  quite  another  to  prove  that  it  can  also  be  trans- 
ported with  sufficient  speed  across  the  thickness  of  the  alveolar  wall 
into  the  blood.  A  direct  test  of  this  question,  made  by  Krogh,  has 
also  yielded  an  affirmative  answer.  He  determined  the  amount  of 
carbon  monoxide  actually  taken  up  in  a  given  time  in  a  hinnan  subject. 
It  was  about  10  c  c.  per  mm.  of  partial  pressure  in  the  alveolar  air  per 
minute  when  the  subject  was  at  rest,  and  a  little  above  30  c.c.  when 
breathing  was  forced,  as  it  would  be  during  heavy  work.  Now  the 
speed  of  diffusion  of  oxygen  is  somewhat  greater  than  that  of  carbon 
monoxide,  so  that  at  rest  the  subject  could  have  absorbed  between 
200  and  300  c.c.  of  oxygen  per  minute  with  a  difference  of  oxvgen 
tension  of  only  10  mm.  of  mercury  between  the  alveolar  air  and  the 
arterial  blood.  Even  during  hard  muscular  work  the  observed  differ- 
ences of  oxygen  tension  seem  adequate  to  the  transport  of  the  necessary 
amount  of  oxygen. 


264  RESPIRATION 

So  far.  then,  as  the  absorption  oj  oxxi^en  is  concerned,  thcr<r  ir.  rvcry 
reason  to  conclude  that  it  is  managed  by  physical  processes  alone. 
Haldane,  it  is  true,  still  contends  that  under  exceptional  conditions 
when  the  call  for  oxygen  is  much  increased,  as  during  active  mus- 
cular exercise,  or  when  an  adequate  intake  is  hampered  by  reduced 
atmospheric  pressure,  as  at  high  altitudes,  the  oxygen  tension  in 
the  arterial  blood  may  materially  exceed  that  in  the  alveolar  air. 
Those  who  have  worked  with  other  methods  do  not,  however,  grant 
that  even  under  these  conditions  there  is  any  excess  of  oxygen 
pressure  in  the  blood.  It  may,  of  course,  be  formally  admitted  that 
even  if  diffusion  can  account  for  the  absorption  of  the  whole  of  the 
oxygen,  this  is  not  of  itself  a  proof  that  it  is  by  diffusion  that  the 
thing  is  actually  done ;  it  is  only  a  reason  for  refusing  to  call  in  the 
aid  of  a  more  recondite  hypothesis,  until  the  necessity  for  doing  so 
is  clearly  demonstrated. 

As  regards  the  carbon  dioxide  the  evidence  is  fully  as  clear.  The 
speed  of  diffusion  of  carbon  dioxide  across  such  a  membrane  as  the 
alveolar  wall  being  much  greater  than  that  of  oxygen,  still  smaller 
differences  of  tension  would  suffice  to  permit  the  whole  normal  out- 
put of  that  gas  to  be  eliminated  by  diffusion. 

According  to  the  obserxations  of  Buhr,  nearly  300  c.c.  of  carbon 
dioxide  per  miuTite  could  pass  out  of  the  blood  by  diffx'.sion  into  the 
alveolar  air  ipider  a  difference  of  partial  pressure  of  i  mm.  of  mercury. 
This  is  with  the  ordinary  breathing  of  a  man  at  rest.  With  the  in- 
creased respiration  associated  with  hard  muscular  work,  this  quantity 
would  be  increased  to  between  700  and  800  c.c.  The  amount  of  carbon 
dio.xide  eliminated  during  rest  in  an  average  adult  (300  c.c.)  can  there- 
fore be  easily  excreted  by  diffusion  with  a  tension-difference  of  i  mm. 
of  mercury.  Even  during  very  hard  work  the  necessary  tension  differ- 
ence need  not  be  more  than  3  mm.  With  a  movement  of  carbon  dioxide 
so  free  as  this,  it  is  obvious  that  if  the  excretion  (jf  that  gas  is  solely  a 
matter  of  diffiision  its  partial  pressure  in  the  arterial  blood  must  be 
nearly  identical  with  its  partial  pressure  in  the  alveolar  air. 

A  glance  at  the  table  on  p.  261  shows  that  while  the  carbon  di- 
oxide tension  of  venous  blood  may  sometimes,  perhaps  generally, 
exceed  that  of  the  alveolar  air,  the  difference  is  quite  small.  The 
average  for  the  observations  on  man  with  the  pulmonary  catheter 
was  45  mm.,  which  compares  with  an  average  alveolar  tension  of 
42  mm. 

Experiments  made  by  more  modern  methods  have  placed  the 
matter  bevond  doubt.  Krogh  pro\ed,  for  example,  that  in  rabbits 
the  carbon  dioxide  tension  in  the  arterial  blood  was  always  slightly 
(on  the  average  0-4  per  cent,  of  an  atmosphere,  or  3  mm.  of  mercury; 
higher  than  in  air  taken  from  the  bifurcation  of  the  trachea.  Now 
this  air  is  known  to  contain  shghtly  less  carbon  dioxide  than  the 
alveolar  air.  Haldane 's  results  on  the  regulation  of  the  respiration 
(p.  281)  would  be  unintelligible  unless  the  carbon  dioxide  pressure 
in  the  arterial  blood  adjusted  itself  with  great  rapidity,  to  changes 


THE  GASES  OF  THE  BLOOD  265 

in  tlio  tension  of  carbon  dioxide  in  the  aKiohir  air,  so  as  always 
to  preserve  a  definite  relation.  It  is  quite  generally  assumed  that 
this  relation  is  one  of  practical  equality,  and  the  classical  method 
of  measuring  the  carbon  dioxide  tension  in  the  arterial  blood  in  man 
is  to  determine  it  in  the  alveolar  air. 

Evidence  in  favour  of  the  view  that  there  is,  besides  diffusion, 
an  element  of  selective  secretion  in  the  exchange  of  gases  through 
the  pulmonary  membrane  has  been  found  by  some  writers  in  the 
results  of  a  studv  of  the  gases  of  the  swim-bladder  in  fishes.  This 
study  has  demonstrated  the  existence  of  animal  cells  which  actually 
secrete  gases.  This  fact,  however,  even  if  it  removes  a  presump- 
tion against,  does  not  establish  a  presumption  in  favour  of,  the 
secretion  theory  of  external  respiration.  These  gases  consist  of 
oxygen,  nitrogen,  and  usually  a  small  quantity  of  carbon  dioxide, 
but  in  verv  different  proportions  from  those  in  which  they  exist  in 
the  air  or  the  water.  Thus,  as  much  as  87  per  cent,  of  oxygen  has 
been  found  in  the  bladder  of  fishes  taken  at  a  considerable  depth, 
but  a  smaller  amount  in  those  captured  near  the  surface.  When 
the  gas  is  withdrawn  by  puncturing  the  bladder  with  a  trocar,  the 
organ  rapidly  refills,  and  the  percentage  of  oxygen  increases. 
Further,  this  process  of  gaseous  secretion  is  under  the  influence  of 
nerves,  for  gas  ceases  to  accumulate  in  the  organ  when  the  branches 
of  the  vagi  that  supply  it  are  cut.  In  the  tortoise  stimulation  of 
the  peripheral  end  of  the  vagus  causes  a  fall  of  gaseous  exchange 
in  the  corresponding  lung,  with  an  accompanying  rise  in  the  other 
lung.  But  this  is  a  consequence  of  an  alteration  in  the  pulmonary 
circulation  through  the  vasomotor  fibres  for  the  lungs  which  are 
known  to  run  in  the  vagus  in  this  animal.  In  the  mammal,  no  such 
effect  has  been  demonstrated,  and  the  decisive  proof  that  the  lungs 
are  gas-secreting  glands  which  would  be  afforded  by  the  discovery 
of  secretory  nerves  is  wanting. 

We  have  now  completed  the  description  of  the  phenomena  of 
external  respiration,  with  the  discussion  of  its  central  fact,  the 
exchange  of  gases  between  the  blood  and  the  air  at  the  surface  of 
the  lungs.  It  remains  to  trace  the  fate  of  the  absorbed  oxygen, 
and  to  determine  where  and  how  the  carbon  dioxide  arises. 

Section  V. — Internal  or  Tissue  Respiration. 

Seats  of  Oxidation. — The  suggestion  which  lies  nearest  at  hand 
and  which,  as  a  matter  of  fact,  was  first  put  forward,  is  that  the 
oxygen  does  not  leave  the  blood  at  all,  but  that  it  meets  with 
oxidizable  substances  in  it,  and  unites  with  their  carbon  to  form 
carbon  dioxide.  WTiile  there  is  a  certain  amount  of  truth  in  this 
\new,  oxygen,  as  already  mentioned,  being  to  some  extent  taken  up 
by  freshly  shed  blood,  and  also  by  blood  under  other  conditions, 
to  oxidize  bodies,  other  than  hemoglobin,  either  naturally  contained 


266  RF.SPIHATION 

in  it  or  artificially  added,  tlK-re  is  no  cl(jubt  that  tlic  colls  of  the  body 
arc  the  busiest  seats  of  oxidation.  TliL*^  is  shown  by  the  presence 
of  carbon  dioxide  in  larf<e  amount  in  lynipli  and  tether  licjuid^  wliich 
are,  or  liave  been,  in  intimate  relation  with  tissue  elements;  by  its 
presence,  also  in  considerable  amount,  in  the  tissues  themselves — 
in  muscle,  for  instance ;  by  its  continued  and  scarcely  lessened  pro- 
duction not  only  in  a  frog  whose  blood  has  been  replaced  by  physio- 
logical salt  solution,  and  which  continues  to  live  in  an  atmosphere 
of  pure  oxygen,  but  in  excised  muscles;  and  by  the  remarkable  con- 
nection between  the  amount  of  this  produ<tion  and  the  functional 
state  of  those  tissues.  In  insects  the  finest  twigs  of  the  trachea, 
through  which  oxygen  passes  to  the  tissues,  actually  end  in  the  cells ; 
and  in  luminous  insects,  like  the  glow-worm,  it  has  been  noticed 
that  the  phosphorescence,  which  is  certainly  dependent  on  oxidation, 
begins  and  is  most  brilliant  in  those  parts  of  tlie  cells  of  the  light- 
producing  organ  that  surround  the  ends  of  the  trachea;.  Microscopic 
evidence  has  been  obtained  that  intracellular  oxidation  proceeds 
most  rapidly  near  surfaces  like  the  nuclear  and  plasma  membranes 
— e.g.,  in  the  indophenol  (p.  272)  and  similar  reactions  the  coloured 
oxidation  products  are  deposited  chiefly  in  and  around  the  nuclei  of 
such  cells  as  liver  and  kidney  cells  and  frog's  red  corpuscles  (Lillie). 

The  Passage  of  Oxygen  from  the  Blood  into  the  Tissues. — A 
fundamental  fact  of  tissue  respiration  is  that  the  amount  of  oxygen 
taken  up  by  the  cells  depends  essentially  upon  their  needs,  and  not 
upon  the  amount  of  oxygen  offered  to  them  in  the  blood.  In  every 
case  studied,  an  increase  of  functional  activity  on  the  part  of  an 
organ  leads  to  an  increased  call  for  oxygen  by  that  organ,  and  an 
increased  consumption  of  oxygen  in  it.  The  cells  cannot  be  cajoled, 
so  to  say,  into  consuming  more  oxygen  merely  by  increasing  the 
available  supply.  Nor  can  they  be  prevented  from  absorbing  and 
consuming  more  of  whatever  supply  is  available  when  they  are 
caused  to  work  harder. 

For  skeletal  muscle  at  rest,  Barcroft  gives  0*004  ^'-C-  per  gramme 
per  minute  as  the  oxygen  consumption ;  during  maximal  activity 
twenty  times  as  much  (o«o8  gramme).  In  the  heart  of  a  small  dog 
through  which  blood  was  pumped  by  a  larger  dog  the  oxygen  intake 
when  the  heart  was  beating  feebly  was,  on  the  average,  about 
O'Oi  c.c.  per  gramme  of  heart-muscle  per  minute.  Wlien  the  heart 
was  caused  to  beat  very  strongly  under  the  influence  of  adrenalin, 
the  oxygen  intake  rose  in  one  case  to  o«o8,  and  in  two  others  to  0*04. 
In  the  resting  pancreas  the  oxygen  intake  has  been  found  to  be  0*03 
to  0'05  c.c.  per  gramme  per  minute;  in  the  active  pancreas,  0*1  c.c. 
The  corresponding  number  for  the  submaxillary  gland  at  rest  is 
0*03,  and  in  activity  0*09;  for  the  kidney,  0*03  at  rest  or  during 
scanty  secretion,  and  0*07  or  even  0-09  during  active  secretion ;  for 
the  liver  in  fasting  animals  o«oi.  in  fed  animals  o-ojs. 


IXTF.RXAL  OR  TISSUE  Rl-SPI RATION  267 

Wf  arc  as  yet  less  precisely  inlornied  as  to  the  manner  in  which 
the  tissues  regulate  the  amount  of  oxygen  which  they  take  up  from 
the  blood,  than  in  the  case  of  the  passage  of  oxvgen  into  the  blood 
from  tlie  lungs.  Tlie  ])robIem,  indeed,  is  superficially  at  least  a 
different  and  probably  a  more  complex  one.  In  the  lungs  the  task 
is  to  saturate,  or  nearly  to  saturate,  the  h;emogl(jbin  with  oxygen, 
whether  the  blood  passes  fast  or  slow.  It  is  a  monotonous  invariable 
process  of  -oxygen-grabbing,'  with  no  possibility  of  its  ever  being 
overdone.  In  the  tissues,  the  task  is  to  meet  the  widely  varjang 
demand  from  blood  which  is  always  charged  with  oxygen  to  ap- 
])roximately  the  same  degree.  How  is  this  tiling  managed  ?  There 
is  little  doubt  that  the  process  is  again  fundamentally  a  matter  of 
diffusion.  The  oxygen  dissociated  from  the  oxyha^moglobin  in  the 
capillaries  must  find  its  way  through  the  plasma  across  the  capillary 
walls  into  the  tissue  lymph,  and  thence  into  the  interior  of  the  cells. 
There  is  evidence  that  it  can  do  so  by  physical  diffusion.  For  the 
oxygen  tension  in  the  capillary  blood  is  in  general  higher  than  the 
oxygen  tension  in  the  tissues.  The  common  statement  that  the 
partial  pressure  of  ox^'gen  in  the  tissues  is  zero,  or  nearly  zero,  fits 
in  very  well  with  the  conclusion  that  the  oxygen  is  transported  into 
the  cells  from  the  blood  of  the  capillaries  by  a  process  of  diffusion. 
For  the  slope  of  oxygen  pressure  thus  maintained  would  ordinarily  be 
greater  than  in  the  lungs,  since  even  at  the  end  of  the  capillary  tract 
the  venous  blood  still  has  a  considerable  partial  pressure  of  oxygen. 

The  fact  that  such  liquids  as  lymph,  bile,  urine,  the  serous  fluids, 
saUva,  pancreatic  juice  and  milk  contain  little  or  no  oxygen  was  sup- 
posed to  support  the  view  that  the  pressure  of  oxygen  must  be  very  low 
in  the  tissues  by  which  they  are  secreted,  or  with  which  they  have  been 
in  intimate  contact.  From  isolated  muscles  no  free  oxygen  at  all  can 
be  pumped  out,  and  mu.scle  being  taken  as  a  type  of  the  other  tissues 
in  regard  to  the  problems  of  internal  respiration,  it  was  concluded  that 
the  scarcity  of  oxygen  in  the  parenchymatous  liquids  which  bathe  the 
tissues  deepens  in  the  tissues  themselves  into  actual  famine.  The 
inference  seemed  plain.  Either  the  tissues  used  up  oxygen  so  rapidly 
that  with  an  average  blood  flow  their  wants  could  just  be  supplied, 
or  without  actually  consimiing  it  they  '  fixed  '  and  stowed  it  away  in 
some  compound  in  which  it  was  still  available  for  oxidation  in  the  meta- 
bolic processes  of  the  cell,  but  had  lost  the  properties  of  free  oxygen. 
On  the  first  alternative,  an  increased  consumption  of  oxygen  could  only 
be  met  by  an  increase  in  the  blood  flow;  on  the  second  assumption 
the  stored  oxygen  would  supply  the  means  of  temporarily  increasing 
the  metabolism  even  without  an  immediate  augmentation  of  the  blood 
flow.  Although  it  was  recognized  that  even  the  resting  metabolism 
of  certain  organs  was  not  inconsiderable,  and  required  a  good  supply 
of  oxygen,  it  was  always  difficult  to  understand  why  inactive  tissues 
should  have  such  an  avidity  for  oxvgen  that  practically  every  molecule 
seemed  to  be  captured  as  soon  as  it  appeared.  Xor  did  it  help  much  to 
assume  that  some  of  the  tissue  oxidation  might  really  take  place  in 
the  tissue  lymph,  oxidizable  products  split  off  in  the  metabolism  of 
the  cells  passing  out  into  the  lymph  before  being  burnt,  and  thus 
diminishing  the  oxygen  tension  outside  the  capillary  walls. 


268  RESFIHATION 

Recent  work  has  indicated,  however,  that  the  oxygen  pressure 
in  some  tisbues  is  far  from  neghgible.  In  the  nsting  submaxillary 
gland,  indeed,  it  seems  to  be  practically  equal  to  the  oxygen  pres- 
sure in  the  venous  blood  leaving  the  organ  (over  40  mm.  of  mercury 
in  certain  experiments).  In  general,  the  same  was  found  to  be 
the  case  for  the  kidney.  This  does  not  mean,  of  course,  that  in 
such  organs  there  is  no  slope  of  oxygen  pressure  from  blood  to 
tissue,  in  virtue  of  which  oxygen  can  be  moved  out  of  the  blood 
by  diffusion.  For  at  the  beginning  of  the  capillarv  tract  the  whole 
difference  in  oxygen  pressure  between  the  arterial  and  the  venous 
blood  would  be  available.  At  the  end  of  the  capillary  tract,  the 
blood  by  the  loss  of  oxygen  to  the  tissues  would  have  come  approxi- 
mately into  equilibrium  with  them.  These  observations  enable  us 
to  understand  better  the  manner  in  which  the  tissues  themselves 
can  regulate  their  mtake  of  oxygen.  If  the  glands  are  using  little 
oxygen  their  oxygen  tension  will  be  relatively  high,  and  the  passage 
of  a  comparatively  small  amount  of  oxygen  from  the  blood  in  the 
capillaries  will  suffice  to  bring  it  into  equilibrium  with  the  tissues, 
after  which  the  diffusion  of  oxygen  will  cease.  If,  on  the  other 
hand,  the  consumption  of  oxygen  in  the  glands  is  suddenly  in- 
creased, their  oxygen  pressure  will  fall,  the  pressure  gradient  be- 
tween them  and  the  blood  will  become  steeper,  and  oxygen  will 
diffuse  more  rapidly  into  them  from  the  capillaries.  It  must  be 
remarked,  also,  that  up  to  a  certain  point  the  existence  of  a  sub- 
stantial oxygen  pressure  in  the  tissues  permits  them  at  once  to 
increase  their  intake  of  oxygen  from  the  blood  without  the  neces- 
sity of  an  immediate  increase  in  the  blood  flow.  For,  as  the  cells 
consume  the  oxygen  already  present  in  and  between  them,  the 
tissue  oxygen  tension  falls,  and  the  gradient  between  the  interior 
and  the  exterior  of  the  capillaries  is  thus  rendered  more  abrupt. 

These  results  were  not  obtained  by  direct  tonometric  measurement 
of  the  oxygen  pressure  in  the  glands  investigated,  but  were  deduced 
from  observations  on  the  quantities  of  oxygen  taken  up  by  them  when 
different  oxygen  pressures  were  produced  in  the  capillaries  by  altering 
the  oxygen  tension  in  the  inspired  air.  The  quantity  of  oxygen  which 
diffuses  out  of  the  capillaries  in  a  given  time  will  be  proportional  to 
the  difference  of  oxygen  pressure  on  the  two  sides  of  the  capillary  wall. 
If  the  pressure  on  the  side  of  the  tissues  is  always  zero,  then  the  quantity 
of  oxygen  passing  out  will  vary  directly  as  the  intracapillary  oxygen 
pressure.  Far  from  doing  this,  the  amount  of  oxygen  taken  up  by  the 
glands  was  found  to  be  about  the  same  with  intra-capillary  oxygen 
pressures  as  different  as  61  mm.  and  16  mm.  of  mercury.  It  should  be 
distinctly  understood  that  no  great  importance  must  be  attached  to 
the  actual  numbers  in  experiments  of  this  kind.  But  the  general  con- 
clusion that  in  some  tissues,  at  any  rate  in  the  resting  condition,  a 
sensible  partial  pressure  of  oxygen  exists,  seems  to  be  established 
(Verzir).  The  application  of  the  same  method  to  muscle  has  led  to 
a  different  result.  Here,  the  possible  partial  pressure  of  oxygen  was 
found  decidedly  less  than  that  of  the  venous  blood,  although  at  times 
a  small  oxygen  pressure  was  detected  in  resting  muscle  (25  mm.  or  less) 


ISTERXAL  OR  TISSUE  RESPIRATION 


269 


Muscle  may  accordingly  be  taken  as  a  type  of  tissues  in  which 
the  oxygen  pressure  is  so  low  that  the  blood-flow  through  them 
cannot  be  much  diminished  without  interference  with  their  absorp- 
tion of  oxygen,  while  in  tissues  like  the  resting  submaxillary  gland 
■<\  considerable  diminution  of  the  blood-fiow  can  occur  without 
diminution  of  the  oxygen  consumption  of  the  tissue.  Whether 
this  difference  is  merely  a  quantitative  one,  depending  upon  the 
great  oxygen  requirement  of  active  muscle,  or  a  qualitative  difference 
connected  with  the  peculiar  relations  of  oxygen  to  the  muscular 
contraction,  is  unknown.  These  relations  have  so  great  an  interest 
in  connection  with  the  problem  of  intracellular  oxidation,  and  have 
been  so  much  more  minutely  studied  than  the  relations  of  oxygen 
to  the  functional  work  of  other  tissues,  that  a  few  words  on  the 
respiration  of  muscle  may  fitly  be  introduced  here.  The  subject 
must  be  returned  to  later  on  (Chapters  XII.  and  XIII.). 


Fig.  123. — Fatigue  of  a  Pair  of  Sartorius  Muscles  (Fletcher).  A,  in  an  atmosphere  of 
oxygen;  B,  in  an  atmosphere  of  nitrogen.  A  is  partially  restored  by  a  rest  of 
five  minutes. 


Respiration  of  Muscle. — It  is  a  remarkable  fact  that  an  excised 
frog's  muscle  is  capable  of  going  on  yielding  carbon  dioxide  for  a 
long  time,  in  the  entire  absence  of  oxygen,  in  a  chamber,  for  instance, 
filled  with  nitrogen  or  other  indifferent  gas.  Not  only  so,  but  it 
can  be  made  to  contract  many  times  in  this  oxygen-free  atmosphere, 
although  it  loses  its  power  of  contraction  sooner  than  in  oxygen, 
and  does  not  show  the  same  capacity  for  recuperation  during  an 
interval  of  rest.  In  mammals  the  muscles  can  also  be  made  to 
contract  repeatedly  when  the  dissociable  oxygen  has,  as  far  as  pos- 
sible, been  got  rid  of  from  the  blood  by  asphyxiating  the  animal,  and 
to  give  off  a  correspondingly  large  quantity  of  carbon  dioxide, 
although  they  lose  their  contractibility  much  more  rapidly  than  the 
muscles  of  the  frog.  This  has  usually  been  interpreted  as  meaning 
that  the  carbon  dioxide  does  not  arise,  so  to  speak,  on  the  spot,  from 


270  iiESPr  RATIOS* 

the  immediate"  union  ul  curbon  .uul  u.\yg(.'n,  but  that  a  stuck  of 
it  is  taken  up  by  the  muscle,  and  stored  in  some  compound  or 
compounds, which  are  broken  down  during  contraction,  and  more 
slowly  during  rest,  carbon  cUoxide  in  both  cases  being  one  of 
the  end-products.  In  a  normal  muscle  with  intact  circulation, 
while  carbon  dioxide  is  gi\'en  off,  certain  of  the  other  decomposition 
products  are  supposed,  in  conjunction  with  oxygen  and  some  sub- 
stance rich  in  carbon,  like  sugar,  to  be  regenerated  into  the  material 
which  breaks  down  in  contraction.  When  oxygen  is  not  available, 
as  in  an  atmosphere  of  nitrogen,  carl)on  dioxide  is  still  given  off,  but 
the  other  dccompositicjn  products  are  suj)posed  not  to  be  regenerated 
to  contractile  substance,  but  to  accumulate  in  the  muscle,  producing 
the  phenomena  of  fatigue,  and  eventually  of  rigor. 

When  muscle  goes  into  rigor  (Chapter  XIII.) — and  this  is  most 
strikingly  seen  when  the  rigor  is  caused  by  raising  the  temperature 
of  frog's  muscle  to  about  40°  or  41°  C. — there  is  a  sudden  increase  in 
the  quantity  of  carbon  dioxide  given  off.  Moreoxer,  in  an  isolated 
muscle  the  total  quantity  of  carbon  dioxide  obtainable  during  rigor  is 
markedly  less  if  the  muscle  has  been  previously  tetanized.  From  this 
it  has  been  argued  that  the  hypothetical  substance  ('  inogen.'),  the 
decomposition  of  which  3'ields  carbon  dioxide  in  contraction,  is  also 
the  substance  which  decomposes  so  rapidly  in  rigor;  that  a  given 
amount  of  it  exists  in  the  muscle  at  the  time  it  is  removed  from  the 
influence  of  the  blood;  and  that  this  can  all '  explode  '  either  in  con- 
traction or  in  rigor,  or  partly  in  the  one  and  partly  in  the  other. 
However,  according  to  Fletcher,  there  is  no  increase  in  the  amount 
of  carbon  dioxide  given  off  during  tetanus  by  an  excised  frog's 
muscle  unless  the  stimulation  is  so  severe  and  prolonged  as  to 
hasten  the  onset  of  rigor.  He  therefore  supposes  that  in  the  con- 
traction the  decomposition  does  not  proceecl  quite  to  the  formation 
of  carbon  dioxide,  which  in  the  intact  body  is  afterwards  liberated 
from  some  more  complex  carbon-containing  waste-product.  He 
considers  that  the  carbon  dioxide  yielded  by  excised  muscles  is 
really  performed  carbon  dioxide,  already  existing  in  a  state  of  loose 
combination,  from  which  it  is  displaced  by  the  lactic  acid  formed 
after  excision.  There  is  no  reason  to  suppose  that  any  independent 
new  formation  of  carbon  dioxide  occurs  witliin  the  isolated  muscle 
in  the  absence  of  a  good  supply  of  oxygen.  However  this  may  be, 
there  is  good  evidence  that  oxygen  is  used  up  in  recovery  processes 
after  the  contraction  is  over,  and  that  these  recovery  processes  are 
not  completed  when  oxygen  is  lacking.  Hill's  work  on  the  heat 
production  of  muscle  (Chapter  XIII.)  has  tended  to  rehabilitate  the 
older  conceptions,  at  least  to  this  extent,  that  his  results  are  in 
favour  of  the  view  that  oxygen  is  used  largely  during  the  recovery 
after  contraction  in  reactions  '  whereby  the  molecular  machine — like 
a  steam-engine  charging  an  accumulator — builds  up  bodies  contain 


ISTI-USAL  on  TISSUE  kESPI  h'A  I  ION  t;! 

ing  considerable  amouiUs  ot  f)otontial  energy  which  (Hkc  thr  accu- 
mulator) can  be  dis(lun>,'<d  by  ;ipi)r()priatp  stimuli.' 

The  respiration  of  muscles  in  situ  can  be  studied  by  collecting 
samples  of  the  blood  coming  to  and  leaving  them  and  analyzing  the 
gases.  The  mere  difference  of  colour  between  the  \'enous  and 
arterial  blood  of  a  muscle,  or  other  acti\e  organ,  is  sufficient  to  show- 
that  oxygen  is  taken  up  and  carbon  dioxide  given  out  by  it  to  the 
blood.  This  is  the  case  in  muscle  s;it  rest,  and  even  in  muscles 
with  artificial  circulation  after  they  have  become  inexcitable.  In 
active  muscles  more  oxygen  is  used  up  and  more  carbon  dioxide 
produced  than  in  the  resting  state.  Chauveau  and  Kaufmann,  in 
their  experiments  on  the  levator  labii  superioris  muscle  of  the  horse  in 
feeding,  found  that  the  consumption  of  oxygen  and  the  production 
of  carbon  dioxide  might  be  many  times  as  great  in  activity  as  in  rest. 

Thus  in  one  experiment  the  amount  of  oxygen  taken  in,  expressed 
in  CO.  per  gramme  of  muscle  per  minute,  was  o-oo8  during  rest,  and 
0T4  during  work;  the  corresponding  quantities  for  the  carbon  dioxide 
given  oft  were  0-006  and  om8.  The  respiratory  quotient  rose  to  1-3  in 
two  experiments,  and  even  to  1-7  in  a  third,  showing  that  the  increase 
in  tlie  production  of  carbon  dio.xide  was  relatively  greater  than  the 
increase  in  the  intake  of  oxygen.  These  experiments  were  performed 
under  conditions  so  normal  that  the  animal  continued  to  eat  its  hay 
with  seeming  unconcern  throughout  the  observations,  although  these 
involved  the  exposure  of  the  main  bloodvessels  of  the  muscle,  and  the 
collection  of  samples  of  blood  from  them. 

By  means  of  the  modern  technique  permitting  the  use  of  small 
quantities  of  blood  for  the  gas  analysis,  similar  experiments  have  been 
performed  on  a  muscle  as  small  as  the  cat's  gastrocnemius.  In  one 
experiment  it  was  found  that  as  a  result  of  stimulation  of  the  sciatic 
lasting  about  23  seconds  the  intake  of  oxygen  was  increased  for  at  least 
220  seconds.  In  this  time  the  muscle  used  up  0-75  c.c.  of  oxygen,  as 
compared  with  0-26  c.c,  which  it  would  have  consumed  had  it  not  been 
stimulated  (Verzar). 

Nature  of  the  Oxidative  Process. — When  we  have  recognized  the 
cells  as  the  seat  of  oxidation,  the  question  immediately  presents 
itself.  How  do  they  accomplish  the  feat  of  burning  such  masses  of 
food  substances  as  can  only  be  rapidly  oxidized  in  the  laboratory 
at  the  temperature  of  the  body  by  the  most  energetic  chemical 
reagents  ?  The  researches  of  late  years  have  furnished  a  key  to 
the  solution  of  this  long-standing  puzzle  by  demonstrating  the 
existence  in  the  tissues  of  oxidizing  ferments  or  oxydases.  Of  these, 
one  of  the  most  widely  distributed  is  a  ferment  which  splits  off 
oxygen  from  hydrogen  peroxide.  Since  any  oxidation  produced 
is  only  secondary  to  this  decomposition,  ferments  which  decompose 
hydrogen  peroxide  are  often  spoken  of  as  catalases,  to  distinguish 
them  from  the  oxydases  proper.  A  catalase  is  found  in  practically 
all  the  tissues  of  the  body,  as  well  as  in  vegetable  cells,  and  we  have 
already  mentioned  instances  of  its  action  in  connection  with  the 
oxidation  of  the  guaiaconic  acid  in  tincture  of  guaiacum  in  the 


272  RESPIRA  TION 

presence  of  the  peroxide  (p.  yb).  As  regards  the  activity  of  this 
ferment,  blood  comes  first;  then  follow  spleen,  liver,  pancreas, 
thymus,  brain,  muscle,  and  ovary.  It  is  present  in  the  blood-free 
organs  as  well  as  in  the  blood.  Some  tissues,  both  animal  and 
vegetable,  contain  a  ferment,  an  oxydase,  which  causes  the  oxida- 
tion of  guaiaconic  acid  in  the  presence  of  atmospheric  oxygen,  and 
these  do  not  need  peroxide  of  hydrogen  in  order  to  render  guaiacum 
blue.  An  allied  ferment  which  also  induces  the  blue  colour  in 
tincture  of  guaiacum  is  the  so-called  laccase  found  in  the  most  active 
form  in  the  latex  of  the  tree  from  which  Japanese  lacquer  is  ob- 
tained, but  also  in  many  other  plants.  Many  fungi  contain  a  fer- 
ment, tyrosinase,  which  oxidizes  tyrosin,  and  in  certain  animals 
tyrosinases  have  also  been  demonstrated.  Another  well-known 
oxidizing  ferment  in  fresh  animal  tissues  is  characterized  by  the 
property  of  forming  indophenol  by  oxidation  in  an  alkaline  solution 
of  paraphenylenediamin  and  a-naphthol,  and  may  therefore  be 
termed  indophenyloxydase.  The  colourless  solution  becomes 
reddish  or  \'iolet.  This  ferment  is  contained  in  pancreas,  salivary 
glands,  spleen,  thymus,  and  bone  marrow,  but  has  not  been  de- 
tected in  muscle,  lungs,  brain,  kidneys,  and  other  organs.  It  is 
to  be  expected  that  other  oxydases  capable  of  favouring  oxida- 
tion of  specific  kinds  of  food  substances  or  their  decomposition 
products  will  be  discovered,  but  it  ought  to  be  remarked  that 
those  at  present  known  are  only  capable  of  attacking  relatively 
simple  organic  substances,  and  it  would  be  rash  to  conclude 
that  this  is  the  only  way  in  which  living  protoplasm  can  bring 
about  the  rapid,  but  at  the  same  time  the  regulated,  oxidation 
which  is  so  characteristic  a  feature  of  its  activity.  Yet  the  capacity 
of  the  cell  to  regulate  the  intensity  and  the  extent  of  the  intra 
cellular  oxidations  would  seem  to  find  a  simple  explanation  if  we 
assign  an  important  role  to  oxidizing  ferments  formed  by  the  cell 
itself  in  accordance  with  its  needs.  In  this  connection  we  may 
mention  a  ferment,  aldehydase,  which  was  formerly  included 
among  the  oxydases,  but  is  now  known  to  be  a  hydrolytic  enzyme. 
It  splits  aldehydes  so  as  to  yield  the  corresponding  acid — e.g., 
saJicylic  aldehyde  is  split  into  sahcylic  acid  and  sahgenin.  Evidence 
of  its  presence  in  most  organs  has  been  obtaimd. 

The  Passage  of  Carbon  Dioxide  from  the  Tissues  into  the  Blood. 
— Since  nearly  the  whole  of  the  carbon  dioxide  c\cntually  found  in 
the  blood  is  formed  in  the  tissues,  and  only  a  small  amount  in  the 
blood  itself,  it  might  be  supposed  that  the  partiid  pressure  of  the 
gas  in  the  tissues  would  necessarily  be  greater  than  in  the  blood. 
This  would  certainly  be  true  if  the  whole  of  the  carbon  dio.xide 
was  transported  in  the  form  of  dissolved  gas.  This,  however,  is 
not  the  case.  Much  of  it  is  combined,  and  as  the  proportion  of 
free  to  combined  carbon  dioxide  in  the  blood  is  variable,  it  may  be 


INTl-hWAL    OR   TlSSUl-    RESPIRATION  373 

assumed  that  it  is  also  variable  in  the  tissues.  There  is  no  e\i(l<nro 
and  httle  piobabiHty  that  the  variations  are  always  parallel.  Quan- 
titative and  e\en  qualitatixe  differences  in  the  substances  which  can 
bind  carbon  dioxide  are  known  to  exist  between  the  blood  and  the 
tissues,  and  it  is  uncertain  how  much  interchange  of  such  compounds 
carrying  with  them  combined  carbon  dioxide,  which  may  after- 
wards become  dissociated,  takes  place  between  the  blood  and  the 
tissue  lymph  or  the  cells.  However  probable,  then,  it  may  be  that 
the  transportation  of  carbon  dioxide  from  the  cells  to  the  lymph, 
and  from  the  lymph  to  the  blood  is  managed  in  the  same  way  as 
that  of  the  carbon  dioxide  from  the  blood  to  the  alveolar  air,  namely, 
by  diffusion  of  the  gas  in  solution,  it  cannot  be  said  that  at  present 
clear  proof  of  this  has  been  obtained.  Results  are,  indeed,  on 
record,  which  purport  to  show  that  the  partial  pressure  of  carbon 
dioxide  in  various  tissues  or  in  physiological  liquids  which  have 
been  in  contact  with  them  is  higher  than  that  of  the  arterial  or  even 
than  that  of  the  venous  blood.  But  these  results  are  of  unequal 
and  some  of  them  of  doubtful  value  for  the  solution  of  the  problem 
under  discussion. 

Lymph,  bile,  urine,  and  the  eerous  fluids  contain  so  much  carbon 
dioxide  that  the  pressure  of  that  gas  in  all  of  them  is  greater  than  in 
arterial  blood,  while  in  lymph  alone  (taken  from  the  large  thoracic 
duct)  has  it  been  found  less  than  that  of  venous  blood.  And  it  is  pro- 
bable that  lymph  gathered  nearer  the  primary  seats  of  its  production 
(the  spaces  of  areolar  tissue)  would  show  a  higher  proportion  of  carbon 
dioxide.  Strassburg  found  that  with  a  pressure  of  carbon  dioxide  in 
the  arterial  blood  of  21  mm.  of  mercury,  the  pressure  in  bile  was  50  mm., 
in  peritoneal  fluid  58  mm.,  in  urine  68  mm.,  in  the  surface  of  the  empty 
intestine  58  mm.  Saliva,  pancreatic  juice,  and  milk,  also  contain  much 
carbon  dioxide.  From  muscle  as  much  as  15  volumes  per  100  of  carbon 
dioxide  can  be  pumped  out,  some  of  which  is  free — that  is,  is  given 
up  to  the  vacuum  alone — while  some  of  it  is  fixed,  and  only  comes  off 
after  the  addition  of  an  acid. 

Before  leaving  the  subject  of  the  gaseous  exchange  between 
tissues  and  blood  and  between  blood  and  air  some  important  con- 
sequences of  the  form  of  the  dissociation  curve  of  oxyhaemoglobin, 
and  of  the  modifications  produced  in  it  by  change  of  temperature, 
by  salts  and  by  acids,  must  be  alluded  to.  They  have  been  developed 
in  masterly  fashion  by  Barcroft.  The  flattening  of  the  hyperbolic 
dissociation  curve  of  dialyzed  oxyhaemoglobin  when  the  tempera- 
ture is  raised  (Fig.  119)  makes  it  obvious  that  for  any  percentage 
saturation  which  can  exist  in  blood  as  it  leaves  the  systemic  capil- 
laries, the  corresponding  partial  pressure  of  oxygen  must  be  much 
greater  at  the  body  temperature  (38°  C.)  than  at  16°  C.  For  haemo- 
globin which  is  50  per  cent,  saturated  it  is  twenty-five  times  as 
great.  This  favours  the  gi\ing  up  of  oxygen  to  the  tissues  by  blood 
in  which  the  percentage  saturation  is  considerably  reduced.     On 


274  Rl-.Sni  RATION 

the  other  li.unl.  the  iibsorption  of  oxygen  in  th<  hmgs  is  not  seriously 
interfered  with,  Ijecanse  the  available  alveolar  jjartial  pressure  of 
oxygen  is  so  high  (loo  mm.  or  more)  that  it  cyn  be  considerably 
diminished  without  causing  any  appreciable  diminution  in  the 
percentage  saturation. 

There  is  evidence  that  in  dialyzed  haemoglobin  solutions  the 
haemoglobin  is  all  in  the  form  of  single  molecules.  The  addition  of 
salts  as  they  exist  in  blood  produces  a  certain  amount  of  aggrega- 
tion or  clumi)ing  of  the  molecules,  and  as  already  pointed  out,  this 
alters  the  shape  of  the  dissociation  curve.  The  S-shape  of  the 
curve  of  blood  indicates  that  blood  will  part  with  its  oxygen  at 
low  oxygen  pressures,  as  in  passing  through  the  tissues,  much  more 
readily  than  a  corresponding  solution  of  salt-free  oxyha;mogl(j])in; 
and  that  it  will  take  up  oxygen  more  easily  at  high  pressures,  as 
in  passing  through  the  lungs.  As  regards  the  effect  of  acids,  it 
was  observed  by  Bohr  (p.  255)  that  an  increase  in  the  carbon  dioxide 
tension  of  blood  diminishes  its  combining  power  for  oxygen,  and 
therefore  favours  the  giving  up  of  oxygen  to  the  lymph  and  tissues. 
This  maj?  have  an  important  influence  on  internal  respiration.  The 
effect  is  much  more  marked  where  the  oxygen  tension  is  low  than 
where  it  is  high,  so  that  in  the  lungs  the  taking  up  of  oxygen  is 
scarcely  interfered  with  even  by  a  high  carbon  dioxide  tension. 

According  to  Barcroft,  the  combined  effect  of  the  increased  tem- 
perature, the  salts  and  the  carbon  dioxide  of  blood  (at  the  partial 
pressure  of  40  mm.  of  mercury)  is  to  make  possible  a  diffusion  of 
oxygen  into  the  tissues  at  100  times  the  speed  at  which  it  would 
diffuse  from  a  salt-free  solution  of  oxyhaemoglobin  at  a  tempera- 
ture of  16°  C.  This  astonishing  feat  is  accomplished  without 
sensibly  decreasing  the  percentage  saturation  with  oxygen  of  the 
blood  passing  through  the  lungs. 

Section  VI. — Relation  of  Respiration  to  the  Nervous 

System. 

The  Respiratory  Centre  and  its  Connections.— Unlike  the  beat  of 
the  heart,  the  respiratory  mo\ements  are  entirely  dependent  on  the 
central  nervous  system.  The  '  centre  '  which  presides  o\'er  them  is 
situated  in  the  spinal  bulb.  It  is  a  bilateral  centre — that  is,  it  has 
two  functionally  symmetrical  halves,  one  on  each  side  of  the  middle 
line.  Each  of  these  halves  has  to  do  more  particularly  with  the 
i-esi)iratory  muscles  of  its  own  side,  for  destruction  of  one-half  of 
the  spinal  bulb  causes  paralysis  of  respiration  only  on  that  side. 
Anatomically  the  respiratory  centre  has  not  been  sharply  localized, 
l)ut  it  lies  lower  than  the  vaso-motor  centre,  not  far  from  the  point 
of  the  cahimus  scriptorius.  Stimulation  of  this  region  dming  apn(X'a 
(p.  283)  is  stated  to  cause  co-ordinated  inspiratory  movements  and 


Ri:i.ATli)M  OF  KJiSJ'JHATlON  TO    I'lII'    NICh'VOUS  SYSTRM      275 

widening  of  tlu-  opening  of  the  glottis  tiirough  abduction  of  the 
vocal  cords.  The  centre  is  brought  into  relation  with  the  muscles 
of  respiration  by  efferent  nerves.  The  phrenic  nerves  to  the  dia- 
phragm, and  the  intercostal  nerves  to  the  muscles  which  elevate 
the  ribs,  are  the  most  important  of  those  concerned  in  ordinary 
breathing.  The  respiratory  centre  is  further  related  to  afferent 
nerves,  of  which  the  most  influential  are  those  which  supply  the 
respiratory  tract  itself,  particularly  the  pulmonary  fibres  and  superior 
laryngeal  branch  of  the  vagus.  But  almost  any  afferent  nerve  ma\' 
powerfully  affect  the  centre;  and  it  is  also  influenced  by  fibres  pass- 
ing to  it  from  the  higher  parts  of  the  central  nervous  system. 

Section  of  the  spinal  cord  in  animals  above  the  origin  of  the 
phrenic  nerves  causes  complete  paralysis  of  respiration,  and  con- 
sequent death.  The  phrenics  arise  from  the  third  and  fourth 
cervical  nerves,  and  are  joined  by  a  branch  from  the  fifth;  and  in 
man  fracture  of  any  of  the  four  upper  cervical  vertebrae  is  as  a  rule 
instantly  fatal.  But  in  one  case  respiration  was  carried  on,  and 
life  maintained  for  thirty  minutes,  merely  by  the  contraction  of  the 
muscles  of  the  neck  and  shoulders  in  a  man  entirely  paralyzed 
below  this  level  (Bell).  Section  of  the  cord  just  below  the  origin  of 
the  phrenics  leaves  the  diaphragm  working,  although  the  other 
respiratory  muscles  are  paralyzed.  A  case  has  been  recorded  of  a 
man  in  whom,  from  disease  of  the  spine  in  the  lower  cervical  region, 
all  the  ribs  became  completely  immovable.  He  was  able  to  lead 
an  active  life,  and  to  carry  on  his  business,  although  he  breathed 
entirely  by  his  diaphragm  and  abdominal  muscles. 

Section  of  one  phrenic  is  followed  by  paralysis  of  the  correspond- 
ing half  of  the  diaphragm,  section  of  both  phrenics  by  complete 
paralysis  of  that  muscle,  and  although  respiration  still  goes  on  by 
means  of  the  muscles  which  act  upon  the  ribs,  it  is  usually  inadequate 
to  the  prolonged  maintenance  of  life.  In  the  horse,  however,  not  only 
has  survival  been  seen  after  this  operation,  but  the  animal,  after 
the  first  temporary  increase  in  the  frequency  of  the  breathing  had 
disappeared,  could  be  driven  in  a  light  vehicle  without  any  marked 
dyspnoea.  The  phrenic  nuclei  in  the  two  halves  of  the  cord  are 
connected  across  the  middle  line.  For  when  a  semisection  of  the 
cord  is  made  between  this  level  and  the  respiratory  centre  in  the 
medulla,  respiratory  impulses  are  still  able  to  reach  both  phrenic 
nerves.  In  some  animals  both  halves  of  the  diaphragm  go  on  con- 
tracting. But  when,  as  usually  happens,  this  is  not  the  case,  and 
the  diaphragm  on  the  side  of  the  semisection  has  ceased  to  act,  it 
at  once  begins  to  contract  again  when  the  opposite  phrenic  nerv€ 
is  cut,  and  the  respiratory  impulse,  descending  from  the  bulb,  is 
blocked  out  from  the  direct,  and  forced  to  follow  the  crossed  path. 
It  has  been  shown  that  the  crossing  takes  place  at  the  level  of  the 
phrenic  nuclei,  and  nowhere  else  (Porter). 


276  h-HSFl  NATION 

The  Regulation  of  the  Respiration  through  the  Afferent  Vagus 
Fibres. — When  one  vagus  is  divided,  tlien-  is  little  or  no  change  in 
the  respiratory  movements.  Half  an  inch  of  one  vagus  nerve  has 
been  excised  in  removing  a  tumour,  and  the  patient  showed  no 
symptoms  whatever.  But  section  of  both  vagi  in  such  animals  as 
the  dog,  cat  and  rabbit  causes  respiration  to  become  much  deeper 
and  slower,  the  one  change  for  a  time  compensating  the  other,  so 
that  the  total  amount  of  air  taken  in  and  given  out,  the  amount  of 
carbon  dioxide  eUminated,  and  the  partial  pressure  of  that  gas  in 
the  pulmonary  alveoli  are  not  greatly  altered.  The  relative  dura- 
tion of  the  two  respiratory  phases  is  completely  changed,  inspira- 
tion being  much  more  prolonged  than  expiration.  It  has  been 
shown  that  the  effect  is  really  due  to  the  loss  of  impulses  that  nor- 
mally ascend  the  vagi,  not  to  any  irritation  of  the  cut  ends.  For  a 
nerve  can  be  frozen  without  exciting  it ;  and  when  a  portion  of  each 
vagus  is  frozen,  the  respiration  is  affected  in  precisely  the  same 
way  as  when  the  nerves  are  divided. 

After  section  of  both  vagi  certain  fibres  coming  from  the  brain 
above  the  respiratory  centre  appear  to  take  a  share  in  the  regulation 
of  the  respiratory  movements.  The  bloodvessels  supplying  these 
fibres,  or  the  centres  from  which  they  come,  can  be  blocked  by 
injection  of  paraffin  wax  into  the  common  or  internal  carotid,  or 
the  bulb  can  be  severed  with  the  knife  above  the  level  of  the  re- 
spiratory centre,  without  any  effect  being  produced  upon  the  breath- 
ing, except  that  the  rate  is  as  a  rule  somewhat  lessened.  But 
when  both  the  vagi  and  these  upper  paths  are  cut  the  character  of 
the  respiration  is  changed,  exceedingly  prolonged  inspiratory 
spasms  alternating  with  long  periods  of  complete  relaxation  of  the 
diaphragm  till  the  animal  dies. 

From  these  facts  it  appears  that  the  periodic  automatic  discharges 
of  the  respiratory  centre  are  being  continually  controlled  and  modi- 
fied by  impulses  passing  up  the  vagus,  and  that  in  the  absence  of 
these  impulses  a  certain  degree  of  control  is  exercised  by  the  higher 
paths,  which,  however,  do  not  appear  to  be  normally  in  action,  at 
any  rate  to  the  full  measure  of  their  capacity.  When  the  vagi  are 
severed,  the  control  of  the  higher  paths  comes  into  play,  and  is 
sufficient  still  to  keep  the  breathing  regular,  although  it  is  slowed. 
When  the  higher  paths  are  cut  off,  the  vagus  of  itself  is  able  to  regu- 
late the  discharge.  But  when  both  are  gone,  the  respiratory  centre, 
freed  from  nervous  control,  passes  into  a  condition  of  alternate 
spasm  and  exhatistion.  Of  the  central  connections  of  these  upper 
paths  but  little  is  surely  known.  The  corpora  quadrigemina,  how- 
ever, seem  to  contain  centres  which  can  affect  the  respiration. 
Certain  areas  on  the  cerebral  cortex  have  also  been  described,  the 
excitation  of  which  modifies  the  r(;spiratory  movements.  There  is 
no  question  that  the  cortex  is  connected,  and  extensively  connected, 


RELATION  OF  RliSPI RATION   TO  THE  NERVOUS  SYSTEM     277 

with  the  respiratory  centre,  since  the  rate  and  depth  of  the  co- 
ordinated respiratory  movements,  which  are  universally  acknow- 
ledged to  involve  the  activity  of  the  centre,  can  be  altered  not  only 
by  the  will,  but  by  the  most  varied  psychical  events. 

The  rhythmical  excitation  of  the  regulating  vagus  fibres  must 
be  brought  about  by  either  mechanical  stimulation  of  the  nerve- 
endings  in  the  lungs,  due  to  the  alternate  stretching  and  shrinking, 
or  by  chemical  stimulation  of  these  endings  depending  on  the  changes 
that  occur  with  each  respiration  in  the  content  of  oxygen  and  carbon 
dioxide  in  the  alveolar  air,  and  therefore  in  their  pressure  (p.  260) 
in  the  blood.  Both  views  have  found  advocates,  but  whatever 
influence  the  chemical  changes  in  the  blood  may  exert,  there  is  no 
doubt  that  the  mechanical  factors  are  the  more  important.  That 
the  vagus  is  really  excited  is  shown  by  the  fact  that  a  negative  varia- 
tion (p.  824)  is  set  up  in  the  nerve  when  the  lungs  are  inflated. 
An  electrical  change  is'  also  observed  when  air  is  sucked  out  of  the 
lungs  (Alcock  and  Secmann,  Einthoven). 

When  the  normal  excitation  of  the  vagus  fibres  by  expansion  of 
the  lungs  is  exaggerated  by  closing  the  trachea  at  the  end  of  in- 
spiration, the  diaphragm  immediately  relaxes,  and  a  long  expira- 
tory pause  ensues,  broken  at  last  by  a  series  of  inspirations  much 
deeper  and  more  prolonged  than  those  which  were  taking  place 
before  occlusion.  When  the  trachea  is  occluded  at  the  end  of 
expiration,  a  series  of  deep  and  long-drawn  inspirations  occurs,  the 
iirst  of  which  begins  at  the  moment  when  the  next  normal  inspira- 
tion ought  to  have  taken  place  had  the  windpipe  been  left  free. 
The  most  obvious  explanation  of  these  results  is  that  the  expansion 
of  the  lungs  sets  up  impulses  in  the  vagi  which  cut  short  the  in- 
spiratory activity  of  the  respiratory  centre  (inspiration-inhibiting 
fibres),  while  in  collapse  impulses  are  set  up  which  excite  it  to  re- 
newed inspiratory  discharge  (inspiration-exciting  fibres).  Since 
ordinary  expiration  is  in  the  main  not  associated  with  active  muscular 
contraction,  the  inspiration-inhibiting  fibres  would  be  at  the  same 
time  expiration-exciting.  Clearly  this  would  constitute  a  so-called 
'  self-steering  '  arrangement,  each  inspiration  leading  inevitably  to 
the  succeeding  expiration,  and  each  expiration  providing  the  neces- 
sary stimulus  for  the  succeeding  inspiration.  On  this  hypothesis 
section  of  the  vagi  must  necessarily  be  followed  by  slowing  of  the 
respiratory  movements,  and  we  have  seen  that  this  is  the  case. 

A  rival  hypothesis  is  that  the  automatic  activity  of  the  respira- 
tory centre  leads  normally  to  the  discharge  of  motor  impulses  to 
the  inspiratory  muscles,  which  are  cut  short  at  each  expansion  of 
the  lungs  by  the  inhibitory  action  of  the  vagus,  the  nerve  not  being 
excited  during  pulmonar^^  collapse,  and  therefore  carrying  no  in- 
spiratory impulses  to  the  centre.  On  this  assumption,  we  may 
think  of  the  centre  as  being  '  wound  up  '  hke  a  clock,  the  periodic 


27  S  RESPIRATION 

arrival  of  regulating  impulses  acting  like  an  escapement  movement, 
and  allowing  a  certain  amount  of  discharge.  \\'hen  the  vagi  are 
cut,  the  inspirations  are  greatly  prolonged  and  deepened,  because 
the  check  on  the  discharge  of  the  centre  has  been  removed. 

Attempts  have  been  made  by  experimental  stimulation  of  the 
vagus  trunk  to  determine  whether,  as  a  matter  of  fact,  it  contains 
both  inspiratory  and  expiratory  fibres.  But  the  results  are  neither 
so  clear  nor  so  constant  that  we  can  confidently  appeal  to  them  in 
making  a  decision,  and  even  some  of  the  investigators  who  main- 
tain the  existence  of  but  one  anatomical  set  of  fibres  believe  that 
these  are  affected  differently  by  different  kinds  of  stimulation — 
momentary  stimuli,  for  example,  setting  up  in  them  impulses 
which  we  may  call  inspiratory,  and  long-lasting  stimuli  impulses 
which  we  may  call  expiratory. 

Excitation  of  the  central  end  of  the  cut  vagus  below  the  origin 
(A  its  superior  lar\-npeal  branch,  with  induction  shocks  of  moderate 


Fig.  1^4. —  Kcspiratory  Tracings:  Uog.  .■\.  U'jrinal;  B,  eilect  of  stimulation  of  the 
central  end  of  vagus;  C,  effect  of  section  of  both  vagi.  (Tracing  taken  as  in 
Fig-  135-  P-  301)     Time-tracing,  seconds. 

strength,  certainly  causes  quickening  of  respiration.  If  the  excita- 
tion be  strong,  there  is  arrest  in  the  inspiratory  phase.  A  brief 
mechanical  stimulus,  or  a  series  of  such,  has  a  similar  effect.  But 
chemical  stimulation  {e.g.,  with  a  strong  solution  of  potassium 
chloride)  or  long-continued  mechanical  excitation  like  that  produced 
by  stretching  or  compression  of  the  nerve,  or  certain  kinds  of  elec- 
trical stimulation — for  instance,  the  very  weakest  induction  shocks, 
or  the  closure  of  an  ascending  voltaic  current* — cause  slowing  of 
the  respiratory  movements  or  expiratory  standstill.  This  is  also 
the  usual,  though  not  the  invariable  result  of  stimulating  the 
superior  laryngeal,  even  when  weak  induction  shocks  are  employed. 
With  stronger  stimulation  energetic  contractions  of  the  expiratory 
muscles  may  occur.  These  facts  undoubtedly  suggest  the  existence 
in  the  vagus  of  two  kinds  of  afferent  nerve-fibres  that  affect  the 
*  I.e.,  a  current  passiog  towards  the  head  in  the  nerve. 


RELATION  OJ-   UliSPl RATIOS  TO  THE  NERVOUS  SYSTEM     27* 

respiratory  centre  in  opposite  ways — inspiratory  fibres,  which 
stimulate  it  to  greater  activity  of  discharge,  and  expiratory  fibres, 
whicli  inhibit  its  action.  The  latter  variety  we  may  suppose  to  be 
more  numerous  in  the  superior  laryngeal,  the  former  in  the  pul- 
monary branches  of  the  vagus.  And  there  is  nothing  forced  in  the 
hypothesis  that  certain  kinds  of  stimuli  act  particularly  on  the  one 
set  of  fibres,  and  certain  kinds  on  the  other,  for  we  have  already 
seen  an  instance  of  this  in  studying  the  differences  between  the  vaso- 
constrictor and  the  vaso-dilator  nerves  (p.  170). 

The  most  probable  conclusion,  and  the  one  which  best  reconciles  the 
conflicting  hypotheses,  is  that  two  sets  of  fibres  are  present :  (i)  Fibres 
which  inhibit  inspiration  {and  cause  expiration),  and  are  excited  in 
ordiuai'v  iu'^piration  h\<  the  expansion  of  the  lungs.     (2)  Fibres  which 


Fig.  125. — Effect  of  Stimulation  of  Central  End  of  Vagus  in  a  Cat.  Upper  Trac;, 
Respiration;  Lower  Trace,  Blood- Pressure.  At  the  top  are  the  time-trace 
(seconds),  and  below  it  the  signal  line,  the  depression  in  which  indicates  the 
duration  of  the  excitation.  Practically  no  eSect  was  produced  on  the  respira- 
tion, but  a  fall  of  blood -pressure  with  slowing  of  the  heart. 

cause  inspiration  {and  inhibit  expiration),  and  are  excited  in  st/ong 
expiration,  as  in  dyspncsj,  by  the  collapse  of  the  lungs,  but  are  not 
active  in  ordinary  expiration. 

However  this  may  be,  the  facts  we  have  been  discussing  have  an 
importance  of  their  own,  apart  from  any  hypothetical  explanations 
of  them.  Some  of  them  have  been  more  than  once  unintentionally 
illustrated  on  man.  In  one  case  the  left  vagus  trunk  was  included 
in  a  ligiture  with  the  common  carotid.  The  respiratory  move- 
ments immediately  stopped,  the  pulse  was  slowed,  and  death 
occurred  in  thirty  minutes  (Rouse).  The  superior  lar^Tigeal  fibres, 
unlike  those  of  the  vagus  proper,  are  not  constantly  in  action,  as 
section  of  both  nerves  has  no  effect  on  respiration.  An}^  source  of 
irritation  in  the  larynx  may  stimulate  these  fibres  and  produce  a 


2S-) 


RhSH  RATIOS 


cough,  whicli  may  also  be  caused  by  irritation  of  the  puhnonary 
fibres  of  the  vagus. 

Action  of  Other  Afferent  Fibres  on  the  Respiration. — The  cutaneous 
nervfs,  and  c^juTially  thoM-  of  tlic  face  (fifth  nrrvc),  abdomen  and 
chest,  havr  a  marked  influence  on  respiration.  They  can  be  easily 
excited  in  the  intact  body  by  thermal  and  mechanical  stimulation. 
A  cold  bath,  for  instance,  usually  causes  acceleration  and  deepening 
of  the  respiratory  movements;  and  the  efficacy  of  meclianical  stimu- 
lation of  sensory  nerves  in  stirring  up  a  sluggish  respiratory  centre 
iswcll  known  t(^  midwives,  who  sometimes  slap  the  buttocks  of  a  new- 


Fig.  126. — Effect  of  Stimulation  of  Central  End  of  Brachial  Nerve  on  Respiration 
(Upper  Tracing)  and  Blood-Pressure  (Lower  Tracing)  in  the  Cat.  At  the  top  of 
the  figure  are  the  time-trace  (seconds)  and  the  signal  line,  showing  beginning  and 
end  of  stimulation. 

born  child  to  start  its  breathing.  The  reflex  expiratory  standstill 
caused  in  rabbits  by  inhalation  of  such  sharp-smelling  substances  as 
ammonia,  acetic  acid,  and  tobacco-smoke  is  due  to  afferent  impulses 
passing  up  the  trigeminus  fibres  from  the  mucous  membrane  of  the 
nose,  and  is  still  obtained  after  section  of  the  olfactory  nerves. 

Another  set  of  afferent  nerves  which  have  been  supposed  by  some 
to  bear  an  important  relation  to  the  respiratory  centre  are  those 
which  supply  the  muscles.  We  have  already  noticed  that  the 
frequency  of  respiration  is  greatly  augmented  by  muscular  exercise. 
The  simplest  e.xplanation  would  seem  tf)  hv  thftt  afferent  muscular 
nerves  are  stimulated  either  by  mechanical  compression  of  their 


RELATIOX  Ol-   RhSril^AflON  TO  THIi  MiRl'UUS  SYSIILM    281 

terminal  'spindles,'  or  by  the  chemical  action  on  them  of  certain 
waste  products  produced  in  contraction.  It  is  quite  likely  that  this 
is  one  way  in  which  the  adjustment  is  achieved.  But  this  is  not 
the  only,  and  perhaps  not  the  most  important,  way.  For  an  in- 
crease in  the  respiratory  movements  is  caused  by  tetanizing  the 
muscles  of  a  limb  whose  nerves  have  been  completely  severed,  and 
which  is  indeed  connected  with  the  rest  of  the  body  by  no  other 
structures  than  its  bloodvessels.  This  can  only  be  due  to  two  things : 
a  direct  action  on  the  respiratory  centre  by  the  blood  that  has 
])asse(l  tlirough.  and  been  altered  in,  the  contracting  muscles,  or  an 
action  exerted  l)y  the  blood  indirectly  on  the  centre  through  the 
excitation  of  afferent  respiratory  nerves  whose  connection  with  it 
is  still  intact — for  example,  the  other  muscular  nerves  or  the  pul- 
monary branches  of  the  vagus.  That  the  action  is  direct  is  shown 
by  the  fact  that  after  section  of  the  vagi,  the  sympathetic,  and  the 
spinal  cord  below  the  origin  of  the  pluenics,  an  increase  in  the 
respiratory  movements  is  still  ])ro(luct(l  by  tetanizing  a  limb. 

The  Chemical  Regulation  of  the  Respiration.  However  im- 
portant the  regulation  of  respiration  by  afferent  nervous  impulses 
may  be,  the  normal  discharge  of  the  respiratory  centre  is  intimately 
associated  with  the  gases  of  the  blood. 

It  is  generally  acknowledged  that  the  centre  may  be  excited  both 
by  blo(xl  tliat  is  rich  in  carbon  dioxide  and  by  blood  that  is  poor  in 
oxygen.  Stimulation  by  deiiciency  of  oxygen  has  to  some  minds 
presented  a  metaphysical  difficulty — namely,  that  it  is  not  easy  to 
see  how  the  absence  of  a  thing  could  cause  stimulation.  The  diffi- 
culty does  not  exist,  but  none  the  less  there  is  some  evidence  that 
when  oxygen  is  lacking  the  respiratory  centre  can  be  excited  by 
substances  likv  lactic  acid,  which  are  easily  oxidizable  and  rapidly 
disappear  from  properly  oxygenated  blood. 

Be  that  as  it  may,  it  has  been  the  subject  of  long-continued  dis- 
cussion whether  excess  of  carbon  dioxide  or  deficiency  of  oxygen  is 
the  more  potent  stimulus  for  the  respiratory  centre.  The  best  evi- 
dence points  to  the  conclusion  that  comparatively  small  alterations 
in  the  amount  of  carbon  dioxide  in  the  inspired  air  cause  a  relatively 
great  increase  in  the  respiration,  while  in  the  case  of  the  oxygen  the 
departure  from  the  normal  proportion  must  be  much  more  decided 
to  bring  about  any  notable  effect.  Nor  is  it  at  all  out  of  harmony 
^vith  this  that,  when  very  large  quantities  of  carbon  dioxide  (30  per 
cent,  and  upwards  in  rabbits)  are  inhaled,  a  condition  of  narcosis 
comes  on  without  an}-  previous  respiratory  distress.  For  many 
substances  act  differently  in  large  and  in  small  doses.  Haldane  has 
pointed  out  how  exquisitely  sensitive  the  respiratory  centre  is  to  even 
small  changes  in  the  partial  pressure  of  carbon  dioxide  in  the  alveo- 
lar air,  and  therefore  in  the  arterial  blood  and  the  centre  itself,  and 
has  demonstrated  that  this  is  the  way  in  which  the  amount  of  the 


282  liESPl  RATIOS 

pulmonary  ventilation  (tlic  volume  of  air  breathed  per  unit  of  time) 
is  rhiefiy  regulated  in  ordinary  breathing. 

For  instance,  an  increase  of  as  little  as  o-z  per  cent,  of  carbon 
dioxide  in  the  alveolar  air,  corresponding  to  an  increase  of  1-4  mm. 
of  mercury  in  the  partial  pressure  (p.  247)  of  the  gas.  caused  an 
increase  in  the  pulmonary  ventilation  of  100  per  cent.  The  alveolar 
oxygen  pressure  had  to  be  diminished  to  13  per  cent,  of  an  atmo- 
sphere before  any  decided  increase  in  the  respiration  occurred. 
During  moderate  muscular  work  the  percentage  of  carbon  dioxide 
in  the  alveolar  air,  and  therefore  in  the  blood,  increases  slightly, 
causing  an  increase  in  the  ventilation,  and  this  is  one  of  the  ways  in 
which  the  hyperpncea  associated  with  muscular  exercise  is  brought 
about.  In  severe  work  lack  of  oxygen,  with  accumulation  of  lactic 
acid  and  other  metabolic  products,  which  increase  the  hydrogen-ion 
concentration  in  the  blood  and  thus  stimulate  the  respiratory 
centre  or  render  it  e.xcitable  by  smaller  pressures  of  carbon  dioxide, 
also  plays  a  part.  There  is  some  evidence  that  in  the  case  of 
carbon  dioxide  also  the  actual  excitation  of  the  respiratory  centre  is 
due  to  the  increased  hydrogen-ion  concentration.  Some  phvsiolo- 
gists  hold  the  view  that  the  respiratory  centre  reacts  in  the  same 
way  to  a  given  increase  in  hydrogen-ion  concentration  no  matter 
what  the  acid  may  be,  and  that  there  is  nothing  specific  in  the 
action  of  carbon  dio.xide.  If  it  be  assumed  that  changes  in  the 
hydrogen-ion  concentration  of  the  blood  are  only  caused  bv  sub- 
stances like  carbon  dioxide,  which  are  ehminated  by  the  lungs, 
or  by  substances  Hke  lactic  acid,  which  are  either  got  rid  of  by  oxi- 
dation or  are  not  liberated  into  the  blood  in  the  presence  of  a  good 
oxygen  supply,  no  serious  theoretical  objection  can  be  urged  against 
this  conclusion.  For  increased  activity  of  the  respiratory  centre 
would  favour  the  elimination  of  carbon  dioxide  and  absorption  of 
oxygen,  and  in  both  wa^'s  would  tend  to  maintain  the  normal 
hydrogen-ion  concentration  in  the  blood.  If,  however,  the  hvdrogen- 
ion  concentration  can  be  influenced  by  substances  which  are  not 
directly  affected  by  the  respiratory  process,  it  would  seem  unlikely 
that  the  respiratory  centre  should  blindly  respond  to  such  changes 
just  as  if  they  had  been  produced  by  substances,  the  amount  of 
which  it  can  effectively  control. 

To  sum  lip,  the  regulation  of  nortnal  breathing  is  twofold — a  chemical 
regulation  (through  the  carbon  dioxide,  possibly  by  changes  produced 
in  the  hydrogen-ion  concentration  in  the  blood)  of  the  amount  of  air 
moved  into  and  out  of  the  lungs  per  unit  of  time  ;  and  a  nervous  regu- 
lation (chiefly  through  the  vagi)  of  the  rate  and  depth  of  the  movements 
necessary  to  effect  the  given  amount  of  ventilation. 

When  the  vagi  have  been  divided,  an  increase  in  the  carbon 
dioxide  pressure  within  certain  limits  is  responded  to  bv  an  increase 
in  the  total  ventilation,  just  as  in  the  normal  animal,  but  the  form 
oi  the  response  is  different.     \Miercas  in  the  normal  animal  both 


RELATION  OF  RISSPl RATION  TO  Tllli  NERVOUS  SYSTEM     283 

the  rate  and  the  depth  of  respiration  are  increased,  in  the  vagoto- 
niized  animal  there  is  a  marked  increase  in  depth,  with  httle  or  no 
increase  in  rate  (Scott). 

WTien  the  gaseous  exchange  in  the  lungs  from  any  cause  becomes 
insufficient,  the  respiratory  movements  are  exaggerated,  and  ulti- 
mately every  muscle  which  can  directly  or  indirectly  act  upon  the 
chest-wall  is  called  into  play  in  the  struggle  to  pass  more  air  into 
and  out  of  the  lungs.  To  a  lesser  and  greater  degree  of  this  exag- 
geration of  breathing  the  terms  Hyperpncca  and  Dyspnoea  have  been 
respectively  applied.  If  the  gaseous  interchange  remains  insuffi- 
cient, or  is  altogether  prevented,  asphyxia  sets  in.  Sometimes  in 
man  impending  asphyxia  from  loss  of  function  by  a  part  of  the  lungs 
(with  crippling  of  the  lesser  circulation),  as  in  pneumonia,  may  be 
warded  of^  by  inhalations  of  oxygen.  Increase  in  the  temperature 
of  the  blood  circulating  through  the  spinal  bulb,  as  when  the  carotid 
arteries  of  a  dog  are  laid  on  metal  boxes  through  wliich  hot  water 
is  kept  flowing,  also  causes  dyspnoea  {heat-dyspncea)  (p.  302).  But 
if  the  temperature  be  too  high,  the  respiratory  movements  maj^  be 
slowed,  perhaps  by  a  partial  paralysis  or  inhibition  of  the  respiratory 
centre.  When  the  blood  is  cooled  the  respiration  becomes  deeper 
and  slower,  but  if  the  temperature  is  greatly  and  suddenly  lowered, 
the  centre  may  be  stimulated  and  the  breathing  quickened.  In 
man  the  increased  temperature  of  the  blood  in  fever  is  a  cause, 
though  not  the  only  one,  of  the  increase  in  the  rate  of  respiration. 

Apnoea. — The  phj^siological  opposite  of  dyspnoea  is  apncei.  This 
condition  may  be  produced  in  an  animal  by  rapid  or  prolonged 
artificial  respiration.  It  is  especiall^^  easy  to  obtain  in  an  animal 
in  which  the  circulation  through  the  brain  and  bulb  is  interrupted 
for  a  time  and  then  restored,  while  artificial  respiration  is  being  kept 
up.  Spontaneous  respiration  returns  after  a  longer  or  shorter 
interval,  but  if  the  artificial  respiration  be  still  maintained,  it  again 
ceases.  In  a  successful  experiment  the  animal  remains  without 
breathing  for  many  seconds  after  the  artificial  respiration  is  stopped. 
In  apnoea  the  chest  remains  at  rest  in  the  expiratory  phase  if  the 
lungs  have  been  inflated  by  the  artificial  respiration  and  then  allowed 
to  collapse  of  themselves  (expiratory  apnoea),  but  in  the  inspiratory 
phase  if  they  have  been  emptied  by  suction  and  then  permitted  of 
themselves  to  expand  (inspiratory  apnoea).  The  apnoea  is  not  pro- 
duced, as  some  have  thought,  by  the  accumulation  of  an  excess  of 
oxygen  in  the  blood,  for  rapid  and  repeated  inflation  of  the  lungs 
with  hydrogen  may  cause  the  condition.  Indeed,  towards  the  end 
of  the  apnoeic  period  the  venous  blood  may  be  very  distinctly  poorer 
in  oxygen  than  normal  venous  blood.  Apnoea  is  easily  caused  in 
man  by  a  period  of  deep  and  rapid  breathing  and  in  other  ways. 
The  essential  thing  in  this  chemical  or  true  apnoea  {apnoea  vera) 
is  the  lowering  of  the  partial  pressure  of  carbon  dioxide  in  the 
alveolar  air,  and  therefore  in  the  arterial  blood  and  the  respiratory 


284  HESPIRATION 

centre.  The  carbon  dioxide  \-  \va  lied  out  of  the  body,  so  to  say, 
by  the  excessive  pulmonary  ventilation. 

In  addition  to  chemical  apnoea,  which  is  obtainable  whether  the 
vagi  are  intact  or  not,  a  so-called  mechanical  apnoea,  or  apnax  vagi, 
exists— that  is  to  say,  a  stoppage  of  the  respiration  due  to  an 
inhibitory  effect  produced  through  the  vagi  on  the  respiratory  centre 
when  the  vagus  endings  in  the  lungs  are  excited  mechanically  by 
inflation.  Some  observers  state  that  this  vagus  apnoea  does  not 
outlast  the  inflation.  Others  believe  that  the  results  of  successive 
inflations  can  be  '  summated  '  in  the  centre,  giving  rise  to  an  apnoea 
which  persists  after  stoppage  of  the  artificial  respiration.  That  a 
'  memory '  of  a  prolonged  rhythmical  inflation  of  the  lungs  can 
impress  itself  in  some  way  on  the  respiratory  centre  is  shown  by 
the  cmious  phenomenon  that  in  resuscitation  of  the  bulb  after  a 
period  of  an;emia  the  natural  respiration,  when  it  returns,  msiy 
have  for  a  short  time  exactly  the  same  rhythm  as  the  artificial 
respiration  which  has  just  been  stopped. 

That  the  blood  when  the  gaseous  exchange  in  the  lungs  is  inter- 
ferea  with  produces  dyspnoea  by  acting  on  some  portion  of  the  brain 
may  be  shown  in  an  interesting  manner  by  establishing  what  is 
called  a  cross-circulation  in  two  rabbits  or  dogs.  The  vertebral 
arteries  and  one  carotid  are  tied  in  both  animals;  the  remaining 
carotids  are  divided  and  coimected  crosswise  by  glass  tubes,  or, 
what  is  better,  as  it  avoids  the  risk  of  clotting,  they  are  crossed  by 
suturing  the  cut  ends,  so  that  the  brain  of  each  is  supplied  by  blood 
from  the  otheT.  When  the  respiration  is  artificially  hindered  or 
stopped  in  one  of  the  animals,  it  shows  no  dyspnoea;  it  is  in  the 
other,  whose  brain  is  being  fed  with  improperly  ventilated  blood, 
that  the  respiratory  movements  become  exaggerated.  The  point 
of  attack  of  the  '  venous  '  blood  has  been  further  localized  in  the 
spinal  bulb  by  the  observation  that  when  the  brain  has  been  cut 
away  above  it,  the  cord  severed  below  the  origin  of  the  phrenics, 
and  all  other  nerves  connected  with  the  region  between  the  two 
planes  of  section  divided,  any  interference  with  the  gaseous  ex- 
change in  the  lungs  is  at  once  followed  by  dyspnoea.* 

Automaticity  of  the  Respiratory  Centre. — The  question  has  been 
raised  whether,  in  the  absence  of  this  '  natural '  stimulation  by  the 
blood,  and  of  the  impulses  that  constantly  reach  the  centre  along 
its  afferent  nerves,  it  would  continue  to  discharge  itself,  or  whether 
it  would  sink  into  inaction.  We  have  already  discussed  a  similar 
(luestion  in  regard  to  the  cardiac  and  vaso-motor  centres,  and  the 
subject  must  again  present  itself  when  we  come  to  examine  the 
functions  of  the  central  nervous  system.  In  the  meantime  it  is  only 
necessary  to  say  that  there  is  evidence  that  it  is  not  the  mere 

*  The  conclusion  is  doubtless  correct,  but  this  experiment  is  not  decisive. 
For  the  phrenic  nerves  themselves  contain  afferent  fibres,  the  stimulation  of 
which  can  influence  the  respiration  after  section  of  the  vagi. 


REI.ATIOX  OF  h'i:SFlh'AriON  TO  Till:  Ni:h'VOI'S  S'^STEM     2S5 

presence  of  carbon  dioxide  (or  other  substances)  in  the  blood  circu- 
lating through  the  respiratory  centre  wliich  determines  the  constant 
excitation  of  the  centre,  but  rather  the  a(  cuinulati(Mi  of  tarbon 
dioxide,  or  the  increase  of  hydrogen-ion  concentration,  in  the 
centre  itself  when  the  partial  pressure  of  that  gas  in  the  blood 
is  raised.  The  idea  that  the  ( onti  uious  excitation  of  the  centre 
is  '  autochthonous  ' — in  other  words,  that  it  is  due  to  an  internal 
stimulating  substance  or  substances  manufactured  in  the  centre 
itself,  as  well  as  carried  to  it  in  the  blood — renders  it  easy  to  under- 
stand that  the  discharge  of  the  respiratory  centre,  although  modified 
by  the  quality  of  the  blood  which  circulates  in  it,  is  not  essen- 
tially dependent  on  it.  Indeed,  in  cold-blooded  animals  whose 
blood  has  been  replaced  by  phj'siological  salt  solution,  and  (in  frogs) 
even  after  the  circulation  has  been  stopped  altogether  by  excision 
of  the  heart,  quiet,  regular  breathing  may  be  seen  for  a  considerable 
time.  Of  course,  blood  is  essential  for  the  continued  nutrition  of  the 
centre  and  its  connections,  and  it  eventually  breaks  down  and  ceases 
to  discharge.  The  respiratory  discharge  is  still  less  dependent  for  its 
initiation  upon  the  arrival  of  afferent  impulses.  For  after  section 
of  the  bulb  above  the  centre,  of  the  cord  below  the  origin  of  the 
l)hrenics,  of  the  vagi  and  of  the  posterior  roots  of  all  the  upper  cer- 
vical nerves,  the  spasmodic  respiration  which  we  have  already 
described  as  occurring  when  the  vagi  and  the  higher  paths  have  been 
severed  continues  without  essential  modification.  It  has  also  been 
observed  that  during  resuscitation  of  the  bulb  and  upper  cervical 
cord  after  a  period  of  anaemia,  stimulation  of  afferent  nerves,  in- 
cluding the  vagi,  is  entirely  without  influence  on  the  respiratory 
movements  for  some  time  after  respiration  has  returned,  presumably 
because  the  synapses  (p.  852)  on  the  afferent  paths  lying  within  the 
previously  anaemic  area  are  as  yet  unable  to  conduct  the  nerve 
impulses.  Nevertheless,  the  respiratory  centre  continues  steadily 
to  discharge  itself  along  the  efferent  paths,  whose  sjmapses  are 
situated  beyond  the  anaemic  region.  Section  of  the  bulb  above 
the  level  of  the  respiratory  centre,  and  of  the  cord  below  the  origin 
of  the  phrenic  nerves,  in  addition  to  the  anaemia,  makes  no  essential 
difference  in  the  result.  The  initial  rate  of  discharge  of  the  centre 
thus  isolated  from  afferent  impulses  is  approximately  constant  in 
different  experiments  (about  four  a  minute  in  cats). 

Spinal  Respiratory  Centres. — Although  the  chief  respiratory  centre 
lies  in  the  medulla  oblongata,  under  certain  conditions  impulses  to 
the  respiratory  muscles  may  originate  in  the  spinal  cord.  Thus,  in 
young  mammals  (kittens,  puppies),  especially  when  the  excitability 
of  the  cord  has  been  increased  by  strychnine,  in  birds  and  in  alli- 
gators, movements,  apparently  respiratory,  have  been  seen  after 
destruction  of  the  brain  and  spinal  bulb.  In  adult  cats,  when 
the  functions  of  the  brain,  medulla,  and  cervical  cord  have  been 
abolished  by  occlusion  of  their  vessels,  similar  movements  of  the 


286  RESPl  RATION 

thoracic  and  abdominal  muscles  may  be  seen,  but  they  are  not  sufTi 
cient  for  effective  respiration.  No  proof  has  ever  been  given  that 
in  the  intact  organism  the  spinal  cord  below  the  level  of  the  bulb 
takes  any  other  part  in  respiration  than  that  of  a  mere  conductor  of 
nerve  impulses;  and  it  is  not  justifiable  to  assume  the  existence  of 
automatic  spinal  respiratory  centres  on  the  strength  of  such  experi- 
ments as  these. 

Death  after  Double  Vagotomy. — Alterations  in  the  rhj^hm  of  respira- 
tion are  not  the  only  effects  that  follow  division  of  both  vagi  (or  vago- 
sympathetics)  in  the  neck.  In  certain  animals,  at  least,  this  operation 
is  incompatible  with  life.  In  the  rabbit,  as  a  rule,  death  takes  place  in 
twenty-four  hours.  A  sheep  may  live  three  days,  and  a  horse  five  or 
six.  bogs  often  live  a  week,  occasionally  a  month  or  even  two,  and  in 
rare  instances  they  survive  indefinitely.  The  most  prominent  symp- 
toms (in  the  dog),  in  addition  to  the  marked  and  permanent  slowing 
of  respiration,  quickening  of  the  pulse  and  contraction  of  the  pupils, 
are  difficult  deglutition,  accompanied  by  frequent  vomiting  and  pro- 
gressive emaciation.  The  appetite  is  sometimes  ravenous,  but  no 
sooner  is  the  food  swallowed  than  it  is  rejected ;  and  this  is  particularly 
true  of  water  or  liquid  food.  Sometimes  the  rejected  food  is  simply 
regurgitated  after  having  reached  the  lower  end  of  the  oesophagus, 
without  entering  the  stomach.  The  fatal  result  is  usually  caused,  or 
at  least  preceded,  by  changes  of  a  pneumonic  nature  in  the  lungs.  The 
precise  significance  of  the  pulmonary  lesion  is  obscure.  But  it  would 
seem  that  paralysis  of  the  laryngeal  and  oesophageal  muscles,  with  the 
consequent  entrance  of  saliva,  food,  or  foreign  bodies,  carrying  bacteria 
into  the  lungs,  is  responsible  to  a  great  extent.  And  when  only  a  partial 
palsy  of  the  glottis  is  produced,  by  dividing  the  right  vagus  below  the 
origin  of  the  recurrent  laryngeal,  and  the  left  as  usual  in  the  neck,  pneu- 
monia either  does  not  occur  or  is  long  delayed.  It  may  be  that  the  tissue 
of  the  lungs  is  rendered  particularly  susceptible  to  such  insults  in  conse- 
quence of  trophic  or  vascular  changes  induced  by  section  of  the  pul- 
monary and  cardiac  fibres  in  the  ^'agi.  It  may  be  quite  clearly  demon- 
strated, however,  in  animals  which  live  for  some  weeks,  that,  not- 
withstanding the  paralysis  of  the  glottis  associated  with  aphonia,  no 
pulmonary  symptoms  may  be  present  till  a  day  or  two  before  death. 
The  picture  presented  in  these  cases  is  that  of  an  animal  suffering, 
above  all,  from  alimentary  disturbances.  The  respiration  is,  to  be  sure, 
very  different  from  the  normal  in  frequency,  depth,  and  type,  but  there 
is  nothing  to  suggest  that  the  lungs  are  the  seat  of  any  pathological 
process.  Suddenly  the  picture  changes.  Pulmonary  symptoms  ob- 
trude themselves.  The  physical  signs  of  consolidation  of  the  lungs 
may  be  detected,  and  in  a  short  time  the  animal  is  inevitably  dead. 
Occasionally  the  determining  cause  of  the  pulmonary  lesion  seems  to 
be  some  external  circumstance,  as  a  sudden  fall  of  the  air  temperature. 
The  idea  is  exceedingly  apt  to  present  itself  to  the  observer  that  the 
pneumonia  is  an  accident,  an  acute  intercurrent  affection  breaking  the 
course  of  a  chronic  malnutrition,  which  in  any  case  must  have  ended 
in  death.  Of  course,  the  vagotomizcd  animal  is  predisposed  to  this 
accident,  but  there  is  no  definite  time  after  section  of  the  nerves  at 
which  it  must  take  place.  The  vomiting  is  certainly  connected  with  the 
paralysis  and  consequent  dilatation  of  the  oesophagus ;  and  by  previously 
making  an  artificial  opening  into  the  stomach  or  by  a  surgical  prophy- 
laxis still  more  heroic,  the  establishment  of  a  double  gastric  and 
oesophageal  fistula  (p.  4^1),  death  may  be  prevented  for  many  months. 
Elimination  of  all  the  pulmonary  fibres  of  the  vagi,  by  extirpation  of 


Rlll.ATlOS  OF  Kr.SPrRATTON  TO  Ttll.   SlUiVOUS  SYSTJ:M     287 

one  lunj;,  followed  after  an  interval  by  section  of  the  opposite  vagus 
in  the  neck,  is  not  fatal  in  rabbits.  This  is  also  in  favour  of  the  vicv; 
that  in  double  vagotomy  the  stress  fails  mainly  on  the  digestive  system 

Innervation  of  the  Bronchial  Muscles. — Both  constrictor  and 
dilator  fibres  for  the  bronchi  arc  contained  in  the  vagus.  They  are 
not  constantly  in  action,  but  can  be  reflexly  excited,  most  easily 
(in  the  dog  and  cat)  by  stimulating  the  nasal  mucous  membrane, 
and  particularly  a  small  area  well  back  upon  the  nasal  septum. 
Cauterization  of  the  corresponding  area  in  man  is  said  to  give  per- 
manent relief  in  certain  cases  of  spasmodic  asthma,  a  condition  in 
which  the  recurrent  attacks  of  dyspnoea  seem,  according  to  the  most 
generally  accepted  view,  to  be  associated  with  spasm  of  the  bronchial 
muscles. 

Special  Modifications  of  the  Respiratory  Movements. — Cheyne- 
Stokcs  Respiration  is  the  name  given  to  a  peculiar  type  of  breathing, 
marked  by  pauses  of  many  seconds  alternating  with  groups  of 
respirations.  In  each  group  the  movements  gradually  increase  to 
a  maximum  amplitude,  and  then  become  graduall}^  shallower  again, 
till  they  cease  for  the  next  pause.  The  phenomenon  often  occurs  in 
certain  diseases  of  the  brain  and  of  the  circulation,  and  pressure  on 
the  spinal  bulb  may  produce  it.  In  cats  in  which  the  circulation 
in  the  brain  and  medulla  oblongata  has  been  interrupted  for  a  time 
and  then  restored  it  is  often  noticed  at  a  certain  stage  of  resuscita- 
tion of  the  respiratory  centre.  In  frogs,  Cheyne- Stokes  breathing 
has  been  observed  as  the  result  of  interference  with  the  circulation 
in  the  spinal  bulb,  '  drowning,'  or  ligature  of  the  aorta,  and  also  as 
a  consequence  of  removal  of  the  brain,  or  parts  of  it  (hemispheres 
and  optic  thalami).  But  it  is  not  pecuHar  to  pathological  conditions, 
being  also  seen,  more  or  less  perfectly,  in  normal  sleep,  especially  in 
children,  in  healthy  men  at  high  altitudes,  in  hibernating  animals, 
and  in  morphine  and  chloral  poisoning. 

Well-marked  Cheyne-Stokes  breathing  can  be  obtained  experi- 
mentally in  normal  persons  in  a  variety  of  ways.  If,  for  example, 
the  subject  is  caused  to  breathe  deeply  and  frequently  for  about  two 
minutes,  so  as  to  produce  a  prolonged  apnoea,  the  respiration,  when 
it  is  resumed  spontaneously,  is  of  the  Cheyne-Stokes  t\'pe  (Haldane). 
The  explanation  given  by  Haldane  is  that  the  fall  in  the  partial 
pressure  of  the  oxygen  in  the  pulmonary  alveoli  (p.  283)  during  the 
primary  apnoea,  with  the  consequent  fall  of  oxygen  pressure  in  the 
arterial  blood  and  the  respiratory  centre,  leads  to  the  production 
of  lactic  acid  in  the  respiratory  centre  and  elsewhere,  which  stimu- 
lates the  centre  in  the  same  way  as  carbon  dioxide,  and  thus  permits 
it  to  be  excited  by  a  smaller  partial  pressure  of  carbon  dioxide  than 
that  normally  necessary.  As  soon  as  the  pressure  of  carbon  dioxide, 
which  is  increasing  during  the  period  of  apncea,  has  reached  the 
exciting  value  breathing  is  resumed.  The  respirations,  beginning 
as  very  feeble  movements,  rapidly  increase  in  strength  till  the 


288  RESPI/iATin>! 

breathing  becomes  quit"'  deep  or  actually  dyspna-ic.  The  store  of 
oxygen  is  replenished  by  this  thorough  ventilation  of  the  lungs,  the 
changes  in  the  excitability  of  the  respiratory  centre  due  to  lack  of 
oxygen  disappear  (perhaps  by  oxidation  of  the  lactic  acid),  and  the 
centre  relapses  into  a  period  of  repose.  During  this  period  of  apna-a 
the  oxygen  pressure  sinks  once  more  to  the  point  at  which  the  change 
in  the  excitability  of  the  respiratory  centre  by  carbon  dioxide  occurs, 
and  the  breathing  again  starts.  In  pathological  cases  the  want  of 
oxygen  may  be  associated  either  with  deficient  circulation  through 
the  bulb-centre  or  with  deficient  intake  by  the  lungs.  The  adminis- 
tration of  oxygen  through  a  mask  has  been  shown  in  such  cases  to 
abolish  the  periodicity  in  the  respiration,  and  to  render  it  more 
normal. 

Peculiarly  modified,  but  more  or  less  normal,  respiratory  acts  are 
coughing,  sneezing,  yawning,  sighing,  and  hiccup. 

A  cough  is  an  abrupt  expiration  with  open  mouth,  which  forces 
open  the  previously  closed  glottis.  It  may  be  excited  reflexly  from 
the  mucous  membrane  of  the  respiratory  tract  or  stomach  through 
the  afferent  fibres  of  the  vagus,  from  the  back  of  the  tongue  or 
mouth,  and  (by  cold)  from  the  skin. 

Sneezing  is  a  violent  expiration  in  which  the  air  is  chiefly  expelled 
through  the  nose.  It  is  usually  excited  reflexly  from  the  nasal 
mucous  membrane  through  the  branch  of  the  fifth  nerve  which 
suppUes  it.  Pressure  on  the  course  of  the  nasal  nerve  \vi\\  often 
stop  a  sneeze.  A  bright  light  sometimes  causes  a  sneeze,  and  so  in 
some  individuals  does  pressure  on  the  supra-orbital  nerve,  when  the 
skin  over  it  is  slightly  inflamed. 

Yawning  is  a  prolonged  and  very  deep  inspiration,  sometimes 
accompanied  with  stretching  of  the  arms  and  the  whole  body.  It 
is  a  sign  of  mental  or  physical  weariness. 

A  sigh  is  a  long-drawn  inspiration,  followed  by  a  deep  expiration. 

Hiccup,  or  'hiccough,  is  due  to  a  spasmodic  contraction  of  the  dia- 
phragm, which  causes  a  sudden  inspiration.  The  abrupt  closure  of 
the  glottis  cuts  this  short  and  gives  rise  to  the  characteristic  sound. 
The  following  readings  of  the  intervals  between  successive  spasms 
were  obtained  in  one  attack:  13  sees.,  12  sees.,  15  sees.,  9  sees., 
14  sees.,  etc. — i.e.,  one-fourth  or  one-fifth  of  the  frequency  of  the 
ordinary  respiratory  movements.  The  mere  fixing  of  the  attention 
on  the  observations  soon  stopped  the  hiccup. 

Hiccup  is  generally  considered  to  be  a  reflex  movement,  brought 
about  through  the  respiratory  centre  by  afferent  impulses  originating 
in  the  stomach.  The  irritation  may  be  merely  due  to  some  slight 
digestive  disturbance  set  up  by  overfilling  of  the  stomach,  perhaps. 
This  is  exceedingly  common  in  infants.  But  persistent  hiccup  may 
also  be  a  distressing  symptom  of  very  formidable  diseases — for 
example,  carcinoma  of  the  pylorus.  Experimentally,  reflex  con- 
tractions of  the  diaphragm  can  sometimes  be  elicited  by  stimulation 


INFLUEXCI-:  oi'  in:si'ih\rnu.\  ox  riii-:  bloou  i'ia-.ssri<E    2S9 

of  the  central  end  of  the  \agu.s  at  a  time  when  no  s])Mntancous 
respiratory  movements  are  going  on.  This  has  been  observed,  for 
instance,  in  cats  during  resuscitation  of  the  brain  after  a  period  of 
anjemia.  In  man  also,  in  a  case  of  Chey ne-Stokes  respiration  accom  - 
panied  by  hiccup,  it  was  seen  that  tlie  hiccup  persisted  during  tlie 
periods  of  apncva.  If  the  respiratory  centre  is  the  centre  for  the 
hiccup  reflex,  it  can  therefore  be  excitetl  by  afferent  nervous  im- 
pulses at  a  time  when  it  is  not  excited  by  the  normal  chemical 
stimulus  (MacKenzie  and  Cushny). 

Section  VII. — The  Influen'ce  of  Respiration  on  the  Blood- 
Pressure. 

We  have  already  stated,  in  treating  of  arterial  blood-pressure 
(p.  Ill),  that  a  normal  tracing  shows  a  series  of  waves  corresponding 
with  the  respiratory  movements. 

The  relationship  between  the  respiratory  phases  and  the  rise  and 
fall  of  the  blood-pressure  is  not  by  any  means  a  simple  and  invariable 
one.  It  depends  upon  a  number  of  factors,  which  need  not  be 
equally  influential  under  different  conditions  or  in  different  animals 
(Lewis).  Something  depends  upon  the  rate,  something  upon  the 
relative  preponderance  of  costal  and  abdominal  respiration,  and 
something  probably  upon  the  size  of  the  animal.  For  instance,  an 
inspiratory  rise  of  blood-pressiure  occm^s  in  man  with  pure  dia- 


Fig.  127. — Respiratory  Waves  in  ihe  Blood-Pressure:  Simultaneous  Tracings  of 
Movements  of  Respiration  and  of  Radial  Pulse  in  Human  Subject  (Lewis).  In 
A  the  respiration  was  diaphragmatic;  in  B,  costal.  In  A  the  respiratory  tracing 
was  taken  from  the  abdominal  wall ;  in  B,  from  the  chest. 

phragmatic,  and  a  fall  with  pure  thoracic,  breathing  (Fig.  127).  In 
cats  with  fairly  fast  and  not  very  deep  respiration  the  blood- pressure 
rises  in  expiration  and  sinks  in  inspir^.tkrn.  With  deep  and  slow 
respiration  the  opposite  effect  may,  upon  the  whole,  be  seen.  In 
dogs,  according  to  Einbrodt,"  although  the  mean  blood-pressure  is 
falling  for  a  short  time  at  the  beginning  of  inspiration,  it  soon  reaches 
its  minimum,  then  begins  to  rise,  and  continues  rising  during  the 

19 


290 


RESPIRATION 


rest  of  this  p  riou.  At  the  commencement  of  expiration  it  is  still 
mounting,  but  soon  reaches  its  maximum,  begins  to  fall,  and  con- 
tinues falling  through  the  remainder  of  the  expiratory  phase. 

A  partial  explanation  is  afforded  by  a  consideration  of  the  mechan- 
ical changes  produced  in  the  thorax  by  the  respiratory  movements. 
Of  these,  the  influence  of  variations  in  the  intrathoracic  pressure 
on  the  filling  of  the  heart  is  of  special  importance.  With  deep 
abdominal  breathing  the  changes  of  intra-abdominal  pressure  also 
affect  the  rilling  of  the  heart,  an  increase  of  pressure  (in  inspiration) 
tending  to  cause  more  blood  to  be  squeezed  from  the  abdominal 
veins  towards  the  chest.  The  changes  of  vascular  resistance  in  the 
lungs,  due  to  the  alteration  in  the  calibre  of  the  pulmonary  vessels, 
may  also  contribute,  but,  for  such  variations  of  intrathoracic 
pressure  as  normally  occur,  only  in  a  minor  degree.  The  changes 
in  the  vascular  capacity  of  the  lungs — that  is,  in  the  amount  of 
blood  contained  in  the  pulmonary  vessels — are  of  importance  espe- 
cially in  delajang  or  accelerating  the  alterations  of  blood-pressure  in 
the  systemic  arteries  due  to  the  other  factors. 

The  intrathoracic  pressure,  which,  as  we  have  seen,  is  always  less 
than  that  of  the  atmosphere,  unless  during  a  forced  expiration  when 
the  free  escape  of  air  from  the  lungs  is  obstructed,  diminishes  in 
inspiration  and  increases  in  expiration.  The  great  veins  outside  the 
chest,  the  jugular  veins  in  the  neck,  for  example,  are  under  the 
atmospheric  pressure,  which  is  readily  transmitted  through  their 

thin  walls,  while  the  heart  and 
thoracic  veins  are  under  a 
smaller  pressure.  The  venous 
blood  both  in  inspiration  and  ex- 
piration will,  accordingly,  tend 
to  be  drawn  into  the  right 
auricle.  In  inspiration  the  ven- 
ous flow  will  be  increased,  since 
the  pressure  in  the  thorax,  and 
therefore  in  the  pericardial 
cavity,  is  diminished;  and  upon 
the  whole  more  venous  blood 
will  pass  into  the  right  heart 
during  inspiration  than  during  expiration.  Now,  the  right  ventricle  is 
not  in  general  working  as  hard  as  it  can  work.  Hence,  the  excess  of 
blood  which  reaches  it  during  an  inspiration  is  at  once  sent  into  the 
lungs,  although  not  even  the  first  of  it  can  have  passed  through  to 
the  left  side  of  tJie  heart  at  the  end  of  the  inspiration,  since  the 
pulmonary  circulation-time  (four  to  five  seconds  in  a  small  dog, 
two  to  three  seconds  in  a  rabbit)  is  longer  than  the  time  of  a  com- 
plete inspiration  at  any  ordinary  rate.  The  increase  in  the  quantity 
of  blood  pumped  into  the  pulmonary  artery  will,  if  not  counteracted 
by  other  circumstances,  tend  to  raise  the  blood-pressure  in  the 


/ 

/ 

J 

/ 

rig.  128.— The  upper  tracing  shows  the 
respiratory  movements  in  a  rabbit  with 
rather  deep  and  slow  diaphragmatic 
breathing;  the  lower  tracing  is  the 
blood-pressure  curve;  /,  inspiration; 
E,  expiration,  including  the  pause. 


iXFLUF.xcE  or  h'i:si'iriATio.\  o.\  Tin:  Bi.ooi)i'Ri:ssrRE    291 

artery  and  its  hi  am  Iks,  and  thcn-forc  at  once  to  accelerate  tlie  out- 
flow through  the  pulmonary  veins.  This  will  be  aided  if  at  the 
same  time  the  vascular  resistance  in  the  lungs  is  reduced,  as  is 
generally  stated  to  be  the  case.  The  left  ventricle,  hke  the  right, 
is  capable  of  discharging  more  blood  than  it  ordinarily  receives.  The 
excess  of  blood  coming  to  it  is  easily  and  promptly  ejected.  The 
systemic  arteries  are  better  filled  and  the  arterial  pressure  rises. 

In  expiration  the  contrary  will  hap])en.  The  return  of  blood  to 
the  thorax  will  be  checked.  This  is  well  shown  by  the  swelling  of 
the  veins  at  the  root  of  the  neck  in  expiration,  their  shrinking  in 
inspiration,  the  so-called  respiratory  venous  pulse.  Less  blood 
being  drawn  into  the  right  heart,  less  will  be  pumped  into  the  pul- 
monary artery,  in  which  the  pressure  will,  of  course,  fall.  The  out- 
flow into  the  left  auricle  will  thus  be  diminished — all  the  more  if  in 
the  expiratory  phase  the  vascular  resistance  in  the  lungs  is  increased 
— and  the  systemic  arterial  pressure  will  be  lowered.  In  both  cases, 
however,  the  change  seen  in  the  blood-pressure  curve  will  be  belated, 
and  will  not  coincide  exactly  with  the  commencement  of  the  inspira- 
tion or  the  expiration.  If  it  is  delayed  for  a  period  about  equal  to 
the  length  of  an  inspiration  or  an  expiration,  the  blood-pressure 
will  be  seen  to  sink  in  inspiration  and  to  rise  in  expiration.  If 
the  period  of  delay  is  less  than  this,  the  pressure  will  be  mounting 
during  a  part  of  each  respiratory  phase  and  falling  during  the 
rest.  As  to  the  explanation  of  the  delay,  several  factors  may  be 
concerned. 

The  negative  pressure  of  the  thorax  acts  on  the  aorta,  as  well  as 
on  the  thoracic  veins,  although,  on  account  of  the  greater  thickness 
of  its  walls,  to  a  smaller  extent  than  on  the  veins.  The  diminution 
of  pressure  in  inspiration  tends  to  expand  the  thoracic  aorta,  and  to 
draw  blood  back  out  of  the  S3'stemic  arteries,  while  expiration  has 
the  opposite  effect.  And  although  the  hindrance  caused  in  this  way 
to  the  flow  of  blood  into  the  arteries  during  inspiration,  and  the 
acceleration  of  the  flow  during  expiration  may  not  be  great,  they 
will,  of  course,  be  better  marked  in  small  animals  with  compara- 
tively yielding  arteries  than  in  large  animals.  Yet,  whether  great 
or  small,  the  tendency  will  be  to  diminish  the  pressure  in  the  one 
phase  and  increase  it  in  the  other.  As  soon  as  the  changes  of  pres- 
sure produced  by  alterations  in  the  flow  of  venous  blood  into  the 
chest  and  through  the  lungs  are  thorouglily  established,  the  arterial 
effect  will  be  overborne;  but  before  this  happens — that  is,  at  the 
beginning  of  inspiration  and  expiration — it  will  be  in  evidence,  and 
will  help  to  delay  the  main  change. 

Another  factor  in  this  delay  is  found  in  the  changes  of  vascular 
capacity  which  take  place  in  the  lungs  when  they  pass  from  the 
expanded  to  the  collapsed  condition.  The  expansion  of  the  lungs 
in  natural  respiration  causes  a  widening  of  the  pulmonary  capillaries, 
with  a  consequent  increase  of  their  capacity  and  diminution  of  their 


292  PhSPI  NATION 

resistance.  When  the  vessels  at  the  base  of  the  heart  are  hgatured 
either  at  the  height  of  inspiration  or  the  end  of  expiration,  so  as 
to  obtain  the  vvliole  of  the  blood  in  the  lungs,  it  is  found  that  they 
invariably  contain  more  blood  in  inspiration  than  in  expiration. 
During  inspiration,  as  we  have  seen,  the  right  ventricle  is  sending 
an  increased  supply  of  blood  into  the  pulmonary  artery;  but  before 
any  increase  in  the  outflow  through  the  pulmonary  veins  can  take 
place,  the  vessels  of  the  lung  must  be  filled  to  their  new  capacity. 
The  first  effect,  then,  of  the  lessened  vascular  resistance  of  the  lungs 
in  inspiration  is  a  temporary  falling  off  in  the  outflow  through  the 
aorta,  and  therefore  a  fall  of  arterial  pressure.  As  soon  as  a  more 
copious  stream  begins  to  flow  through  the  lungs,  this  is  succeeded 
by  a  rise.  In  like  manner  the  first  effect  of  expiration,  which  in- 
creases the  resistance  and  diminishes  the  capacity  of  the  pulmonary 
vessels,  is  to  force  out  of  the  lungs  into  the  left  auricle  the  blood 
for  which  there  is  no  room.  This  causes  a  rise  of  arterial  blood- 
pressure,  succeeded  by  a  fall  as  soon  as  the  lessened  blood-flow 
through  the  lungs  is  established. 

The  changes  in  the  diastolic  capacity  of  the  chambers  of  the  heart 
itself,  with  the  changes  of  pericardial  pressure,  must  also  act  in  the 


Fig.  129. — Effect  on  Blood-Pressure  of  Inflation  of  the  Lungs:  Rabbit.  Artificial 
respiration  stt^pped  in  inflation  at  i.  Interval  between  2  and  3  (not  reproduced) 
51  seconds,  during  which  the  curve  was  almost  a  straight  line.  Time  tracing 
shows  seconds. 

same  direction.  It  is  obvious,  then,  how  greatly  the  rate  and  depth 
of  respiration  in  relation  to  the  size  of  the  animal  and  the  other  cir- 
cumstances already  mentioned  may  influence  the  time  relations  of 
the  respiratory  oscillations  in  the  arterial  pressure  curve,  so  that  we 
ought  not  to  expect  them  to  be  absolutely  constant. 

In  artificial  respiration  oscillations  of  blood-pressure,  synchronous 
with  the  movements  of  the  lungs,  are  also  seen.  During  inflation 
(inspiration)  the  arterial  pressure  rises;  during  deflation  (expiration)  it 
falls.  When  artificial  respiration  is  stopped  at  the  height  of  inflation 
and  the  lungs  kept  inflated  (Fig.  129),  the  arterial  blood-pressure  falls 
rapidly,  and  continues  low  until  the  rise  of  asphyxia  begins.     In  the 


tKFLVENCE  OF  UliSPIRATION  OX  THE  BLOOU-PRLbSURE      293 

fall  of  pressure  the  increased  intrathoracic  pressure  due  to  the  inflation 
is  an  important  factor.  When  the  respiration  is  stopped  in  collapse, 
instead  of  a  fall  a  steady  rise  of  pressure  occurs  (as  in  Fig.  84,  p.  188). 
This  ultimately  merges  in  the  elevation  due  to  asphyxia,  which  shows 
itself  sooner  than  in  inflation.  When  the  tracheal  cannula  is  closed  in 
natural  respiration,  no  initial  fall  of  pressure  takes  place  (Fig.  130). 

Besides  the  mechanical  effects  of  the  respiratory  movements  on 
the  circulation,  it  may  be  influenced  by  changes  in  the  cardio- 
inhibitory  and  vaso-motor  centres  synchronous  with  the  rhythm  of 
the  respiratory  centre.  In  many  animals  (the  dog,  for  instance) 
and  in  man,  it  can  be  ver}'  easily  made  out  that  the  rate  of  the  heart 
is  greater  during  inspiration,  especially  towards  its  end,  than  in 
expiration.  The  phenomenon  is  especially  distinct  in  deep  and 
slow  respiration.  It  is  caused  by  a  rhythmical  rise  and  fall  in  the 
activity  of  the  cardio-inhibitory  centre,  synchronous  with  the 
respiratory  movements,  for  the  difference  disappears  after  di\'ision 
of  both  vagi.  The  normal  respiratory  oscillations  of  blood- pressure 
are  not  due  in  any  great  degree  to  such  changes  in  the  rate  of  the 
heart,  for  they  persist  after  section  of  the  vagi,  and  they  are  seen  in 
animals  like  the  rabbit,  in  which  in  ordinary  breathing  little  or  no 
variation  in  the  rate  of  the  heart  is  connected  with  the  phases  of 
respiration.     The   most   probable   explanation   of  the   respiratory 


Fig.  130.— Blood-Pressure  Tracing:  Rabbit,  under  Chloral.  Natural  respiration 
stopped  at  I  in  inspiration,  at  E  in  expiration.  The  mean  blood-pressure  is 
scarcely  altered;  but  the  respiratory  waves  become  much  larger  owing  to  the 
abortive  efforts  at  breathing.     Time  tracing  shows  seconds. 

variations  in  the  pulse-rate  is  that  the  respiratory  centre,  when  it  is 
discharging  itself  in  inspiration,  sends  out  impulses  as  a  sort  of  over- 
flow along  fibres  connecting  it  with  the  cardio-inhibitory  centre. 
These  increase  the  tone  of  that  centre,  but,  owing  to  the  long  latent 
period  of  the  cardio-inhibitory  apparatus,  the  inhibition  does  not 
reveal  itself  till  the  succeeding  expiration.  It  may  be,  however,  that 
the  impulses  discharged  from  the  respiratory  centre  in  inspiration 
diminish  the  tone  of  the  cardio-inhibitory  centre,  and  thus  lead  to 
acceleration  of  the  heart  towards  the  end  of  the  inspiratory  phase. 
In  certain  pathological  conditions  the  influence  of  the  respiration  on 
the  pulse-rate  is  exaggerated  (so-called  '  respiratory  arhythmia  '). 

Traube-Hering  Curves.— Rhythmical  changes  in  the  activity  of 
the  vaso-motor  centre,  also  associated  with  periodic  discharges  from 


294     •  RESPIRA  HON 

the  vaso-motor  centre,  also  associated  with  periodic  discharges  from 
the  respiratory  centre,  may  be  observed  under  certain  conditions — 
e.g.,  wlicn  in  an  animal  paralyzed  by  curara,  and  therefore  unable  to 
breathe  spontaneously,  the  artificial  respiration  is  slopped  for  a  time. 
If  such  a  dose  of  curara  be  given  as  will  still  permit  slight  spontaneous 
respiration  to  go  on,  and  both  vagi  be  cut,  it  can  be  seen  on  stopping 
the  artificial  respiration  that  the  waves  on  the  blood-pressure  curve 
are  exactly  synchronous  with  the  slow  respiratory  movements.  The 
Traube-Hering  waves  sink  in  inspiration  and  rise  in  expiration. 

The  fact  that  they  have  invariably  a  longer  period  than  the 
natural  respiratory  movements  indicates  that  thej'  are  not  concerned 
in  the  production  of  the  normal  respiratory  oscillations  of  arterial 
pressure.  Probably  the  reason  why  the  Traube  waves  appear  after 
section  of  the  vagi  is  the  increased  vigour  of  the  slow  respiratory 
discharges,  coupled  with  a  hj'perexcitability  of  the  vaso-motor 
centre,  due  to  the  long  pauses  in  the  aeration  of  the  blood.  In  the 
asphyxial  rise  of  pressure  in  a  curarized  dog  they  are  constantly 
seen,  and  are  often  observed  when  the  circulation  in  the  medulla 


Fig.  131.— Traube-Hering  Waves  as  the  Bluod-Prcssure  is  falling  during  Occlusion 
of  the  Cerebral  Arteries  in  a  Cat. 

oblongata  is  in  any  way  interfered  with  (Fig.  131).  In  addition  to 
the  true  Traube-Hering  waves,  other  and  much  longer  periodic 
variations  in  the  blood-pressure  are  sometimes  noticed.  If  spon- 
taneous respiration  is  going  on,  their  long  sweeping  curves  then  show 
the  ordinary  respiratory  waves  superposed  on  them. 

The  normal  respiratory  oscillations  in  the  veins,  as  might  be 
expected,  run  precisely  in  the  opposite  direction  to  those  in  the 
arteries,  and  so  do  the  Traube-Hering  curves.  The  increased  flow 
from  the  veins  to  the  thorax  during  inspiration  lowers  the  pressure 
in  the  jugular  vein,  while  it  increases  the  pressure  in  the  carotid. 
The  constriction  of  the  small  bloodvessels  to  which  the  Traube- 
Hering  curves  are  due  increases  the  blood-pressure  in  the  arteries, 
because  it  increases  the  peripheral  resistance  to  the  blood-flow;  in 


EI-FECTS  Of  URIiATHlNG  CONDENSED  AND  RARhElEU  MR    295 

the  veins  it  lowers  the  pressure,  because  less  blood  gets  through  to 
them.  Accordingly,  when  the  Traube-Hcring  curve  is  ascending  in 
the  carotid,  it  is  descending  in  the  jugular. 

The  respiratory  variations  in  the  volume  of  the  brain,  wliich  are 
so  striking  a  phcnt)nienon  when  a  trephine  hole  is  made  in  the 
skull,  but  which  can  also  take  place,  thanks  to  the  displacement  of 
cerebro-spinal  fluid  (p.  174),  when  the  cranium  is  intact,  have  by 
some  been  attributed  to  interference  with  the  venous  outflow  from 
the  cranial  cavity  during  expiration,  and  by  others  to  those  changes 
in  the  arterial  pressure  whose  causes  we  have  just  btxin  discussing. 
The  truth  is  that  neither  factor  is  exclusively  concerned.  The  ques- 
tion turns  largely  upon  the  time-relations  of  the  movements.  The 
swelling  of  the  brain  is  sometimes  synchronous  with  expiration,  and 
the  shrinking  with  inspiration.  Here  the  damming  back  of  the 
blood  in  the  sinuses  when  the  outflow  is  checked  by  the  expiratory 
rise  of  pressure  in  the  thoracic  veins  either  conspires  with  an  expira- 
tory rise  of  arterial  pressure  or  is  more  than  enough  to  counter- 
balance an  expiratory  fall  of  pressure  in  the  cerebral  arteries  if  the 
respiratory  conditions  are  such  as  to  lead  to  an  expiratory  fall.  But 
sometimes  the  dura  mater  bulges  into  the  trephine  hole  in  inspira- 
tion and  sinks  down  in  expiration.  Here  the  increase  in  the  volume 
of  the  brain  produced  by  the  increased  pressure  in  the  arteries  and 
capillaries  in  inspiration  is  more  than  sufficient  to  counterbalance 
the  quickened  escape  of  blood  from  the  cerebral  veins. 

Section  VIII.-=-The   Effects   of   breathing   Condensed    and 

Rarefied  Air. 

These  are — (i)  mechanical,  shown  chiefly  by  changes  in  the  cir- 
culation, in  the  blood-pressure,  for  instance;  (2)  chemical. 

The  mechanical  effects  differ  according  to  whether  the  whole  body, 
or  only  the  respiratory  tract,  is  exposed  to  the  altered  pressure. 
When  the  trachea  of  an  animal  is  connected  with  a  chamber  in 
which  the  pressure  can  be  raised  or  lowered,  it  is  found  that  at  first 
the  arterial  blood-pressure  rises  as  the  pressure  of  the  air  of  respira- 
tion is  increased  above  that  of  the  atmosphere.  But  a  maximum 
is  soon  reached;  and  when  respiration  begins  to  be  impeded,  the 
pressure  falls  in  the  arteries  and  increases  in  the  veins.  When  the 
pressure  of  the  air  in  the  chamber  is  diminished  a  little  below  that 
of  the  atmosphere,  there  is  a  slight  sinking  of  the  arterial  blood- 
pressure,  which  rises  if  the  air-pressure  is  further  diminished. 

It  is  clear  that  any  change  of  the  air-pressure  which  tends  to  diminish 
the  intrathoracic  pressure  will  favour  the  venous  return  to  the  heart, 
and  therefore,  if  the  exit  of  blood  from  the  thorax  is  not  proportionally 
impeded,  the  filling  of  the  arteries.  An  increase  in  the  intra-alveolar 
pressure  must  tend  on  the  whole  to  increase,  and  a  diminution  in  it  to 
lessen,  the  pressure  inside  the  thorax,  which  always  remains  equal  to 
the  intra-alveolar  pressure,  minus  the   elastic   tension   of   the    lungs. 


290 


liESPIRATlON 


fvjvKM^^Aa.. 


Breathing  cdmpressetl  air  slioiiUl,  therefore,  under  the  conditions 
tloscribcd,  be  upon  the  whole  unfavourable  to  the  venous  return  to  the 
heart  and  1o  the  filling  of  the  arteries,  and  the  arterial  pressure  should 
fall;  while  breathing  rarefied  air  should  have  the  opposite  effect.  But 
a  very  great  diminution  of  the-  intrathoracic  pressure  is  not  necessarily 
favourable  to  the  circulation,  since  the  auricles  are  then  unable  to  con- 
tract perfectly. 

Certain  chest  diseases  have  been  treated  by  the  use  of  apparatus  by 
which  the  patient  is  made  to  breathe  either  compressed  or  rarefied  air; 
or  to  inspire  air  at  one  pressure  and  to  expire  into  air  at  another  pressure. 
And  it  has,  upon  the  whole,  been  found,  in  agreement  with  theory', 
tliat  condcu.scd  air  cannot  help  the  circulation  however  it  is  applied,  but 
always  hinders  it;  while  rarefied  air  aids  the  circulation  both  in  inspira- 
tion and  in  expiration.  But 
the  increased  work  of  the  in- 
spiratory muscles  may  coun- 
terbalance the  advantage. 

Valsalva's  ex perimettt, 
w'hich  is  performed  by  closing 
the  mouth  and  nostrils  after 
a  previous   inspiration,   and 
Fig.  132. — Pulse  Tracing  in  Valsalva's  Experi-     then  forcibly  tryingto  expire, 
mcnt  (Rollett).  is  an  imitation  of  breathing 

into  compressed  air.  The 
intrathoracic  pressure  is  raised,  it  may  be,  to  considerably  more  than 
that  of  the  atmosphere;  the  venous  return  to  the  heart  is  impeded, 
and  may  b^^  stopped;  and  the  pulse  cur\'e  is  altered  in  such  a  way  as 
to  indicate  first  an  increase  and  then  a  decrease  of  the  arterial  blood- 
prcssurc  succeeded  by  a  second  ris:"  (Fig-  i.^-^)- 

Muller's  expeyiment,  which  should  be  bracketed  with  Valsalva's, 
consists  in  making,  after  a  previous  expiration,  a  strong  inspiratory 
effort  with  mouth  and  nostrils  closed.  Here  the  intrathoracic  pressure 
is  greatly  diminished,  more  blood  is  drawn  into  the  chest,  and  upon  the 
whole  effects  opposite  to  those  of  Valsalva's  experiment  are  produced 
(Fig.  133).  Neither  experiment  is 
quite  free  from  danger.  In  both 
the  dicrotism  of  the  pulse  becomes 
more  marked. 

When  the  wliolc  body  is  sub- 
jected to  the  changed  pressure, 
as  in  a  balloon  or  on  a  mountain, 
in  a  diving-bell  or  a  caisson  used 
in  building  the  piers  of  a  bridge,  the  conditions  are  very  different 
For  the  blood-pressure,  the  intrathoracic  pressure,  and  the  intra- 
alveolar  pressure,  all  fall  together  when  the  pressure  of  the  atmo- 
sphere is  diminished,  and  all  rise  together  when  it  is  increased.  It 
is  possible  not  onlj^  to  live,  but  to  do  hard  manual  labour,  at  very 
di^erent  atmospheric  pressures. 

As  regards  the  chemical  effects  of  condensed  and  rarefied  air, 
Loewy  io\\n([  that  the  quantity  of  o.wgen  absorbed  by  a  man  breath- 
ing air  in  tlie  pneumatic  cabinet  remained  constant  at  all  pressures 
between  about  two  atmospheres  and  half  an  atmosphere.  At  440  mm. 
of  mercury  d3'spnoea  became  evident ;  but  if  the  i)erson  was  now  made 
to  work,  the  dyspnoea  passed  away,  and  did  not  again  manifest  itself 


Fig. 


133. — Pulse    Tracing    in 
Experiment  (Rollett). 


Muller's 


/■:/-7'/y'/-.s"  ni-  nRr.ATiiiNc  coNDhNsno  a  so  uaiu:i-ied  air  297 

till  tlu'  pressure  was  reduced  to  410  mm.  There  are  towns  on  the 
high  tablelands  of  the  Andes,  and  in  the  Himalayas,  where  the 
barometric  pressure  is  not  more  than  16  to  20  inches,  yet  the  in- 
habitants feel  no  ill  effects.  And  in  the  caissons  of  the  Forth  Bridge 
the  workmen  were  engaged  in  severe  toil  under  a  maximum  pressure 
of  over  three  atmospheres,  while  in  the  caissons  of  the  St.  Louis 
Bridge  in  America  a  maximum  pressure  of  over  four  atmospheres 
[i.e.,  more  than  three  atmospheres  in  addition  to  the  ordinary  air- 
pressure)  was  reached. 

Inside  the  caissons  the  men  sometimes  suffer  from  pain  and  noise  in 
the  ears,  due  to  excessive  pressure  on  the  external  surface  of  the  tym- 
panic membrane.  If  the  pressure  in  the  tympanum  is  raised  by  a 
swallowing  movement,  which  opens  the  Eustachian  tube  and  permits 
air  to  enter  it,  the  symptoms  generally  disappear.  The  suddenness  of 
the  change  of  pressure  has  much  to  do  with  its  effects,  and  it  is  found 
that  the  men  are  most  liable  to  dangerous  symptoms  while  passing 
through  the  air-lock  from  the  cais.sons  to  the  external  air.  It  may  be 
concluded,  from  experiments  on  animals,  that  some  of  the  most  serious 
of  these — the  localized  paralysis  usually  affecting  the  legs  (paraplegia) 
and  the  circulatory  disturbances — are  due  to  the  formation  of  gaseous 
emboli,  by  the  liberation  of  nitrogen  in  the  blood  and  other  body- 
fluids  when  the  pressure  is  abruptly  reduced.  And,  indeed,  it  is  found 
that  the  symptoms  can  often  be  caused  to  disappear,  both  in  animals 
and  men,  by  promptly  subjecting  them  again  to  compressed  air.  To 
avoid  gis  cmbohsm  on  decompression,  the  shift  should  be  so  short  that 
the  body-fluids  do  not  become  fully  saturated  with  nitrogon,  and  the 
decompression  should  be  slow.  Even  with  a  rate  of  decompression  of 
twenty  minutes  for  each  atmosphere  of  excess  pressure,  the  equilibrium 
between  the  dissolved  and  the  atmospheric  nitrogen  is  not  entirely 
established  fifteen  minutes  after  decompression. 

But  that  the  action  of  air  under  a  high  pressure  is  not  merely  mechan- 
ical follows  from  the  singular  fact  that  in  pure  oxygen  at  a  pressure 
of  4  to  5  atmospheres,  winch  corresponds  to  air  at  20  to  25  atmospheres, 
convulsions  arc  often  produced  in  vertebrate  animals,  while  exposure 
to  6  to  25  atmospheres  of  oxygen  causes  dyspnoea  and  coma,  usually 
without  convulsions.  All  animals,  so  far  as  investigated,  are  instantly 
convulsed  and  killed  under  a  pressure  of  50  atmospheres  of  oxygen 
(Hill  and  Macleod).  Even  seeds  and  vegetable  organisms  in  general 
are  killed  in  a  short  time  in  oxygen  at  3  to  5  atmospheres;  and  an 
atmosphere  of  pure  oxygen,  equal  to  5  atmospheres  of  air,  hinders 
the  development  of  eggs.  Lorrain  Smith  has  shown  that  in  small  birds 
and  mice  exposure  for  many  hours  to  a  pressure  of  between  i  and  2 
atmospheres  of  pure  oxygen  causes  pneumonia.  He  confirms  Bert's 
observations  on  the  acute  toxic  effects  produced  by  higher  pressures, 
and  supposes  that  in  the  production  of  caisson  disease  the  special  action 
of  the  oxygen  at  high  pressure  may  play  a  part  as  well  as  the  rapid 
decompression.  Even  atmospheres  containing  80  to  96  per  cent,  of 
oxygen  under  normal  barometric  pressure  prodvice  in  rabbits,  in  24  to 
48  hours,  congestion  and  oedema  of  the  lungs,  and  finally  a  fibrinous 
broncho-pneumonia.  Still  smaller  oxygen  pressures  may  cause  similar 
effects  in  a  longer  time  (Karsner). 

When  the  air-pressure  is  diminished  below  a  certain  limit,  death 
takes  place  from  asphyxia,  more  or  less  gradual  according  to  the 
rate  at  which  the  pressure  is  reduced.     Tlie  haemoglobin  cannot  get 


298  kESPl  RATIOS 

or  retain  enough  (•.\\{^<.ii  lo  enal>le  it  to  perform  its  respiratory  func- 
tion; its  dissociation  tension  is  no  longer  balanced  by  an  equal  or 
greater  partial  pressure  of  oxygen  in  the  air.  The  tension  of  carbon 
dioxide  in  the  blood  is  also  lessened,  ovvnng  to  the  dyspnoea  and 
the  consequent  increase  of  pulmonary  ventilation. 

To  such  changes,  as  well  as  to  the  cold,  some  of  the  deaths  in  high 
balloon  ascents  must  be  attributed.  Messrs.  Glaisher  and  Coxwcll 
supposed  that  they  reached  the  height  of  37,000  feet ;  the  former  became 
unconscious  at  29,000  feet  (8,800  metres),  at  which  height  the  amount 
of  oxygen  in  the  arterial  blood  would  probably  not  exceed  10  volumes 
per  cent.,  but  recovered  during  the  descent.  The  symptoms  of  the 
'  mountain  sickness  '  so  familiar  to  Alpine  climbers  (nausea,  headache, 
and  marked  depression),  the  undue  hypcrpnoea  produced  by  muscular 
exertion,  and  the  sleep  disturbed  by  irregular  breathing,  are  also  mainly 
due  to  deficiencv  of  o.xvgen  in  the  blood.  The  most  rational  prophy- 
laxis is  to  leave  the  high  peaks  severely  alone.  But  for  the  enthusiasts 
who  cannot  do  this  a  portable  apparatus  for  generating  oxygen  has  been 
devised.  Experiments  in  the  pneumatic  cabinet  indicate  that  the 
hvperpnoea  is  due  to  the  indirect  action  of  want  of  oxygen  already 
referred  to  in  discussing  the  normal  regulation  of  respiration  (p.  281) 
— that  is,  to  the  formation,  in  consequence  of  the  insufficient  oxygen 
supply,  of  lactic  acid  or  other  substances  which  have  the  same  influence 
as  carbon  dioxide  on  the  respiratory  centre — so  that  less  carbon  dioxide 
is  required  to  excite  the  centre.  Although  the  hyperpnoea  leads  to  a 
diminution  in  the  partial  pressure  of  carbon  dioxide  in  the  pulmonary 
alveoli,  there  is  no  evidence  that  lack  of  carbon  dioxide  ('  acapnia  ')  is 
the  primary  cause  of  mountain  sickness  (Haldanc).  It  must  be  remem- 
bered, however,  that  here  the  influence  of  the  low  barometric  pressure 
is  complicated  by  other  conditions,  l-or  example,  while  in  the  pneu- 
matic cabinet,  as  alrcaclv  stated,  diminution  of  the  pressure  does  not 
affect  the  oxvgen  consumption,  it  is  relatively  much  gfeatcr  on  the 
high  mountain  levels  both  during  rest  and  during  work  than  on  the 
plains.  This  is  not  the  case  in  balloon  ascents.  And  evidence  has  been 
brought  forward  that  changes  in  the  mechanics  as  well  as  in  the  chem- 
istry of  respiration  arc  concerned  (the  breathing,  for  instance,  taking 
on  a  periodic  character,  with  some  approach  to  the  Cheyne-Stokes  type 
— p.  287),  and  that  there  is  something  not  connected  with  the  want  of 
oxygen  which  diminishes  the  capacity  for  muscular  work.  This  '  some- 
thing '  is  perhaps  a  peculiar  excitation  of  the  nervous  system  in  the 
fierce  light  of  those  high  levels,  which  acts  not  only  on  the  retina,  but 
on  the  skin,  and  may  even  affect  the  distribution  of  the  blood.  It  is 
said  that  a  so-called  light  bath,  as  used  in  the  treatment  of  certain 
diseases,  may  increase  the  quantity  of  blood  in  rabbits  by  23  per  cent, 
in  four  hours.  The  shorter  wave-lengths  which  are  relatively  more 
intense  in  the  mountain  light  are  most  effective.  Recent  investigations 
of  the  effects  of  high  mountain  chmatcs  have  been  conducted  by 
Haldane,  Henderson,  and  others,  on  Pike's  Peak,  and  by  Barcroft  and 
his  associates  on  the  Peak  of  Teneriffe  and  in  the  Alps.  As  already 
mentioned,  Haldane  concluded  that  there  was  evidence  of  oxygen 
secretion  by  the  lungs  which  became  more  marked  with  the  duration 
of  residence  on  the  mountain  (14,000  feet  above  sea-level).  The  total 
oxygen  capacity,  and  therefore  the  total  amount  of  ha?moglobin, 
gradually  increased.  The  total  volume  of  the  blood  was  but  slightly 
augmented,  and  the  percentage  of  haemoglobin  rose  decidedly.  The 
changes  in  the  circulation  have  been  especially  studied  by  Schneider, 


CUTAXEOUS  RESPIRATION  icjcf 

who  found  a  marked  increase  in  tlic  rate  of  blood-fl(Jvv  througli  tlie 
hands,  associated  with  an  acceleration  of  the  heart  beat,  dilatation  of 
the  arterioles  and  a  fall  in  the  venous  pressure.  In  '  aviator's  sick- 
ness '  the  essential  factor  is  also  oxygen  deficiency. 

Section  IX. — Cutaneous  Respiration. 

It  has  already  been  remarked  that  a  frog  survives  the  loss  of  its  lungs 
for  some  time,  respiration  going  on  through  tiie  skin.  Indeed,  it  has 
been  c^Uculatcd  that  in  the  intact  frog,  under  ordinary  conditions,  as 
much  as  three-quarters  of  the  total  gaseous  exchange  may  be  cutaneous. 
Two  frogs  were  seen  to  live  thirty-three  days,  and  one  e\'en  forty  days, 
after  excision  of  the  lungs.  The  effect  of  exclusion  of  the  pulmonary 
respiration  on  the  gaseous  exchange  depends  on  the  previous  intensity 
of  the  metabolism.  If  this  is  high  the  gaseous  exchange  sinks  markedly ; 
if  it  is  low  there  is  scarcely  any  alteration.  At  their  ma.ximum  efficiency, 
the  frog's  lungs  are  capable  of  sustaining  a  much  greater  exchange 
than  the  skin.  Besides  this  quantitative,  there  is  a  qualitative  differ- 
ence, the  carbon  dioxide  passing  more  easily  through  the  skin  than  the 
oxygen,  so  that  the  respiratory  quotient  is  increased  by  elimination  of 
the  lungs.  In  mammals  the  structure  of  the  skin  is  different,  and 
respiration  can  only  go  on  through  it  to  a  very  slight  extent.  The 
amount  of  carbon  dioxide  excreted  in  man,  although  only  about  4  grm. 
or  2  litres  in  twenty-four  hours,  is  much  greater  than  corresponds  to 
the  quantity  of  oxygen  absorbed  through  the  skin.  It  has  been  as- 
serted, and  no  doubt  with  justice,  that  some  at  least  of  the  carbon 
dioxide  given  off  is  due  to  putrefactive  processes  taking  place  on  the 
surface  of  the  body.  Such  processes,  as  has  already  been  pointed  out, 
seem  also  responsible  in  part  for  the  heavy  odour  of  a  '  close  '  room. 
For  no  harmful  products  appear  to  be  exhaled  from  the  skin  w^hen  it  is 
prop^rly  cleansed.  In  spite  of  the  romantic  statements  to  the  con- 
trary in  ancient  and  modern  books  (for  instance,  the  story  of  the  child 
that  was  gilded  to  play  the  part  of  an  angel  at  the  coronation  of  a 
medieval  popL\  but  died  before  the  ceremony  began),  the  w-Iiole  of  the 
human  skin  may  be  coated  with  an  impermeable  tarnish  without  any 
ill  effects.  The  entire  surface  of  the  body  of  a  patient  wdtli  cutaneous 
disease  was  covered  with  tar,  and  kept  covered  for  ten  days.  There  was 
not  the  least  disturbance  of  any  normal  function.  The  serious  effects 
of  varnishing  the  skin  in  animals  are  due,  not  to  retention  of  poisonous 
substances,  but  to  increased  heat  loss.  Varnishing  is  not  so  rapidly 
harmful  in  large  animals  like  dogs  as  in  rabbits,  which  have  a  relatively 
great  surface  and  a  delicate  skin.  The  danger  of  widespread  superficial 
bums  is  well  known.  But  it  is  not  due  to  diminished  excretion  by  the 
skin,  for  death  occurs  when  large  cutaneous  areas  remain  uninjured. 
The  patient  nearly  always  dies  when  a  quarter  of  the  whole  skin  is 
burnt;  yet  the  remaining  ti.ree-quarters  may  surely  be  considered 
capable,  from  all  analogy,  of  making  up  the  loss  by  increased  acti\'ity. 
One  kidney  is  enough  to  eliminate  the  products  of  the  nitrogenous 
metabolism  of  the  whole  body.  It  is  difficult  to  see  why  the  excretion 
of  the  trifhng  amount  of  solid  matter  in  the  perspiration  should  be 
interfered  with  by  the  loss  of  25  per  cent,  of  the  sweat-glands.  The  real 
explanation  of  the  serious  effects  of  extensive  superficial  bums  is 
perhaps  the  excessive  irritation  of  the  sensory  nerves,  which  may  lead 
to  changes  in  the  nervous  centres,  or  reflcxly  in  other  organs,  or  the 
chemical  changes  in  the  damaged  tissue,  for  example,  in  the  blood- 
corpuscles,  or  the  transudation  of  lymph  at  the  injured  part,  and  con- 
seqvient  increase  in  the  concentration  of  the  blood. 


300 


RESPIRA  TION 


PKACTICAL  EXERCISES  ON  CHAPTER  IV. 

I.  Tracing  of    the  Respiratory   Movements  in   Man. — Pass  a  tape 
through  the  rings  B  of  the  stethograph  shown  in  Fig.  134,  and  then 

around   the  neck   or   over 
the  shoulders,  so  as  to  sup- 
ort    the    instrument    on 
the  chest  at  a  convenient 
lieight.      Fasten  tapes  to 
the    hooks    and    tie 
them  by  a  shp-knot 
'  round  the  chest.  The 
tube  E  is  connected 
recording    tambour, 
writing  on  a  drum.    Or  use 
the     belt    stethograph    or 
spirograph  of  Fitz  (p.  233), 
fastening  the  elastic  tube 
round  the  chest  with  the 
chain,   and    connecting   it 
with    a    tambour    or    the 
bellows  recorder  shown  in 
Fig.  137.    Compare  the  ex- 
tent of  the  excursion  when 


Stethograph. 


the  tube  is  adjusted  at  different  levels  over  the  thorax  and  abdomen. 

2*  Production  of  Apnoea  and  Periodic  Breathing  in  Man. — Arrange 
for  taking  tracings  of  the  respiratory  movements  from  a  fellow-student 
as  in  I.  Let  the  subject  of  the  experiment  recline  in  a  perfectly  easy 
position  in  an  armchair.  Let  him  then  breathe  deeply  and  frequently 
for  about  two  minutes,  so  as  to  produce  a  prolonged  apnoea  of  about 
two  minutes'  duration.  Whenever  any  desire  to  breathe  returns,  the 
breathing  is  to  be  allowed  to  take  its  own  course.  It  may  be  expected 
at  first  to  be  of  the  periodic  (Cheyne-Stokes)  type. 

3.  Tracing  of  the  Respiratory  Movements  in  Animals. —  (a)  Set  up 
the  arrangement  shown  in  Fig.  135,  and  test  whether  it  is  air-tight. 
Have  also  in  readiness  an  induction  machine  and  electrodes  arranged 
for  an  interrupted  current.  Anaesthetize  a  rabbit  with  chloral  or 
ether  (p.  217),  or  a  small  dogf  with  morphine  and  ether,  or  A.C.E. 
mixture.  Insert  a  cannula  into  the  trachea  (p.  201),  and  connect  it 
with  the  large  bottle  by  a  tube.  Connect  the  bottle  with  a  recording 
tambour  adjusted  to  write  on  a  drum,  and  regulate  the  amount  of  the 
excursion  of  the  lever  by  slackening  or  tightening  the  screw-clamp. 
Set  the  drum  off  at  slow  speed,  and  take  a  tracing. 

(b)  Then  disconnect  the  cannula  from  its  tube.  Dissect  out  the  vagus 
in  the  lower  part  of  the  neck,  pass  a  ligature  under  it,  but  do  not  tie  it. 
Connect  the  cannula  again  with  the  bottle,  and  while  a  tracing  is  being 
taken  ligature  the  vagus.  Cut  below  the  ligature  and  stimulate  its  central 
end  with  weak  shocks,  marking  the  time  of  stimulation  on  the  drum. 
Repeat  the  stimulation  with  strong  shocks,  and  observe  the  results. 

•  This  experiment  is  only  to  be  attempted  under  the  direct  supervision  of 
the  demonstrator. 

t  If  a  large  dog  is  used  the  bottle  should  be  omitted,  the  tracheal  cannula 
being  connected  with  the  stem  of  a  T-tube.  One  end  of  the  horizontal  limb 
of  the  T-tube  is  connected  with  the  tambour;  the  other  is  provided  with  a 
rubber  tube,  which  can  be  partially  closed  by  a  screw-clamp  to  regulate  the 
excursion.  ^  Ether  may  be  given  when  required  by  connecting  the  horizontal 
Umb  of  the  T-tube  with  a  bottle  with  two  glass  tubes  in  the  cork  (p.  201). 


PRACTICAL  EXr:RCISF.S 


301 


(c)  Apply  a  strong  solution  of  potassium  chloride  with  a  camei's- 
hair  brush  to  the  central  end  of  the  vagus  wliile  a  tracing  is  being  taken, 
and  observe  the  efiect. 

(d)  Isolate  the  sciatic  nerve  (p.  212),  ligature  it,  and  cut  below  the 
ligature.  Stimulate  its  central  end  while  a  tracing  is  being  taken. 
The  respiratory  movements  will  be  increased. 

{e)  Disconnect  the  cannula,  and  isolate  the  vagus  on  the  other  side. 
While  a  tracing  is  being  taken,  divide  it.  The  respiratory  movements 
will  probably  at  once  become  deeper  and  less  frequent. 

(f)  Again  disconnect  the  cannula.  Isolate  the  superior  laryngeal 
bmnch  of  the  vagus.  This  will  be  found  entering  the  lar\nix  at  the 
point  where  the  laryngeal  hom  of  the  hyoid  bone  is  connected  with  the 
thyroid  cartilage.     li  the  finger  is  passed  back  along  the  upper  border 


^rachful    Canrtu.ia 


Fig-  135- — -A^rrangement  for  Respiratory  Tracing.  Two  glass  tubes  are  inserted 
through  a  cork  in  the  mouth  of  the  large  bottle.  One  of  them  has  a  small  piece  of 
indiarubber  tubing  on  it,  which  is  closed  or  opened,  as  may  be  required,  by  a 
screw -clamp.  The  other  is  connected  by  a  rubber  tube  with  a  recording  tambour. 
The  tubulure  at  the  bottom  of  the  bottle  is  closed  by  a  cork,  through  which 
passes  a  glass  tube,  connected  by  a  rubber  tube  with  the  tracheal  cannula.  If 
no  bottle  with  tubulure  is  available,  it  is  only  necessary  to  pass  through  the  cork, 
down  to  the  bottom  of  the  bottle,  a  third  glass  tube,  which  is  connected  with  the 
tracheal  cannula.  While  a  tracing  is  being  taken  the  animal  breathes  the  air 
contained  in  the  bottle.  When  this  becomes  vitiated  the  respiratory*  movements 
are  exaggerated  and  a  normal  tracing  is  no  longer  obtained.  For  this  reason 
the  tracheal  cannula  must  be  connected  with  the  bottle  only  at  the  moment 
when  a  tracing  is  to  be  taken.  The  arrangement  is  most  suitable  for  a  small 
animal. 


of  the  thjToid  cartilage,  this  point  mil  easily  be  felt.  Ligature  the 
ner^'e,  and  divide  it  between  the  lar\Tix  and  the  ligature.  Reconnect 
the  cannula.  Take  a  tracing  first  with  weak,  and  then  with  strong 
stimulation  of  the  central  end  of  the  superior  lar^mgeal. 

(?)  Make  an  incision  through  the  abdominal  wall  in  the  linea  alba, 
and  study  the  movements  of  the  diaphragm.  Find  the  nerves  from 
which  the  phrenics  take  origin  in  the  neck.  In  the  dog  they  arise  from 
the  fifth,  sixth,  and  seventh  cervical  nerves.     Di\'ide  the  phrenic  fibres 


302 


RESPIRATION 


on  one  side,  and  observe  that  the  diaphragm  on  the  corresponding  side 
is  now  paralyzed. 

{h)  Insert' a  cannula  into  the  carotid  artery.  While  a  respiratory 
tracing  is  being  taken,  allow  blood  to  flow  from  the  artery.  Dyspnoea  and 
exaggeration  of  the  respiratory  movements  will  be  seen  when  a  consider- 
able quantity  of  blood  has  been  lost.     Mark  and  varnish  the  tracings. 

In  the  whole  of  this  experiment  the  tracheal  cannula  is  to  be  dis- 
connected, except  when  the  lever  is  actually  writing  on  the  drum,  in 
order  that  the  period  during  which  the  animal  must  breathe  into  the 
confined  space  of  the  bottle  may  be  diminished  as  much  as  possible. 
Instead  of  the  method  described,  the  stetliograph  shown  in  Fig.  136 
may  be  used  to  obtain  respiratory  tracings  from  animals,  a  broad  canvas 
band  being  put  round  the  animal's  chest.  To  each  end  of  this  band  is 
clamped  with  sufficient  tension  a  strong  thread  (F),  fastened  to  a  small 
metal  disc  on  the  inside  of  the 
rubber  dam  closing  the  obliquely- 
cut  ends  of  the  metal  cylinder  D. 
The  tube  G  is  connected  with  a 
tambour  or  with  a  bellows  recorder 

(Fig-  137)- 

4.  The  Effect  of  Temperature  on 
th 3  Respiratory  Centre  -Heat  Dysp- 
noea.— Set  up  an  arrangement  for 


Stethograph  (Crile). 


Fig.  137. — Bellows  Recorder.  B,  a 
lead  tube  connected  with  the 
small  bellows  A,  which  consists  of 
a  light  wooden  base  and  top,  to 
which  is  cemented  very  flexible 
(organ  key)  leather,  properly 
creased  for  expansion  and  con- 
traction; C,  writing  lever. 


taking  a  respiratory  tracmg  as  m  2 
(footnote,  p.  300).  Anaesthetize  a 
dog,  and  fasten  it,  back  dowTiward, 
on  a  holder.  Make  an  incision  in 
the  middle  line  of  the  neck,  com- 
mencing a  little  below  the  cricoid 
cartilage,  and  extending  down  for 

4  or  =  inches.  Insert  a  cannula  into  the  trachea.  Isolate  both  carotid 
arteri'.s  for  as  great  a  distance  as  possible,  and  arrange  them  on  the 
brass  tubes  shown  in  Fig.  138.  Connect  two  adjacent  ends  of  the 
tubes  by  a  short  rubber  tube.  Connect  one  of  the  remaining  ends  to  a 
funnel ,  supported  on  a  stand,  and  the  other  to  a  rubber  tube  hanging 
over  t':^'  table  above  a  large  jar.  Slip  two  or  three  folds  of  paper 
betwec-i  the  tubes  and  the  vagus  nerves.  Heat  two  or  three  litres  ot 
water  io  about  65°  C.  (a)  Now  connect  the  tracheal  cannula  with  the 
tambo.:!-.  As  soon  as  the  tracing  is  under  way,  let  the  hot  water  run 
througl'  the  funnel  and  tubes  into  the  jar.  Mark  on  the  tracing  the 
point  a.  which  the  flow  of  the  hot  water  was  begun,  and  go  on  passing 
it  until  it  has  produced  an  effect.  Then  stop  the  drum,  and  circulate 
water  at  the  ordinary  temperature  till  the  breathing  is  again  normal. 
Then,  while  a  tracing  is  being  taken,  pass  ice-cold  water  through  the 
tubes,  and  again  notice  the  effect. 


PRACTICAL  EXERCISES 


303 


(6)  Expose  the  sciatic.  Pass  ice-water  through  the  tubes,  and  while 
a  respiratory  tracing  is  being  taken  stimulate  its  central  end  \^'ith  in- 
duction shocks  so  weak  as  just  to  cause  an  effect.  Pass  water  at  air 
temperature  through  the  tubes,  and  repeat  the  stimulation  with  the 
coils  at  the  same  distance.  Do  the  same  while  hot  water  is  being  passed 
through  the  tubes,  and  compare  the  results.  Always  allow  the  water 
to  pass  for  a  time  before  making  an  observation. 

5.  Measurement  of  Volume  of  Air  inspired  or  expired — Vital  Capacity. 
— A  spirometer  (Fig.  114,  p.  233)  of  sufficient  accuracy  for  this  experi- 
ment can  be  made  by  removing  the  bottom  of  a  large  bottle  with  a 
capacity  of  not  less  than  4  litres.  A  good  cork,  through  which  passes 
a  glass  tube  connected  with  a  rubber  tube,  is  fitted  into  the  neck.  The 
bottle  is  fixed  vertically,  mouth  downwards,  the  glass  tube  being  closed 
for  the  time,  and  graduated,  by  pouring  in  measured  quantities  of  water, 
say  100  c.c.  at  a  time,  and  marking  the  level.  The  divisions  are  then 
etched  in.  If  the  cork  does  not  fit  air-tight,  it  is  covered  with  wax. 
The  bottle  is  swung  on  two  pulleys,  counterpoised  and  immersed, 
bottom  down,  in  a  large 
glass  jar  or  a  small  cask 
nearly  full  of  water.  A 
smaller  bottle  may  be  used 
for  the  detennination  of  the 
tidal  air,  so  as  to  reduce  the 
error  of  reading. 

(i)  Submerge  the   bottle  -^ 

to  the  stopper,  afteropcning   Fig.   138.— Arrangement  for  Heating  or  Cooling 


the  Blood  in  the  Carotid  Arteries.  A,  cylin- 
drical portion  of  tube;  B,  flattened  portion  in 
the  groove,  between  which  and  A  the  artery 
lies;  C,  cross-section,  showing  the  lumen  extend- 
ing into  B;  D,  rubber  tube  attached  to  a  brass 
tube  soldered  into  A.  The  other  end  of  A  has 
a  similar  brass  tube  soldered  into  it  (not  shown 
in  the  figure).  This  is  connected  by  a  rubber 
tube  with  a  similar  apparatus,  on  which  the 
other  carotid  lies.  D  is  connected  with  a  funnel 
containing  hot  or  cold  water  or  with  the  outflow 
tube,  as  the  case  may  be. 


the  pinchcock  on  the  rub- 
ber tube.  Breathe  into  the 
bottle,  close  the  cock,  ad- 
just the  bottle  so  that  the 
level  of  the  water  is  the 
same  inside  and  outside,  and 
then  read  off  the  level.  De- 
termine the  volume  of  air 
expired  in — 

(a)  A  normal  expiration 
after  a  normal  inspiration 
(tidal  air) ; 

{b)  The  greatest  possible  expiration  after  a  normal  inspiration 
(supplemental  air  plus  tidal  air) ; 

(c)  The  greatest  possible  expiration  after  the  greatest  possible 
inspiration  (vital  capacity). 

(2)  Open  the  cock  and  raise  the  bottle  till  it  is  nearly  full  of  air. 
Determine  the  volume  of  air  inspired  in — 

(a)  A  normal  inspiration  after  a  normal  expiration  (tidal  air) ; 

(6)  The  greatest  possible  inspiration  after  a  normal  expiration 
(complemental  air  plus  tidal  air) ; 

(c)  The  greatest  possible  inspiration  after  the  greatest  possible 
expiration  (vital  capacity). 

^lake  several  observations  of  each  quantity,  and  take  the  mean. 

(3)  Q)unt  the  rate  of  respiration  for  three  minutes,  keeping  the 
breathing  as  nearly  normal  as  possible ;  repeat  the  observation ;  and 
from  the  mean  result  and  the  amount  of  the  tidal  air  calculate  the 
quantity  of  air  taken  into  the  lungs  in  twenty-four  hours  (pulmonary 
ventilation). 

6.  Cardio-Pneumatic  Movements.  —  Fill  a  U-tube  with  tobacco- 
smoke.     One  end  of  the  tube  is  placed  in  the  nostril  of  a  fellow-student. 


304  RESPIIWnON 

and  niadi-  tight  with  a  little  cotton-wool.  Tho  other  nostril  and  the  mouth 
are  closed,  and  respiration  suspended.  The  column  of  smoke  moves 
in  and  out  at  each  beat  of  the  heart.  By  feeling  the  apex-beat,  try  to 
verify  the  fact  that  during  systole  the  cardio-pneumatic  movement  is 
inspiratory,  and  in  diastole  expiratory. 

7.  Auscultation  of  the  Lungs. — -This  is  taught  in  the  course  of  physical 
diagnosis,  but  in  connection  with  the  subject  the  student  may  perform 
the  following  experiment  on  a  dog  used  for  sonic  other  purpose:  Open 
the  trachea  as  described  on  p.  201.  Insert  into  it  the  cross-piece  of  a 
glass  T-tube  of  as  large  a  bore  as  possible,  tying  the  trachea  over  it  on 
each  side  of  the  stem.  The  stem  projecting  from  the  woimd  is  armed 
with  a  short  piece  of  rubber  tubing,  which  can  be  closed  at  will  with  a 
clip.  When  the  tube  is  thus  closed  the  animal  breathes  through  the 
glottis  in  the  ordinary-  way.  When  the  tube  is  open,  and  the  mouth 
and  nose  covered  tightly  with  a  cloth,  no  air  goes  through  the  glottis. 
The  tube  being  closed,  listen  with  the  stethoscope  or  the  ear  alone  over 
a  part  of  the  chest  where  the  vesicular  murmur  is  well  heard.     If  the 


139. — Haldauc's  Apparatus  for  measuring  thr  Quantity  of  CO.j  aiul  Aqueous 
Vapour  given  off  by  an  .\uimal.  A,  chaniLicr  into  wiiirh  the  animal  is  put; 
I  and  4,  Woulff's  bottles  filled  with  soda-lime  to  absorb  carbon  dioxide;  2,  3,  and 
5,  Woulff's  bottles  filled  with  jMimice-stone  soaked  in  sulphuric  acid  to  absorb 
watery  vapour;  B,  glass  bell-jar  suspended  in  water,  by  means  of  which  the 
negative  pressure  is  known;  P,  water-pump  which  sucks  air  tiu"ough  the  appar- 
atus; I  and  2  are  simply  for  absorbing  the  carbon  dioxide  and  water  of  the 
ingoing  air. 

rubbing  of  the  hairs  below  the  stethoscope  causes  disturbing  sounds, 
shave  a  portion  of  the  skin.  Continue  listening  while  an  assistant 
closes  the  tube  and  covers  up  the  animal's  muzzle.  Determine  whether 
any  change  takes  place  in  the  vesicular  sound. 

Repeat  the  observation  while  listening  over  the  lower  part  of  the 
trachea,  and  determine  whether  any  change  takes  place  in  the  bronchial 
breathing  sound. 

8.  Respiratory  Pressure. — Connect  a  strong  rubber  tube  with  a  glass 
bulb,  and  the  bulb  with  a  mercurial  manometer  provided  with  a  scale. 
(i)  Fasten  the  tube  with  a  little  cotton-wool  in  one  no.stril,  breathe 
through  the  other  with  closed  mouth,  and  observe  the  amount  by  wliich 
the  level  of  the  mercury  is  altered  in  ordinary  inspiration  and  ex- 
piraton. 

(z)  Rep?at  the  observation  with  forced  breathing,  pinching  the  tube 
at  the  height  of  inspiration  and  expiration,  and  reading  off  the  maximum 
inspiratory  and  expiratory  pressure. 


PRACTICAL  EXERCISES 


305 


(3)  Repeat   (i)   with  tlic  tube  connected  to  the   moutli   by  a  glass 
tube  held  between  tiic  lips,  and  the  nostrils  open. 

(4)  Repeat  (2)  with  the  tube  in  the  nioutli  and  the  nostrils  closed. 

9.  Estimation  of  the  Quantity  of  Water  and  of  Carbon  Dioxide  given 
off  by  an  Animal  {Haldanc's  Me'/iod). — (i)  Connect  the  appanilu.-. 
shown  in  Fig.  139  with  the  water-pump.  Allow  a  negative  pressure 
of  5  or  6  inches  of  water  to  be  established  in  it,  as  shown  by  the  rise  of 
water  in  the  bell-jar  B.  Then  close  th('  open  tube  of  carbon  dioxide 
bottle  I,  and  clamp  the  tube  between  the  water-pump  and  the  bell-jar. 
If  the  negative  pressure  is  maintained,  the  arrangement  is  air-tight. 
Now  weigh  bottle  3  and  bottles  4  and  5,  the  last  two  together.  Place 
a  cat  in  the  respiratory  chamiier  A,  connect  the  chamber  directly  with 
the  water-pump,  and  test  wlicther  it  is  tight.  Then  take  the  stopper 
out  of  bottle  I,  and  adjust  the  rate  at  which  air  is  drawn  through  the: 
apparatus.  Let  the  ventilation 
go  on  for  a  few  minutes,  then 
insert  bottles  3,  4,  and  5  again. 
Note  the  time  exactly  at  this 
point,  and  after  an  hour  dis- 
connect 3,  4,  and  5,  and  again 
weigh.  The  difference  of  the 
two  weighings  of  3  shows  the 
quantity  of  water  given  ofE  by 
the  animal  in  an  hour;  the  dif- 
ference in  the  combined  weight 
of  4  and  5,  the  quantity  of 
carbon  dioxide .  Weigh  the  cat . 
and  calculate  the  amount  of 
water  and  of  carbon  dioxide 
given  off  per  kilo  per  hour. 

(2)  For  the  student  it  is 
more  convenient  to  use  smaller 
animals.  The  mouse  may  be 
taken  as  an  example  of  a 
warm-blooded  animal,  and  the 
frog  of  a  cold-blooded.  Instead 
of  the  Woulff's  bottles  use  wide 
test  -  tubes  connected  as  in 
Fig.  140,  and  for  the  animal 
chamber  a  small  beaker,  closed 
with   a    very   carefully    fitted 

cork  which  has  been  boiled  in  paraffin.  The  inlet  and  outlet  tubes  of 
the  chamber  are  to  be  introduced  through  this  cork.  The  holes  for  these 
are  to  be  bored  with  the  greatest  care,  and  the  tubes  to  be  put  in  while 
the  cork  is  still  hot  from  boiling  in  paraffin.  Also  insert  a  thermom- 
eter about  6  inches  long  registering  from  o"  C.  to  45°  C.  Modeller's 
wax  is  to  be  used  finally  to  render  all  the  junctions  air-tight. 

Add  to  the  series  of 'tubes  described  in  the  apparatus  a  single  tube 
containing  baryta-water.  This  is  placed  to  the  left  of  tube  5,  and  so 
arranged  that  the  air-current  bubbles  through  the  water.  As  long 
as  the  absorption  of  carbon  dioxide  is  complete,  the  baryta-water 
remains  clear.  Beyond  this  a  water-bottle  should  be  placed  to  act 
as  a  valve  and  to  indicate  the  negative  pressure  in  the  apparatus.  It 
can  be  most  simply  constructed  by  using  a  cylinder  of  stout  glass 
tubing  in  a  wide-mouthed  bottle  containing  some  water,  the  inlet  and 
outlet  tubes  passing  through  a  paraffined  cork  which  seals  the  upper 
end  of  the  cylinder.  20 


Fig.  140. — Absorption  Tubes  for  CO.^  and 
Moisture.  A,  soda -lime  tube;  B,  [sul- 
phuric acid  tube;  C,  wooden  frame,  in 
which  A  and  B  are  supported  by  wires  d  ; 
'),  wire  hook,  which  grips  the  glass  tube 
firmly,  and  by  means  of  which  the  tubes 
are  lifted  out  of  the  frame  in  order  to  be 
weighed;  a,  short  piece  of  glass  tubing, 
by  taking  out  which  the  absorption  tubes 
are  disconnected  from  the  rest  of  the 
apparatus;  e,  glass  tube  going  off  to  animal 
chamber. 


3°^  HESPIRA]  lOJ^ 

Before  making  an  observation,  test  whether  the  apparatus  is  air- 
light,  as  cxpl;inK(l  above,  after  introdnring  fho  animal  into  the  cham- 
ber, seahng  the  latter  with  wax  and  connecting  it  with  tl)e  absorption - 
tubes.  But  a  negative  pressure  of  2  or  3  inches  of  water  is  a  sufficient 
test  for  the  small  apparatus. 

To  make  an  observation,  set  the  air-current  going  at  the  desired 
rate.  Allow  it  to  run  for  a  few  minutes  till  the  carbon  dioxide,  which 
has  accumulated  duriiig  the  testing,  has  been  swept  out.  At  a  time 
which  has  been  decided  on  and  noted,  stop  the  current  by  disconnecting 
the  water-pump.  Disconnect  and  stopper  up  the  animal  chamber,  and 
weigh  it  as  quickly  as  possible.  Connect  up  again,  using  only  recently- 
weighed  absorption-tubes,  and  finally  connect  with  the  water-pump 
and  allow  the  current  to  pass  for  a  definite  period,  say  an  hour. 

The  soda-lirae  should  not  be  too  dry,  or  absorption  is  not  sufficiently 
rapid.  The  following  facts  are  made  out:  [a)  Loss  of  weight  by  the 
animal  chamber  (chiefly  loss  by  th'^  animal) ;  {b)  gain  of  the  sulphuric 
acid  tube  in  water;   (c)  gain  of  the  i-oda-lime  tubes  in  carbon  dioxide. 

The  total  loss  and  total  gain  do  not  correspond,  the  gain  being  always 
greater  than  the  loss.  The  surplus  can  only  be  oxj'gen  absorbed  by  the 
animal  and  added  to  tlie  hydrogen  and  carbon  of  its  substance  to  form 
water  and  carbon  dioxide.     Calculate  the  respiratory  quotient  (p.  241J. 

10.  Muscular  Contraction  in  the  Absence  of  Free  Oxygen  (see  p.  267). 
— Pith  a  frog  (brain  and  cord).  Cut  off  one  hind-leg  at  the  middle 
of  the  thigh,  and  strip  the  skin  from  it.  Pass  a  thread  under  the  tendo 
Achillis,  tie  it,  and  divide  the  tendon  below  it.  Free  the  tendon  and 
the  gastrocnemius  muscle  from  the  loose  connective  tissue  lying  between 
them  and  the  bones  of  tlie  leg.  and  divide  the  latter  just  below  the  knee, 
l^cmove  superfluous  thigh  muscles,  and  fasten  the  gastrocnemius  in 
a  moist  cliamber  by  means  of  the  femur.  Attach  the  thread  on  the 
tendon  to  a  lever.  Connect  the  poles  of  the  secondary  coil  of  an  induc- 
tion machine  by  fine  copper  wires  to  the  femur  and  the  tendon.  Put 
a  battery  and  simple  key  in  the  primary,  and  arrange  it  for  single  shocks. 
Stimulate  the  muscle  and  observe  the  height  of  the  contraction.  Now 
pass  into  the  chamber  a  current  of  washed  hydrogen  gas  from  a  bottle 
containing  granulated  zinc,  upon  which  a  little  dilute  sulphuric  acid 
is  poured  from  time  to  time.  The  air  in  the  moist  chamber  will  soon 
be  entirely  displaced  by  the  hydrogen,  but  the  muscle  will  contract  on 
being  stimulated,  and  the  stimulation  can  be  repeated  many  times. 

11.  Oxidizing  Ferments. — Wash  out  the  bloodvessels  of  a  dog  or 
rabbit  (Practical  Exercises,  p.  65).  Chop  up  finely  portions  of  pancreas, 
spleen,  muscle,  lungs,  and  kidney,  keeping  each  separate,  and  avoiding 
any  contamination  of  one  by  another.  Grind  up  half  of  each  portion 
with  sand  in  a  small  mortar,  and  extract  v/lth  a  small  quantity  of  water, 
keeping  all  the  extracts  separate.  Into  each  of  eleven  test-tubes  put 
10  c.c.  of  a  colourless  dilute  alkaline  solution  of  paraphenylenediamin 
and  a-naphthol  (freshly  made  by  mixing  solutions  of  the  two  sub- 
stances in  equimolecular  proportions*  and  adding  a  little  sodium 
carbonate).  To  five  of  the  tubes  add  the  chopped  organs,  to  five  the 
watcr}^  extracts  of  the  organs,  and  enough  water  to  make  the  volume 
equal  in  all  the  tubes.  To  the  remaining  tube  add  the  same  amount 
of  water.     Observe  in  which  tube  a  change  of  colour  takes  place  (p.  272 ). 

♦  I.e.,  the  weight  of  each  of  the  two  substances  in  the  mixture  should  be 
proportional  to  its  molecular  weight.  A  convenient  solution  contains  0144 
per  cent,  ot  a-naphthol  and  o'io8  pei  cent,  of  paraphenylenediamin.  These 
quantities  are  one-hundrcdth-molecular.  Sod  um  carbonate  is  added  to  the 
amount  of  o"25  per  cent.  The  a-naphthol  can  be  kept  as  a  i  per  cent,  solu- 
tion in  50  per  cent,  alcohol. 


CHAPTER  V 
VOICE  AND  SPEECH 

Voice. — Sounds  of  various  kinds  are  frequently  produced  by  the 
movements  of  animals  as  a  whole,  or  of  individual  organs.  The 
muscular  sound,  the  sounds  of  the  heart  and  of  respiration,  we  have 
already  had  to  speak  of.  Such  sounds  may  be  considered  as  purely 
accidental  as  the  footfall  of  a  man  or  the  buzzing  of  a  fly.  The 
wings  of  an  insect  beat  the  air,  not  to  cause  sound,  but  to  produce 
motion;  the  respiratory  murmur  is  a  mere  indication  that  air  is 
finding  its  way  into  the  lungs,  it  is  in  no  way  related  to  the  oxidation 
of  the  blood  in  the  pulmonary  capillaries.  But  in  many  of  the 
higher  animals  mechanisms  exist  which  are  specially  devoted  to  the 
utterance  of  sounds  as  their  prime  and  proper  end.  In  man  the 
voice-producing  mechanism  consists  of  a  triple  series  of  tubes  and 
chambers:  (i)  The  trachea,  through  which  a  blast  of  air  is  blown; 
(2)  the  larynx,  with  the  vocal  cords,  by  the  vibrations  of  which 
sound-waves  are  set  up ;  and  (3)  the  upper  resonance  chambers,  the 
pharynx,  mouth,  and  nasal  cavities,  in  which  the  sounds  produced 
in  the  larynx  are  modified  and  intensified,  and  in  which  independent 
notes  and  noises  arise. 

The  larynx  is  a  cartilaginous  box,  across  which  are  stretched, 
from  front  to  back,  two  thin  and  sharp-edged  membranes,  the  (true) 
vocal  cords.  In  front  the  cords  are  attached  to  the  thyroid  carti- 
lage, one  a  little  to  each  side  of  the  middle  line;  behind  they  are 
connected  to  the  vocal  or  anterior  processes  of  the  p)n:amidal 
arytenoid  cartilages.  The  thjnroid  and  the  two  arjrtenoids  are 
mounted  upon  a  cartilaginous  ring,  the  cricoid.  The  arytenoids 
can  rotate  on  the  cricoid  about  a  vertical  axis,  while  the  cricoid  can 
rotate  on  the  thyroid  cartilage  around  a  transverse  horizontal  axis. 
The  cricoid  can  thus  be  raised  by  the  contraction  of  the  crico- 
thyroid muscle,  and  the  vocal  cords  stretched.  By  the  pull  of  the 
posterior  crico-arytenoid  muscles,  attached  to  the  external  or  mus- 
cular processes  of  the  arytenoid  cartilages,  the  vocal  processes  are 
rotated  outwards,  the  cords  separated  from  each  other  or  abducted, 
and  the  chink  between  them,  the  rima  glottidis,  widened.  When 
the  vocal  processes  are  approximated  by  contraction  of  the  lateral 

307 


3o« 


VOICE  AND  SPEECH 


crico-arytenoid  muscles  and  the  consequent  forward  movement  of 
the  muscular  processes,  the  vocal  cords  are  brought  close  together, 
or  addncted,  and  the  rima  is  narrowed.  The  transverse  or  posterior 
arytenoid  muscle,  which  connects  the  two  arytenoid  cartilages 
behind,  also  helps,  by  its  contraction,  to  narrow  the  glottis  by  shift- 
ing the  cartilages  on  their  articular  surfaces  somewhat  nearer  the 
middle  Une.  Running  in  each  vocal  cord,  and,  in  fact,  incorporated 
with  its  elastic  tissue,  is  a  muscle,  the  thyro-arytenoid,  the  external 
portion  of  which  may  to  some  extent  cause  inward  rotation  of  the 
vocal  processes  and  adduction  of  the  cords;  but  the  main  function, 
at  least  of  its  inner  part,  is  to  alter  the  tension  of  the  cords.  The 
diagrams  in  Figs.  141  and  142  illustrate  the  action  of  the  abductors 
and  adductors  of  tlic  vocal  cords. 

The  crico-thj-Toid  muscle  and  the  deflectors  of  the  epiglottis  are 
supplied  by  the  superior  laryngeal  branch  of  the  vagus,  which  also 


z^'^^^. 


Fig.  141. — Diagrammatic  Hori- 
zontal Section  of  Larynx  to 
show  the  Direction  of  Pull  of 
the  Posterior  Crico-Arytenoid 
Muscles,  which  abduct  the 
Vocal  Cords.  Dotted  lines 
show  position  in  abduction. 


Fig.  142. — Direction  of  Pull-  of 
the  Lateral  Crico-Arytenoids. 
which  adduct  the  Vocal 
Cords.  Dotted  lines  show 
position  in  adduction. 


contains  the  sensory  fibres  for  the  mucous  membrane  of  the  larynx 
above  the  vocal  cords.  In  the  dog  and  rabbit  motor  fibres  also  reach 
the  crico-thyroid  by  the  so-called  middle  laryngeal  nerve  which 
arises  from  the  superior  pharyngeal  branch  of  the  vagus.  All  the 
other  intrinsic  muscles  are  supplied  by  the  recurrent  laryngeal 
branch  of  the  vagus.  It  receives  these  motor  fibres  from  the  spinal 
accessory,  and  supplies  sensory  fibres  to  the  mucous  membrane  of 
the  larynx  below  the  vocal  cords  and  to  the  trachea. 

The  voice  is  produced,  like  the  sounds  of  a  reed  instrument,  by 
the  rhythmical  interruption  of  an  expiratory  blast  of  air  by  the 
vibrating  vocal  cords.  When  a  bell  is  struck,  vibrations  are  set  up 
in  the  metal,  which  are  communicated  to  the  air.  It  is  not  the  same 
with  the  vibrations  of  the  vocal  cords;  if  they  were  plucked  or 
struck,  they  would  only  produce  a  feeble  note.  The  air  in  the 
mouth,  phar^Tix,  larynx,  trachea,  and  lungs  is  the  real  sounding 


V01C1-:  30f 

body;  a  pulse  of  alternate  rarefaction  and  condensation  is  set  up  in 
it  by  the  inter-ference,  at  regular  intervals,  of  the  vocal  cords  with 
the  expiratory  blast.  Forced  abruptly  from  their  position  of  equi- 
librium as  the  blast  begins,  they  almost  immediately  regain  and 
pass  below  it,  in  virtue  of  their  elasticity,  and  continue  to  vibrate  as 
long  as  the  stream  of  air  continues  to  issue  in  sufficient  strength. 
Not  only  do  they  vibrate  up  and  down,  but  also  towards  and  away 
from  the  middle  line,  so  that,  at  least  in  the  chest  voice,  they  come 
into  contact  with  each  other  at  each  swing.  The  sound-waves  thus 
set  up  spread  out  on  every  side,  impinge  on  the  tympanic  membrane, 
set  it  quivering  in  response,  and  give  rise  to  the  sensation  of  sound. 
We  may  say,  in  a  word,  that  the  whole  exquisite  mechanism  of 
cartilages,  hgamcnts,  and  muscles,  has  for  its  object  the  production 
of  a  sufficient  pressure  in  the  blast  of  air  driven  through  the  wind- 
pipe by  an  expiratory  act,  and  of  a  suitable  tension  in  the  vibrating 
cords.  An  approximation  of  the  cords,  a  narrowing  of  the  glottis, 
is  essential  to  the  production  of  voice ;  with  a  widely-opened  glottis 
the  air  escapes  too  easily,  and  the  necessary  pressure  cannot  be 
attained.  The  pressure  in  the  windpipe  was  found  in  a  woman 
with  a  tracheal  fistula  to  be  about  12  mm.  of  mercury  for  a  note  of 
medium  height,  about  15  mm.  for  a  high  note,  and  about  72  mm. 
for  the  highest  possible  note.  The  period  of  vibration  of  structures 
like  the  vocal  cords  depends  on  their  length,  thickness,  density  and 
tension;  the  shorter,  thinner,  more  dense  and  less  tense  a  stretched 
string  is,  the  greater  is  the  vibration  frequency,  the  higher  the  note. 
In  the  child  the  cords  are  short  (6  to  8  mm.),  in  woman  longer 
(10  to  12  mm.  when  slack,  13  to  15  mm.  when  stretched),  in  man 
longest  of  all  (14  to  18  mm.  in  the  relaxed,  and  18  to  22  mm.  in  the 
stretched  position) ;  and  the  lower  limit  of  the  voice  is  fixed  by  the 
maximum  length  of  the  relaxed  cords.  A  boy  or  a  woman  cannot 
utter  a  deep  bass  note,  because  their  vocal  cords  are  relatively 
short,  and  do  not  vibrate  with  sufficient  slowness.  It  is  true  that 
by  the  action  of  the  crico-thyroid  muscle  the  cords  can  be  length- 
ened, and  that  the  maximum  length  in  a  woman  approaches  or 
exceeds  the  minimum  length  in  a  man.  But  the  lengthening  of  the 
vocal  cords  in  one  and  the  same  individual  is  always  accompanied 
by  other  changes — increase  of  tension,  decrease  of  breadth  and 
thickness — which  tell  upon  the  vibration  frequency  in  the  opposite 
way,  and  more  than  compensate  the  effect  of  the  increase  of  length, 
so  that  for  high  notes  the  cords  are  longer  than  for  low.  The  con- 
traction of  the  thyro-arytenoid  muscle  is  a  more  influential  factor 
in  altering  the  tension  of  the  cords  than  the  contraction  of  the  crico- 
thjTToid.  It  is  probable  that,  when  the  highest  notes  are  uttered, 
only  the  anterior  portions  of  the  cords  are  free  to  vibrate,  their 
posterior  portions  being  damped  by  the  approximation  of  the  vocal 
processes  of  the  arytenoid  cartilages  by  the    contraction  of  the 


3IO  VOICE  AND  SPEECH 

lateral  crico-arytenoid  and  transverse  arytenoid  muscles.  The 
range  of  an  ordinary  voice  is  2  octaves;  by  training  2^  octaves  can 
be  reached;  but  in  exceptional  cases  a  range  of  3,  and  even  31^, 
octaves  (as  in  the  celebrated  singer  Catalini)  has  been  known. 

The  development  of  the  voice  in  children  is  of  great  interest.  At 
the  age  of  six  years  the  boy's  voice  has  a  rather  narrower  range  tlian 
the  girl's  in  both  directions.  The  boy's  voice  reaches  its  full  height 
in  the  twelfth  and  its  full  depth  in  the  thirteenth  year,  when  the  range 
is  almost  3  octaves,  its  upper  limit  being  a  semitone  higher  than  the 
girl's,  but  its  lower  limit  a  wliole  tone  deeper.  When  the  voice  '  breaks  ' 
in  boys  at  the  age  of  puberty  it  falls  about  an  octave.  The  control  of 
the  vocal  organs  becomes  so  incomplete  that  only  in  one-fourth  of  the 
cases  can  notes  of  sufficient  steadiness  to  be  used  in  music  be  produced. 
The  vocal  cords,  as  may  be  seen  with  the  laryngoscope,  are  frequently, 
though  not  always,  congested. 

The  pilch  of  a  note,  while  it  depends  chiefly,  as  has  been  said,  on 
the  tension  of  the  vocal  cords,  rises  and  falls  somewhat  with  the 
strength  of  the  expiratory  blast ;  the  highest  notes  are  only  reached 
with  a  strong  expiratory  effort.  The  intensity  of  all  vocal  sounds 
is  determined  by  the  strength  of  the  blast,  for  the  amplitude  of 
vibration  of  the  cords  is  proportional  to  this.  Besides  pitch  and 
intensity,  the  ear  can  still  distinguish  the  quality  or  timbre  of  sounds; 
and  the  explanation  is  as  follows:  Two  simple  tones  of  the  same 
pitch  and  intensity,  that  is,  the  sounds  caused  by  two  series  of  air- 
waves of  the  same  period  and  amplitude — of  the  same  frequency 
and  height,  to  use  less  technical  terms — would  appear  absolutely 
identical  to  the  sense  of  hearing;  just  as  the  aerial  disturbances  on 
which  they  depend  would  be  absolutely  alike  to  any  physical  test 
that  could  be  applied.  But  no  musical  instrument  ever  produces 
sound-waves  of  one  definite  period,  and  one  only;  and  the  same  is 
true  of  the  voice.  When  a  stretched  string  is  displaced  in  any  way 
from  its  position  of  rest,  it  is  set  into  vibration ;  and  not  only  does 
the  string  vibrate  as  a  whole,  but  portions  of  it  vibrate  independently 
and  give  out  separate  tones.  The  tone  corresponding  to  the  vibra- 
tion period  of  the  whole  string  is  the  lowest  of  all.  It  is  also  the 
loudest,  for  it  is  more  difficult  to  set  up  quick  than  slow  vibrations. 
The  ear  therefore  picks  it  out  from  all  the  rest;  and  the  pitch  of  the 
compound  note  is  taken  to  be  the  pitch  of  this,  its  fundamental 
tone.  The  others  are  called  partial  or  overtones,  or  harmonics  of 
the  fundamental  tone,  their  vibration  frequency  being  twice,  three 
times,  four  times,  etc.,  that  of  the  latter.  Now,  the  fundamental 
tone  of  a  compound  note  or  clang  produced  by  two  musical  instru- 
ments may  be  the  same,  while  the  number,  period,  and  intensity 
of  the  harmonics  are  different;  and  this  difference  the  ear  recognizes 
as  a  difference  of  timbre  or  quality.  The  timbre  of  the  voice  de- 
pends for  the  most  part  on  partial  tones  produced  or  intensified  in 
the  upper  resonance  chambers. 


VOICE 


3" 


A  great  deal  of  our  knowledge  as  to  the  mode  and  mechanism  of 
the  production  of  voice  has  been  acquired  by  means  of  the  laryngo- 
scope (Fig.  143).  This  consists  of  a  small  plane  mirror  mounted  on 
a  handle,  which  is  held  at  the  back  of  the  mouth  in  such  a  position 
that  a  beam  of  light,  reflected  from  a  larger  concave  mirror  fastened 
on  the  forehead  of  the  observer,  is  thrown  into  the  larynx  of  the 
patient.  The  observer  looks  through  a  hole  in  the  centre  of  the 
large  mirror;  and  an  image  of  the  interior  of  the  larynx  is  seen  in 
the  small  mirror,  in  which  the  parts  that  are  anterior  appear  as 
posterior,  the  arytenoid  cartilages  in  front,  the  thyroid  behind,  and 
the  vocal  cords  stretching  between.  The  small  mirror  is  warmed  to 
body-temperature  before  being  introduced,  so  as  to  prevent  the 
condensation  of  moisture  on  it.     The  tendency  to  retch,  which  is 


LamfD 


Conca/e  Mirror 


Fig.  143. — Diagram  of  Laryngoscope. 

caused  by  contact  of  the  instrument  with  the  soft  palate,  may  be 
removed  or  lessened  by  the  application  of  a  solution  of  cocaine. 

Examined  with  the  laryngoscope  during  quiet  respiration,  the 
glottis  is  seen  to  be  moderately,  though  not  widely,  open,  and  the 
vocal  cords  almost  motionless.  Although  the  portion  between  the 
arytenoid  cartilages  has  received  the  name  of  glottis  respiratoria,  in 
contradistinction  to  the  glottis  vocalis  between  the  vocal  cords,  the 
rima  in  its  whole  extent  from  front  to  back  is  really  concerned  in 
the  respiratory  act.  In  deep  expiration  the  vocal  cords  come  nearer 
to  the  middle  line,  and  the  glottis  is  narrowed ;  in  deep  inspiration 
they  are  widely  separated,  and  the  rings  of  the  trachea,  and  even 
its  bifurcation,  may  be  disclosed  to  view.  When  a  sound  is  produced 
— a  note  sung,  for  example— the  cords  are  approximated  (Figs.  144 
and  145) ;  and  with  a  high  note  more  than  with  a  low. 


312 


VOICE  AND  SPEECH 


The  essential  difference  between  the  production  of  notes  in  the  lower 
register,  or  chest  voice,  and  in  the  higher  register,  or  falsetto,  has  been 
much  debated.  The  lowest  notes  which  can  be  uttered  by  any  given 
voice  are  chest  notes,  the  highest  are  falsetto  notes;  but  there  is  a  de- 
batable land  common  to  both  registers,  and  medium  notes  can  be  sung 
eithf^r  from  tlie  chest  or  from  the  head.  Chest  notes  impart  a  vibration 
or  fremitus  to  the  thoracic  walls,  from  the  resonance  of  the  lower  air- 
chambers,  the  trachea  and  bronchi;  and  tliis  can  be  distinctly  felt  by 
the  hand.  In  head  notes  or  falsetto  the  resonance  is  chiefly  in  the 
upper  cavities,  the  phar^mx,  mouth,  and  nose.  As  to  the  mechAnical 
conditions  in  the  larjmx,  there  is  a  pretty  general  agreement  that  during 
the  production  of  falsetto  notes  the  vocal  cords  are  less  closely  approxi- 
mated than  in  the  sounding  of  chest  notes.  The  escape  of  air  is  conse- 
quently more  rapid  in  the  head  voice,  and  a  falsetto  note  cannot  be 
maintained  so  long  as  a  note  sung  from  the  chest.  But  it  is  only  the 
anterior  part  of  the  rima  glottidis  that  is  wider  in  the  falsetto  voice ; 
the  whole  of  the  glottis  rcspiratoria,  and  even  the  posterior  portion  of 
the  glottis  vocalis,  are  closed  during  the  emission  of  falsetto  notes. 


Fig.  144.  —  Position  of  t!ie 
Glottis  preliminary  to  the 
Utterance  of  Sound,  rs,  false 
vocal  cord;  ri,  true  vocal 
cord;  ar,  arytenoid  cartilage; 
b,  pad  of  the  epiglottis. 


Fig.  145. — Position  of  Open  Glottis, 
/,  tongue;  e,  epiglottis;  ae,  ary- 
epiglottidean  fold;  c,  cartilage  of 
Wrisberg;  ar,  arytenoid  cartilage; 
0,  glottis;  V,  ventricle  of  Mor- 
gagni;  ti,  true  vocal  cord;  is,  false 
vocal  cord. 


Oertel  has  stated,  and  the  statement  has  been  confirmed  by  others, 
that  the  free  edge  of  the  vocal  cord  alone  vibrates  in  the  falsetto  voice, 
one  or  more  nodes  or  motionless  lines  parallel  to  the  edge  being  formed 
by  the  contraction  of  the  internal  part  of  the  thyro-arytenoid  muscle, 
which  thus  acts  like  a  stop  upon  the  cord. 

Approximation  of  the  vocal  cords  may  take  place  in  certain 
acts  unconnected  with  the  production  of  voice.  Thus,  a  cough,  as 
has  already  been  mentioned,  is  initiated  by  closure  of  the  glottis. 
During  a  strong  muscular  effort,  too,  the  chink  of  tlie  glottis  is 
obliterated,  and  respiration  and  phonation  both  arrested.  The 
object  of  this  is  to  fix  the  thorax,  and  so  afford  points  of  support 
for  the  action  of  the  muscles  of  the  limbs  and  abdomen.  But  con- 
siderable efforts  can  be  made  even  by  persons  with  a  tracheal  fistula. 

Speech. — Ordinary  speech  is  articulated  voice — voice  shaped  and 
fashioned  by  the  resonance  of  the  upper  air-cavities,  and  jointai 


SPEECH 


313 


together  by  the  sounds  or  noises  to  which  the  v^arying  form  of  these 
cavities  gives  rise.  Here  we  come  upon  the  fundamental  distinction 
between  vowels  and  consonants.  Vowels  are  musical  sounds;  con- 
sonants are  not  musical  sounds,  but  noises — that  is  to  say,  they  are 
due  to  irregular  vibrations,  not  to  regularly  recurring  waves,  the 
frequency  of  which  the  ear  can  appreciate  as  a  definite  pitch.  This 
difference  of  character  corresponds  to  a  difference  of  origin:  the 
vowels  are  produced  by  the  vibrations  of  the  vocal  cords;  the  con- 
sonants are  due  to  the  rushing  of  the  expiratory  blast  through 
certain  constricted  portions  of  the  buccal  chamber,  where  a  kind  of 
temporary  glottis  is  established  by  the  approximation  of  its  walls. 
One  of  these  '  positions  of  articulation  '  is  the  orifice  of  the  lips;  the 
consonants  formed  there,  such  as  p  and  b,  are  called  labials.  A 
second  articulation  position  is  between  the  anterior  part  of  the 
tongue  and  the  teeth  and  hard  palate.  Here  are  formed  the  dentals, 
/,  d,  etc.  The  ordinary  English  r,  and  the  r  of  the  Berwickshire  and 
East  Prussian  '  burr,'  also  arise  in  this  position  through  a  vibratory 
motion  of  the  point  of  the  tongue.  The  third  position  of  articul;.- 
tion  is  the  narrow  strait  formed  between  the  posterior  portion  of  th  : 
arched  tongue  and  the  soft  palate.  To  the  consonants  arising  here 
the  name  of  gutturals  has  been  given.  They  include  k,  g,  the 
Scottish  ch,  and  the  uvular  German  r.  The  latter  is  produced  by 
a  vibration  of  the  uvula.  The  aspirated  /;  is  a  noise  set  up  by  the 
air  rushing  through  a  moderately  wide  glottis,  and  some  have  there- 
fore included  the  glottis  as  a  fourth  articulation  position  for  con- 
sonants. Certain  sounds  like  n,  m,  and  ng,  when  final  (as  in  pen, 
dam,  ring),  although  produced  at  the  glottis,  are  intensified  by  the 
resonance  of  the  air  in  the  nose  and  pharynx,  and  are  sometimes 
spoken  of  as  nasal  consonants. 

As  we  have  said,  the  vowels  are  produced  by  vibrations  of  the 
vocal  cords,  but  to  what  they  owe  their  special  timbre  or  quality  has 
been  much  discussed.  According  to  the  view  with  which  Helm- 
holtz's  name  is  particularly  connected  this  is  due  to  the  reinforce- 
ment of  certain  overtones  by  the  resonating  cavities,  the  shape  and 
fundamental  tone  of  which  are  different  for  each  vowel. 

When  a  vowel  is  whispered,  the  mouth  assumes  a  characteristic 
shape,  and  emits  the  fundamental  tone  proper  to  the  form  and  size 
of  the  particular  '  vowel-cavity,'  not  as  a  reinforcement  of  a  tone  set 
up  by  the  vibrations  of  the  vocal  cords,  but  in  response  to  the  rush  of 
air  through  the  cavity;  just  as  a  bottle  of  given  shape  and  size  gives  out 
a  definite  note  when  the  air  which  it  contains  is  set  in  vibration,  by 
blowing  across  its  mouth.  A  whisper,  in  fact,  is  speech  without  voice ; 
the  larynx  takes  scarcely  any  part  in  the  production  of  the  sound ;  the 
vocal  cords  remain  apart  and  comparatively  slack ;  and  the  expiratory 
blast  rushes  through  without  setting  them  in  vibration. 

The  fundamental  tone  of  the  '  vowel-cavity  '  may  be  found  for  each 
vowel  by  placing  the  mouth  in  the  position  necessary  for  uttering  it, 
then  bringing  tuning-forks  of  different  period  in  front  of  it,  and  noting 


314 


WILE  AND  -SPEECH 


which  of  them  sets  up  s^Tnpathctic  resonance  in  the  air  of  the  mouth, 
and  so  causes  its  sound  to  be  intensified.  The  fundamental  tone  is 
lowest  for  u  (as  in  lute).  Next  comes  o  ;  then  a  (as  in  path) ;  then  a  (as 
in  fa}ie) ;  then  i  ;  while  e  is  highest  of  all.  A  simple  illustration  of 
this  may  be  found  in  the  fact  that  when  the  vowels  are  whispered  in 
the  order  given,  the  pitch  rises.  When  «  or  o  is  sounded,  the  buccal 
cavit^^  has  the  form  of  a  wide-beUied  flask,  with  a  short  and  narrow  neck 
for  u,  a  still  shorter  but  wider  neck  for  o.  For  e  the  tongue  is  raised 
and  almost  in  contact  with  the  palate,  and  the  cavity  of  the  mouth 
is  shaped  like  a  flask  with  a  long  narrow  neck  and  a  very  short  belly. 
For  i  the  shape  is  similar,  but  the  neck  is  not  so  narrow.  For  a  (as  in 
path)  the  vowel-caN^ty  is  intermediate  in  form  between  that  of  u  and  e. 
being  roughly  funnel-shaped,  and  the  mouth  is  rather  widely  opened. 
For  u  {oo)  the  resonating  cavity  is  made  as  long  as  possible,  the  larynx 
being  depressed  and  the  lips  protruded;  for  e  the  resonating  cavit\  is 
at  its  shortest,  the  lar\-nx  being  raised  as  much  as  possible  and  the  lips 
retracted  (Figs.  146  to  148). 

According  to  Helmholtz,  all  that  the  resonating  cavity  does  is  to 
strengthen  certain  of  the  partials  or  overtones  of  the  larvTigeal  note. 


Fig.  146 


If  this  is  true,  the  partials  which  give  a  vowel-sound  the  timbre  by 
which  we  recognize  it  as  different  from  other  vowel-sounds  cannot 
preser\'e  the  same  numerical  relation  to  the  fundamental  tone  when 
the  pitch  of  the  latter  is  altered.  Suppose,  for  example,  that  a  given 
vowel  is  sounded  with  a  pitch  corresponding  to  100  vibrations  a  second, 
and  that  the  partial  which  is  particularly  strengthened  by  the  resonance 
of  the  mouth  cavity  is  the  fifth  overtone,  corresponding  to  600  vibra- 
tions. Then  when  the  same  vowel  is  sounded  with  a  pitch  of  200  vibra- 
tions, the  reinforced  partial  which  will  now  give  the  quality  to  the  sound 
will  still  correspond  to  600  vibrations  a  second,  since  this  is  the  rate 
which  most  easily  elicits  the  resonance,  but  it  will  not  now  be  the  fifth 
but  the  second  overtone. 

Universally  accepted  for  a  time,  the  Helmholtz  theory  has  been  in 
recent  years  assailed,  especially  by  Hermann,  wlio  baises  his  criticism 
on  microscopic  examination  of  curves  obtained  by  the  Edison  phono- 
graph, and  on  reproductions  of  such  records  obtained  by  photographing 
on  a  mo\ing  drum  covered  with  sensitive  paper  a  beam  of  light  re- 
flected from  a  small  mirror  attached  to  a  system  cf  levers  whose  move- 
ments follow  the  curves  faithfully  and  greatly  magnify  them.     Hermann 


SPEECH  315 

has  come  to  the  conclusion  that  the  mouth  docs  not  act  as  a  mere 
resonator,  but  that  for  each  vowel,  in  addition  to  the  fundamental 
note  due  to  the  vibration  of  the  vocal  cords,  the  pitch  of  which  is,  of 
course,  variable,  one  or,  it  may  be,  two  other  notes  (formants,  as  he 
calls  them),  not  necessarily  harmonics  of  the  laryngeal  note,  but  separ- 
ated from  it  by  a  constant  or  nearly  constant  musical  interval,  are 
directly  produced  by  the  passage  of  the  regularly  interrupted  expiratory 
blast  through  the  mouth,  the  air  contained  in  that  cavity  being  for 
an  instant  set  into  vibration  at  each  interruption.  On  this  view  it 
is  the  musical  effect  produced  by  the  oscillation  or  continual  recurrence, 
in  short  series,  of  these  vibrations  which  gives  the  vowels  tlieir  quality. 
The  fact  that  it  is  by  no  means  difficult  to  sing  (with  the  lan^Tix)  and 
whistle  (with  the  mouth)  at  the  same  time,  shows  the  possibility  of 
Hermann's  view,  that  a  fixed  tone  can  be  generated  in  the  mouth  by 
the  intermittent  stream  of  air  issuing  from  between  the  vibrating  vocal 
cords,  just  as  a  tone  is  generated  in  a  pipe  by  blowing  into  or  over  it, 
and  his  records  do  show  continually  recurring  groups  of  vibrations  as 
his  theory  requires.  McKendrick  takes  up  a  middle  position,  beheving 
that  both  theories  are  partially  true,  and  this  seems  to  be  the  best 
conclusion  which  can  at  present  be  arrived  at.  It  seems  clear,  at  any 
rate,  that  more  than  one  factor  is  concerned  in  the  timbre  of  the  vowel 
sounds. 

When  the  vowels  are  being  uttered,  the  soft  palate  closes  the 
entrance  to  the  nasal  chambers  completely,  as  may  be  shown  by 
holding  a  candle  in  front  of  the  nose,  or  trying  to  inject  water 
through  the  nares.  If  the  cavities  of  the  nose  are  not  completely 
blocked  off,  the  voice  assumes  a  nasal  character  in  pronouncing 
certain  of  the  vowels;  and  in  some  languages  this  is  the  ordinary 
and  correct  pronunciation. 

Many  animals  have  the  power  of  emitting  articulated  sounds;  a 
few  have  risen,  like  man,  to  the  dignity  of  sentences,  but  these  only 
by  imitation  of  the  human  voice.  Both  vowels  and  consonants  can 
be  distinguished  in  the  notes  of  birds,  the  vocal  powers  of  which 
are  in  general  higher  than  those  of  mammalian  animals.  The  latter, 
as  a  rule,  produce  only  vowels,  though  some  are  able  to  form  con- 
sonants too. 

The  nervous  mechanism  of  voice  and  speech  will  have  to  be 
again  considered  when  we  come  to  study  the  physiology  of  the  brain 
and  spinal  cord.  But  the  curious  physiological  antithesis  between 
the  functions  of  abduction  and  of  adduction  of  the  vocal  cords  may 
be  mentioned  here.  The  abductor  muscles  are  not  employed  in  the 
production  of  voice;  they  are  associated  with  the  less  specialized, 
the  less  skilled  and  purposive  function  of  respiration.  The  adductor 
muscles  are  not  brought  into  action  in  respiration;  they  are  asso- 
ciated with  the  highly  specialized  function  of  speech.  Correspond- 
ing to  this  difference  of  function,  we  find  that  adduction  is  pre- 
ponderatingly  represented  in  the  cortex  of  the  brain,  abduction  in 
the  medulla  oblongata.  Stimulation  of  an  area  in  the  lower  part 
of  the  ascending  frontal  convolution,  near  the  fissure  of  Rolando,  in 
the  macaque  monkey,  causes  adduction  of  the  vocal  cords,  never 


3i6  VOICE  AND  SPEECH 

abduction.  In  the  cat,  however,  abduction  of  the  cords  may  ako 
be  obtained  by  stimuJition  of  the  cortex.  The  same  is  true  of  the 
dog,  but  only  when  tiie  peripheral  adductor  nerves  have  been 
divided.  Stimulation  of  tiit  medulla  oblongata  (accessory  nucleus) 
causes  abduction,  never  adduction.  The  skilled  adductor  function 
is,  therefore,  placed  under  control  of  the  cortex.  The  vitally  im- 
portant, but  more  mechanical,  abductor  function  is  governed  by 
the  medulla.  The  abductor  movements  are  more  likely  to  be 
affected  by  organic  disease,  the  adductor  movements  by  functional 
changes.  But  the  distinction  between  the  two  groups  of  muscles 
is  not  entirely  due  to  a  difference  of  central  connections,  since  by 
altering  the  strength  of  the  stimulus  and  the  external  conditions 
the  one  or  the  other  may  be  separately  excited  through  the  inferior 
laryngeal  nerve.  Thus,  strong  stimulation  of  the  inferior  laryngeal 
causes  closure  of  the  glottis,  for  although  it  supplies  both  abductors 


Fig.  149. — Diagram  of  Vocal  Cords  in  Paralyses  of  the  Larynx,  a.  Paralysis  of  both 
inferior  laryngeal  nerves.  The  vocal  cords  have  taken  up  the  '  mean  '  position. 
b.  Paralysis  of  right  inferior  laryngeal  nerve.  An  attempt  is  being  made  to 
narrow  the  glottis  for  the  utterance  of  sound.  The  right  cord  remains  in  its 
■  mean  '  position,  'c.  Paralysis  of  the  abductor  muscles  only,  on  both  sides.  The 
cords  are  approximated  beyond  the  '  mean  '  position  by  the  action  of  the 
adductors. 

and  adductors,  the  latter,  as  the  stronger  muscles,  prevail.  With 
weak  stimulation,  and  in  young  animals,  the  abductors,  owing  to 
the  greater  excitability  of  the  neuro-muscular  apparatus,  carry  off 
the  victory,  and  the  glottis  is  opened  (Russell). 

When  the  nerve  is  cooled  the  abductors  give  way  before  the 
adductoi  ;.  The  same  is  true  when  it  is  allowed  to  become  dry. 
And  after  death  in  a  cholera  patient  it  was  observed  that  the  pos- 
terior crico-arytenoid,  an  abductor  muscle,  was  the  first  of  the 
intrinsic  larjmgeal  muscles  to  lose  its  excitability.  Lesions  of  the 
medulla  oblongata  are  often  accompanied  by  marked  changes  in 
the  character  of  the  voice  and  the  power  of  articulation. 

Section  or  paralysis  of  the  superior  laryngeal  nerve  causes  the 
voice  to  become  hoarse,  and  renders  the  sounding  of  high  notes  an 
'■mpossibility,  oN^ing  to  the  want  of  power  to  make  the  vocal  cords 
tense.    Stimulation  of  the  vagus  within  the  skull  causes  contraction 


SPEECH 


3x7 


of  the  crico-thyroid  muscle  and  increased  tension  of  the  cords.  Sec- 
tion or  paralysis  of  the  inferior  laryngeal  nerves  leads  to  loss  of  voice 
or  aphonia,  and  dyspnoea  (Fig.  149).  Both  adductor  and  abductor 
muscles  are  paralyzed ;  the  vocal  cords  assume  their  mean  position — 
the  position  they  have  in  the  dead  body — and  the  glottis  can  neither 
be  narrowed  to  allow  of  the  production  of  a  note,  nor  widened  during 
inspiration.  It  is  said,  however,  that  young  animals,  in  which  the 
structures  around  the  glottis  are  more  yielding  than  in  adults,  can 
still  utter  shrill  cries  after  section  of  the  inferior  laryngeals,  the 
contraction  of  the  crico-thyroid  muscle  alone  being  able,  while  in- 
creasing the  tension  of  the  cords,  to  draw  them  together. 

Interference  with  the  connections  on  one  side  between  the  higher 
cerebral  centres  and  the  medulla  oblongata,  as  by  rupture  of  an 
artery  and  effusion  of  blood  into  the  posterior  portion  of  the  internal 
capsule  (giving  rise  to  hemiplegia,  or  paralysis  of  the  orposite  side 
of  the  body),  is  not  followed  by  loss  of  voice;  the  laryngeal  muscles 
on  both  sides  are  still  able  to  act. 


CHAPTER    VI 
DIGESTION 

In  the  last  chapter  we  have  described  the  manner  in  which  the 
interchange  of  gases  between  the  tissues  and  the  air  is  carried  out. 
We  have  now  to  consider  the  digestion  and  absorption  of  the  soHd 
and  Hquid  food,  its  further  fate  in  relation  to  the  chemical  changes 
or  metabolism  of  the  tissues,  and  finally  the  excretion  of  the  waste 
products  by  other  channels  than  the  lung. 

Logically,  we  ought  to  take  metabolism  after  absorption  and 
before  excretion,  tracing  the  food  through  all  its  vicissitudes  from  the 
moment  when  it  enters  the  blood  or  lymph  till  it  is  cast  out  as  useless 
matter  by  the  various  excretory  organs.  Unfortunately,  however, 
many  of  the  intermediate  steps  of  the  process  are  as  j'^et  hidden  from 
us ;  we  know  best  the  beginning  and  the  end.  We  can  follow  the  food 
from  the  time  it  enters  the  alimentary  canal  till  it  is  taken  up  by  the 
tissues  of  absorption;  and  we  have  really  a  fair  knowledge  of  this 
part  of  its  course.  We  can  collect  the  end-products  as  they  escape 
in  the  urine,  or  in  the  breath,  or  in  the  sweat;  and  our  knowledge  of 
them  and  of  the  manner  in  which  they  are  excreted  is  considerable. 
But  of  the  wonderful  pathway  by  which  the  dead  molecules  of  the 
food  mount  up  into  life,  and  then  descend  again  into  death,  we 
catch  only  a  glimpse  here  and  there.  Only  the  introduction  and 
the  conclusion  of  the  story  of  metabolism  are  at  present  in  our 
possession  in  fairly  continuous  and  legible  form.  We  will  read  these 
before  we  try  to  decipher  the  handful  of  torn  leaves  which  represents 
the  rest. 

Section  I. — Preliminary  Anatomical  and  Chemical  Data. 

Comparative. — In  the  lowest  kinds  of  animals,  such  as  the  amoeba, 
there  is  neither  mouth,  nor  alimcntars'  canal,  nor  anus:  the  food, 
wrapped  round  by  pseudopodia,  is  taken  in  at  any  part  of  the  animal 
with  which  it  happens  to  come  in  contact.  A  vacuole  is  formed  around 
it.  Acid  is  secreted  into  the  vacuole,  the  food  is  digested  within  the 
cell-substance,  and  the  part  of  it  which  is  useless  for  nutrition  is  cast 
out  again  at  any  part  of  the  surface. 

Coming  a  little  higher,  we  find  in  the  Ccelenterates  a  mouth  and 
alimentary'  tube,  which  opens  into  the  body-cavity,  where  a  certain 

31S 


PliELlMINARV  AXATOMICAL  AND  CHEMICAL  DATA        jig 

amount  of  digestion  seems  to  take  place,  and  from  which  the  food  is 
absorbed  cither  through  the  cells  of  the  endodcnn,  or,  as  in  Medusa, 
by  means  of  fine  canals,  which  radiate  from  the  body-cavity  into  its 
walls,  and  form  part  of  the  so-called  gastro-vascular  system.  In  the 
Echinodcrniata  we  have  a  further  development,  a  complete  alimentary 
canal  with  mouth  and  anus,  and  entirely  shut  off  from  the  body-cavity. 
In  many  Arthropods  it  is  possible  already  to  distinguish  parts  corre- 
sponding to  the  stoma<h,  and  the  small  and  large  intestines  of  higher 
forms,  the  digestive  glands  being  represented  by  organs  which  in  some 
groups  seem  to  be  homologous  with  the  liver,  and  in  others  with  the 
salivary  glands  of  the  higher  Vertebrates.  A  few  Molluscs  seem  in 
addition  to  possess  a  pancreas. 

Among  V'ertcbrates  fishes  have  the  simplest,  and  birds  and  mammals 
the  most  complicated,  alimentary  system.  In  the  lowest  fishes  the 
stomach  is  only  indicated  by  a  slight  widening  of  the  anterior  part  of 
the  digestive  tube.  In  water-living  Vertebrates  there  are  no  sa.livar^ 
glands.  In  birds  the  oesophagus  is  generally  dilated  to  form  a  crop, 
from  which  the  food  passes  into  a  stomach  consisting  of  two  parts, 
one  pre-eminently  glandular  (proventriculus),  the  other  pre-eminently 
muscular  (ventriculus).  Among  mammals  a  twofold  division  of  the 
stomach  is  distinctly  indicated  in  rodents  and  cetaceae.  but  this  organ 
reaches  its  greatest  complexity  m  ruminants,  which  possess  no  fewer 
than  four  gastric  pouches.  The  differentiation  of  the  intestine  into 
small  and  large  intestine  and  rectiun  is  more  distinct,  both  anatomically 
and  functionally,  in  mammals  than  in  lower  forms ;  but  there  are  marked 
dift'crences  between  the  various  mammalian  groups  both  in  the  relative 
size  of  the  several  parts  of  the  digestive  tube,  and  in  the  proportion 
between  the  total  length  of  the  alimentar\-  canal  and  the  length  of  the 
bodv.  In  general,  the  canal  is  longest  in  hcrbivora,  shortest  in  carni- 
vora.  Thus,  the  ratio  between  length  of  body  and  length  of  intestine 
is  in  the  cat  i  :  4,  dog  i  :  6,  man  i  :  5  or  6,  horse  1:12,  cow  i  :  20,  sheep 
I  :  27.  The  relative  capacity  of  the  stomach,  small  intestine,  and  large 
intestine,  is  in  the  dog  6  :"2  :  1-5,  in  the  horse  i  :  3'5  :  7,  in  the  cow 
7:2:1.  The  area  of  the  mucous  surface  of  the  alimentary  canal  is 
very  considerable,  in  the  dog  more  than  half  that  of  the  skin,  the 
surface  of  the  small  intestine  being  three  times  that  of  the  stomach 
and  four  times  that  of  the  large  intestine.  In  the  horse  the  mucous 
surface  has  twice  the  area  of  the  skin. 

Anatomy  of  the  Alimentary  Canal  in  Man. — The  alimentary  canal 
is  a  muscular  tube,  which,  beginning  at  the  mouth,  runs  under  the 
various  names  of  pharynx,  oesophagus,  stomach,  small  intestine,  large 
intestine,  and  rectum, "till  it  ends  at  the  anus.  Its  walls  are  largely 
composed  of  muscular  fibres;  its  lumen  is  clad  with  epithelium,  and 
into  it  open  the  ducts  of  glands,  which,  morphologically  speaking,  are 
involutions  or  diverticula  formed  in  its  course.  In  virtue  of  its  muscular 
fibres  it  is  a  contractile  tube;  in  virtue  ot  its  epithelial  lining  and  its 
special  glands  it  is  a  secreting  tube ;  in  virtue  of  both  it  is  fitted  to  per- 
form those  mechanical  and  chemical  actions  upon  the  food  which 
are  necessary  for  digestion.  Its  inner  surface  is  in  most  parts  richly 
supplied  with  bloodvessels,  and  in  special  regions  beset  with  peculiarlj'- 
arranged  lymphatics;  by  both  of  these  channels  the  alimentary  tube 
performs  its  function  of  absorption.  From  the  beginning  of  the  oeso- 
phagus to  the  end  of  the  rectum  the  muscular  wall  consists,  broadly 
speaking,  of  an  outer  coat  of  longitudinally-arranged  fibres,  and  a 
thicker  inner  coat  of  fibres  running  circularly  or  transversely  around 
the  tube.  Between  the  layers  lies  a  plexus  of  non-medullated  nerves 
and  nerve-cells  (Auerbach's  plexus).     In  the  stomach  the  longitudinal 


32«  DIGESTION 

fibres  arc  found  only  on  the  two  curvatures,  and  a  third  incomplete 
coat  of  obUque  fibres  makes  its  appearance  internal  to  the  circular 
layer.  In  the  large  intestine,  again,  the  longitudinal  fibres  are  chiefly 
collected  into  three  isolated  strands.  In  the  pharynx  the  typical 
arrangement  is  departed  from,  inasmuch  as  there  is  no  regular  longi- 
tudinal layer;  but  the  three  con.strictor  muscles  represent  to  a  certain 
extent  the  great  circular  coat.  The  muscles  of  the  mouth  and  of  the 
pharynx  are  of  the  striped  variety.  So  is  the  muscle  of  the  upper  half 
of  the  oesophagus  in  man  and  the  cat,  and  of  the  whole  oesophagus 
in  the  dog  and  the  rabbit.  In  the  rest  of  the  alimentary  canal  the 
muscle  is  smooth,  except  at  the  very  end,  where  the  external  sphincter 
of  the  anus  is  striped.  In  certain  situations  the  circular  coat  is  de- 
veloped into  a  regular  anatomical  sphincter,  a  definite  muscular  ring, 
whose  function  it  is  to  shut  one  part  of  the  tube  off  from  another 
(sphincter  pylori,  ileo-colic  sphincter),  or  to  help  to  close  the  external 
opening  of  the  tube  (internal  sphincter  of  anus).  Elsewhere  a  tonic 
contraction  of  a  portion  of  the  ciicular  coat,  not  anatomically  de- 
veloped bevond  the  rest,  creates  a  functional  sphincter  (cardiac  sphincter 
of  stomach). 

Throughout  the  greater  part  of  the  digestive  tract  the  peritoneum 
forms  a  thin  serous  layer,  external  to  the  muscular  coat.  Internally 
the  muscular  coat  is  separated  from  the  mucous  membrane,  the  lining 
of  the  canal,  by  some  loose  areolar  tissue  containing  bloodvessels, 
lymphatics,  and  nerves  (]\Ieissner's  plexus),  and  called  the  submucous 
coat.  Between  the  mucous  and  submucous  layers,  but  belonging  to 
the  former,  in  the  whole  canal  below  the  beginning  of  the  oesophagus, 
is  a  thin  coat  of  smooth  muscular  fibres,  the  muscularis  mucosae,  con- 
sisting in  some  parts,  e.g.,  in  the  stomach,  of  two.  or  even  three, 
layers.  Between  this  and  the  lumen  of  the  canal  lie  the  ducts  and 
alveoli  of  glands,  surrounded  by  bloodvessels  and  embedded  in  adenoid 
or  Ivraphoid  tissue,  which  in  particular  regions  is  collected  into  well- 
defined  masses  (solitary  follicles.  Peycr's  patches,  tonsils),  extending, 
it  may  be,  into  the  submucous  tissue.  In  the  mouth,  pharynx,  and 
oesophagus,  the  glands  lie  in  the  submucosa.  as  do  the  glands  of  Brunner 
in  the  duodenum;  evcr^-where  else  they  are  confined  to  the  mucous 
membrane  proper.  Between  the  openings  of  the  glands  the  mucous 
membrane  is  lined  with  a  single  layer  of  columnar  epithelial  cells,  some- 
times (in  the  small  intestine)  arranged  along  the  sides  of  tiny  projec- 
tions or  \'illi.  When  the  intestine  is  contracted  the  villi  are  long  and 
cylindrical  in  shape,  when  it  is  relaxed  or  distended  they  are  flat  and 
conical.  At  the  ends  of  the  alimentary  canal,  viz.,  in  the  mouth, 
pharynx,  and  oesophagus,  and  at  the  anus,  the  epithelium  is  stratified 
squamous,  and  not  colunmar. 

The  purpose  of  food  is  to  supply  the  waste  of  the  tissues,  to 
replenish  the  stores  of  material  from  the  oxidation  of  which  the 
energy  required  for  the  running  of  the  bodily  machine  is  derived, 
and  thus  to  maintain  the  normal  composition  of  the  body.  In  the 
body  we  find  a  multitude  of  substances  marked  oft  from  each  other, 
some  by  the  sharpest  chemical  differences,  others  by  characters 
much  less  distinct,  but  falling  upon  the  whole  into  the  few  fairly 
definite  groups  already  described  (p.  i). 

Now,  although  it  is  by  no  means  necessary  that  a  substance  in 
the  body  belonging  to  one  of  these  great  groups  should  be  derived 
from  a  substance  of  the  same  group  in  the  food,  it  has  been  found 


PRELIMISARY  AXAIOMICAL  AND  CHIIMICAI.  DATA  321 

that  upon  the  whoU-  no  diet  is  sufticient  for  man  unless  it  contains 
representatives  of  all;  a  proper  diet  must  include  proteins,  carbo- 
hydrates, fats,  inorganic  salts,  and  water.  These  proximate  prin- 
ciples have  to  be  obtained  from  the  raw  material  of  the  foodstuffs — 
that  is,  as  regards  the  first  three  groups,  which  can  alone  yield 
energy  in  the  body,  from  the  tissues  and  juices  of  other  living  things, 
plants  or  animals;  it  is  the  business  of  digestion  to  sift  them  out  and 
to  prepare  them  for  absorption.  This  preparation  is  partly  mechan- 
ical, partly  chemical. 

The  water  and  salts  and  some  carbo-hydrates,  such  as  dextrose, 
are  ready  for  absorption  without  change.  Fats  are  split  into 
glycerin  and  fatty  acids  before  absorption.  Indiffusible  colloidal 
carbo-hydrates,  like  starch  and  dextrin,  are  changed  into  diffusible 
and  readily  soluble  sugars,  and  the  natural  proteins  into  diffusible 
peptones,  and  eventually  into  much  simpler  decomposition  products. 
These  changes  are  obviously  favourable  to  absorption.  But  this  is 
not  their  whole  significance.  For  disaccharides,  such  as  cane-sugar, 
maltose,  or  lactose,  although  easily  soluble  in  the  contents  of  the 
gut,  and  in  themselves  perfectly  capable  of  being  absorbed  without 
change,  are,  unless  present  in  unusually  large  amount,  all  converted 
into  monosaccharides,  such  as  dextrose,  levulose,  or  galactose,  either 
in  the  lumen  or  in  the  wall  of  the  alimentary  tube.  The  reason  is 
that  the  disaccharides  are  unsuitable  as  pabulum  for  the  cells. 
Digestion  is  not  only  a  preparation  of  the  food  for  absorption  by 
the  gut,  but  for  assimilation  by  the  tissues  after  absorption.  An 
equally  important  instance  of  this  double  function  is  seen  in  the 
digestion  of  proteins.  The  complete  shattering  of  the  protein  mole- 
cule into  amino-acids  and  the  other  groups  jaelded  by  its  decom- 
position (p.  360)  is  required,  in  the  case  of  that  portion  of  the  protein 
which  goes  to  build  up  the  tissues,  because  of  the  high  degree  of 
specificity  of  the  tissue  proteins.  The  myosinogen  of  beef  cannot 
be  cobbled  into  the  myosinogen  of  human  muscle,  still  less  we  may 
suppose  into  the  serum-albumin  of  human  blood.  It  is  necessary 
that  the  food  protein  should  be  completely  '  wrecked  '  in  digestion 
so  that  protein  which  is  to  take  its  place  in  protoplasm  may  be  built 
exactly  to  order  from  the  bricks.  A  satisfactory  '  fit  '  cannot  be 
obtained  with  ready-made  protein.  Mechanical  division  of  the  food 
is  an  important  aid  to  the  chemical  action  of  the  digestive  juices.  We 
shall  see  that  this  mechanical  division  forms  a  great  part  of  the  work 
of  the  stomach,  but  it  is  normally  begun  in  the  mouth,  and  it  is  of 
consequence  that  this  preliminary  stage  should  be  properly  performed. 

Section  II. — The  Mechanical  Phenomena  of  Digestion. 

Mastication. — It  is  among  the  mammaha  that  regular  masrication 
of  the  food  first  makes  its  appearance  as  an  important  aid  to  diges- 
tion.    The  amphibian  bolts  its  fly,  the  bird  its  grain,  and  the  fish 


322  DIGESTION 

its  brother,  without  the  ceremony  of  chewing.  In  ruminating 
mammals  we  see  mastication  carried  to  its  highest  point ;  the  teeth 
work  all  day  long,  and  most  of  them  are  specially  adapted  for 
grinding  the  food.  The  carnivora  spend  but  a  short  time  in  masti- 
cation; their  teeth  are  in  general  adapted  rather  for  tearing  and 
cutting  than  for  grinding.  Where  the  diet  is  partly  animal  and 
partly  vegetable,  as  in  man,  the  teeth  are  fitted  for  all  kinds  of  work ; 
and  the  process  of  mastication  is  in  general  neither  so  long  as  in  the 
purely  vegetable  feeders,  nor  so  short  as  in  the  carnivora. 

In  man  there  are  two  sets  of  teeth :  the  temporary  or  milk  teeth, 
and  the  permanent  teeth.  The  milk  teeth  are  twenty  in  number, 
and  consist  on  each  side  of  four  incisors  or  cutting-teeth,  two 
canines  or  tearing-teeth,  and  four  molars  or  grinding-teeth.  The 
central  incisors  emerge  at  the  seventh  month  from  birth,  the  other 
incisors  at  the  ninth  month,  the  canines  at  the  eighteenth,  and  the 
molars  at  the  twelfth  and  twenty-fourth  month  respectively. 
Each  tooth  in  the  lower  jaw  appears  a  little  before  the  corresponding 
one  in  the  upper  jaw.  Each  of  the  milk  teeth  is  in  course  of  time 
replaced  by  a  permanent  tooth,  and  in  addition  the  vacant  portion 
of  the  gums  behind  the  milk  set  is  now  filled  up  by  twelve  teeth, 
six  on  each  side,  three  above  and  three  below.  These  twelve  are 
the  permanent  molars;  they  raise  the  number  of  the  permanent 
teeth  to  thirty-two.  The  permanent  teeth  which  occupy  the 
position  of  the  milk  molars  now  receive  the  name  of  premolars. 
The  first  tooth  of  the  permanent  set  (the  first  true  molar)  appears 
at  the  age  of  6|  years;  the  last  molar,  or  wisdom-tooth,  does  not 
emerge  till  the  seventeenth  to  the  twenty-fifth  year. 

In  mastication  the  lower  jaw  is  moved  up  and  down,  so  as  to 
alternately  separate  and  approximate  the  two  rows  of  teeth.  It  has 
also  a  certain  amount  of  movement  from  side  to  side,  and  from  front 
to  back.  The  masseter,  temporal  and  internal  pterygoid  muscles 
raise,  and  the  digastric,  with  the  assistance  of  the  mylo-  and  genio- 
hyoid, depresses,  the  lower  jaw,  but  its  downward  movement  is 
rnainly  a  passive  one.  The  external  pterygoids  pull  it  forward 
when  both  contract,  forward  and  to  one  side  when  only  one  con- 
tracts. The  lower  fibres  of  the  temporal  muscle  retract  the  jaw. 
The  buccinator  and  orbicularis  oris  muscles  prevent  the  food  from 
passing  between  the  teeth  and  the  cheeks  and  lips.  The  tongue 
keeps  the  food  in  motion,  works  it  up  with  the  saliva,  and  finally 
gathers  it  into  a  bolus  ready  for  deglutition. 

Deglutition. — This  act  consists  of  a  voluntary  and  an  involun- 
tary stage.  Just  before  the  beginning  of  the  voluntary  stage 
mastication  is  suspended,  and  a  slight  contraction  of  the  dia- 
phragm generally  takes  place.  The  anterior  part  of  the  tongue 
is  suddenly  elevated  and  pressed  against  the  hard  palate,  and  the 
elevation  travels  back  from  the  tip  towards  the  root,  as  the  mylo- 


THE  MECHANICAL  PHENOMENA   Of  DIGESTION  323 

hyoid  muscles  in  the  floor  of  the  mouth  contract  sharply  so  as  to 
thrust  the  bolus  through  the  isthmus  of  the  fauces.  As  soon  as  this 
has  happened,  and  the  food  has  reached  the  posterior  portion  of  the 
tongui',  it  has  passed  beyond  the  control  of  the  will,  and  the  second 
or  involuntary  stage  of  the  process  begins. 

This  stage  may  be  divided  into  two  parts:  (i)  Pharyngeal, 
(2)  oesophageal — both  being  reflex  acts.  During  the  first  the  food 
has  to  pass  through  the  pharjmx,  the  upper  portion  of  which  forms 
a  part  of  the  respiratory  tract,  and  is  in  free  communication  with 
the  laryn.x  during  ordinary  breathing.  It  is  therefore  necessary 
that  respiration  should  be  interrupted  and  the  larynx  closed  while 
the  food  is  being  moved  through  the  pharynx.  But  that  the  inter- 
ruption may  be  short,  the  food  must  be  rapidly  passed  over  this 
perilous  portion  of  its  descent.  The  main  propelling  force  under 
which  the  bolus  is  shot  through  the  back  of  the  pharynx  is  derived 
from  the  contraction  of  the  mylo-hyoid  muscles  already  mentioned, 
assisted  to  some  extent  by  the  stylo-  and  palato-glossi ;  and  that 
none  of  the  purchase  may  be  lost,  the  pharyngeal  cavity  is  cut  off 
from  the  nose  and  mouth  as  soon  as  the  bolus  has  entered  it.  The 
soft  palate  is  raised  by  the  levator  palati  and  palato-pharyngei 
muscles;  at  the  same  time  the  upper  part  of  the  phar^mx,  narrowed 
by  the  contraction  of  the  superior  constrictor,  comes  forward  to 
meet  the  soft  palate,  closes  in  upon  it,  and  so  prevents  the  food 
from  passing  into  the  nasal  cavities.  The  pharynx  is  cut  off  from 
the  mouth  by  the  closure  of  the  fauces  through  the  contraction  of 
the  palato-pharjmgeal  muscles  which  lie  in  their  posterior  pillars. 
The  upper  free  end  of  the  epiglottis  (the  so-called  pharyngeal  part) 
aids  the  back  of  the  tongue  in  completing  a  movable  partition  across 
the  phar^Tix,  which  keeps  close  to  the  bolus  as  it  passes  down 
between  the  posterior  surface  of  the  epiglottis  and  the  posterior 
wall  of  the  pharynx.  Almost  immediately  after  the  contraction 
of  the  mylo-hyoids  the  larynx  is  pulled  upwards  and  forwards  by 
the  contraction  of  the  thyro-hyoid  muscle,  and  the  elevation  of  the 
hyoid  bone  by  the  muscles  which  connect  it  to  the  lower  jaw. 
The  base  of  the  tongue  is  simultaneously  drawn  backwards  by  the 
stylo-  and  palato-glossus.  The  lower  or  laryngeal  portion  of  the 
epiglottis  is  thus  caused  to  come  into  contact  with  the  upper  orifice 
of  the  larynx,  occluding  it  completely,  but  the  pharyngeal  portion 
projects  beyond  the  larynx,  and  takes  no  share  in  its  closure 
(Eykman).  The  glottis  is  closed  by  the  approximation  of  the  vocal 
cords  and  the  arytenoid  cartilages.  The  epiglottis,  however,  is  not 
absolutely  indispensable  for  closing  the  lar^Tix,  since  swallo\ving 
proceeds  in  the  ordinary  way  when  it  is  absent.  The  morsel  of 
food,  grasped  by  the  middle  and  lower  constrictors  as  it  leaves  the 
back  of  the  tongue,  passes  rapidly  and  safeh^  over  the  closed  lar5-nx, 
the  process  being  accelerated  by  the  pulling  up  of  the  lower  portion 


324  DIGESTION  I 

of  the  pharynx  over  the  bolus  by  the  action  of  the  palato-  and  stylo- 
pharyngei. 

The  second  or  oesophageal  portion  of  the  involuntary  stage  is 
a  more  leisurely  performance.  The  bolus  is  carried  along  by  a 
peculiar  '  peristaltic  '  contraction  of  the  muscular  wall  of  the 
oesophagus,  which  travels  down  as  a  wave,  constricting  the  tube 
and  pushing  the  food  before  it.  In  front  of  the  constricting  wave 
moves  a  wave  of  inhibition,  so  that  the  part  of  the  oesophagus  into 
which  the  bolus  is  about  to  pass  is  always  relaxed,  while  the  part 
behind  it  is  contracted.  This  exact  co-ordination  of  inhibition 
and  contraction  is  the  essential  thing  in  peristalsis.  When  the  food 
reaches  the  lower  end  of  the  gullet  the  tonic  contraction  of  that  part 
of  the  tube  is  for  a  moment  relaxed  by  reflex  inhibition,  and  the 
morsel  passes  into  the  stomach.  Beaumont  saw,  in  the  case  of 
St.  Martin,  that  the  oesophageal  orifice  of  the  stomach  contracted 
firmly  after  each  morsel  was  swallowed,  and  so  did  the  gastric  walls 
in  the  neighbourhood  of  the  fistula  when  food  was  introduced  b}^ 
this  opening.  In  the  dog  the  whole  process  of  swallowing  from 
mouth  to  stomach  has  been  shown  to  occupy  four  to  five  seconds, 
but  the  time  is  by  no  means  constant.  In  man  the  peristaltic  wave 
requires  about  five  to  six  seconds  to  travel  from  the  level  of  the 
glottis  to  the  cardiac  orifice.  The  rate  of  movement  is  greater  in  the 
upper  than  in  the  lower  portion  of  the  oesophagus. 

Such  is  the  mechanism  of  deglutition  when  the  bolus  is  of  such 
consistence  and  size  that  it  actually  distends  the  oesophagus.  But 
it  has  been  shown  that  hquid  food  is  swallowed  in  a  different  way. 
The  food  lying  on  the  dorsum  of  the  tongue,  suddenly  put  under 
pressure  by  the  sharp  contraction  of  the  mylo-hyoid  muscles,  is 
shot  rapidly  down  to  the  lower  part  of  the  lax  oesophagus,  or,  occa- 
sionally, some  of  it  even  into  the  stomach.  So  far  the  process  has 
only  occupied  one-tenth  of  a  second.  After  several  seconds,  the 
food,  or  the  portion  which  still  remains  in  the  oesophagus,  is  forced 
through  the  cardiac  sphincter  into  the  stomach  by  the  arrival  of 
the  tardy  peristaltic  contraction  of  the  oesophageal  wall  (Kronecker 
and  Meltzer).  Two  sounds  may  be  heard  in  man  on  listening  in 
the  region  of  the  stomach  or  oesophagus  during  deglutition  of  hquids, 
especially  when,  as  generally  happens,  they  are  mixed  with  air. 
The  first  sound  occurs  at  once,  and  is  due  to  the  sudden  squirt  of 
the  liquid  along  the  gullet ;  the  second,  which  is  heard  after  a  distinct 
interval  (about  six  seconds),  is  caused  by  the  forcing  of  the  fluid 
through  the  cardiac  orifice  of  the  stomach  by  the  contraction  of  the 
oesophagus. 

There  are  certain  peculiarities  which  distinguish  this  peristaltic 
movement  of  the  oesophagus  from  that  of  other  parts  of  the  alimen- 
tary canal.  It  is  far  more  closely  related  to  the  central  nervous 
system,  and,  unlike  the  peristaltic  contraction  of  the  intestine,  can 


THE  MECHANICAL  PHENOMENA  OF  DIGESTION  325 

pass  over  any  muscular  block  caused  by  ligature,  section,  or  crush- 
ing, so  long  as  the  nervous  connections  are  intact.  But  division 
of  the  oesophageal  nerves  causes,  as  a  rule,  stoppage  of  oesophageal 
movements;  although  an  excised  portion  of  the  tube  retains  its 
vitahty  for  a  long  time,  and  may,  under  certain  circumstances,  go 
on  contracting  in  the  characteristic  way  after  removal  from  the  body 
(p.  81/).  Stimulation  of  the  mucous  membrane  of  the  phar^-Tix  will 
cause  reflex  movements  of  the  oesophagus,  while  stimulation  of  its 
own  mucous  membrane  is  ineffective.  From  these  facts  we  learn 
that  although  the  oesophageal  wall  may  possess  a  feeble  power  of 
spontaneous  peristaltic  contraction,  yet  this  is  usually  in  abeyance, 
or  at  least  overmastered  by  central  nervous  control ;  so  that  impulses 
discharged  as  a  '  fusillade  '  from  successive  portions  of  the  vagus 
centre,  and  travelling  down  the  oesophageal  nerves,  excite  the 
muscular  fibres  in  regular  order  from  the  upper  to  the  lower  end 
of  the  tube. 

Nervous  Mechanism  of  Deglutition.— The  centre  for  the  whole 
involuntary  stage  (both  pharyngeal  and  oesophageal)  lies  in  the 
upper  part  of  the  medulla  oblongata.  When  the  brain  is  sliced 
away  above  the  medulla,  deglutition  is  not  affected;  but  if  the  upper 
part  of  the  medulla  is  removed,  the  power  of  swallowing  is  abolished. 
In  man,  disease  of  the  spinal  bulb  interferes  far  more  with  deglutition 
than  disease  of  the  brain  proper. 

Normally,  the  afferent  impulses  to  the  centre  are  set  up  by  the 
contact  of  food  or  saH  va  with  the  mucous  membrane  of  the  posterior 
part  of  the  tongue,  the  soft  palate  and  the  fauces,  the  nerve- 
channels  being  the  superior  laryngeal,  the  pharyngeal  branches  of 
the  vagus,  and  the  palatal  branches  of  the  fifth  nerve.*  A  feather 
has  sometimes  been  swallowed  involuntarily  by  a  reflex  movement 
of  deglutition  set  up  while  the  soft  palate  or  pharynx  was  being 
tickled  to  produce  vomiting.  Artificial  stimulation  of  the  central 
end  of  the  superior  laryngeal  will  cause  the  movements  of  deglutition 
independently  of  the  presence  of  food  or  liquid;  but  if  the  central 
end  of  the  glosso- pharyngeal  nerve  be  stimulated  at  the  same  time, 
the  movements  do  not  occur.  The  glosso-pharyngeal  is  therefore 
able  to  inhibit  tlie  deglutition  centre,  and  it  is  owing  to  the  action 
of  this  nerve  that  in  a  series  of  efforts  at  swallowing,  repeated  within 
less  than  a  certain  short  interval  (about  a  second),  only  the  last  is 
successful.  It  is  also  through  the  glosso-pharyngeal  nerve  that 
the  respiratory  movements  are  inhibited  during  deglutition.  When 
the  central  end  of  this  nerve  is  stimulated,  respiration  is  stopped 

*  It  appears  that  the  most  influential  reflex  paths  may  differ  in  different 
animals.  In  the  rabbit,  e.g.,  the  reflex  is  set  up  by  excitation  of  the  ti-igeminal 
fibres  which  suppl}^  the  mucous  membrane  anterior  to  the  tonsils,  in  the  dog 
and  cat  by  excitation  of  the  glosso-pharyngeal  fibres  in  the  posterior  wall  of 
the  pharynx,  and  in  monkeys  by  excitation  of  the  trigeminal  branches  dis- 
tributed to  the  mucous  membrane  over  the  tonsils  (Kahn). 


326  DIGESTION 

for  four  or  five  seconds,  and  this  cessation  is  distinguished  from 
that  produced  by  any  other  afferent  nerve  by  the  circumstance 
that  it  occurs  not  in  expiration  exclusively  or  in  inspiration  ex- 
clusively, but  with  the  respiratory  muscles  in  the  precise  degree  of 
contraction  in  which  they  happened  to  be  at  the  moment  of  stimu- 
lation. The  efferent  nerves  of  the  reflex  act  of  deglutition  are  the 
hypoglossal  to  the  tongue  and  the  thyro-hyoid  and  other  muscles 
concerned  in  raising  the  larynx;  the  glosso-pharyngeal,  vagus, 
facial  and  fifth  to  the  muscles  of  the  palate,  fauces,  and  pharynx ; 
the  fifth  to  the  mylo-hyoid;  and  the  vagus  to  the  larynx  and 
oesophagus.  Section  of  the  vagus  interferes  with  the  passage  of 
food  along  the  oesophagus;  stimulation  of  its  peripheral  end  causes 
oesophageal  movements. 

Movements  of  the  Stomach. — The  whole  of  the  stomach  does 
not  take  part  equally  in  the  movements  associated  with  digestion. 
We  may  divide  the  organ,  both  anatomically  and  functionally,  into 
two  portions — a  pyloric  portion,  or  antrum  pylori,  comprising  about 
a  fifth  of  the  stomach,  and  a  larger  cardiac  portion,  or  fundus* 
At  the  junction  of  the  antrum  and  the  fundus  the  circular  muscular 
coat  is  slightly  thickened  into  a  ring  called  the  '  transverse  band,' 
or  '  sphincter  of  the  antrum.'  In  the  living  stomach  the  region 
of  the  transverse  band  is  usually  contracted  so  strongly  and  con- 
tinuously that  a  distinct  groove  is  seen  to  separate  the  tubular 
antrum  from  the  bag-like  cardiac  end.  The  suggestion  of  a  massive 
constricting  ring  of  muscle  is  belied  by  an  examination  of  the  dead 
viscus.  The  transverse  band  is  really  little  more  than  a  physio- 
logical sphincter.  The  empty  stomach  is  contracted  and  at  rest. 
A  few  minutes  after  food  is  taken  contractions  begin  in  the  antrum, 
and  run  on  in  constricting  undulations  (in  the  cat  at  the  rate  of 
six  in  the  minute)  towards  the  pj^loric  sphincter.  Each  wave  takes 
about  twenty  seconds  (in  the  cat)  to  pass  from  the  middle  of  the 
stomach  to  the  pylorus.  Feeble  at  first,  they  become  stronger  and 
stronger  as  digestion  proceeds,  and  gradually  come  to  involve  the 
portion  of  the  fundus  next  the  sphincter  of  the  antrum,  but  their 
direction  is  always  towards  the  pylorus,  never,  in  normal  diges- 
tion, away  from  it.  The  food  is  thus  subjected  to  energetic  churn- 
ing movements  in  the  pyloric  end  of  the  stomach,  and  worked  up 
thoroughly  with  the  gastric  juice.  Kept  in  constant  circulation, 
it  gradually  becomes  reduced  to  a  semi-liquid  mass,  the  chyme, 
which  is  at  intervals  driven  against  the  pylorus  by  strong  and 
regular  peristaltic  contractions  of  the  lower  end  of  the  stomach, 

*  Here  '  fundus  '  is  used  in  the  sense  in  which  it  is  generally  employed  in 
speaking  of  the  stomach  of  the  dog  Oi  cat  as  signifying  the  wnolc  of  the  organ 
with  the  exception  of  the  antrum  pyiori.  By  the  fundus  of  the  human  stomach 
most  writers  mean  only  the  cul-'ie-sac  at  the  cardiac  end;  the  portion  inter- 
vening between  it  and  the  n.icrum  pylori  is  often  term.^i  the  body  of  the 
ttomach. 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION 


327 


II  A.M. 


the  sphincter  relaxing  from  time  to  time  by  a  reflex  inhibition  to 
admit  the  better-digested  portions  into  the  duodenum,  but  tighten- 
ing more  stubbornly  at  the  impact  of  a  hard  and  undigested  morsel. 
The  nature,  as  well  as  the  consistence  of  the  food,  influences  the 
length  of  its  sojourn  in  the  stomach.  Carbo-hydrate  food  passes 
more  rapidly  through  the  pylorus  than  fatty  food,  and  fat  more 
rapidly  than  protein.  The  reason  is  that 
the  acidity  of  the  gastric  juice  varies 
with  the  different  kinds  of  food,  hydro- 
chloric acid  being  secreted  in  abundance 
in  the  presence  of  proteins,  and  to  a 
much  smaller  extent  in  the  presence  of 
fats  and  carbo-hydrates.  Now,  dilute 
hydrochloric  acid  when  introduced  into 
the  stomach  remains  there  for  a  much 
longer  time  than  water.  This  depends 
upon  the  fact  that  such  portions  of  the 
acid  as  get  into  the  duodenum  stimulate 
afferent  fibres  in  its  mucous  membrane, 
and  so  cause  reflex  spasm  of  the  pyloric 
sphincter.  When  the  acid  chyme  be- 
comes neutralized  to  a  certain  point  by 
the  bile  and  pancreatic  juice,  inhibitory 
impulses  pass  up  from  the  duodenum 
and  cause  the  sphincter  to  relax.  The 
cardiac  division  of  the  stomach,  with 
the  exception  of  the  portion  that  borders 
the  transverse  band,  takes  no  share  in 
the  peristaltic  movements.  And,  indeed, 
it  is  far  more  difficult  to  cause  such  con- 
tractions by  artificial  stimulation  in  the 
fundus*  than  in  the  pyloriis.  The  two 
portions  of  the  stomach  are  partially,  or 
in  certain  animals  from  time  to  time 
completely,  cut  off  from  each  other  by 
the  contraction  of  the  sphincter  of  the 
antrum.  The  fundus,  so  far  as  its 
mechanical  functions  are  concerned,  acts 
chiefly  as  a  reservoir  for  the  food,  which, 
like  a  hopper,  it  gradually  passes  into 
the  pyloric  mill  as  digestion  goes  on  by  a  tonic  contraction  of  its 
walls.  The  existence  of  this  reservoir  enables  larger  quantities  of 
food  to  be  taken  at  one  meal,  which  can  then  be  digested  gradually. 

*  The  common  idea,  however,  that  the  fundus  is  completely  inactive  is 
erroneous.  Rhythmical  variations  in  tone  with  a  period  of  i  to  3  minutes  have 
been  observed  during  digestion.  In  hunger  vigorous  peristaltic  contractions 
sweep  over  the  whole  stomach,  beginning  at  the  cardiac  end. 


Fig.  150. — Cat's  Stomach  seen 
by  Rontgen  Rays  (Cannon). 
The  outlines  of  the  stomach 
containing  food  mixed  with 
bismuth  subnitrate  were 
drawn  at  intervals  from 
II  a.m.  to  4.30  p.m. 


3^8 


DIGESTION 


These  farts  have  been  mainly  ascertained  by  observations  on 
animals,  such  as  the  dog  and  the  cat,  cither  by  direct  inspection 
after  opening  the  abdomen  (Rossbach),  or  in  tht:  intact  body,  under 
absolutely  physiological  conditions,  by  means  of  the  Kontgen  rays 
(Cannon).  In  the  latter  method  the  food  is  mixed  with  subnitrate 
of  bismuth,  which  is  opaque  to  these  rays,  so  that  when  the  animal 
is  looked  at  through  a  fluorescent  screen  the  stomach  appears  as  a 
dark  shadow  in  the  field  (Fig.  150).  This  method  has  even  been 
applied  with  success  to  the  study  of  the  passage  of  the  food  along 
the  human  alimentary  canal  from  deglutition  to  defaecation  (Hertz). 
It  has  been  shown  in  this  way  that  in  the  living  body  in  the  erect 
position  the  long  axis  of  the  stomach  is  much  more  nearly  vertical 
than  had  been  supposed.  When  food  is  taken  it  sinks  into  the 
lower  (pyloric)  end,  and  at  the  ui)per  end  gas  collects. 

When  the  j^erson  lies  down  the  lower  end  of  the  stomach  passes 
more  towards  the  left,  so  that  the  long  axis  lies  more  transversely. 
Other  methods  have  thrown  light  on  the  gastric  movements — e.g., 
direct  inspection  through  a  fistula  of  the  stomach,  and  the  study 


Fig.  131. — Human  Stomnch  studied  by  Rontgcii  Rays.  a.  Empty  stomach  iu  ver- 
tical  p jsitioii  ;  b.  shortly  after  a  meal  (peristaltic  contractions  are  occurring  at 
the  pyloric  end) ;  c,  full  stomacii  in  vertical  position.     (Halliburton  after  Hertz.) 

of  records  showing  the  changes  of  pressure  in  the  viscus  obtained 
by  means  of  small  balloons  introduced  into  it.  Such  balloons 
attached  to  a  rubber  tube  have  been  swallowed  by  normal  men 
and  kept  for  long  periods  in  the  stomach  (Carlson).  Even  in  the 
excised  stomach,  kept  in  salt  solution  at  the  body-temperature, 
the  typical  movements  can  be  observed  proceeding  for  some  time. 
Movements  of  the  Small  Intestine.— In  the  small  intestine  two 
kinds  of  movements  are  to  be  seen :  (1)  Gentle,  swaying, '  pendulum  ' 
movements,  sometimes  irregular,  but  often  recurring  rhythmically 
at  the  rate  (in  the  dog)  of  10  or  12  in  the  minute.  Both  the  longi- 
tudinal and  the  circular  muscular  coats  contract,  causing  slight 
waves  of  constriction,  which  may  originate  at  any  part  of  the  gut, 
but,  under  normal  circumstances,  nearly  always  travel  from  above 
downwards,  with  a  velocity  of  2  to  5  centimetres  per  s(>c(md.  These 
movements  cause  the  coils  of  the  intestine  to  sway  gently  from  side 


rinc  MiiciiASK  .11.  I'lii-xoMJis.i  f)i-  i)i(,i:sri()\'        -520 

to  side.  Under  abnormal  conditions,  as  in  the  exposed  '  sur\aving  ' 
intestines  of  the  rabbit,  contractions,  probably  sinular  to  the 
pendulum  movements,  but  running  indifferently  in  buth  direc- 
tions, can  be  set  up  by  local  stimulation.  The  function  of  these 
pendulum  movements  seems  to  be  the  thorough  mixing  of  the  food 
with  the  digestive  juices  in  the  intestine.  When  an  animal  is  fed 
with  food  containing  bismuth  subnitrate  and  observed  with  the 
Ront^en  rays,  it  is  seen  that  the  food  in  a  coil  is  often  divided  into 
small  segments,  which  then  join  together  to  form  longer  masses, 
these  being  in  turn  again  divided.  This  segmentation  is  rhyth- 
mically repeated  (in  the  cat  at  the  rate  of  thirty  times  a  minute). 
Although  of  itself  it  insures  only  the  mixing  of  the  contents  of  the 
gut,  and  not  their  onward  progress,  it  is  usually  accompanied  by 
peristalsis,  so  that  while  the  food  is  undergoing  segmentation  it  is 
also  slowly  passing  down  the  intestine.  Often,  however,  a  column 
of  food  remains  for  a  considerable  time,  dividing,  uniting,  and  divid- 
ing again,  without  sensibly  shifting  its  position.  In  addition  to  the 
relatively  rapid  pendulum  movements,  much  slower  periodic  varia- 
tions of  tone  of  the  whole  musculature  may  be  normally  observed. 

(2)  True  peristaltic  movements,  in  which  a  ring  of  constriction, 
obliterating  the  lumen,  moves  slowly  down  the  tube,  with  a  speed, 
it  may  be,  no  greater  than  i  mm.  per  second.  The  portion  of  the 
intestine  immediately  below  the  advancing  constriction  is  relaxed 
and  motionless,  so  that  we  may  say  that  a  wave  of  inhibition  pre- 
cedes the  wave  of  contraction.  The  peristaltic  movements  of  the 
small  intestine,  the  most  typical  of  their  kind,  are  most  easily 
excited  by  mechanical  stimulation  of  the  mucous  membrane,  as 
by  the  contact  of  a  morsel  of  food  or  an  artificial  bolus  of  cotton- 
wool. Travelling,  under  normal  conditions,  always  downwards, 
the  constriction  squeezes  the  contents  of  the  tube  before  it,  and  the 
wave  usually  ends  at  the  ileo-caecal  valve,  which  separates  the  small 
intestine  from  the  large.  The  cause  of  the  definite  direction  of  the 
peristaltic  wave  is  grounded  in  the  anatomical  relations  of  the 
intestinal  wall.  For  when  a  portion  of  the  intestine  is  resected, 
turned  round  in  its  place  and  sutured,  so  that  what  was  before  its 
upper  is  now  its  lower  end,  the  contraction  wave  is  unable  to  pass, 
and  the  obstruction  to  the  onward  flow  of  the  intestinal  contents 
causes  marked  dilatation  of  the  gut,  and  sometimes  serious  disturb- 
ance of  nutrition.  The  most  probable  explanation  is  that  the  peri- 
stalsis is  governed  by  a  local  reflex  nervous  mechanism  (Auerbach's 
plexus),  the  stimulation  of  which  by  the  contact  of  the  food  with 
the  mucous  membrane  or  by  the  distension  of  the  gut  causes 
excitation  of  the  circular  muscular  fibres  above  the  point  of  stimula- 
tion, and  inhibition  of  them  below  it.  The  automatic  pendulum 
movements,  and  also  the  slow,  rhythmical  variations  of  tone,  have 
a  different  relation  to  the  local  nervous  mechanism,  for  they  behave 
differently  to  poisons  like  cocaine  and  nicotine,  which  act  on  that 


330 


DJGF.STIOS^ 


mechanism.  The  pendnUim  movements  are,  ii  anytliing,  increased 
in  intensity  and  made  more  regular.  But  the  pe  ista'tic  waves, 
although  they  can  be  locally  excited  by  direct  stimulation  of  the 
muscular  fibres,  are  no  longer  propagated,  and  a  bolus  introduced 
into  the  intestine  remains  at  rest  where  it  is  placed.  Some  have 
interpreted  these  facts  as  indicating  that  the  pendulum  movements 
are  m5'ogenic  in  origin.  But  evidence  has  lately  been  obtained  that, 
although  they  are  not  reflex  movements  elicited  by  afferent  impulses 
from  the  mucous  membrane,  since  the}'  continue  in  unaltered  in- 
tensit}^  in  isolated  loops  of  intestine  immersed  in  Ringer's  (or 
Locke's)  solution  (p.  66)  after  removal  of  both  mucosa  and  sub- 
mucosa,  they  are  nevertheless  dependent  upon  Auerbach's  plexus. 
For  when  the  circular  muscular  coat  is  separated  from  this  plexus, 
^he  automatic  movements  of  this  coat  are  abolished,  although  the 

excitability  of  the  musculature  to 
direct  stimulation  is  not  affected. 
The  longitudinal  coat,  which  is 
still  in  connection  with  Auerbach's 
plexus,  goes  on  contracting  spon- 
taneously (Magnus).  Under  certain 
conditions  a  movement  of  food  or 
secretions  in  the  reverse  of  the 
normal  direction  can  be  set  up  in 
the  small  intestine  in  the  intact 
body — e.g.,  in  the  case  of  obstruc- 
tion of  the  intestine  leading  to 
vomiting  of  its  contents.  But  this 
does  not  necessarily  indicate  a  re- 
versal of  the  normal  direction  of 
the  peristalsis.  Such  a  reversal, 
if  it  occurs  at  all,  is  not  easy  to  realize  b}'  artificial  stimulation,  and 
even  when  an  antiperistaltic  wave  is  apparently  started,  it  travels 
up  the  intestine  onlj'  for  a  short  distance  and  then  dies  out.  A 
third  variety  of  intestinal  movement  has  sometimes  been  described, 
the  so-called  '  peristaltic  rush  '  (Meltzer,  etc.).  It  consists  of  a 
rapidly  moving  peristaltic  contraction,  preceded  by  relaxation  of 
a  long  portion  of  the  tube.  Such  a  contraction  may  even  sweep 
down  without  pause  from  the  duodenum  to  the  end  of  the  ileum. 

The  Movements  of  the  Large  Intestine  differ  from  those  of  the 
small  mainly  in  the  great  frequency  of  antiperistalsis.  This,  indeed, 
seems  to  be  the  usual  movement  of  the  transverse  and  ascending 
colon.  The  antiperistalsis  recurs  in  periods  about  every  fifteen 
minutes,  and  each  period  generally  lasts  about  five  minutes.  The 
constrictions,  running  towards  the  caecum,  thoroughly  churn  and 
mix  the  remnants  of  the  food,  a  considerable  absorption  of  which 
may  take  place  in  the  upper  part  of  the  large  intestine.  Regurgita- 
tion into  the  ileum  in  man  is  prevented  partly  by  the  oblique  entry 


Fig.  152. — Intestine  Segment  beating 
in  Ringer's  Solution.  At  6  the  oxy- 
gen stream  was  increased.  To  be 
read  from  left  to  right.  Time  trace, 
half -minutes.   ( Reduced  to  one  -half . ) 


THE  MECHANICAL  PHESuMESA   Ut   DIGESTION  331 

of  the  ileum  through  the  wall  of  the  colon  (so-called  ileo-caecal 
valve),  but  essentially  by  the  tonic  contraction  of  the  ileo-colic 
sphincter.  The  sphincter  usually  permits  the  passage  of  material 
only  in  the  direction  from  small  to  large  intestine.  But  as  an 
occasional  phenomenon,  a  reverse  movement  may  occur.  Thus 
food  may  actually  pass  back  through  the  ileo-colic  sphincter  into 
the  small  intestine  under  the  action  of  a  long-continued  and  vigorous 
antiperistalsis,  and  in  this  way  a  considerable  portion  of  a  bulky 
enema  may  be  eventually  disposed  of  (Cannon).  This  so-called 
antiperistalsis  is  not  precisely  the  same  kind  of  movement,  leaving 
out  of  account  its  direction,  as  the  peristalsis  already  described  in  the 
small  intestine,  since  it  is  not  preceded  by  a  wave  of  inhibition. 
True  peristaltic  contractions  preceded  by  relaxation  of  the  gut  may 
also  be  observed  to  start  in  the  caecum,  and  to  travel  down  the  large 
intestine.  They  are  not  very  frequent  in  comparison  with  those 
of  the  small  intestine,  and  they  die  away  before  reaching  the  end 
of  the  colon,  allowing  the  food  to  be  driven  back  again  towards 
the  caecum  by  the  antiperistalsis.  A  true  downward  peristalsis 
is  more  commonly  seen  in  the  descending  colon,  and  is  here  asso- 
ciated with  the  propulsion  and  collection  of  the  faces,  which  are 
mainly  stored  in  the  sigmoid  flexure.  These  peristaltic  contractions 
do  not  normally  reach  the  rectum,  which,  except  during  defaecation, 
remains  at  rest. 

Influence  of  the  Central  Nervous  System  on  the  Gastro- Intestinal 
Movements. — As  we  have  already  said,  these  movements  are  much 
less  closely  dependent  on  the  central  nervous  system  than  are  those 
of  the  oesophagus.  They  can  not  only  go  on,  but  are  in  general 
better  marked  when  the  extrinsic  nervous  connections  are  cut ;  they 
cannot  spread  when  the  continuity  of  the  tube  is  destroyed,  and 
the  mere  presence  of  food  will  excite  them  when  other  than  local 
reflex  action  has  been  excluded  by  section  of  the  nerves.  Never- 
theless, the  central  nervous  system  does  exercise  some  influence 
in  the  way  of  regulation  and  control,  if  not  in  the  way  of  direct 
initiation  of  the  movements,  and  the  swallowing  or  even  the  smell 
of  food  has  been  observed  to  strengthen  the  contractions  of  a  loop 
of  intestine  severed  from  the  rest,  but  with  its  nerves  still  intact. 
The  vagus  is  the  efferent  channel  of  this  reflex  action:  stimulation 
of  its  peripheral  end  may  cause  movements  of  all  parts  of  the 
alimentary  canal  from  oesophagus  to  large  intestine,  and  may 
strengthen  movements  already  going  on;  but  section  of  it  does  not 
stop  them,  nor  hinder  the  food  from  causing  peristalsis  wherever 
it  comes.  The  vagus  also  contains  inhibitory  fibres  for  the  lower 
end  of  the  oesophagus  and  the  whole  of  the  stomach.  Stimulation 
of  it  is  followed  first  by  inhibition,  and  then,  after  an  interval,  by 
an  increase  of  tone  and  augmentation  of  the  contraction  of  the 
whole  stomach,  including  the  cardiac  and  pyloric  sphincters.     The 


332  DIGESTION 

splanchnic  nerves  contain  fibres  by  which  the  intestinal  movf  nients 
can  be  inhibited,  and  they  appear  to  be  always  in  action,  for  after 
section  of  these  nerves  the  movements  are  strengthened.  On  the 
other  hand,  stimulation  of  the  peripheral  end  of  the  cut  splanchnic 
causes  arrest  of  the  movements.  Occasionally,  however,  it  has 
the  opposite  effect.  Contractions  of  the  small  intestine  are  more 
easily  caused  by  excitation  of  the  vagus  after  the  inhibitory  splanch- 
nic nerves  have  been  cut.  The  splanchnics  also  contain  inhibitor}' 
fibres  for  the  stomach,  and  it  is  only  when  these  are  intact  that 
complete  reflex  inhibition  of  the  organ  can  be  obtained  in  the  rabbit 
(Auer).  The  gastric  movements  are  not  permanently  affected  by 
section  of  these  nerves  alone,  or  even  by  simultaneous  section  of 
the  splanchnics  and  the  gastric  branches  of  the  vagi.  But  if  the 
vagi  are  cut  while  the  splanchnics  remain  intact,  the  peristalsis  of 
the  stomach  is  weakened,  its  onset  delayed,  and  the  proper  emptying 
of  the  viscus  through  the  pylorus  interfered  with.  In  all  probability 
these  results  are  due  to  the  uncontrolled  action  of  the  inhibitory 
libres.  The  splanchnics  have  a  special  relation  to  the  ileo-colic 
sphincter,  which  closes  when  they  are  stimulated,  and  becomes  in- 
sufficient when  they  are  cut.     The  vagus  does  not  affect  it. 

The  lower  part  of  the  large  intestine  is  influenced  by  the  sacral  nerves 
(second,  third,  and  fourth  sacral  in  the  ra,bbit),  and  by  certain  lumbar 
nerves,  in  the  same  way  as  the  higher  parts  of  the  alimentary  canal,  and 
particularly  the  small  intestine,  are  influenced  by  the  vagus  and  the 
splanchnics.  Stimulation  of  these  sacral  nerves  within  the  spinal 
canal,  or  of  the  pelvic  nerves  (nervi  erigentes)  into  which  they  pass, 
causes  contraction  of  the  parts  of  the  large  intestine  concerned  in 
defalcation — that  is,  in  the  dog,  of  the  whole  colon,  with  the  exception 
of  the  caecum;  in  the  cat,  of  the  distal  two-thirds  of  the  colon.  The 
colon  first  undergoes  rapid  shortening  due  to  the  contraction  of  the 
longitudinal  fibres  and  the  rccto-coccygcus  muscle.  After  a  few 
seconds  this  is  followed  by  contraction  of  the  circular  fibres,  beginning 
at  the  lower  limit  of  the  region  in  which  antiperistalsis  can  occur,  and 
spreading  downwards,  so  as  to  empty  the  portion  of  the  bowel  involved 
in  the  contraction.  This  is  a  very  close  imitation  of  what  occurs  in 
natural  defaecation.  In  man  the  parts  involved  in  these  movements 
are  probably  the  sigmoid  flexure  and  rectum.  In  addition  to  these 
characteristic  motor  effects  on  the  lower  part  of  the  large  intestine, 
stimulation  of  the  pelvic  nerves  causes  an  increase  in  the  antiperi-stalsis 
of  its  upper  portions.  Stimulation  of  the  lumbar  nerves  or  of  the  por- 
tions of  the  sympathetic  into  which  their  visceral  fibres  pass  (lumbar 
sympathetic  chain  from  second  to  sixth  ganglia,  or  the  rami  from  it  to 
the  inferior  mesenteric  ganglia)  causes  inhibition  of  the  movements  of 
the  caecum  and  the  whole  colon,  including  the  antiperistiiltic  move- 
ments. Excitation  of  the  sacral  nerves  initiates  or  increases  the  con- 
traction of  both  coats  of  the  portions  of  the  large  intestine  on  which 
they  act,  excitation  of  the  lumbar  nerves  inhibits  both.  And  in  the  small 
intestine  the  same  law  holds  good ;  the  two  coats  are  contracted  together 
by  the  action  of  the  vagus  or  inhibited  together  by  that  of  the  splanclinics. 

Defaecation  is  partly  a  voluntary  and  partly  a  reflex  act.     But 
in  the  infant  the  voluntary  control  has  not  yet  been  developed; 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  3J3 

in  tliL'  lulult  it  may  hv  lost  by  disease;  in  an  animal  it  may  be 
abolished  by  ojieration,  and  in  each  case  the  action  becomes  wholly 
reflex.  Owing  to  the  tonic  contraction  of  the  rectum  and  the  acute 
angle  formed  at  the  pelvi-rectal  flexure,  the  faces  arc  arrested  at 
this  point.  In  consequence  the  pelvic  colon  becomes  filled  with 
faeces  from  below  upwards,  and  the  rectum  remains  empty  till 
immediately  before  defalcation.  This  has  been  verified  in  man  by 
observations  with  the  Rcintgen  rays  (Hertz).  In  persons  whose 
bowels  are  opened  regularly  after  breakfast,  the  passage  of  faeces 
into  the  rectum  gives  rise  to  the  characteristic  sensation  which 
may  be  termed  the  '  call  to  defaecation. '  It  is  the  distension  of  the 
rectum,  and  of  the  rectum  alone,  which  is  associated  with  this 
sensation,  for  in  persons  from  whom  the  entire  rectum  has  been 
removed  for  malignant  disease  the  sensation  is  absent,  and  it  may 
be  elicited  by  artificially  distending  the  rectum,  though  not  any 
other  part  of  the  alimentary  canal.  The  minimum  pressure  required 
to  elicit  the  sensation  is  smaller  the  greater  the  length  of  the  gut 
exposed  to  it,  varying  in  one  individual  from  32  to  48  mm.  of 
mercury,  according  to  the  length  of  a  balloon  introduced  into  the 
rectum.  The  passage  of  the  fseces  from  the  pelvic  colon  into  the 
rectum  is  due  to  the  discharge  of  that  reflex  contraction  of  the  lower 
portion  of  the  bowel  already  described  (p.  332),  of  which  the  pelvic 
nerves  constitute  the  efferent  path.  This  reflex  peristalsis  is  elicited 
by  various  causes,  among  which  one  of  the  most  important  is  the 
taking  of  food  at  breakfast  into  the  empty  stomach,  and  another 
the  muscular  activity  associated  with  getting  up  and  dressing. 
The  desire  to  defaecate  may  for  a  time  be  resisted  by  the  will,  or  it 
may  be  yielded  to.  In  the  latter  case  the  abdominal  muscles,  and, 
according  to  Hertz,  the  diaphragm  also,  are  forcibly  contracted; 
and  the  glottis  being  closed,  the  whole  effect  of  their  contraction 
is  expended  in  raising  the  pressure  within  the  abdomen  and  pelvis, 
and  so  aiding  the  muscular  wall  of  the  bowel  itself  in  driving  the 
faeces  from  the  sigmoid  flexure  to  the  rectum.  The  two  sphincters 
which  close  the  anus — ^the  internal  sphincter  of  smooth  muscle, 
and  the  external  of  striated — are  now  relaxed  by  the  inhibition  of 
a  centre  in  the  lumbar  portion  of  the  spinal  cord,  through  the 
activity  of  which  the  tonic  contraction  of  the  sphincters  is  normally 
maintained.  This  relaxation  is  partly  voluntary,  the  impulses 
that  come  from  the  brain  acting  probably  through  the  medium 
of  the  lumbar  centre.  But  in  the  dog,  after  section  of  the  cord  in 
the  dorsal  region,  the  whole  act  of  defaecation,  including  contraction 
of  the  abdominal  muscles  and  relaxation  of  the  sphincters,  still 
takes  place,  and  here  the  process  must  be  purely  reflex.  Even  after 
complete  destruction  of  the  lumbar  and  sacral  portions  of  the  spinal 
cord  the  tone  of  the  sphincters  returns  after  a  time,  and  defaecation 
is  carried  on  as  in  a  normal  animal,  the  control  of  the  sphincters 


334  DIGESTION 

being  due  either  to  a  property  of  the  muscular  tissue  itself  or  to 
local  ganglia.  The  contraction  of  the  levatores  ani  helps  to  resist 
overdistension  of  the  pelvic  floor  and  to  pull  the  anus  up  over  the 
faeces  as  they  escape.  The  nervi  erigentes  carry  efferent  constrictor 
fibres,  and  the  hypogastrics,  as  a  rule,  efferent  dilator  fibres,  to  the 
sphincters.  While  the  internal  sphincter  is  by  itself  capable  of 
maintaining  a  tonus  of  considerable  strength,  the  external  sphincter 
contributes  an  important  share  (30  to  60  per  cent.)  to  the  closure 
of  the  rectum.  If  the  call  to  defalcation  is  neglected,  the  desire 
passes  away.  This  is  not  due  to  the  faces  being  carried  back  into 
the  pelvic  colon  by  antiperistalsis,  as  has  generally  been  stated. 
The  faeces  which  have  passed  into  the  rectum  remain  there,  as  can 
be  shown  by  examination  with  the  finger  after  the  desire  to  empty 
the  bowels  has  disappeared.  The  reason  for  the  disappearance 
of  the  sensation  is  the  relaxation  of  tone  which  occurs  in  the 
muscular  coat  of  the  rectum  after  a  period  of  distension.  It  is  not 
till  it  has  been  again  distended  by  the  entrance  of  a  further  portion 
of  faeces  that  the  call  to  defaecation  is  again  experienced.  When 
the  call  is  repeatedly  neglected,  the  sensibility  of  the  rectum  to  dis- 
tension becomes  blunted,  and  this  is  a  common  cause  of  constipation. 

The  time  of  passage  of  substances  through  the  alimentary  canal 
has  been  studied  by  administering  collodion  capsules  filled  with 
subnitrate  of  bismuth  to  human  beings,  and  observing  their  pro- 
gress by  taking  shadow  pictures  of  them  at  intervals  with  the 
Rontgen  rays.  During  the  first  twenty  minutes  two  such  capsules 
swallowed  at  the  same  time  by  a  healthy  young  man  were  clearly 
seen  in  the  greater  curvature  of  the  stomach,  but  in  the  interval 
between  the  first  half-hour  and  the  seventh  or  eighth  hour  no  further 
trace  of  them  was  detected.  About  the  eighth  hour  they  re- 
appeared in  the  caecum,  where  they  remained  with  little  or  no 
onward  movement  till  the  fourteenth  hour.  From  the  fourteenth 
to  the  sixteenth  hour  they  travelled  along  the  ascending  colon,  and 
tarried  a  long  time  at  the  left  angle  of  the  colon.  From  the  nine- 
teenth to  the  twenty-second  or  twenty-fourth  hour  they  slowly 
passed  downward  in  the  descending  colon,  and  stopped  at  the  sig- 
moid flexure  till  their  expulsion  in  defaecation.  In  some  subjects 
the  entire  passage  of  the  capsules  was  complete  in  sixteen  hours,  in 
others  not  until  after  thirty  hours.  A  one  cent  piece  swallowed  by 
a  healthy  child  four  years  old  was  recovered  in  the  faeces  52  hours 
later,  and  a  button,  slightly  larger,  swallowed  by  the  same  child, 
appeared  after  almost  exactly  the  same  interval. 

Vomiting. — ^We  have  seen  that  under  normal  conditions  the 
movements  of  the  alimentary  canal  always  tend  to  carry  the  food 
in  one  definite  direction,  along  the  tube  from  the  mouth  to  the 
rectum.  The  peristaltic  waves  generally  run  only  in  this  direction, 
and,   further,  regurgitation  is  prevented  at  three  points  by  the 


THE  MECHANICAL  PHE\OME\A   01-   DIGESTION  335 

cardiac  and  pyloric  sphincters  of  the  stomach  and  the  ilco-cohc 
sphincter  and  valve.  But  in  certain  circumstances  the  peristalsis 
may  be  reversed,  one  or  more  of  the  guarded  orifices  forced,  and  the 
onward  stream  of  the  intestinal  contents  turned  back.  In  obstruc- 
tion of  the  bowel,  the  faecal  contents  of  tlie  large  intestine  may  pass 
up  beyond  the  ilco-caecal  valve,  and,  reaching  the  stomach,  be  driven 
by  an  act  of  vomiting  through  the  cardiac  orifice;  in  what  is  called 
a  '  bilious  attack,'  the  contents  of  the  duodenum  may  pass  back 
through  the  pylorus  and  be  ejected  in  a  similar  way;  or,  what  is 
by  far  the  most  common  case,  the  contents  of  the  stomach  alone 
may  be  expelled. 

\'omiting  is  usually  preceded  by  a  feeling  of  nausea  and  a  rapid 
secretion  of  saliva,  which  perhaps  serves,  by  means  of  the  air 
carried  down  with  it  when  swallowed,  to  dilate  the  cardiac  orifice 
of  the  stomach,  but  may  be  a  mere  by-play  of  the  reflex  stimula- 
tion bringing  about  the  act,  since  evidence  of  stimulation  of  other 
bulbar  centres  (vaso-motor  and  cardio-inhibitory)  has  also  been 
obtained.  The  diaphragm  is  now  forced  down  upon  the  ab- 
dominal viscera,  first  with  open  and  then  with  closed  glottis.  The 
thoracic  portion  of  the  oesophagus  is  thus  placed  under  diminished 
pressure,  and  therefore  widened,  while  saliva  and  air  are  aspirated 
into  it  out  of  the  mouth.  The  abdominal  muscles  strongly  con- 
tract. At  the  same  time  the  stomach  itself,  and  particularly 
the  antrum  pylori,  contracts,  the  cardiac  orifice  relaxes,  and  the 
gastric  contents  are  shot  up  into  the  lax  oesophagus,  and  through 
it  into  the  pharynx,  and  issue  by  the  mouth  or  nose.  The  move- 
ments of  the  stomach  during  vomiting  induced  by  apomorphine 
have  been  studied  in  the  cat  by  the  Rontgen  ray  method.  There  is 
first  observed  extreme  relaxation  of  the  cardiac  end;  then  a  deep 
constriction  appears  a  little  below  the  cardiac  orifice,  and  runs 
towards  the  pylorus,  increasing  in  depth  as  it  goes.  When  the 
transverse  band  is  reached,  this  contracts  firmly  and  remains  con- 
tracted, and  the  constriction  passes  on  over  the  antrum  pylori. 
Ten  or  twelve  similar  waves  follow,  at  the  end  of  which  time  the 
constriction  in  the  region  of  the  transverse  band  divides  the  stomach 
into  the  firmly-contracted  antrum  and  the  relaxed  fundus.  Now 
follows  a  sudden  contraction  of  the  diaphragm  and  abdominal 
muscles  accompanied  by  the  opening  of  the  cardiac  orifice.  Either 
the  diaphragm  and  abdominal  muscles  alone,  without  the  stomach, 
or  the  diaphragm  and  stomach  together,  without  the  abdominal 
muscles,  can  carry  out  the  act  of  vomiting.  For  an  animal  whose 
stomach  has  been  replaced  by  a  bladder  filled  with  water  can  be 
made  to  \-omit  by  the  administration  of  an  emetic  (Magendie) ; 
and  Hilton  saw  that  a  man  who  lived  fourteen  years  after  an  injury 
to  the  spinal  cord  at  the  height  of  the  sixth  cervical  nerve,  which 
caused  complete  paralysis  below  that  level,  could  vomit,  though 
with  great  difficulty.     In  a  young  child  in  which  very  shght  causes 


336  DTCRSTION 

will  iiuUuo  vomiting,  th''  stomach  alone  ((Mitracts  duiing  the  a<t. 
But  in  the  adult  such  a  contraction  is  ineffectual,  and  the  same  is 
the  case  in  animals,  for  a  dog  under  the  influence  of  a  moderate 
dose  of  curara,  which  paralyzes  the  voluntary  muscles  but  not  the 
stomach,  cannot  vomit. 

The  nerve-centre  is  in  the  medulla  oblongata.  It  may  be 
excited  by  many  afferent  channels:  the  sensory  nerves  of  the  fauces 
or  pharynx,  of  the  stomach  or  intestines  (as  in  strangulated  hernia), 
of  the  liver  or  kidney  (as  in  cases  of  gall-stone  or  renal  calculi),  of 
the  uterus  or  ovary,  and  of  the  brain  (as  in  cerebral  tumour),  are 
all  capable,  when  irritated,  of  causing  vomiting  by  impulses  passing 
along  them  to  the  vomiting  centre. 

The  vagus  nerve  in  man  certainly  contains  afferent  fibres  by  the 
stimulation  of  which  this  centre  can  be  excited,  for  it  has  been 
noticed  that  when  the  vagus  was  exposed  in  the  neck  in  the  course 
of  an  operation,  the  patient  vomited  whenever  the  nerve  was 
touched  (Boinet,  quoted  by  Gowers).  In  meningitis,  vomiting  is 
often  a  prominent  symptom,  and  is  sometimes  due  to  irritation  of 
the  vagus  nerve  by  the  inflammatory  process. 

Some  drugs  act  as  emetics  by  irritating  surfaces  in  which  efficient 
afferent  impulses  may  be  set  up,  the  ga.stric  mucous  membrane, 
for  example;  sulphate  of  zinc  and  sulphate  of  copper  act  mainly 
in  this  way.  Apomorphine,  on  the  other  hand,  stimulates  the 
centre  directly,  and  this  is  also  the  mode  in  which  vomiting  is  pro- 
duced in  certain  diseases  of  the  medulla  oblongata.  The  efferent 
nerves  for  the  diaphragm  are  the  phrenics,  for  the  abdominal 
muscles  the  intercostals.  The  impulses  which  cause  contraction 
of  the  stomach  pass  along  the  vagi.  Dilatation  of  the  cardiac 
orifice  is  brought  about  by  the  inhibitory  fibres  in  the  vagus  already 
mentioned. 


Section  III. — The  Chemistry  of  the  I  igestive  Juices. 

Ferments. — The  chemical  changes  wrought  in  the  food  as  it 
passes  along  the  alimentary  canal  are  due  to  the  secretions  of 
various  glands  which  line  its  cavities  or  pour  their  juices  into  it 
through  special  ducts.  These  secretions  owe  their  power  for  the 
most  part  to  substances  present  in  them  in  very  small  amount, 
but  which,  nevertheless,  act  with  extraordinary  energy  upon  the 
various  constituents  of  the  food,  causing  profound  changes  with- 
out, upon  the  whole,  being  themselves  used  up,  or  their  digestive 
power  affected.  The  active  agents  are  the  enzymes,  sometimes, 
spoken  of  as  unformed  or  unorganized  ferments — unorganized 
because  their  action  does  not  depend  upon  the  growth  of  living 
cells,  which  was  long  supposed  to  be  the  case  for  some  other  fer- 
ments, such  as  yeast.  Since  it  has  been  shown  that  specific  enzymes 
can  be  separated  from  cells  which  were  formerly  believed  to  act 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  337 

by  thoir  more  growth,  the  distinction  between  formed  and  unformed 
ferments  has  lost  its  significance,  and  has  to  a  great  extent  been 
superseded  by  the  distinction  between  intra-  and  extra-cellular 
enzymes  (also  called  endo-  and  exo-enzymcs)  —  i.e.,  between 
ferments  whicli  normally  act  in  the  interior  of  the  cells  where  they 
are  produced  and  ferments  which  act  outside  of  the  cells  that  secrete 
them.  From  yeast  cultures,  for  instance,  by  crushing  the  cells, 
a  ferment  (zymase*)  can  be  obtained  which  in  the  complete  absence 
of  living  yeast-cells,  and,  indeed,  of  any  living  micro-organism,  forms 
alcohol  and  carbon  dioxide  from  sugar,  just  as  living  yeast  does. 
There  is  every  reason  to  believe  that  it  is  by  the  intracellular  action 
of  this  endoenzj^me  that  the  yeast-cell  normally  causes  alcoholic 
fermentation.  The  digestive  ferments  are  typical  extracellular 
enzymes.  Their  chemical  nature  has  not  been  exactly  made  out; 
som(>  of  them  at  least  do  not  appear  to  be  proteins,  or  to  contain 
a  protein  group.  Many  of  them  apparently  exist  in  tlue  colloidal 
condition,  although  this  has  not  been  shown  for  all.  In  certain 
cases  the  more  or  less  stable  union  of  a  definite  inorganic  substance 
with  the  ferment,  or  its  actual  inclusion  in  the  ferment  molecule, 
seems  to  be  a  condition  of  its  action.  Thus  there  is  reason  to  believe 
that  in  gastric  digestion  hydrochloric  acid  is  loosely  combined  with 
the  pepsin.  In  the  plant  oxydase,  laccase  (p.  272),  manganese  is 
present.  And  the  fact  that  manganese  salts  oxidize  certain  substances 
as  laccase  does  suggests  that  it  is  the  manganese  in  combination 
with  some  protein  or  other  organic  compound  in  the  ferment 
molecule  which  confers  upon  laccase  its  oxidizing  power.  A  similar 
relation  between  iron  and  some  animal  oxydases  is  possible,  though 
not  definitely  proved.  But  none  of  the  ferments  of  the  digestive 
juices  has  as  yet  been  satisfactorily  isolated,  and  at  present  it  is 
only  by  their  effects  that  we  recognize  them.  The  difficulty  of 
isolating  them  is  increased  by  the  fact  that,  like  other  colloids, 
they  readily  adhere  to  surfaces,  and  are  carried  down  by  the  most 
diverse  precipitates  of  substances  to  which  they  are  chemically 
indifferent.  On  the  other  hand,  this  very  property  is  taken  advan- 
tage of  to  procure  more  concentrated,  although  still  impure,  solutions 
of  them  than  exist  in  the  natural  secretions.  Thus  in  the  prepara- 
tion of  many  ferments  the  first  step  is  to  produce  an  inert  pre- 
cipitate, such  as  calcium  phosphate,  in  the  juice  or  extract.  Some 
of  the  ferments  act  best  in  an  alkaline,  some  in  an  acid  medium. 
They  all  agree  in  having  an  '  optimum  '  temperature,  which  is  more 
favourable  to  their  action  than  any  other;  a  low  temperature  sus- 
pends their  activity,  and  boiling  abolishes  it  for  ever.  The 
optimum  temperatures  of  the  majority  of  enzymes  lie  between 

*  Ferments  are  usually  designated  by  names  with  the  termination  '  ase.' 
and  indicating  the  kind  of  substances  on  which  they  act,  or  sometimes  their 
source.  Thus  proteases  are  ferments  acting  on  proteins,  amylases  ferments 
acting  on  starch,  etc. 


i^,«  DIGESTION 

37"  unci  53°  C. ;  the  '  killing  '  temperatures  between  60"  and  73°  C. 
when  they  are  heated  in  solutions,  but  considerably  higher  when 
they  are  heated  dry.  The  action  of  the  digestive  enzymes  is 
hydrolytic — i.e.,  it  is  accompanied  with  the  taking  up  of  the  elements 
of  water  by  the  substance  acted  upon.  The  accumulation  of  the 
products  of  the  action  first  checks  and  then  arrests  it.  In  many 
cases  this  seems  to  be  due  to  combination  of  the  ferment  with  one 
or  other  of  the  end  products,  and  the  consequent  segregation  of 
the  ferment  from  the  reaction  mixture.  The  enzyme  is  not  affected 
indiscriminately  by  any  of  the  end  products.  On  the  contrary, 
their  action  is  curiously  selective.  Thus  the  hydrolysis  of  lactose 
by  lactase  is  retarded  by  galactose,  but  not  by  the  other  end 
product  dextrose.  The  hydrolysis  of  cane-sugar  b}^  invertase  is 
retarded  by  levulose,  but  not  by  dextrose.  The  splitting  of  the 
dipeptid  (p.  2)  glycj^-Z-tyrosin  by  a  ferment  in  the  expressed  juice 
of  yeast-cells  is  greatly  delayed  by  one  of  the  products  (/-tyrosin), 
but  not  by  the  other  (glycocoU).  Combination  of  the  ferment  with 
an  end  product  is  not,  however,  the  only  way  in  which  the  reaction 
may  stop  before  the  whole  of  the  substrate,  as  the  substance 
acted  on  by  the  ferment  is  termed,  has  been  changed.  It  has  been 
demonstrated  in  some  cases  that  this  is  due  to  the  action  of  the 
enzymes  being  reversible.  For  example,  lipase  (p.  363)  not  only 
decomposes  the  esters  ethyl  butyrate  or  glycerin  butyrate,  but 
also  builds  them  up  again  from  the  decomposition  products — ethyl 
butyrate  from  ethyl  alcohol  and  butyric  acid,  glycerin  butyrate  from 
glycerin  and  butyric  acid  (Kastle  and  Loevenhart,  Hanriot).  Thus: 
C3H7COOC2H5  +  HgO^ »C3H7COOH  +  C2H5OH, 

Kthyl  butyrate.  Water.  Butyric  acid.        Ethyl  alcohol. 

The  action  of  the  enzyme  is  merely  to  accelerate  the  establish- 
ment of  the  proportions  in  which  the  four  bodies  entering  into  the 
reaction  are  in  equilibrium,  and  the  point  of  equilibrium  is  the  same 
whether  we  start  from  one  or  the  other  side  of  the  equation  repre- 
senting the  reaction.  Such  reversible  reactions  in  the  presence  of 
enzymes  seem  to  afford  the  key  to  the  explanation  of  many  of  the 
syntheses  which  are  known  to  occur  in  the  body-  Sometimes  the 
action  is  not  strictly  reversible  in  the  sense  that  precisely  the  original 
material  is  reconstructed,  but  from  the  products  of  the  hydrolysis 
substances  are  synthesized  or  condensed,  which  are  then  incapable 
of  being  split  by  the  ferment.  When  a  concentrated  solution  of 
dextrose  is  acted  on  for  a  long  time  by  yeast  maltase,  a  ferment 
obtained  from  yeast  which  changes  maltos<-^  into  dextrose,  some  of 
the  dextrose  is  reconverted  into  isomaltose  and  dextrin-like  bodies. 
Isomaltose  is  not  again  hydrolysed  by  maltase.  The  ferment 
emulsin  contained  in  almonds  behaves  in  the  converse  way.  It 
hydrolyses  isomaltose  so  as  to  form  dextrose,  and  then  condenses 
dextrose  to  maltose  (Armstrong). 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  3^9 

Many  of  the  ordinary  substances  of  the  laboratory  will  accelerate 
a  reaction  which  goes  on  slowly  in  their  absence.  These  are  called 
catalysers.  Some  writers  also  speak  of  catalysers  which  retard 
a  reaction  progressing  quickly  in  their  absence.  The  process  by 
which  the  reaction  is  accelerated  (or  retarded)  is  termed  catalysis. 
A  typical  catalyser  can  exert  its  action  when  it  is  present  in  ex- 
ceedingly small  amount  in  comparison  with  the  substance  acted 
upon.  However  it  may  enter  into  the  reaction,  it  does  not  take 
part  in  the  formation  of  the  final  products  nor  contribute  to  the 
energy  changes,  and  for  this  reason  is  often  apparently  unaltered 
at  the  end  of  the  process.  The  catalysers  have  therefore  been 
compared  to  the  lubricants  used  for  machinery  as  contrasted  with 
the  coal  or  other  source  of  energy.  If  it  be  remembered  that  the 
expression  is  a  purely  metaphorical  one,  we  may  say  that  the 
catalyst  oils  the  reaction  so  that  it  sHps  on  smoothly  and  swiftly 
to  an  end-point  which  would,  however,  have  been  reached  just  the 
same  in  time.  A  classical  instance  of  catalysis  is  the  inversion 
of  cane-sugar  by  weak  acids,  i.e.,  the  change  of  the  cane-sugar  into 
a  mixture  of  equal  quantities  of  dextrose  and  levulose — a  reaction 
which  may  be  represented  by  the  equation 

Cane-sugar,        Water.      Dextrose.  Levulose. 

This  is  a  reaction  which  occurs  also  when  the  sugar  is  simply  dis- 
solved in  water,  but  with  exrtreme  slowness  at  the  ordinary  tempera- 
ture, although  more  rapidly  at  100°  C.  The  effect  of  the  acid  is 
to  catalyse  the  reaction,  to  markedly  accelerate  it.  The  hydrogen 
ions  of  the  free  acid  are  responsible  for  the  catalysis,  and  they  are 
not  used  up  in  the  process,  for  the  reaction  at  the  end  is  unaltered. 
The  same  action  upon  cane-sugar  is  exerted  by  an  enzyme,  invertase, 
found  in  intestinal  juice,  although  the  laws  governing  the  reaction 
are  somewhat  different.  Reversibility  of  the  reaction  can  be  even 
more  clearly  demonstrated  for  catalysers  than  for  enzymes.  For 
example,  the  condensation  of  acetone  to  diacetone-alcohol,  which 
is  accelerated  by  hydroxyl  ions  (as  by  the  addition  of  sodium 
hydroxide,  ammonia,  etc.),  only  proceeds  to  a  certain  point,  at  which 
equihbrium  is  established  between  the  proportions  of  acetone  and 
the  condensation  product.  Henceforth  as  much  of  the  latter  is 
decomposed  as  is  condensed.     Thus: 

2CH3.CO.CH3,^=>CH8.CO.CH2.C(CH8),OH. 

Acetone.  Acetone  alcohol. 

On  the  other  hand,  the  final  equilibrium  point  need  not  be  the  same 
for  a  catalyser  and  an  enzyme.  For  example,  amyl  but5rrate  is 
formed  and  decomposed  according  to  the  equation 

CgHnOH  -fCgHTCOOH^ZZ::?'  CgHjCOO.CgHu  +H2O. 

Amyl  alcohol.        Butyric  acid.  Amyl  butyrate.  Water. 


340  DIGESTlOtJ 

The  roaction  can  be  accelerated  either  by  a  catalyst — e.g.,  H  ion<5— 
as  by  addition  of  free  hydrochloric  or  picric  acid,  or  by  pancreas 
lipase.  When  the  concentrations  of  the  reacting  substances  are 
appropriately  chosen,  the  same  equilibrium  point  will  be  reached 
from  cither  side  of  the  equation — i.e.,  the  same  percentage  of  the 
butyric  acid  will  be  converted  into  the  ester  if  we  start  with  the 
alcohol  and  acid,  as  will  remain  combined  as  ester  if  we  start  with 
the  amyl  butyrate.  But  the  proportion  will  not  be  the  same  when 
the  reaction  is  acclerated  by  H  +  as  when  it  is  accelerated  by  the 
enzyme.  And  although  it  is  probable  that  there  is  no  fundamental 
difference  between  the  action  of  the  digestive  enzymes  and  that  of 
the  inorganic  catalysers,  it  is  much  too  early  to  dogmatize. 

Not  even  the  m  rkedly  specific  action  of  the  digestive  ferments 
can  be  considered  an  essential  distinction.  It  is  true  that  invertase 
will  act  upon  dextrose,  and  not  at  all  upon  maltose  or  lactase. 
But  there  are  other  sugars,  e.g.,  raffinose,  a  trisaccharide  with  the 
formula  CjgHgjOjg,  obtained  from  beet-sugar  residues,  which  it  will 
hydrolyse.  Rafhnose  is  made  up  of  one  molecule  each  of  dextrose, 
levulose,  and  galactose.  On  heating  \\nth  dilute  acids,  it  is  decom- 
posed into  these  substances.  Invertase,  however,  only  splits  off 
the  levulose  molecule,  leaving  a  disaccharide  isomeric,  but  not 
identical  with  lactose.  Similarly  lactase,  which  is  without  action 
upon  cane-sugar  or  maltose,  will  hydrolyse  the  ^-galactosides,  and 
maltase,  inert  as  regards  cane-sugar  or  lactose,  will  hydrolyse  the 
a-glucosides.  On  the  other  hand,  emulsin  decomposes  the  ;S-gluco- 
sides,  to  which  group  most  of  the  natural  glucosides  belong,  as  well 
as  the  /3-galactosides  and  lactose.  From  rafhnose  emulsin  splits 
off  galactose,  leaving  cane-sugar.  Since  the  a  and  /3  compounds 
are  isomeric,  and  differ  not  in  their  composition  but  in  their  struc- 
ture, it  has  been  concluded  that  the  structure  of  the  molecule  of 
a  substance  must  be  related  to  the  structure  of  the  enzyme  which 
can  act  on  it,  in  some  such  way  as  a  lock  is  related  to  its  proper  key. 
Thus  the  key  lactase  fits  in  the  lock  lactose,  but  not  in  the  lock 
dextrose  or  the  lo^k  maltose.  Although  the  same  specificity  is 
not  to  be  observed  in  the  action  of  catalysers  as  in  the  action  of 
enzymes,  it  is  not  difficult  to  find  many  instances  in  which  inorganic 
substances  show  a  marked  limitation  of  their  catalj^-ic  effects  to 
particular  reactions.  Thus  hydriodic  acid  is  slowly  oxidized  in 
presence  of  hydrogen  peroxide,  with  formation  of  iodine  and  water. 
This  reaction  is  accelerated  by  the  addition  of  many  substances, 
e.g.,  tungstic  acid.  But  tungstic  acid  has  no  catalytic  effect  on  the 
oxidation  of  hydriodic  acid  by  bromic  acid. 

The  existence  of  an  optimum  temperature  for  ferment  action, 
above  which  it  rapidly  decreases,  and  eventually  comes  to  a  com- 
plete stop,  is  also  in  all  probability  only  a  superficial  distinction 
between  enzymes  and  catalysers.     For  enzymes  are  easily  altered, 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  34^ 

or  even  destroyed,  at  temperatures  which  very  likely  would  favour 
their  action  were  they  as  thermostable  as  the  majority  of  catalysing 
agents.  And  inorganic  catalysts  are  known  which  also  sliow  the 
phenomenon  of  an  optimum  temperature  depending  on  changes 
produced  in  their  physical  condition  when  the  temperature  is 
raised  above  this  point.  Thus  a  colloidal  solution  (or  '  sol,'  as  it  is 
called)  of  platinum,  prepared  by  passing  electric  sparks  between 
two  platinum  electrodes  immersed  in  distilled  water,  and  containing 
the  metal  in  the  form  of  ultra-microscopic  particles,  acts  as  a  cata- 
lyser  of  a  number  of  reactions.  As  the  temperature  is  increased 
up  to  a  certain  '  optimum,'  the  velocity  of  the  catalysed  reaction 
is  increased.  But  beyond  this,  as  the  boiling-point  is  approached, 
the  colloidal  platinum  is  precipitated,  and  ceases  to  influence  the 
reaction. 

As  to  the  manner  in  which  an  enzyme  increases  the  velocity  of  its 
appropriate  rciiction,  it  is  not  easy  to  make  any  verj'  positive  statement. 
Several  possibilities  are  recognized,  of  which  two  ha\e  been  especially 
discussed,  (i)  The  existence  of  the  enzyme  in  colloidal  solution  may 
be  important.  It  is  characteristic  of  colloidal  solutions,  in  which  the 
dissolved  substance  is  present  in  the  form  of  extremely  fine  particles, 
that  the  total  surface  of  the  particles  is  very  great  in  proportion  to 
the  mass  of  the  substance  in  solution.  Thus,  a  sphere  of  about  the 
same  volume  as  the  eyeball,  with  a  diameter  of,  say,  2  centimetres, 
would  have  a  surface  of  I2'5  square  centimetres.  If  this  material  were 
subdivided  into  spheres  of  about  the  same  volume  as  a  leucocyte,  with 
a  diameter  of,  say,  10  yx,  it  would  form  eight  thousand  million  of  these 
spheres,  with  a  total  surface  of  over  2|  square  metres.  If  the  small 
spheres  were  further  subdivided  into  spherical  particles,  with  a  diameter 

only  the  thousandth  part  of  that  of  a  leucocyte,  say  -^,  each  would 

form  a  thousand  million  of  these  particles,  and  the  total  surface  of  all 
the  particles  would  be  about  2,500  square  metres. 

Now,  it  is  known  that  the  intensity  of  action  of  some  of  the  inorganic 
catalyse rs  is  proportional  to  the  surface  exposed.  For  example, 
hydrogen  peroxide,  if  left  to  itself,  is  slowly  decomposed  into  water  and 
oxygen.  The  addition  of  finely  divided  platinum,  in  the  form  of 
platinum  black,  greatly  hastens  the  decomposition,  and  the  oxygen 
bubbles  off.  The  colloidal  platinum  sol  is  still  more  effective.  The 
nature  of  the  surface  effect  is  not  entirely  clear.  One  factor  has  been 
thought  to  be  an  increase  in  the  concentration  of  dissolved  substances 
or  condensation  of  gases  at  the  surface,  and  the  better  opportunity 
for  mutual  action  thus  afforded  to  the  ferment  and  the  substrate. 
The  great  extension  of  the  surface  cannot  be  the  only  factor  in  the 
catalysis;  otherwise  any  fine  powder  or  suspension  would  have  a  cata- 
lytic action.  But  kaolin,  or  fine  sand,  or  colloidal  solutions  of  ordinary 
proteins  or  gelatin,  have  little,  if  any,  effect  on  the  decomposition  of 
hydrogen  peroxide. 

(2)  Enzymes  may  produce  their  effects  by  contributing  to  the  for- 
mation of  bodies  intermediate  between  the  substrate  and  the  end- 
products.  If  the  time  required  for  the  formation  of  a  given  quantity 
of  the  intennediate  compound  and  the  time  required  for  the  decom- 
position of  this  compound  into  the  final  products  of  the  ferment  action 
are  in  sum  less  than  the  time  required  for  the  direct  change  of  the 


w« 


DIGESTION 


substrate  into  the  end-products,  the  enzyme  will  clearly  act  as  a  cata- 
lyser  of  the  reaction.  It  has  been  shown  that  in  the  case  of  certain 
inorganic  catalysers  this  does  occur.  Thus,  in  the  oxidation  of  hydriodic 
acid  by  hydrogen  peroxide,  which  has  been  already  referred  to, 
raolybdic  acid  has  the  power  of  acting  as  a  catalyser.  It  has  been  proved 
that  the  reaction  occurs  in  two  stages,  pcmiolybdic  acid  being  first 
formed  by  the  action  of  the  peroxide  on  molybdic  acid.  The  permol- 
ybdic  acid  then  acts  on  hydriodic  acid,  producing  iodine  and  water, 
and  being  itself  reduced  again  to  molybdic  acid,  which  therefore  comes 
out  at  the  end  of  the  reaction  unchanged.  The  velocity  of  the  double 
reaction  is  much  greater  than  that  of  the  direct  oxidation  of  hydriodic 
acid  by  hydrogen  peroxide. 

There  is  evidence  that  the  ferment  actually  combines  with  the  sub- 
strate, the  combination  then  breaking  up  to  form  the  end-products. 
For  instance,  it  ha.s  been  shown  that  the  amount  of  lactose  hydrolysed 
by  lactase  in  a  given  time,  when  tlic  ferment  is  present  in  very  small 
quantity  in  comparison  with  the  substrate,  is  proportional  to  the  con- 
centration of  the  ferment,  and  independent  of  the  concentration  of 
the  lactose.  Also  with  a  given  small  concentration  of  ferment  the 
amount  of  lactose  hydrolysed  is  at  first  the  same  for  successive  equal 
intervals  of  time.  These  facts  can  only  be  explained  by  the  assump- 
tion that  the  ferment  first  combines  with  a  portion  of  the  substrate,  the 
rest  of  which  remains  inactive  as  regards  the  reaction,  and  that  this 
combination  then  takes  up  water  and  decomposes  into  the  end- 
products,  in  this  case  dextrose  and  galactose,  setting  free  the  ferment 
to  combine  with  another  portion  of  the  substrate. 

The  Quantitative  Estimation  of  Ferment  Action. — Since  we  have  as  yet 
no  certain  method  of  freeing  the  digestive  ferments  from  impurities, 
our  only  quantitative  test  is  their  digestive  activity.  And  since  a  very 
small  quantit}'  of  ferment  can  act  upon  a  practically  indefinite  amount 
of  material  if  allowed  sufficient  time,  we  can  only  make  comparisons 
when  the  time  of  digestion  and  all  other  conditions  are  the  same.  If 
we  find  that  a  given  quantity  of  one  gastric  extract,  acting  on  a  given 
weight  of  fibrin,  dissolves  it  in  half  the  time  required  by  an  equal 
amount  of  another  gastric  extract,  or  dissolves  twice  as  much  of  it  in  a 
given  time,  wc  conclude  that  the  digestive  activity  of  the  pepsin  is  twice 
as  great  in  the  first  extract  as  in  the  second.  But  this  does  not  pennit 
us  to  say  that  the  one  contains  twice  as  much  pepsin  as  the  other.  For 
it  has  been  found  that  the  amount  of  digestion  in  a  given  time  is  not 
directly  proportional  to  the  quantity  of  ferment  present,  but  to  the 
square  root  of  the  quantity  of  ferment  (Schiitz's  law).  This  law  was 
deduced  by  Schiitz  for  pepsin,  but  is  said  to  hold  also  for  tiypsin, 
stcapsin,  and  ptyalin  (Pawlow,  Vernon).  To  determine  the  amount  of 
proteolysis  the  nitrogen  of  the  protein  which  has  gone  into  solution  may 
be  estimated  (p.  521).  The  following  table  shows  the  results  of  one 
experiment : 


Pepsin  Solution  used 
in  C.C. 

Digested  Nitrogen  in  Grammes. 

Found. 

Calculated. 

I 

4 

9 

IG 

00230 
0*0427 
00686 
0*0889 

0*0223 
0*0440 
0*0669 
00892 

THE  CHEMISJRY  Of  THE  DIGESTIVE  JUICES  m 

Or  a  piece  of  a  glass  capillary-tulx-  filled  with  heat-coagulated  egg-white 
may  be  cut  ofl  and  placed  in  the  digestive  mixture  (Mett's  tubes).  At 
the  end  of  the  period  oi  digestion  the  length  of  the  piece  of  tube  and 
that  of  the  undigested  remnant  of  the  column  of  coagulated  protein 
are  measured  with  a  millimetre  scale  under  a  low-power  microscope. 
The  difference  gives  the  length  of  the  column  digested.  If  I  c.c.  of 
gastric  juice  caused  in  a  given  time  digestion  of  2  mm.  of  the  egg-white, 
4  c.c.  of  the  same  juice  would  digest  in  the  same  time  and  under  identical 
conditions  about  4  mm.,  and  9  c.c.  about  6  mm.  As  a  test  of  the 
activity  of  a  diastatic  ferment,  we  take  the  amount  of  sugar  formed  in 
a  given  time  in  a  given  quantity  of  a  standard  starch  solution.  To 
determine  the  activity  of  a  licjuiil,  say,  the  pancreatic  juice,  as  regards 
fat-splitting  ferment,  the  acidity  (>i  the  emulsion  formed  by  the  juice 
and  fat  after  standing  for  a  definite  time  at  a  gi\-en  temperature  (with 
occasional  shaking)  can  be  estimated  by  titration  with  baryta  solution. 

In  addition  to  the  ferments  of  the  digestive  juices  which  act  extra- 
cellularly  in  the  lumen  of  the  ahmentary  canal,  and  those  which 
do  their  work  intracellularly  in  its  walls,  micro-organisms  are 
present  in  the  gut,  and  even  in  normal  digestion  contribute  to  the 
changes  brought  about  in  the  food ;  while  under  abnormal  conditions 
they  may  awaken  into  troublesome,  and  even  dangerous,  activity. 
It  is  now  known  that  these  act  by  producing  intracellular  enzymes. 

It  may  be  noted  here,  although  the  subject  must  be  again  referred 
to  (p.  390),  that  specific  substances  capable  of  inhibiting  the  action 
of  ferments  exist.  Some  of  these  antiferments  are  normally  present 
in  the  body — an  antitrypsin,  for  instance,  in  normal  blood-serum. 
Numerous  antiferments  may  be  artificially  obtained  by  immunizing 
animals  with  the  original  ferments.  Thus  an  antilipase  is  found 
in  the  serum  of  rabbits  after  injection  of  pancreatic  lipase,  and  an 
antiemulsin  after  injection  of  emulsin.  Injection  of  rennin  causes 
the  formation  of  antirennin,  which  can  be  demonstrated  in  the 
blood-serum  and  milk  of  the  immunized  animal.  Besides  the  anti» 
ferments,  bodies,  sometimes  spoken  of  as  '  co-enzymes,'  are  known 
which  aid  the  action  of  certain  enzymes,  not  in  the  general  way 
in  which,  for  instance,  increase  of  temperature  up  to  the  optimum 
does,  but  in  some  quite  special  manner.  Thus,  as  we  shall  see, 
bile  salts  greatly  facilitate  the  fat-splitting  action  of  lipase.  This 
co-operation  is  not  to  be  confounded  with  the  activation  of  the 
proferment  or  zymogen  which  in  many  cases  represents  the  inactive 
form  of  the  enzyme,  while  it  is  still  within  the  secreting  cells.  For, 
once  activated,  the  fully  formed  enzyme  cannot  be  made  to  revert 
to  the  zymogen  stage.  For  example,  the  active  trj^sin  of  the 
pancreatic  juice  cannot  be  changed  into  inactive  trypsinogen, 
whereas  substances  which  simply  co-operate  or  co-act  with  enzj^mes 
leave  the  latter  unaltered  when  they  are  removed.  Thus  hpase  does 
not  preserve  the  increased  activity  conferred  upon  it  by  bile  salts 
when  the  bile  salts  are  again  separated  from  the  digestive  mixture. 

It  is  now  necessary  to  consider  in  detail  the  nature  of  the  variou? 


544  DIGESTION 

juices  yielded  by  the  digestive  glands,  and  the  mechanism  of  their 
secretion.  Since  it  is  along  the  digestive  tract  that  glandular  action 
is  seen  on  the  greatest  scale,  this  discussion  will  practically  embrace 
the  nature  of  secretion  in  general.  And  here  it  may  be  well  to  say 
that,  although  in  describing  digestion  it  is  necessary  to  break  it  up 
into  sections,  a  true  view  is  only  got  when  we  look  upon  it  as  a 
single,  though  complex,  process,  one  part  of  which  fits  into  the  other 
from  beginning  to  end.  It  is,  indeed,  the  business  of  the  physiologist, 
wherever  it  is  possible  to  insert  a  cannula  into  a  duct  and  to  drain 
off  an  unmixed  secretion,  to  investigate  the  properties  of  each  juice 
upon  its  own  basis;  but  it  must  not  be  forgotten  that  in  the  body 
digestion  is  the  joint  result  of  the  chemical  work  of  five  or  six 
secretions,  the  greater  number  of  which  are  actually  mixed  together 
in  the  alimentary  canal,  and  of  the  mechanical  work  of  the  gastro- 
intestinal walls. 

Saliva. — The  saliva  of  the  jnouth  is  a  mixture  of  the  secretions 
of  three  large  glands  on  each  side,  and  of  many  small  ones.  The 
large  glands  are  the  parotid,  which  opens  by  Stenson's  duct  opposite 
the  second  upper  molar  tooth;  the  submaxillary,  which  opens  by 
Wharton's  duct  under  the  tongue;  and  the  sublingual,  opening  by 
a  number  of  duets  near  and  into  Wharton's.  The  small  glands  are 
scattered  over  the  sides,  floor,  and  roof  of  the  mouth,  and  over  the 
tongue. 

Two  types  of  sahvary  glands,  the  serous  or  albuminous  and  the 
mucoiis,  are  distinguished  by  structural  characters  and  by  the 
nature  of  their  secretion;  and  the  distinction  has  been  extended 
to  other  glands.  The  parotid  of  many,  if  not  all,  mammals  is  a 
purely  serous  gland;  it  secretes  a  watery  juice  with  a  general  re- 
semblance in  composition  to  dilute  blood-serum.  The  submaxillary 
of  the  dog  and  cat  is  a  typical  mucous  gland;  its  secretion  is  viscid, 
and  contains  mucin.  The  submaxillary  gland  of  man  is  a  mixed 
gland;  mucous  and  serous  alveoli,  and  even  mucous  and  serous 
cells,  are  intermingled  in  it.  The  submaxillary  of  the  rabbit  is 
purely  serous.  The  sublingual  is,  in  general,  a  mixed  gland,  but 
with  fir  more  mucous  than  serous  alveoli.  Some  of  the  small 
glands  are  serous,  others  mucous  in  type. 

The  mixed  sahva  of  man  is  a  somewhat  viscous,  colourless  hquid 
of  low  specific  gravity  (1002  to  1008,  average  about  1005),  alkaline 
to  litmus,  acid  to  phenolphthalein,  but  when  tested  by  the  electrical 
method  (p.  24)  almost  neutral.  Besides  water  and  salts,  it  contains 
mucin  (entirely  from  the  submaxillary,  the  sublingual  and  the 
small  mucous  glands  of  the  mouth),  to  which  its  viscidity  is  due, 
traces  of  serum-albumin  and  serum-globulin  (chiefly  from  the 
parotid),  and  a  ferment,  which  hydrolyscs  starch,  and  therefore 
belongs  to  the  group  of  amlyases  or  diastases.  It  differs  somewhat 
from  the  amylase  of  pancreatic  juice.     But  the  small  differences 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES 


345 


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346  DIGEST]  UN 

usually  found  bctwcL-n  fuiine-nts  of  the  sanu-  kind  derived  from 
different  sources  may  be  due  to  the  presence  of  other  substances, 
and  do  not  necessarily  indicate  that  the  ferments  are  distinct.  For 
the  present  it  may  be  assumed  that  the  amylase  of  saliva  is  the 
same  ferment  encountered  in  the  pancreatic  juice,  and  in  many, 
or  all,  of  the  tissues.  An  oxydase  or  oxidizing  ferment  is  also 
present  in  saliva.  The  salts  are  calcium  carbonate  and  phosphate 
(often  deposited  as  '  tartar  '  around  the;  teeth,  occasionally  as 
aahvary  calculi  in  the  glands  and  ducts),  sodiimi  bicarbonate, 
sodium  and  potassium  chloride,  and  almost  always  a  trace  of  sul- 
pliocyanide  of  potassium,  detected  by  the  red  colour  which  it  strikes 
with  ferric  chloride.*  The  total  solids  amount  only  to  five  or  six 
parts  in  the  thousand.  A  great  deal  of  carbon  dioxide  can  be 
pumped  out  from  saliva,  as  much  as  60  to  70  c.c.  from  100  c.c. 
of  the  secretion — i.e.,  more  than  can  be  obtained  from  venous  blood. 
Only  a  small  proportion  of  this  is  in  solution,  the  rest  existing  as 
carbonates.  Oxygen  is  also  present  even  in  saliva  which  has  not 
come  into  contact  with  the  air,  and,  indeed,  in  somewhat  greater 
quantity  than  in  serum  (about  o-6  vohmie  per  cent,  in  dog's  saliva). 
Under  the  microscope  epithelial  scales,  dead  and  swollen  leucocytes 
(the  so-called  salivary  corpuscles),  bacteria,  and  portions  of  food, 
may  be  found.  All  these  things  are  as  accidental  as  the  last — 
they  are  mere  flotsam  and  jetsam,  washed  by  the  saliva  from  the 
inside  of  the  mouth.  But  greater  significance  attaches  to  certain 
peculiar  bodies,  either  spherical  or  of  irregular  shape,  that  are  seen 
in  the  viscid  submaxillary  saliva  of  the  dog  or  cat.  They  appear 
to  be  masses  of  secreted  material.  The  quantity  of  saliva  secreted 
in  the  twenty-four  hours  varies  a  good  deal.  On  an  average  it  is 
from  I  to  2  litres  (Practical  Exercises,  p.  454)- 

Besides  its  functions  of  dissolving  sai)id  substances,  and  so  allow- 
ing them  to  excite  sensations  of  taste,  of  moistening  the  food  for 
deglutition  and  the  mouth  for  speech,  and  of  cleansing  the  teeth 
after  a  meal,  sahva,  in  virtue  of  its  ferment,  amylase,  has  the  power 
of  digesting  starch  and  converting  it  into  the  disaccharide  maltose, 
a  reducing  sugar  (QaHaeOn)-  I"  ^^^  *he  secretion  of  any  of  the 
three  great  sahvary  glands  has  this  power,  although  that  of  the 
parotid  is  most  active.  In  the  dog,  on  the  other  hand,  parotid  saliva 
has  little  action  on  starch,  and  submaxillary  none  at  all;  while  in 
animals  hke  the  rat  and  the  rabbit  the  parotid  secretion  is  highly 
active.  In  the  horse,  sheep,  and  ox,  the  saliva  secreted  by  all  the 
glands  seems  equally  inert. 

When  starch  is  boiled,  the  granules  are  ruptured,  and  the  starch 

*  In  100  student.s  the  saliva  only  once  failed  to  give  the  reaction,  and  in 
this  individual  a  trace  of  sulphocvanule  was  present  3  days  later.  It  is  absent 
from  the  saliva  of  many  animal's.  In  25  dogs  submaxillary  saliva  obtained 
by  stimulation  of  the  chorda  tympani  only  once  gave  the  ferric  chloride 
reaction,  and  then  faintly. 


THE  CIIEMISIRV  or  Tin-   DIGESTIVE  JUICES  347 

passes  into  colloidal  solution,  yit-ldiiig  an  opalescent  liquid.     If  a 
little  saliva  be  added  to  some  boiled  starch  solution  which  is  free 
from  sugar,  and  the  mixture  be  set  to  digest  at  a  suitable  temperature 
(say  40°  C.).  the  solution  in  a  very  short  time  loses  its  opales«^ence 
and  becomes  clear.     It  still,  however,  gives  the  blue  reaction  with 
iodine;  and  Trommer's  test  (p.  10)  shows  that  no  sugar  has  as  yet 
been  formed.     Later  on  the  iodine  reaction  passes  gradually  through 
violet  into  red;  and  finally  iodine  causes  no  colour  change  at  all, 
while  maltose  is  found  in  large  amount,  along  with  some  isomaltose 
(P-  5i^)<  ^  sugar  having  the  same  formula  as  maltose,  but   differing 
from  it  in  the  melting-point  of  the  crystalline  compound  formed  by 
it   with   phenyl-hydrazine   (p.   525).     Traces  of  dextrose,   a  sugar 
which  rotates  the  plane  of  polarization  less  than  maltose,  but  has 
greater  reducing  power,   may  be  found  among  the  end-products 
when  the  digestion  is  conducted  in  vitro.     It  is  probable  that  this 
is  produced  from  the  maltose  by  another  enzyme  (maltase),  present 
in  smiU  amount  in  saliva.     In  any  case  it  is  well  known  that  mal- 
tose may  be  a  stage  in  the  hydrolysis  of  starch  to  dextrose,  and  can 
be  detected  among  the  intermediate  products  when   the  starch  is 
acted  on  by  dilute  acid  under  conditions  which  permit  a  gradual 
decomposition  of   the    fragments  into  which    the    polysaccharide 
molecule  is  successively  spHt.     But  the  observation  has  also  been 
made  that  the  saliva  itself  (in  the  cat)  may  contain  a  trace  of  dex- 
trose (Carlson). 

The  red  colour  indicates  the  presence  of  a  kind,  or  a  group,  of 
dextrins  sometimes  called  erythrodextrin,  because  of  this  colour 
reaction;  the  violet  colour  shows  that  at  first  this  is  still  mixed  with 
some  unchanged  starch.  Soon  the  dextrins  which  give  the  red  colour 
disappear,  and  are  succeeded  by  other  dextrins,  which  give  no  colour 
with  iodine,  and  are  therefore  called  achrodextrins.  These  are 
partly,  but  in  artificial  digestion  never  completely,  converted  into 
maltose,  and  can  always  at  the  end  be  precipitated  in  greater  or 
less  amount  by  the  addition  of  alcohol  to  the  liquid.  It  is  probable 
that  a  whole  series  of  dextrins  is  formed  during  the  digestion  of 
starch.  But  little  is  known  of  their  chemical  nature.  Recently, 
however,  some  of  these  intermediate  bodies  have  been  obtained 
in  crystaUine  form.  One  of  these  appears  to  be  a  hexa-amylose — 
i.e.,  it  consists  of  six  CgHjoOs  groups,  and  would  therefore  be 
capable  of  yielding,  on  the  assumption  of  water,  three  molecules 
of  maltose  or  six  of  dextrose.  This  is  accordingly  a  relatively 
small  fragment  of  the  big  original  molecule  of  starch.  When  the 
sugar  is  removed  as  it  is  formed,  as  is  approximately  the  case  when 
the  digestion  is  performed  in  a  dialyser,  the  residue  of  unchanged 
dextrin  is  less  than  when  the  sugar  is  allowed  to  accumulate  (Lea). 
In  ordinary  artificial  digestion,  for  instance,  under  the  most  favour- 
able circumstances  at  least  12  to  15  per  cent,  of  the  starch  is  left 


348  DIGESTION 

as  dextrin;  in  dialyser  digestions  the  residue  of  dextrin  may  be 
little  more  than  4  per  cent.  This  goes  far  to  explain  the  complete 
digestion  of  starch  which  takes  place  in  the  alimentary  canal,  a 
digestion  so  exhaustive  that,  although  dextrins  may  be  found  in 
the  stomach  after  a  starchy  meal,  they  do  not  occur  in  the  intestine, 
or  only  in  minute  traces.  Here  the  amyjolytic  ferment  of  the 
pancreatic  juice,  vvliich  is  essentially  the  same  in  its  action  as  the 
amylase  of  saliva,  only  more  powerful,  must  effect  a  very  complete 
conversion  of  the  starch  molecules  accessible  to  its  attack.  It  is 
not  inconsistent  with  this,  that  unchanged  starch  granules  may 
sometimes  be  excreted  in  the  faeces,  especially  when  imbedded  in 
raw  vegetable  structures.  For  it  may  be  easily  shown  that  un- 
boiled starch  is  digested  by  amylase  with  far  greater  difficulty  than 
boiled  starch,  an  illustration  of  the  important  part  played  by 
cooking  in  the  preparation  of  the  food  for  digestion. 

It  is  a  notable  fact  that  amylases,  also  called  diastases,  are  not 
confined  to  the  animal  body,  but  are  widely  distributed  in  plants. 

The  polysaccharide  starch  forms  the  great  reserve  of  carbohydrate 
material  in  plant  nutrition,  and  is  mobilized  for  the  use  of  the 
vegetable  cells  by  being  hydrolysed  to  simple  sugars  under  the  in- 
fluence of  these  enzymes,  just  as  the  polysaccharide  glycogen,  the 
great  carbohydrate  reserve  of  animal  nutrition  (p.  533),  is  mobilized 
in  the  form  of  dextrose  under  the  influence  of  the  diastase  of  the 
hver.  A  diastase,  which  is  present  in  all  sprouting  seeds,  and 
may  be  readily  extracted  by  water  from  malt,  forms  dextrin  and 
maltose  from  starch.  The  optimum  temperature  of  malt  diastase, 
however,  is  about  55°  C,  while  that  of  ptyalin  is  about  40"  C. 

While  a  neutral  or  weakly  alkaline  reaction  is  not  unfavourable 
to  salivary  digestion,  it  goes  on  best  in  a  slightly  acid  medium. 
It  has  been  shown  that  the  activity  of  ptyalin  on  starch,  both 
having  been  previously  dialysed  to  get  rid  as  far  as  possible  of  salts, 
is  increased  by  the  addition  of  very  small  amounts  of  acids  and  of 
the  neutral  salts  of  strong  monobasic  acids.  The  action  is  decreased 
by  larger  amounts  of  acid  (0-0007  to  0-0012  per  cent,  of  hydrochloric 
acid)  and  by  neutral  salts  of  weak  acids.  An  acidity  equal  to  that 
of  a  o-i  per  cent,  solution  of  hydrochloric  acid  stops  salivar}' 
digestion  completely,  although  the  ferment  is  still  for  a  time 
able  to  act  when  the  acidity  is  sufficiently  reduced.  Strong  acids 
or  alkalies  permanently  destroy  it.  These  facts  indicate  that  in 
the  mouth,  where  the  reaction  is  weakly  alkaline,  the  conditions 
are  comparatively  favourable  to  the  action  of  the  ptyalin.  They 
are  still  more  favourable  in  the  stomach  for  some  time  after  the 
beginning  of  a  meal,  while  the  reaction  is  yet  weakly  acid.  It  has 
been  observed  that  (in  cats)  sahvary  digestion  may  go  on  for  an 
hour  or  more  in  the  cardiac  end  of  the  stomach,  since  free  hydro- 
chloric acid  does  not  appear  here  before  that  time.     Since  the  con- 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  340 

tents  of  the  cardiac  end  arc  not  freely  intermixed  with  those  of  the 
pyloric  end,  a  greater  proportion  of  sugar  is  found  in  the  former, 
and  the  difference  is  more  marked  with  solid  than  with  liquid  fond 
(Cannon  and  Day).  But  during  tlie  greater  part  of  gastric  digestion 
the  degree  of  acidit}^  is  such  that  the  ptyalin  must  be  hinderofl. 
Although  the  food  stays  but  a  short  time  in  the  mouth,  there  is  no 
doubt  that,  in  man  at  least,  some  of  the  starch  is  there  changed  into 
sugar  (p.  350)-  But  this  is  not  the  case  in  all  animals.  Something 
depends  on  the  amylolytic  activity  of  the  saliva,  and  something 
upon  the  form  in  which  the  starchy  food  is  taken,  whether  it  is 
cooked  or  raw,  enclosed  in  vegetable  fibres,  or  exposed  to  free  ad- 
mixture with  the  secretions  of  the  mouth. 

The  fact  already  mentioned  that  hydrolytic  changes  of  the  same 
nature  as  those  produced  by  enzymes  can  be  brought  about  in  other 
ways  holds  good  for  the  salivary  amylase.  If  starch  is  heated  for 
a  time  with  dilute  hydrochloric  or  sulphuric  acid,  it  is  changed 
first  into  dextrin,  and  then  into  a  sugar,  which,  however,  is  not 
the  disaccharide  maltose,  but  the  monosaccharide  dextrose — -that 
is  to  say,  the  hydrolysis  with  acid  proceeds  a  step  farther  than  the 
hydrolysis  in  the  presence  of  ptyaUn.  If  maltose  is  treated  with 
acid  in  the  same  way,  it  is  also  changed  into  dextrose.  When 
glycogen  (p.  i)  is -boiled  with  dilute  oxalic  acid  at  a  pressure  of  three 
atmospheres,  isomaltose  and  dextrose  are  formed  (Cremer).  Facts 
already  mentioned,  and  others  to  be  cited  later  on,  show  that  the 
action  of  the  other  digestive  ferments  can  also  be  imitated  by 
purely  artificial  means.  Indeed,  we  may  say  that  the  ferments 
accomplish  at  a  comparatively  low  temperature  what  can  be  done 
in  the  laboratory  at  a  higher  temperature,  and  by  the  aid  of  what 
may  be  called  more  violent  methods. 

Gastric  Juice. — The  Abbe  Spallanzani,  although  not,  perhaps, 
the  first  to  recognize,  was  the  first  to  study  systematically,  the 
chemical  powers  of  the  gastric  juice,  but  it  was  by  the  careful 
and  convincing  experiments  of  Beaumont  that  the  foundation  of 
our  exact  knowledge  of  its  composition  and  action  was  laid. 

It  is  difficult  to  speak  without  enthusiasm  of  the  work  of  Beaumont, 
if  we  consider  the  difficulties  under  which  it  was  carried  on.  An  army 
surgeon  stationed  in  a  lonely  post  in  the  wilderness  that  was  then 
called  the  territory  of  Michigan,  a  thousand  miles  from  a  University, 
and  four  thousand  from  anything  like  a  physiological  laboratory,  he 
was  accidentally  called  upon  to  treat  a  gun-shot  wound  of  the  stomach 
in  a  Canadian  voyageur,  Alexis  St.  Martin.  When  the  wound  healed, 
a  permanent  fistulous  opening  was  left,  by  means  of  which  food  could 
be  introduced  into  the  stomach  and  gastric  juice  obtained  from  it. 
Beaumont  at  once  perceived  the  possibilities  of  such  a  case  for  physio- 
logical research,  and  began  a  series  of  experiments  on  dig.^stion.  After 
a  while,  St.  Martin,  with  the  wandering  spirit  of  the  voyageur,  returned 
to  Canada  without  Dr.  Beaumont's  consent  and  in  his  absence. 
Beaumont  traced  him.  with  great  difficulty,  by  the  help  of  the  agents 
of  a  fur-trading  company,  induced  him  to  come  back,  provided  for  his 


350  DIGESTION 

family  as  well  as  lor  himself,  and  proceeded  with  his  investigations, 
A  second  time  St.  Martin  went  back  to  his  native  country,  and  a  second 
time  the  zealous  investigator  of  the  gastric  juice,  at  heavy  expense, 
secured  his  return.  And  although  his  experiments  were  necessarily  less 
exact  than  would  be  permissible  in  a  modem  research,  the  modest  book- 
in  which  he  published  his  results  is  still  counted  among  the  classics  of 
physiology.  The  production  of  artificial  fistulae  in  animals,  a  method 
that  has  since  proved  so  fruitful,  was  first  suggested  by  his  work. 

Gastric  juice  when  obtained  pure,  as  it  can  be  from  an  acci- 
dental fistula  in  man,  or,  better,  by  giving  a  dog  with  an  oesophageal 
as  well  as  a  gastric  fistula  a  '  sham-meal  '  (p.  402),  is  a  clear,  thin, 
colourless  liquid  of  low  specific  gravity  (in  the  dog  1003  to  1006) 
and  distinctly  acid  reaction.  The  total  sohds  average  about 
5  parts  per  thousand,  of  which  the  ash  (chiefly  sodium  and  potas- 
sium chloride,  with  small  quantities  of  calcium  and  magnesium 
phosphate)  represents  about  a  fourth,  and  heat-coagulable  sub- 
stances (proteins,  nucleoprotein)  about  a  third.  None  of  these  has 
any  special  importance  in  digestion.  Of  quite  a  different  significance 
are  the  three  ferments  present:  pepsin,  which  changes  proteins 
into  peptones;  rennin,  which  curdles  milk;  and  a  fat-splitting  fer- 
ment or  lipase  which,  under  certain  conditions  at  least,  spHts 
up  emulsified  neutral  fats  —  e.g.,  the  fat  of  milk — into  the 
alcohol  (glycerin)  and  the  fatty  acids  linked  with  it,  but  has  so 
little  action  upon  non-emulsified  fat,  that  when  this  is  taken  into 
the  stomach,  it  eventually  passes  into  the  duodenum  practically 
unchanged.  The  acidity  is  due  to  free  hydrochloric  acid,  the  other 
important  constituent  of  the  juice.  In  the  dog  the  proportion  of 
this  acid  varies  from  0-46  to  0-58  per  cent.  In  such  analyses  as 
have  been  made  of  approximately  pure  human  gastric  juice  a  smaller 
percentage  of  hydrochloric  acid  has  usually  been  obtained  (at  most 
0-35  to  0-4  per  cent.).  But  there  is  some  reason  to  beheve  that  if 
the  human  juice  could  be  collected  in  a  faultless  manner,  and 
especially  free  from  any  admixture  with  saliva  or  with  a  pathological 
secretion  of  mucus,  it  would  show  as  high  a  percentage  of  acid  as 
the  dog's  juice. 

In  cases  of  cancer,  whether  the  growth  is  situated  in  the  stomach 
or  not.  the  free  hydrochloric  acid  of  the  gastric  juice  is  usually 
much  reduced,  and  often  absent.  Under  such  conditions  some 
lactic  acid  may  be  present  in  the  stoni-uh.  being  produced  from  the 
carbo-hydrates  by  the  action  of  bacteria  {Bacillus  acidi  ladici), 
which  are  normally  held  in  check  by  the  hydrochloric  acid,  although 
not  rendered  incapable  of  growth  when  they  have  passed  on  into 
the  intestine.  Even  in  the  strength  of  007  to  o-o8  per  cent,  hydro- 
chloric acid  prevents  the  formation  of  lactic  acid  from  dextrose. 
Indeed,  when  all  the  hydrochloric  acid  of  the  gastric  juice  is  com- 
bined with  proteins,  the  protein-acid  compound  still  inhibits  the 
growth  of  bacteria  in  the  stomach,  although  not  so  efficiently  as  the 


7>/K  CHEMlsrnV  OV  THE  DlOLSIlVL  jUlCkS  35t 

saim-  amount  of  free  acid.  That  in  normal  gastric  juice  the  acidity 
is  not  due  to  lactic  acid  can  be  shown  by  shaking  the  juice  with 
ether  which  takes  up  lactic  acid,  and  then  applying  Uffelmann's 
test  to  the  ethereal  extract  (Practical  Exercises,  p.  460)- 

More  than  this,  it  is  not  due  to  an  organic,  but  to  an  inorganic 
acid,  for  healthy  gastric  juice  causes  such  an  alteration  in  the 
colour  of  aniline  dves  like  congo-red  and  methyl  violet  as  would 
be  produced  by  dilute  mineral  acids,  and  not  by  organic  acids,  even 
when  present  in  much  greater  strength.*  Finally,  when  the  bases 
and  acid  radicles  of  the  juice  are  quantitatively  compared,  it  is 
found  that  there  is  more  chlorine  than  is  required  to  combine  with 
the  bases;  the  excess  must  be  present  as  free  hydrochloric  acid 
In  the  pure  gastric  juice  of  fishes  like  the  dogfish  and  skate,  however, 
the  acid  is  said  not  to  be  hydrochloric  but  an  organic  acid.  The 
quantity  of  gastric  juice  secreted  depends  upon  the  nature  and 
amount  of  the  food.  It  has  been  estimated  at  as  much  as  5  litres 
in  twentv-four  hours,  or  several  times  the  quantity  of  saliva  secreted 
in  the  same  time.  With  sham  feeding  a  dog  may  yield  200-300  c.c. 
in  an  hour. 

The  great  action  of  gastric  juice  is  upon  proteins.  In  this  two 
of  its  constituents  have  a  share,  the  pepsin  and  the  free  acid.  One 
member  of  this  chemical  copartnery  cannot  act  without  the  other ; 
peptic  digestion  requires  the  presence  both  of  pepsin  and  of  acid ; 
and.  indeed,  an  active  artificial  juice  can  be  obtained  by  digesting 
the  gastric  mucous  membrane  with  dilute  (0-2  to  0-4  per  cent.) 
hydrochloric  acid.  A  glycerin  extract  of  a  stomach  which  is  not 
too  fresh  also  possesses  peptic  power,  the  zymogen  or  mother 
substance,  pepsinogen,  having  been  activated  to  pepsin.  Free 
acid  very  readily  effects  this  activation,  but  this  is  far  from  being 
the  only  function  of  the  hydrochloric  acid,  for  active  pepsin  still 
requires  the  addition  of  a  sufficient  quantity  of  acid  to  render  its 
proteoKi:ic  power  available. 

Well-washed  fibrin  obtained  from  blood  is  a  convenient  protein 
for  use  in  experiments  on  digestion;  although,  of  course,  for  many 
purposes  only  isolated  purified  proteins  can  be  employed.  Since  the 
blood  contains  traces  of  pepsin,  the  fibrin  should  be  boiled  to  destroy 
any  which  may  be  present  (see  also  p.  453). 

If  we  place  a  little  fibrin  in  a  beaker,  cover  it  with  gastric  juice 
obtained  from  a  dog  or  with  0-4  per  cent,  hydrochloric  acid,  to  which  a 
small  quantity  of  pep.^in  or  of  a  gastric  extract  has  been  added,  and 
put  the  beaker  in  a  water-bath  at  40°  C,  the  fibrin  soon  swells  up  and 
becomes  translucent,  then  begins  to  be  dissolved,  and  in  a  short  time 
has  disappeared  (see  Practical  Exercises,  p.  458).     If  we  examine  the 

*  A  dilute  solution  of  congo-red  is  turned  violet  by  organic  and  blue  by 
inorganic  acids;  the  gastric  juice  turns  it  blue.  Methyl  violet  is  rendered  blue 
by  an  inorganic  acid  like  hydrochloric  acid,  and  tjrecn  if  more  of  the  acid  be 
added.     It  is  not  altered  by  organic  acids.     Gastric  juice  turns  it  blue. 


552  DIGEST  I  OS 

liquifl  before  cligc>stion  lias  proceeded  very  far,  we  shall  find  chiefly 
so-called  acid-albumin  in  solution;  later  on,  chiefly  albumoscs;  and  of 
these  some  authors  distinguish  the  primary  albumoses  (proto-albumose 
and  hctcro-albumose).  the  first  to  appear  in  quantity,  followed  by 
secondary  or  deut^ro-albumoses  (p.  lo).*  Still  later,  peptones  in  large 
and  always  relatively  increasing  amounts  will  be  present  along  with 
the  alburnoscs.  From  this  we  conclude  that  acid-albumin  is  a  stage 
in  the  conversion  of  fibrin  into  albumose,  and  albumose  a  half-way 
house  between  acid-albumin  and  peptone.  It  must  not  be  supposed, 
however,  that  all  the  protein  is  first  changed  into  acid-albumin  before 
any  of  the  acid-albumin  is  changed  into  albumose,  or  that  all  the 
protein  has  already  reached  the  albumose  stage  before  peptone  begins 
to  appear.  On  the  contrary,  a  certain  amount  of  albumoses  and  of 
peptones  are  present  ver>-  early  in  peptic  digestion,  while  the  greater 
part  of  the  original  protein  is  still  unaltered.  Among  the  somewhat 
vaguely  characterized  group  of  bodies  comprised  under  the  term 
peptones,  there  are  no  doubt  decomposition  products  of  the  proteins 
in  which  the  hydrolysis  has  b-^en  carried  to  different  degrees.  Similar, 
but  not  identical,  intermediate  substances  occur  in  the  digestion  of  the 
other  proteins,  including  that  of  bodies  like  gelatin,  which  are  not 
ordinary  proteins,  but  which  pepsin  can  digest.  The  generic  name  of 
proteose  properly  includes  all  bodies  of  the  albumose  type,  the  term 
'  albumose  '  itself  being  sometimes  reserved  for  such  intermediate 
products  of  the  digestion  of  albumin;  while  those  of  fibrin  are  called 
fibrinoses;  of  globulin,  globuloses;  of  casein,  caseoses;  and  so  on.  The 
peptones  produced  from  different  proteins  are  also  not  absolutely 
identical.  If  the  digestion  is  prolonged,  the  peptones  first  formed  are 
in  turn  further  hydrolysed,  so  that  eventually  a  considerable  proportion 
of  the  original  protein  is  converted  into  bodies  which  no  longer  give  the 
biuret  reaction. 

In  the  stomach,  during  the  four  or  five  hours  for  which  gastric 
digestion  ordinarily  lasts,  none  of  the  protein  passes  beyond  the 
stage  of  proteose  and  peptone,  inchiding  those  relafvely  simple 
'  abiuret  '  compounds  which  still  consist  of  several '  building-stones, ' 
chiefly,  it  would  seem,  the  amino-acids,  phenylalanin,  and  prolin, 
linked  together.  When  precautions  are  taken  to  prevent  the 
passage  of  any  portion  of  the  contents  of  the  duodenum  into  the 
stomach,  no  amino-acids  can  be  detected  in  the  gastnc  contents 
during  the  digestion  of  protein.  In  this  connection  it  is  interesting 
to  note  that  none  of  the  polypeptides  hitherto  prepared  (p.  2)  are 
decomposed  by  pepsin.  It  is  not  known  at  what  points  in  the  link- 
age of  the  groups  that  compose  the  complex  protein  molecule  the 
pepsin  ruptures  the  chain,  but  the  points  of  attack  arc  different  from 
those  of  trypsin.     The  pancreatic  juice,  as  we  shall  see  later  on,  not 

•  In  the  light  of  modern  investigation  the  results  of  fractional  precipitation 
by  salts  of  the  products  of  proteolysis  have  lost  a  good  deal  of  their  interest, 
and  it  is  seen  that  undue  importance  has  often  been  attached  to  them.  The 
student  should  be  warned  that  such  terms  as  '  albumose  '  and  '  peptone  '  do 
not  indicate  precise  chemical  differences  between  the  products  separated  in 
this  way,  nor  even  invariably  such  differences  in  molecular  weight  as  the 
current  schemata  of  the  digestive  processes  are  apt  to  imply.  Some  so-called 
'  peptones '  may  indeed  have  a  higher  molecular  wei.qht  and  be  more  nearly 
related  to  the  original  protein  than  some  so-called  '  albumoses.' 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  353 

only  effects  a  more  complete  conversion  into  peptones,  but  can  split 
up  the  whole  or  a  very  large  proportion  of  the  peptones  themselves 
into  amino-acids  and  the  other  '  building-stones  '  of  the  original 
protein.  Since  the  subject  of  protein  digestion  must  come  up  again, 
it  will  be  well  to  postpone  any  closer  discussion  of  the  process  till  we 
can  view  it  as  a  whole.  In  the  meantime  it  is  only  necessary  to 
repeat  that  pepsin  alone  cannot  digest  proteins  at  all.  Its  action 
requires  the  presence  of  an  acid;  in  a  neutral  or  alkaline  medium 
peptic  digestion  stops.  The  precise  mode  of  action  of  the  acid  is  by 
no  means  clear. 

Dilute  acid  alone  does  not  dissolve  coagulated  proteins  like  boiled 
fibrin,  or  does  so  only  with  extreme  slowness.  But  it  causes  them  to 
swell  up  by  imbibition  of  water,  and  probably  in  this  way  facilitates 
the  entrance  of  the  ferment.  Uncoagulated  proteins  are  readily 
changed  by  acid  into  acid-albumin;  and  by  the  prolonged  action  of 
acids,  especially  at  a  high  temperature,  further  changes  of  much  the 
same  nature  as  those  produced  in  peptic  digestion  may  be  caused  in 
all  proteins.  But  under  the  ordinary  conditions  of  natural  gastric 
digestion,  it  may  be  said  that  the  acid  alone  does  little  until  it  is 
aided  by  the  ferment,  just  as  the  ferment  alone  does  nothing  wdthout 
the  aid  of  the  acid.  The  acid  enters  into  a  temporary  combination 
with  the  protein,  the  more  highly  hydrolysed  proteins,  such  as 
peptones,  combining  with  a  greater  proportion  of  acid  than  such 
proteins  as  fibrin  or  albumin.  These  compounds  so  easily  undergo 
hydrolytic  dissociation  that,  in  spite  of  its  union  with  the  proteins, 
the  hydrochloric  acid  is  able  to  act  along  with  the  pepsin,  so  that 
peptic  digestion  goes  on  even  when  enough  protein  is  present  to 
combine  with  all  the  acid.  There  is  some  evidence  that  in  the 
gastric  juice  the  pepsin  exists  in  the  form  of  an  unstable  compound 
with  hydrochloric  acid,  and  it  is  probably  this  pepsin-hydrochloric 
acid  compound  which  is  the  actual  catalytic  agent  in  peptic  digestion. 
Although  hydrochloric  acid  acts  most  powerfully,  other  acids,  such 
as  nitric,  phosphoric,  sulphuric,  or  lactic  (arranged  in  the  order  of 
their  efficacy),  can  replace  it. 

The  Milk-Curdling  Action  of  Gastric  Juice. — The  milk-curdling 
ferment,  rennin,  or  chymosin,  is  contained  in  large  amount  in  an 
extract  of  the  fourth  stomach  of  the  calf,  which,  as  rennet,  has  long 
been  used  in  the  manufacture  of  cheese.  It  exists  in  the  healthy 
gastric  juice  of  man,  but  disappears  in  cancer  of  the  stomach  and  in 
chronic  gastric  catarrh.  It  has  been  stated  by  a  number  of  observers 
that  the  properties  of  rennin  are  never  found  in  gastric  juice  or  any 
preparation  obtained  from  it  or  from  the  gastric  mucous  membrane 
unless  pepsin  is  present.  This  has  suggested  that  there  is  no  separate 
milk-curdling  ferment,  but  that  the  clotting  or  precipitation  of 
caseinogen  is  merely  an  associated  action  of  the  pepsin.  Ferments 
of  the  most  varied  origin  will  curdle  milk.     Pawlow  has  maintained 

23 


351  bicj'snoM 

tliattlu'  niilk-curdling  property  not  only  of  the  gastri<  juicv,  but  also 
of  tlic  pancreatic  juice  and  of  the  secretion  of  Brunner's  glands,  is 
associated  with  the  proteolytic  ferment. 

He  asserts  that  when  the  comparison  is  instituted  under  proper 
conditions  there  is  an  exact  parallelism  between  the  proteolytic  and 
the  milk-curdling  power  of  these  secretions,  no  matter  what  the 
circumstances  may  be  in  which  they  arc  collected,  or  the  influences 
to  which  they  are  exposed  after  collection.  He  has  found  it  im- 
possible to  separate  from  any  one  of  them  a  fraction  which  has 
milk-curdling  power  without  proteol\i:ic  power.  On  the  other  hand, 
the  majority  of  investigators  maintain  the  separate  identity  of 
rennin.  Hammarsten  especially  states  that  he  can  destroy  the 
peptic  activity  without  destroying  the  milk-curdling  power  of  gastric 
extracts,  and  vice  versa.  According  to  Burge,  when  a  solution  dis- 
pla\ang  both  peptic  and  milk-curdling  power  is  electrolyzed,  the 
pepsin  action  is  abolished  at  a  certain  stage,  while  the  rennet  action 
is  miaffected.  It  would  seem,  then,  that  the  balance  of  evidence 
is  in  favour  of  the  separate  identity  of  the  rennet  enz^-me. 

However  this  may  be,  the  cm-dling  of  milk  by  the  gastric  ferment 
includes  two  processes:  (i)  An  action  on  caseinogen  in  the  course  of 
which  it  acquires  new  properties,  becoming  changed  into  casein. 
This  substance  is  not  capable  of  being  converted  into  casein, 
and  remains  in  solution  in  the  whey.  {2)  The  altered  casein- 
ogen or  casein  combines  with  soluble  calcium  salts  and  in  the 
presence  of  these  is  precipitated  as  the  curd.  The  change  which 
occurs  in  the  caseinogen  has  been  the  subject  of  much  discussion, 
which  has  not  yet  led  to  a  definite  conclusion.  According  to  some 
observers,  the  change  consists  in  a  decomposition  of  caseinogen,  in 
the  course  of  which  a  new  substance,  whey-protein,  not  previously 
present  in  the  milk,  is  split  off.  This  substance  is  not  capable  of 
being  precipitated  by  hme  salts,  and  remains  in  solution  in  the  whey. 
According  to  others,  the  molecule  of  caseinogen  is  simply  changed 
into  two  molecules  of  casein  (van  Slyke).  Dilute  acid  will  of  itself 
precipitate  caseinogen,  and  the  presence  of  acid,  and  particularly 
hydrochloric  acid,  in  the  gastric  juice  helps  its  milk-curdling  action. 
But  that  a  ferment  is  really  concerned  is  indicated  by  the  fact  that 
the  juice,  after  being  made  neutral  or  alkaline,  still  curdles  milk,  and 
that  this  power  is  destroyed  by  boiling.  The  optimum  temperature 
is  the  same  as  that  of  the  other  ferments  of  the  digestive  tract,  about 
40°  C.  (p.  337).  The  persistence  of  the  milk-curdling  acti\nty  in  the 
presence  of  OH  ions,  while  for  peptic  activity  free  H  ions  are  neces- 
sary, is  a  further  and,  indeed,  a  strong  argument  in  favour  of  the 
separate  existence  of  the  rennet  ferment. 

As  to  the  exact  function  of  the  milk-curdling  ferment  of  the 
gastric  juice  in  digestion,  we  have  no  precise  knowledge.  It  seems 
superfluous  if  we  suppose  that  the  free  acid  is  able  of  itself  to  do  all 


THE  CHEMISTRY  OE   THE  DIGESTIVE  JUICES  355 

that  tlio  fcnnent  does  along  with  it.  But  there  is  evidence  tliat  the 
curd  produced  by  tlie  ferment  is  more  profoundly  changed  than  the 
precipitate  caused  by  dilute  acids;  for  the  latter  may  be  redissolved, 
and  then  again  curdled  by  rennin  in  the  presence  of  calcium  salts, 
while  this  cannot  be  done  with  the  former.  We  may  suppose,  then, 
that  the  ferment  is  capable  of  effecting  changes  more  favourable  to 
the  subsequent  action  of  the  pepsin  upon  the  casein  than  those 
which  the  acid  alone  would  effect.  Or  it  may  be  that  the  ferment 
acts  in  the  early  stages  of  digestion  before  much  acid  has  been 
secreted.  The  curdling  of  milk  probably  plays  a  part  in  ensuring 
the  retention  of  this  food,  the  proper  digestion  of  which  is  all-impor- 
tant for  the  suckling,  for  a  sufficient  length  of  time  in  the  stomach. 
Otherwise,  hke  water  and  watery  hquids  in  general,  it  would  be 
rapidly  passed  into  the  duodenum.  Even  if  this  were  not  the  case, 
there  is  another  reason  for  early  curdling.  Milk  is  a  very  dilute 
food,  and  the  immense  proportion  of  water  in  it  might  weaken  the 
gastric  juice  too  much  for  rapid  digestion  of  the  proteins.  The 
separation  of  the  whey  and  its  prompt  escape  through  the  pylorus 
would  obviate  this.  But  caution  should  be  exercised  in  giving  a 
physiological  value  to  all  the  details  of  the  milk-curdUng  action  of 
the  gastric  juice.  Milk-curdling  ferments,  or,  at  any  rate,  ferments 
with  a  milk-curdling  influence,  have  an  extremely  wide  distribution, 
both  in  secretions  which  in  normal  circumstances  can  never  come 
into  contact  with  milk,  and  in  the  tissues  of  animals  and  plants. 
Many  bacteria  produce  them.  And  it  appears  that  in  the  suckhng, 
where  it  might  be  expected,  if  anywhere,  to  have  a  definite  and 
important  office,  the  rennet  action  of  the  gastric  juice  is  distinctly 
less  than  in  the  adult.  It  is  worthy  of  note  that  the  curd  formed  by 
rennet  from  human  milk  is  more  finely  divided  than  that  formed 
from  cow's  milk,  and  therefore  is  more  easily  digested.  The  addition 
of  lime-water  or  barley-water  to  cow's  milk  keeps  the  curd  from 
adhering  in  large  masses,  and  thus  aids  its  digestion — a  fact  which 
is  sometimes  usefully  applied  in  the  artificial  feeding  of  infants. 

Gastric  Lipase. — On  fats  gastric  juice  has  usually  been  supposed 
to  have  no  action,  although  everybody  admits  that  it  will  dissolve 
the  protein  constituents  of  fat-cells  and  the  protein  substances  which 
keep  the  fat-globules  of  milk  apart  from  each  other.  It  has,  how- 
ever, been  recently  shown  that  both  in  the  stomach  and  in  vitro 
(with  glycerin  extracts  of  the  gastric  mucous  membrane)  a  consider- 
able amount  of  well -emulsified  fat  may  be  split  up,  and  that  this  is 
due  to  a  ferment  which  is  different  in  several  respects  from  the 
lipase  of  pancreatic  juice.  Gastric  juice  splits  up  tat,  both  in 
neutral  and  in  weakly  acid  solutions.  The  shghtcst  excess  of  alkali 
checks  the  action.  The  glycerin  extract  is  much  more  resistant  to 
alkah,  while  very  sensitive  to  hydrochloric  acid.  This  indicates 
that  the  fat-splitting  ferment  exists  in  the  mucous  membrane  in  a 


35<) 


DIGESTION 


different  form  from  that  in  which  it  exists  in  the  juice — namely,  as 
a  zymogen  or  mother-substance.  But  while  the  zymogen  of  the 
pancreatic  lipase  is  activated  by  bile,  this  is  not  the  case  with  the 
mother-substance  of  the  gastric  lipase.  It  appears  that  in  the 
suckling  the  lipase  of  the  gastric  juice  plays  a  more  important  part 
than  in  later  life.  This  is  obviously  in  accordance  with  the  fact  that 
the  specific  food  of  the  suckling — milk — contains  as  an  essential  con- 
stituent a  large  proportion  of  emulsified  fat.  The  conditions  for 
the  emulsification  of  fat  do  not  exist  in  the  gastric  juice,  and  this  is 
the  reason  why  the  gastric  lipase  has  so  slight  an  effect  upon  un- 
emulsified  fat,  which  presents  a  surface  of  contact  proportionally  so 
small.  In  any  case  the  amount  of  fat  hydrolysed  in  the  stomach 
under  ordinary  con  litions  is  small  in  comparison  with  the  amount 
split  in  the  intestine,  although  it  has  been  shown  that  with  a  diet 
rich  in  fat  some  of  the  intestinal  contents,  including  pancreatic 
lipase,  may  pass  back  into  the  stomach. 

As  regards  the  carbo-hydrates,  the  swallowed  saliva  will  continue 
to  act  on  starch  in  the  stomach,  so  long  as  the  acidity  is  not  too  great ; 
while  the  hydrochloric  acid  of  the  gastric  juice  is  able  to  invert  cane- 
sugar,  changing  it  into  a  mixture  of  dextrose  and  levulose,*  and 
also,  doubtless,  to  hydrolyse  to  dextrose  a  portion  of  the  maltose 
formed  by  the  saliva.  Altogether,  there  is  no  doubt  that  the  pro- 
portion of  the  carbo-hydrates  of  the  food  digested  in  the  stomach  is 
far  from  insignificant. 

The  Antiseptic  Function  of  the  Gastric  Juice. — The  stomach,  with 
its  acid  contents,  forms  during  the  greater  part  of  gastric  digestion 
a  valve  or  trap  to  cut  off  the  upper  end  of  the  intestine  from  the 
bacteria-infested  regions  of  the  mouth  and  phar^^mx,  and  to  destroy 
or  inhibit  the  micro-organisms  swallowed  with  the  food  and  saliva. 
The  occasional  presence  in  vomited  matter  of  sarcinae  or  regularly 
arranged  groups  of  micrococci,  generally  four  to  a  group,  shows  that 
under  abnormal  conditions  the  gastric  contents  are  not  perfectly 
aseptic;  and  even  from  a  normal  stomach  active  micro-organisms 
of  various  kinds  can  be  obtained.  But  upon  the  whole  there  is  no 
doubt  that  the  acidity  of  the  gastric  juice  is  an  important  check  on 
bacterial  activity  during  the  first  part  of  digestion,  and  in  the  upper 
portion  of  the  alimentary  canal.  Koch  has  shown  that  the  acidity 
of  the  gastric  juice  of  a  guinea-pig  is  sufficient  to  kill  the  comma 
bacillus  of  cholera.     Normal  guinea-pigs  fed  with   cholera  bacilli 

*  These  are  both  reducing  sugars,  but,  as  their  names  indicate,  they  rotate 
the  plane  of  polarization  in  opposite  directions.  The  specific  rotatory  power 
of  le\ailose  is  greater  than  that  of  dextrose,  so  that  when  cane-sugar  is  com- 
pletely inverted,  although,  equal  quantities  of  dextrose  and  levulose  are  pro- 
duced, the  plane  of  polarization  is  rotated  to  the  left.  Cane-sugar  itself  rotates 
it  to  the  right.  The  term  '  inversion  '  has  been  extended  to  include  the 
similar  hydrolysis  of  other  sugars  of  the  disacchande  group — e.g..  maltose  to 
dextrose,  and  lactose  to  a  mixture  of  dextrose  and  galactose,  even  although 
the  products  axe  not  levo-rotatory. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  357 

were  unaftected.  But  if  the  gastric  juice  was  neutralized  by  an 
alkali  before  the  administration  of  the  bacilli  the  guinea-pigs  died, 
("harrin  found,  too,  that  digestion  with  pepsin  and  hydrochloric  acid 
causes  an  appreciable  destruction  or  attenuation  of  diphtheria  toxin. 
Bacteria,  like  the  lactic  acid  bacillus,  which  form  acid  products,  may 
be  less  profoundly  affected  by  the  acid  gastric  juice  than  the  putre- 
factive bacteria,  which,  on  the  whole,  form  alkalies,  and  are  there- 
fore accustomed  to  an  alkaline  medium.  Yet  we  have  seen  that  the 
growth  of  even  the  lactic  acid  bacillus  is  very  strictly  controlled  when 
the  gastric  juice  contains  the  normal  amount  of  hydrochloric  acid. 
It  has  been  supposed  by  some  that  this  bactericidal  action  is  the 
chief  function  of  the  stomach,  and  the  question  has  been  asked  why 
we  should  attribute  any  digestive  importance  to  the  secretion  of  that 
viscus,  since  the  pancreatic  juice  can  do  all  that  the  gastric  juice 
does,  and  some  things  which  it  cannot  do.  Further,  it  has  been 
shown  that  a  dog  may  live  five  years  after  complete  excision  of  the 
stomach,  comport  himself  in  all  respects  like  a  normal  dog,  and  when 
killed  for  necropsy  show  every  organ  in  perfect  health  (Czerny).  In 
man,  too,  the  stomach  has  been  excised  with  a  successful  result. 
But  if  this  is  to  be  admitted  as  evidence  against  the  digestive  function 
of  the  stomach,  it  is  just  as  good  evidence  against  the  bactericidal 
function,  particularly  as  it  has  in  addition  been  shown  that  even 
putrid  flesh  has  no  harmful  effect  on  a  dog  after  excision  of  the 
stomach,  any  more  than  on  a  normal  dog.  And,  indeed,  the  reason- 
ing is  fallacious  which  assumes  that  what  may  happen  under  ab- 
normal conditions  must  happen  when  the  conditions  are  normal. 
For  nothing  is  impressed  more  often  on  the  physiological  observer 
than  the  extraordinary  power  of  adaptation,  of  making  the  best  of 
everything,  which  the  animal  organism  possesses.  Doubtless  a  dog 
without  a  stomach  will  use  to  the  best  advantage  the  digestive  fluids 
that  remain  to  him;  and  the  pancreatic  juice,  with  the  aid  of  the  bile 
and  the  succus  entericus,  may  be  adequate  to  the  complete  task  of 
digestion.  So,  too,  a  man  from  whom  the  surgeon  has  removed  a 
kidney,  or  a  testicle,  or  a  lobe  of  the  thyroid  gland,  may  be  in  no 
respect  worse  off  than  the  man  who  possesses  a  pair  of  these  organs. 
But  what  do  we  deduce  from  this  ?  Not,  surely,  that  the  excised 
thyroid,  or  testicle,  or  kidney  was  useless,  or  the  gastric  juice  in- 
active, but  that  the  organism  has  been  able  to  compensate  itself  for 
their  loss.  Further,  it  would  seem  that  the  fate  of  the  protein  or  of 
part  of  the  protein  digested  and  absorbed  by  the  stomach  is  different 
from  that  digested  and  absorbed  by  the  intestine.  For  after  the 
operation  of  gastro-enterostomy  (the  establishment  of  an  artificial 
opening  between  the  stomach  and  the  small  intestine  through  which 
the  food  passes  rapidly  without  having  to  submit  to  the  challenge 
of  the  pyloric  sphincter),  the  ingested  nitrogen  is  more  quickly 
ehminated  than  when  the  protein  is  first  subjected  to  full  gastric 


358  DIGESTION 

digestion.  So  that  when  the  quantity  of  protein  in  the  food  is 
increased  abov^e  that  necessary  for  nitrogen  equilibrium  (p.  602),  none 
of  the  excess  is  assimilated  and  stored  up,  as  is  the  case  in  a  normal 
animal  (Levin,  t;tc.). 

Pancreatic  Juice- — Pancreatic  juice,  bile,  and  intestinal  juice  are 
all  mingled  together  in  the  small  intestine,  and  act  upon  the  food, 
not  in  succession,  but  simultaneously.  But  by  artificial  ftstulae  in 
animals  they  can  be  obtained  separately;  and  occasionally  some  of 
tluMii  ran  be  j:)r()rured  through  accidental  ftstulit  in  man.  It  is  said 
that  under  certain  conditions,  especially  when  fat  or  oil  is  introduced 
into  the  stomach,  the  pylorus  may  remain  open  long  enough  to 
permit  the  passage  of  pancreatic  juice  or  bile  from  the  duodenum  into 
the  stomach,  and  this  has  been  recommended  as  a  practical  method 
of  obtaining  these  secretions  in  man. 

Human  pancreatic  juice,  as  obtained  from  a  fistula,  is  a  clear,  only 
slightly  viscid  liquid  of  distinctly  alkaline  reaction  to  litmus.  Its 
specific  gravity  is  about  1007  to  loio.  The  total  solids  constitute 
about  1-5  or  2  per  cent.,  of  which  a  httle  less  than  i  per  cent,  is  made 
up  of  inorganic  salts,  chiefly  sodium  carbonate,  with  small  quantities 
of  chlorides.  The  balance  of  the  solids  consists  mainly  of  proteins. 
The  alkaline  reaction  is  due  to  the  sodium  carbonate,  and  it  is 
worthy  of  remark,  as  showing  the  important  part  taken  by  this 
secretion  in  the  neutralization  of  the  chyme,  that  when  titrated 
against  standard  acid  the  alkalinity  of  the  pancreatic  juice  is  not 
much  le.ss  than  the  acidity  of  the  gastric  juice  when  titrated  against 
standard  alkali.  The  quantity  of  pancreatic  juice  secreted  during 
the  twenty- four  hours  in  an  average  man  has  been  estimated  at 
500  to  800  c.c.  from  observations  on  cases  of  fistula.  Probably 
under  perfectly  normal  conditions  it  is  greater.  A  so-called  arti- 
ficial pancreatic  juice  can  be  made  by  extracting  the  pancreas  with 
water  or  glycerin.  Since  better  methods  of  obtaining  the  natural 
juice  have  been  developed,  these  extracts  have  lost  some  of  their 
importance. 

Fresh  pancreatic  juice  contains  four  ferments:  (i)  The  zymogen  or 
mother-substance,  trypsinogen,  of  a  proteoljlic  or  protein-digesting 
ferment,  trypsin  ;  (2)  an  amylol}i:ic  ferment,  or  amylase  ;  (3)  a  fat- 
splitting  or  lipolytic  ferment,  steapsin  ;  (4)  a  milk-curdling  ferment. 
The  question  whether  the  last  is  a  different  body  from  the 
proteol>i:ic  ferment  has  been  discussed  just  as  in  the  case  of  the 
gastric  rennin  (see  p.  353).  In  any  case,  it  cannot  be  considered  as 
taking  any  practical  share  in  digestion,  since  it  can  hardly  ever 
happen  that  milk  passes  through  the  stomach  without  being  curdled. 

Trypsinogen  has  no  action  upon  proteins,  but  in  normal  digestion 
it  is  changed  into  active  trypsin  by  the  enterokinase  of  the  intestinal 
juice  (p.  372).  Pancreatic  juice  collected  without  contact  with 
intestinal  contents  or  unth  the  mucous  membrane  of  the  intestine 


THE  CHEMISTRY  OE  THE  DIGESTIVE  JUICES  35*} 

does  not  digest  proteins.  The  same,  is  true  of  extracts  of  perfectly 
fresh  pancreas,  but  if  the  pancreas  is  allowed  to  stand  for  a  time,  the 
extracts  contain  active  trypsin,  perhaps  because  some  decomposition 
product  has  activated  the  trypsinogen.  Some  writers,  however, 
state  that  when  contamination  of  the  gland  with  intestinal  contents 
or  contact  with  the  mucosa  has  been  avoided  in  its  removal  from 
the  body,  such  extracts  will  remain  inactive  for  months,  although 
the  trypsinogen  can  at  once  be  activated  to  trypsin  by  the  addition 
of  t-ntcrokinase. 

Trypsin,  to  a  certain  extent,  corresponds  with  pepsin  in  its  action 
on  proteins.  But  it  acts  energetically  in  an  alkaline  as  well  as  in  a 
not  too  acid  medium  (a  very  slight  amount  of  digestion  may  go  on  in 
distilled  water) ;  and  its  action,  unhke  that  of  pepsin — at  least  in 
digestions  of  moderate  duration — -does  not  stop  at  the  peptone  stage, 
but  goes  on  rapidly  to  the  production  of  the  amino-acids,  the  basic 
substances  arginin,  lysin,  and  histidin,  known  as  the  hexone  bases, 
and  most  of  the  other  decomposition  products  obtained  by  boiling 
proteins  with  dilute  acids.  The  most  important  of  these  products, 
so  far  as  they  have  been  isolated  and  identified,  are  enumerated  in 
the  table  on  p.  360  (see  also  pp.  1-3). 

As  to  tjie  chemical  nomenclature  of  these  bodies,  the  student  should 
refer  to  his  textbook  of  organic  chemistry.  It  need  only  be  remarked 
here,  by  way  of  illustration,  that  when,  e.g.,  leucin  is  designated  as 
a-amino-isobutylacetic  acid,  this  indicates  that  it  can  be  derived  from 
the  fatty  acid  isobutylacetic  acid  by  the  substitution  of  an  amino  group, 
XH.,,  for  a  hydrogen  atom  in  the  a-carbon  group  (see  p.  556)  of  the 
fatty  acid — i.e.,  the  group  next  the  carboxyl  (COOH)  group.     Tims, 

^JJ^NcH.CHa.CHa.COOH  ,  ^^sXcH.CHg.CH.COOH. 
3/  „  3/  I 

Isobutylacetic  acid.  Leucin.      -^Hg 

When  norleucin,  an  amino-acid  found  especially  in  the  proteins  of 
nervous  tissue,  is  termed  a-amino-caproic  acid,  it  is  indicated  that  NH2 
replaces  one  H  in  the  aCH^  group  of  caproic  acid  (CH3.CH2.CH2.CH2. 
CHoCOOH).  The  long  chemical  name  of  isoleucin  (a  compound  also 
derived  from  the  proteins  of  nervous  tissue  and  from  some  plant  protcinsj 
indicates  that  in  propionic  acid, 

CH3.CHa.COOH, 
/3        a 
NH2  is  introduced  into  the  a  group,  yielding 

CH3.CH.COOH, 

NH2 

or  amino-propionic  acid  (alanin);  while  in  the  ,3  group  one  H  is  repl.icod 
by  a  methyl  (CH3)  group,  and  another  H  by  an  ::ihyl  {CM^)  giouu, 
yielding  finally  isonuclein : 

^^^^CH.CH.COOH. 

NH, 


i6« 


DIGESTION 


:t:  u 


CHIEF  DECOMPOSITION  PRODUCTS  OF  PROTEINS. 

MONOAMINO-ACIDS    AND    THEIR    COMPOUNDS. 

/Glycin  or  glycocoll  (aminoacetic  acid),  CHjlNHjjCOOH. 

Alanin  (aminopropionic  acid),  CH3Cli(NH2)COOH. 

Serin  or  oxyalanin  (oxyaminopropionic  acid), 

CH20H.CH(NH,).C00H. 

CH  \ 
Valin  or  aminovalerianic  acid,  q|^3^CHCH(NH2)COOH. 

^     Leucin  (a-aminoisobutylacetic  acid)  ^[j3\cHCH2CH(NH2)COOH. 

~  s  Norleucin  (a-amino-caproic  acid), 

CH3.CH2.CH2.CH2.CH(N'H2).COOH. 

Isoleiicin  (a-amino-/'<-metliyl-/3-ethyl-proi)ionic  acid), 

(?^3  ^CH.CH{NH2).COOH. 

Cystein  (a  -  amino-/3  -  thiopropionic  acid),  CH2  (SH).CH(NH2)COOH, 
which  is  unstable,  two  molecules  of  it  easily  yielding  cystin 
di-(a-amino-/3-thiopropionic  acid) , 

COOH.CH(NH2).CHa.S.S.CH2.CH(NHa).COOH. 

Aspartic  or  aminosuccinic  acid,  CH(NH2).COOH. 

I 
CH2COOH. 

Glutamic  or  glutaminic  acid,  ^i^z'^ ^h'^cOOH^^^ 


^  ^  ^ 

c -S  >  CTvrosin  (para-oxvphenvlaminopropionic  acid), 

IpI^-"     ■  '  CfiH40H.CH2.CH(NH2).COOH. 

S  3.>  (phenylalanin  (phenylanainopropionic  acid),  C6H5CH2CH(NH2)COOH. 


(Prolin  (pyrrolidin  carboxylic  acid). 
Oxyprolin  (oxypyrrolidin  carboxylic  acid). 
Tryptophane  (a-amino-/3-indol-propionic  acid), 
P  5  rt  1  /NH— CH 


?^c  1- 


HC/"  11 

^N  —  C— CH2.CH(NH,).COOH. 
Histidin  ()8-imidazol-a-aminopropionic  acid),  CgH9N302. 


DIAMINO-ACIDS    AND    THEIR    COMPOUNDS. 

«.    /'Lysin  (a-amino-f-amino-caproic  acid,  CH2NH2(CH2)3CH(NH2)COOH. 


^^ 


.\rginin  (guanidinaminovalerianic  acid) 

HN  =  c/^'"2 


N  H  CH2  (CH2)2CH  {NH,)COOH . 


Ammonia  (representing  the  so-called  '  amide-nitrogen,'  and  liberated 
from  the  products  of  acid  hydrolysis  of  proteins  by  heating  the 
mixture  after  addition  of  alkali).  It  has  not  been  shown  that 
ammonia  is  itself  one  of  the  '  Bansteine '  of  the  proteins. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  361 

In  the  artificial  compounds  of  two  or  more  amiiio-acids  which  have 
been  syiithcsiz.'d  by  Fischer  and  named  by  him  polypeptides  (p.  2), 
the  carboxyl  group  of  one  aniino-acid  is  linked  with  the  amino  group 
of  another.  For  example,  a  molecule  of  alanin  and  a  molecule  of  glycin 
form,  with  loss  of  a  molecule  of  water,  a  molecule  of  alanyl-glycin, 
according  to  the  equation 


NHa.CHa.COiOH+HiNH.CH.CHa— H20=NH2.CH2.CO.NH.CH.CH3. 
COOH  COOH 

Glycin.  Alanin.  Glycyl-alanin. 

Two  or  more  molecules  of  the  same  amino-acid  can  be  linked  in  the 
same  way;  e.g.,  two  molecules  of  glycin  yield  a  molecule  of  glycyl-glycin, 
and  so  on.  It  has  been  pro\'ed  that  polypeptides  identical  with  some  of 
these  synthetic  bodies  are  present  in  the  peptone  mixtures  derived  from 
the  native  proteins,  so  that  it  must  be  assumed  that  one  of  the  ways 
at  least  in  which  amino-acids  are  linked  in  the  protein  molecule  is  that 
described. 

It  has  been  suggested  that  the  early  appearance  of  some  of  these 
amino-acids  in  pancreatic  digestion  is  not  really  due  to  trypsin,  but 
to  other  ferments,  peptases,  which  act  upon  the  peptones  formed  by 
the  trypsin.  There  is,  however,  no  clear  evidence  of  the  existence 
of  a  separate  peptone-splitting  enzyme  in  pancreatic  juice,  like  the 
erepsin  of  intestinal  juice,  and  it  is  therefore  most  natural  to  suppose 
that  under  the  influence  of  trypsin  the  protein  molecule  breaks  at 
different  points  from  those  at  which  it  ruptures  under  the  influence 
of  pepsin. 

After  the  most  prolonged  artificial  digestion  with  trypsin,  a 
residue  of  the  protein  remains  unconverted  into  these  relatively 
simple  substances.  But  even  this  small  portion  of  the  original 
protein  has  undergone  a  great  change,  for  it  no  longer  gives  the 
biuret  reaction.  It  can  be  split  into  amino-acids,  etc.,  by  heating 
with  acid,  and  also  by  the  action  of  the  erepsin  of  the  intestinal  juice, 
and  then  yields  mainly  prolin  and  phenylalanin,  substances  which 
are  generally  not  to  be  detected  among  the  decomposition  products 
of  protein  after  digestion  with  pancreatic  juice.  This  illustrates  the 
important  fact  that  some  of  the  '  building  stones  '  of  the  protein 
molecule  can  be  separated  from  it  with  far  greater  ease  than  others. 
T^TOsin,  tryptophane,  and  cystin  appear  very  early  in  the  digestive 
fluid,  and  tyrosin,  as  shown  in  the  following  example  from  Abder- 
halden,  may  be  completely  liberated  at  a  time  when  glutaminic  acid 
is  scarcely  more  than  beginning  to  appear. 

The  plant  protein  edestin,  obtained  from  cottonseed,  was  digested 
with  pancreatic  juice  or  an  extract  containing  trypsin.  The  quan- 
tities of  tyrosin  and  glutaminic  acid  liberated  at  different  periods 
of  the  experiment  are  expressed  as  percentages  of  the  total  amounts 
of  these  substances  contained  in  the  edestin. 


362 

DIGESTION 

Duration  of  Digestion  : 

I  Day. 

1 

2  Days. 

1 

3  Days. 

7  Days. 

t6  Days. 

Tyros  in 
Glutaminic  acid 

784 

43 

976 

'       74 

976 
109 

100 
31- 1 

100 
6o"2 

When  trypsin  acts  upon  protein  already  digested  by  pepsin,  this 
partially  hydrolyscd  residue  is  smaller  than  when  the  trypsin  acts 
alone,  no  matter  for  how  long  a  time.  Also  the  decomposition  of 
a  given  quantity  of  protein  by  trypsin  is  accomplished  in  a  notably 
shorter  time  if  it  has  been  previously  subjected  to  the  action  of 
pepsin.  This  illustrates  the  co-operative  relation  of  these  two 
ferments — a  relation  still  more  clearly  implied  in  the  fact  that, 
although  trypsin  readily  forms  albumoses  and  peptones  from  native 
protein  when  such  is  offered  to  it,  yet  in  natural  digestion  the  great 
albumose-  and  peptone-forming  ferment  is  pepsin.  In  the  lumen  of 
the  intestine  the  trypsin  is  confronted  mainly  with  protein  already 
hydrolysed  to  the  albumose  and  peptone  stage  in  the  stomach.  In 
other  words,  instead  of  the  very  large  molecules  of  the  original 
protein  food  with  a  weight  of  perhaps  5,000  to  7,000,  the  trypsin 
begins  its  action  on  a  much  larger  number  of  much  smaller  molecules 
of  only  one-twentieth  the  initial  weight  or  less.  The  statement  is 
sometimes  made  that  trypsin  is  a  stronger  proteoh^ic  ferment  than 
pepsin.  This  may  be  true  in  the  sense  that  trypsin  carries  the  de- 
composition down  to  bodies  of  smaller  molecular  weight  than  pepsin. 
But  within  the  range  of  its  hydrolytic  action  pepsin  decomposes 
certain  proteins  and  alhed  bodies  more  readily  than  trypsin — e.g., 
the  serum  proteins,  and  especially  elastin  and  the  constituents  of 
connective  tissue. 

In  all  that  we  have  hitherto  said  regarding  tryptic  digestion  we 
have  supposed  that  putrefaction  has  been  entirely  prevented— d."., 
by  the  addition  of  toluol.  If  no  antiseptic  is  added  to  a  tryptic 
digest,  it  rapidly  becomes  filled  with  micro-organisms,  and  emits  a 
very  disagreeable  facal  odour;  and  now  various  bodies  which  are  not 
found  in  the  absence  of  putrefaction  make  their  appearance,  such  as 
indol,  skatol,  and  other  substances,  to  which  the  faecal  odour  is  due. 
They  are  not  true  products  of  tryptic  digestion,  but  are  formed  by 
the  putrefactive  micro-organisms,  which  can  themselves  split  off 
from  proteins  numerous  decomposition  products,  including  tyrosin, 
and  change  tyrosin  into  indol. 

Amylase  or  pancreatic  amylase,  the  diastatic  or  sugar-forming 
ferment  of  pancreatic  juice,  changes  starch  into  dextrin  and  maltose, 
just  as  the  ptvalin  of  saliva  does.  The  two  ferments  are  possibly 
identical,  but  under  the  conditions  of  action  of  the  pancreatic  juice 
its  diastatic  power  is  greater  than  that  of  saliva,  and  it  readily  acts 


THE  CHEMISTRY  OE  THE  DIGESTIVE  JUICES  363 

on  raw  starch  as  well  as  boiled.  Pancreatic  amylase  is  mainly, 
perhaps  entirely,  present  in  the  juice  in  the  form  of  active  ferment. 
If  a  zymogen  stage  exists,  the  mother-substance  is  less  stable  or  less 
easily  extracted  from  the  gland  than  is  trypsinogen.  In  this  respect 
amylase  also  resemljles  ptyalin.  A  small  amount  of  maltatx;  is 
contained  in  pancreatic  juice,  and  further  hydrolyses  to  dextrose  a 
portion  of  the  maltose  formed  by  the  amylase. 

Steapsiii  or  pancreatic  lipase  splits  up  neutral  fats  into  glycerin  and 
the  corresponding  fatty  acids.  The  latter  unite  with  the  alkalies  of 
the  pancreatic  juice  and  the  bile  to  form  soaps.  In  this  important 
process  bile  acts  as  the  helpmate  of  pancreatic  juice;  together  they 
effect  much  more  than  either  or  both  can  accomplish  by  separate 
action.  Many  tissues  contain  fat-splitting  ferments  or  lipases,  some 
of  which  are  perhaps  identical  with  the  pancreatic  lipase.  The  lipase 
exists  as  active  ferment  in  the  pancreatic  juice,  but  there  is  reason 
to  believe  that  a  portion  of  it  may  be  present  as  a  zymogen  in  the 
gland,  and  probably  in  the  secretion  as  well.  It  is  changed  into 
active  ferment  by  the  bile  salts.  Active  lipase  can  also  be  extracted 
from  the  pancreas  by  glycerin  or  water.  It  is  to  be  noted  that  it  is 
only  the  proteolytic  enzyme  which  is  totally  inactive  till  it  reaches 
the  intestine.     The  significance  of  this  will  be  discussed  later  on. 

Bile. — Bile  is  a  liquid  the  colour  of  which  varies  in  different  groups 
of  animals,  and  even  in  the  same  species  is  not  constant,  depending 
on  the  length  of  time  the  fluid  has  remained  in  the  gall-bladder  and 
other  circumstances.  When  it  is  recognized  that  the  colour  is  due 
to  a  series  of  pigments,  which  are  by  no  means  stable,  and  of  which 
one  can  be  caused  to  pass  into  another  by  oxidation  or  reduction, 
this  want  of  uniformity  will  be  easily  intelligible.  The  fresh  bile  of 
carnivora  is  golden-red.  The  bile  of  herbivorous  animals  is  in 
general  of  a  green  tint,  but,  when  it  has  been  retained  long  in  the 
gall-bladder,  may  incline  to  reddish-brown.  Fresh  human  bile,  as 
it  flows  from  a  fistula  just  established,  is  of  a  reddish-brown,  golden- 
yellow  or  yellow  colour.  Beaumont  speaks  of  the  yellowish  bile 
which  he  could  press  into  the  stomach  of  St.  Martin  by  manipulating 
the  abdomen.  In  a  case  observed  by  the  writer,  it  was  seen  that 
when  the  bile  flowing  from  a  fistula  was  allowed  to  spread  out  in  a 
dressing,  it  became  greenish,  because  of  oxidation  of  a  part  of  the 
biHrubin  to  biliverdin,  although  as  it  actually  escaped  from  the  fistula 
it  was  yellow.  The  bile  of  a  monke}'-  taken  from  the  gall-bladder 
immediately  after  death  is  dark  green,  but  if  left  a  few  hours  in  the 
gall-bladder  it  is  brown,  the  green  pigment  having  been  reduced.  It 
should  be  remembered  that  human  bile  from  the  post-mortem  room 
may  alter  its  colour  in  the  interval  which  must  elapse  before  it  can 
usually  be  procured  after  death.  Bile,  as  obtained  from  fistulae  in 
otherwise  healthy  persons,  has  a  specific  gravity  of  about  1008  to 
10 10,     In  the  gall-bladder  water  is  absorbed   from  the  bile  and 


3^4 


DIGESTION 


mucin  added  to  it,  so  that  the  specific  gravity  of  bladder  bile  is  as 
high  as  1030  to  1040.     The  reaction  is  feebly  alkaline  to  litmus. 

The  composition  of  two  specimens  of  human  bile— one  from  a  fistula, 
the  other  from  the  gall-bladder — is  shown  in  the  following  table: 


Bladder  Bile. 

Fistula  Bile. 

Water  -            -            -            -            - 

898-1 

977-4 

SoUds   ----- 

loi-g 

22-6 

Mucin  and  other  substances  insoluble 

in  alcohol      .             -             -             - 

14-5 

2-3 

Sodium     taurocholate     and     sodium 

glycocholate                -              -              . 

56-5 

lO-I 

Inorganic  salts               _             -             - 

6-3 

8-5 

Fat               ] 

Lecithin       |-     - 

30-9 

0-05 

CholesterinJ 

0-56 

The  substance  which  renders  bladder  bile  viscid,  but  which  is  present 
in  much  smaller  amount  in  bile  from  a  fistula,  and  is  probably  entirely 
absent  from  the  fluid  as  it  is  secreted  by  the  liver-cells,  is  commonly 
termed  'mucin.'  It  has  been  shown,  however,  that  in  many  animals — 
for  example,  the  ox,  dog,  sheep,  etc. — the  substance  is  not  a  true  mucin. 
It  does  not  yield,  like  mucin,  on  boiling  with  dilute  acid,  a  carbo- 
hydrate group  (viz.,  glucosamine,  CgHii()5NH2,  corresponding  to 
dextrose  in  which  OH  is  replaced  by  NHg) .  It  is  relatively  rich  in  phos- 
phorus, and  consists — mainly,  at  any  rate — of  a  phospho-protein  (p.  2). 
The  mucilaginous  substance  of  human  bile  consists  largely  of  true  mucin. 

Mucin  is  scarcely  to  be  looked  upon  as  an  essential  constituent  of 
bile;  it  is  not  formed  by  the  actual  bile-secreting  cells,  but  by  mucous 
glands  in  the  walls  and  goblet-cells  in  the  epithelial  lining  of  the  larger 
bile -ducts,  and  especially  of  the  gall-bladder. 

Bile-Pigments. — It  has  been  said  that  these  form  a  series,  but  only 
two  of  the  pigments  of  that  series  are  present  in  normal  bile,  bilirubin, 
and  biliverdin.  In  human  bile,  the  former,  in  herbivorous  bile  and 
that  of  some  cold-blooded  animals,  such  as  the  frog,  the  latter  is  the 
chief  pigment.  But  bilirubin  can  be  extracted  in  large  amount  from 
the  gall-stones  of  cattle ;  while  the  placenta  of  the  bitch  contains  bili- 
verdin in  quantity,  although,  as  in  all  camivora,  it  is  either  absent 
from  the  bile  or  exists  in  it  in  comparatively  small  amount.  These 
facts  show  that  the  two  pigments  are  readily  interchangeable,  but  there 
is  no  question  that  bilirubin  is  the  pigment  which  is  formed  by  the 
liver-cells. 

Bilirubin  (C32H38N4O6)  can  be  prepared  from  powdered  red  gall- 
stones by  dissolving  the  chalk  with  hydrochloric  acid,  and  extracting 
the  residue  with  chloroform,  which  takes  up  the  pigment.  From  this 
solution,  on  evaporation,  or  from  hot  dimethyl  anilin,  beautiful  rhombic 
tables  or  prisms  of  bilirubin  separate  out. 

Biliverdin  (C32H3gN40g)  can  be  obtained  from  the  placenta  of  the 
bitch  by  extraction  with  alcohol.  It  is  insoluble  in  chloroform,  and  by 
means  of  this  property  it  may  be  separated  from  bilirubin  when  the  two 
happen  to  be  present  together  in  bile.  Biliverdin  can  also  be  formed 
from  bilirubin  by  oxidation.     By  the  aid  of  active  oxidizing  agents. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  365 

such  as  yellow  nitric  acid  (which  contains  some  nitrous  acid),  a  whole 
series  of  oxidation  products  of  bilirubin  is  obtained,  beginning  with 
biliverdin,  and  passing  through  bilicyanin,  a  blue  pigment,  and  other 
intermediate  bodies,  to  cholctelin,  a  yellow  substance.  Tt  is  question- 
able whether  these  are  all  definite  compounds.  This  is  the  foundation 
of  GmeUn's  test  for  Inle-pigments  (sec  Practical  Exercises,  p.  462)-  The 
same  colours  arc  produced,  and  in  the  same  order,  when  a  solution  of 
bilirubin  in  chloroform  is  treated  with  a  dilute  alcoholic  solution  of  iodine . 

The  positi\e  pole  of  a  galvanic  current  causes  the  same  oxidative 
changes,  the  same  play  of  colours,  while  the  reducing  action  of  the 
negative  pole  reverses  the  effect,  if  the  action  of  the  positive  electrode 
has  not  gone  too  far.  These  reactions  can  also  be  used  for  the  detection 
of  bile -pigments. 

By  the  reducing  action  of  sodium  amalgam  on  bilirubin,  hemi- 
bilirubin  (C33H44N4O6)  is  obtained.  It  gives  a  beautiful  red  colour  with 
*-dimethylaminobcnzaldehyde  (Ehrlich's  reaction).  Hemibilirubin  is 
identical  with  the  urobilinogen  of  urine  from  which  urobilin  is  derived. 
Urobilinogen  and  urobilin  (often  called  in  this  connection  stercobilin) 
are  also  found  in  the  faeces  from  birth  onwards,  although  not  in'  the 
meconium  (p.  424).  Urobilinogen  is  derived  from  the  normal  bile- 
pigment  by  reduction  in  the  intestine  itself,  where  reducing  substances 
due  to  the  action  of  micro-organisms  are  never  absent  in  extra-uterine  life. 

The  bile  of  most  animals  shows  no  characteristic  absorption  spectrum. 
But  the  fresh  bile  of  certain  animals,  the  ox,  for  instance,  does  show 
bands.  These,  however,  are  not  due  to  the  normal  bile-pigment,  and 
they  are  not  essentially  changed  when  this  is  oxidized  or  reduced  by- 
electrolysis.  MacMunn  attributes  the  spectrum  of  the  bile  of  the  ox 
and  sheep  to  a  body  which  he  calls  cholohaematin,  and  which  does  not 
belong  to  the  bile-pigments  proper. 

The  Bile-Salts. — These  are  the  sodium  salts  of  certain  acids,  of  which 
glycocholic  and  taurocholic  are  the  chief.  In  the  bile  of  omnivora, 
including  man,  both  are  in  general  present,  and  in  various  proportions; 
in  human  bile  there  is  more  glycocholic  than  taurocholic  acid ;  some- 
times taurocholic  acid  is  entirely  absent.  In  the  bile  of  many  camivora 
— e.g.,  the  dog  and  cat — only  taurocholic  acid  is  found;  in  that  of  the 
camivora  generally  it  is  by  far  the  more  important  of  the  two  acids. 
In  the  bile  of  most  herbivora  there  is  much  more  glycocholic  than 
taurocholic  acid.  The  bile  acids  are  paired  acids:  glycocholic  acid 
(better  named  cholyl-glycin)  formed  by  the  union  of  glycin  and  cholic 
acid,  and  taurocholic  acid  (or  cholyl-taurin),  consisting  of  cholic  acid 
united  with  taurin. 

The  decomposition  of  the  bile-acids  into  these  substances  is  effected 
by  boiling  them  with  dilute  acid  or  alkali,  a  molecule  of  water  being 
taken  up;  thus — 

C26H43NOe  +  H2O-  CH2(NH2)  .COOH  -1-  C24H40O5 ; 

Glycocholic  acid.  Glycin.  Cholic  acid. 

C26H45NSO7  -^H20=CH2(NH2).CH2.S02.0H  -FC24H4o05. 

Taurocholic  acid.  Taurin.  Cholic  acid. 

A  notable  difference  between  glycocholic  and  taurocholic  acid  is  that 
the  latter  contains  sulphur.  The  whole  of  this  belongs  to  the  taurin. 
Both  glycin  and  taurin  are  derived  from  the  disintegration  of  proteins. 
We  have  already  seen  that  among  the  products  of  protein  hydrolysis  a 
sulphur-containing  body,  cystein,  which  is  readily  changed  into  cystin, 
is  found,  and  there  is  good  evidence  that  taurin  is  derived  from  cystein 


36^. 


DIGESTION 


or  cystin.  In  certain  pathological  conditions  cystin  appears  in  tho 
urine  (cystin uria).  The  source  of  the  cholic  acid  whicli  goes  to  form 
the  bile  acids  is  unknown,  but  it  has  been  surmised  that  it  may  be 
derived  from  cholesterin.     Thus, 

[CH2.SH+3O     CH2.SO2.OH     CH2.SO2.OH 

I  I  I 

CH.NHg    =     CH.NH2     =     CH.NH2 

I  I 

COOH  COOH— CO2 

Cystein.  Cysteinic  acid.  Taurin. 

Traces  of  cholic  acid,  formed  by  hydrolysis  from  the  bile-acids  by 
the  action  of  putrefactive  bacteria,  are  found  in  the  intestmes,  especially 
in  tlie  lower  portion. 

Pettenkofer' s  test  for  bile-acids  (Practical  Exercises,  p.  462),  acciden- 
tally discovered  in  examining  the  action  of  bile  upon  sugar,  depends  upon 
three  facts:  (i)  That  cholic  acid  and  furfuraldehyde  give  a  purple  colour 
when  brought  together;  (2)  that  the  bile-salts  yield  cholic  acid  when 
acted  upon  by  sulphuric  acid ;  (3)  tliat  when  cane-sugar  is  decomposed 
bv  strong  sulphuric  acid,  furfuraldehyde  is  formed. 

Since  a  similar  colour  is  given  when  the  same  reagents  are  added  to  a 
solution  containing  albumin,  it  is  necessary  to  remove  this,  if  present, 
from  any  liquid  which  is  to  be  tested  for  bile-acids. 

Lecithin  and  cholesterin,  or  cholesterol,  are  by  no  means  peculiar  to 
bile  (p.  4).  They  are  very  widely  distributed  in  the  body.  Ixcithin 
(C44H90NPO9)  belongs  to  the  group  of  phosphatides,  fat-like  phosphorus- 
containing  substances  present  in  all  cells.  It  is  a  comj)OMml  of  glycerin 
with  two  molecules  of  fatty  acid  and  one  of  phosphoric  acid.  The 
phosphoric  acid  is  at  the  same  time  united  with  a  base  cholin  (C5H15NO2). 
Tlie  fatty  acid  (stearic,  palmitic,  oleic,  etc.)  varies  in  different  varieties 
of  lecithin .  Heated  with  baryta-water,  lecithin  yields  the  corresponding 
fatty  acid  in  the  form  of  a  soaji,  along  with  cholin  and  glyceryl-phos- 
phoric  acid.  Glycerj'l-phosphoric  acid  can  be  further  split  so  as  to 
yield  a  molecule  of  glycerin  and  one  of  phosphoric  acid. 

Cholesterin  is  a  substance  with  the  empirical  formula  C27H4eO.  It 
contains  an  alcohol  group  in  virtue  of  which  fatty  acids  can  be  linked 
to  it,  forming  esters.  It  is  best  obtained  from  white  gall-stones,  of 
which  it  is  the  chief,  and  sometimes  almost  the  sole  constituent  (sec 
Practical  Exercises,  p.  4')3). 

All  the  compoimds  related  to  cholesterin  are  grouped  together  under 
the  name  of  sterins.  The  sterins  are  very  widely  distributed  both  in 
animals  (zoostcrins)  and  in  plants  (phytos'terins).  ICvery  cell  seems  to 
contain  sterins  and  sterin  esters  (compounds  of  the  same  nature  as  the 
compounds  of  fatty  acids  with  the  alcohol  glycerin  which  constitute  the 
neutral  fats).  In  the  vertebrates  cholesterin  and  its  product  co  istitute 
the  chief,  j^erhaps  the  only  sterins,  but  in  invertebrate  animals  and 
plants  there  is  a  much  greater  variety  of  these  substances. 

The  chief  inorganic  salts  of  bile  are  sodium  chloride,  sodium  carbonate, 
and  alkaline  sodiiun  phosphate.  The  phosphoric  acid  of  the  ash  comes 
})artly  from  the  phosphorus  of  organic  comjiouiuls  (lecithin  and  bile- 
mucin),  the  sulphuric  acid  from  tlie  sulphur  of  taurocholic  acid,  the 
sodium  largely  from  the  bile-salts.  Iron  is  a  notable  inorganic  con- 
stituent of  bile,  although  it  exists  only  in  traces,  in  the  form  of  phosphate 
of  iron.  Manganese  is  also  present  in  minute  amount.  100  c.c.  of 
fresh  bile  yields  50  to  100  c.c.  of  carbon  dioxide,  part  of  which  is  in 
solution  and  part  combined  with  alkalies. 


TMK  CHEMlSTRV  Of  THE  blCESTlVE  JUICED  3C7 

The  quantity  of  bile  secreted  in  twenty- four  hours  in  an  average 
niiui  is  probably  from  750  c.c.  to  a  htre.  In  nine-  cases  of  fistula  ol 
the  gall-bladder  in  patients  operated  on  for  gall-stones  or  cchino- 
coccus  the  daily  (piaiUity  varied  from  500  to  1,100  c.c.  (Brand). 

Digestive  Functions  of  Bile. — The  great  action  of  the  bile  in 
digestion  is  undoubtedly  the  preparation  of  the  fats  for  absorption. 
In  this  preparation  four  processes  are  important:  two  chemical 
actions,  hydrolysis  of  neutral  fats  to  glycerin  and  fatty  acids,  and 
saponification,  or  the  formation  of  soaps  by  the  union  of  fatty  acids 
with  l)ases,  especially  sodium ;  and  two  physical  processes,  emulsifi- 
cation,  or  the  formation  of  a  mechanical  suspension  of  such  fine 
globules  of  unaltered  neutral  fat  as  exist  in  milk,  and  sohition  of 
soaps  and  fatty  acids.  While  there  has  been  much  discussion  as  to 
the  relative  share  taken  by  these  processes,  and  especially  by  saponi- 
fication and  emulsification  in  the  absorption  of  fat  (p.  441),  there  is 
no  doubt  that  they  are  all  concerned  in  the  digestion  of  fat  or  the 
preparation  of  it  for  absorption  and  assimilation.  In  this,  indeed, 
the  processes  are  complementary  to  each  other,  for  an  essential  pre- 
liminary to  emulsification  in  the  intestine  seems  to  be  the  formation 
of  a  certain  amount  of  soaps,  soluble  in  the  intestinal  contents,  while 
the  formation  of  an  emulsion  enormously  increases  the  surface  of 
contact  between  the  unaltered  fat  and  the  digestive  juices,  and  so 
favours  more  rapid  hydrolysis,  saponification,  and  solution.  In  the 
whole  series  of  changes  the  bile  plays  a  part,  though  not  an  indepen- 
dent one;  it  acts  always  in  conjunction  with  the  pancreatic  juice. 

While  no  complete  explanation  has  been  given  of  the  precise 
nature  of  this  partnership,  it  is  certain  that  the  fat-sphtting  ferment 
of  the  pancreatic  juice  on  the  one  hand,  and  the  bile-salts  on  the 
other,  contribute  largely  to  the  total  action.  An  alkaline  solution, 
a  solution  of  sodium  carbonate,  e.g.,  is  unable  of  itself  to  emulsify 
a  perfectly  neutral  oil ;  but  if  some  free  fatty  acid  be  added,  emulsifi- 
cation is  rapid  and  complete  (p.  12).  Now,  there  is  no  doubt  that 
here  a  soap  is  formed  by  the  action  of  the  alkali  on  the  fatty  acid, 
and  there  is  equally  little  doubt  that  the  formation  of  the  soap  is  an 
essential  part  of  the  emulsification.  But  it  is  not  clear  in  what 
manner  the  soap  acts,  whether  by  forming  a  coating  round  the  oil- 
globules,  or  by  so  altering  the  surface-tension,  or  other  physical 
properties  of  the  solution  in  which  it  is  dissolved,  that  the3^  no  longer 
tend  to  run  together.  Howev^er  this  may  be,  in  pancreatic  juice  we 
have  the  two  factors  present  which  this  simple  experiment  shows 
to  be  necessary  and  sufiicient  for  emulsification  ;  we  have  a  ferment 
which  can  split  up  neutral  fats  and  set  free  fatty  acids,  and  an  alkali 
which  can  combine  with  those  acids  to  form  soaps.  Accordingly, 
pancreatic  juice  is  able  of  itself  to  form  emulsions  with  perfectly 
neutral  oils.  It  is  possible  that  the  protein  constituents  of  pancreatic 
juice  may  have  a  share  in  emulsification,  since  the  addition  of  protein 


368  DIGESTION 

— e.g.,  ogg-vvhjtc — to  a  soap  solution  increases  the  stability  of  the 
emulsions  formed  by  the  soap.  In  bile,  on  the  contrary,  although 
the  alkali  is  present,  there  is  no  fat-splitting  ferment,  and,  according 
to  the  best  experiments,  bile  alone  has  no  emulsifying  power  on 
perfectly  neutral  fat.  But  we  now  come  to  a  remarkable  fact:  this 
inert  bile  when  added  to  pancreatic  juice  greatly  intensifies  its 
emulsifying  action,  and  a  solution  of  bile-salts  has  much  the  same 
effect  as  bile  itself.  The  fact  is  undoubted,  but  the  explanation  is 
obscure.  What  it  is  that  the  bile  or  bile-salts  can  add  to  the 
pancreatic  juice  which  so  increases  its  power  of  emulsification,  we  dc» 
not  know.  It  has  been  surmised  that  a  characteristic  physical 
property  of  bile,  the  diminution  of  the  surface-tension  of  watery 
liquids  to  which  it  is  added,  may  play  an  important  part,  perhaps, 
in  enabling  thq  fat-splitting  ferments  or  the  emulsifying  soaps  to  get 
into  closer  contact  with  the  unaltered  fat.  It  is  also  true  that 
bile,  presumably  in  virtue  of  the  chemical  action  of  its  alkaline 
salts,  can,  in  presence  of  a  free  fatty  acid,  rapidly  form  an  emulsion. 
But  the  pancreatic  juice  itself  contains  so  considerable  a  quantity  of 
sodium  carbonate  that  it  would  scarcely  seem  to  require  the  rela- 
tively feeble  reinforcement  of  the  alkaline  salts  of  the  bile.* 

An  important  part  of  the  effect  of  the  bile  is  certainly  due  to  its 
favouring  the  fat-splitting  action  of  the  pancreatic  juice.  By  the 
addition  of  bile,  the  quantity  of  fat  split  up  by  a  definite  amount  of 
dog's  pancreatic  juice  may  be  increased  two  to  threefold.  It  has 
been  shown  that  this  is  an  action  of  the  bile-salts.  The  sodium 
salts  of  synthetically-obtained  glycochoUc  and  taurocholic  acids 
produce  the  same  effect.  It  is  in  virtue  of  this  action  that  the  bile- 
salts  are  sometimes  spoken  of  as  the  co-ferment  of  the  lipase.  As 
already  pointed  out,  this  action  is  exerted  in  presence  of  the  fully 
formed  enzyme,  and  should  not  be  confounded  with  the  effect  of  the 
bile-salts  in  activating  the  lipase  zymogen.  The  capacity  of  dis- 
solving soaps,  which  is  a  property  of  the  bile-salts,  is  also  of  great 
importance  in  supplementing  the  solvent  power  of  the  intestinal 
liquids  for  the  products  formed  by  the  pancreatic  juice.  The 
solution  of  soaps  in  the  bile-salts  has  the  power  in  its  turn  of  dis- 
solving free  fatty  acids.  The  significance  of  this  in  fat  absorption 
will  be  referred  to  again.  A  further  illustration  of  the  mutual 
adaptation  of  the  various  digestive  juices,  of  the  remarkably  precise 
manner  in  which  the  action  of  each  dovetails  into  the  action  of 
others,  is  afforded  by  the  facts  alread}'  mentioned  in  connection  with 
the  lipase  of  the  stomach.  It  is  highly  probable  that  the  fatty  acids 
formed  by  the  gastric  lipase,  even  if  formed  only  in  small  amount, 
may  exertan  important  influence  in  emulsifying  the  fat  as  soon  as  it 
enters  the  intestine.  The  intestinal  juice  itself  also  unquestionably 
takes  a  share  in  the  digestion  of  fat  along  with  the  pancreatic 

•  It  has  lately  been  shown  that  bile-saUs  accelerate  the  formation  of  soap 
from  oleic  acid  by  sodium  bicarbonate  (Kingsbury). 


THE  LllF.MISTRV  OF  THE  DIGESTIVE  JUICES  369 

secretion  and  the  bile.  Tliere  exists  also,  as  will  be  seen  later  (ni,  a 
certani  adajitation  betvvei'n  the  food  and  the  digestive  secretions. 
Not  tiie  best  illustration  of  this,  but  one  wliich  suits  the  present  topic, 
is  the  fact  that  the  food  itself  probably  always  contains  some  free 
fatty  acids  when  it  contains  fat  at  all.  Although  our  knowledge  of 
the  mutual  action  of  the  pancreatic  juice  and  the  bile  on  the  digestion 
of  fats  is  still  incomplete,  there  is  no  doubt  that  they  are  equally 
necessary.  For  in  some  diseases  of  the  pancreas  fat  or  fatty  acid 
often  appears  in  the  stools,  and  this  token  of  imperfect  digestion  of 
the  fatty  food  may  be  conlirmed  by  the  wasting  of  the  patient.  The 
same  may  occur  when  the  bile  is  prevented  by  obstruction  of  the 
duct  or  by  a  biliary  fistula  from  entering  the  intestine.  Yet  in  some 
cases  of  fistula,  where  there  is  every  reason  to  believe  that  all  the  bile 
is  escaping  externally',  the  nutrition  of  the  patient — at  any  rate,  on  a 
diet  not  abnormally  rich  in  fat — is  unaffected.  The  mere  deficiency 
of  bile  in  the  intestine  is,  of  course,  compUcated  in  obstructive 
jaundice  by  the  harmful  effects  of  the  biliary  constituents  circulating 
in  the  blood. 

The  white  stools  of  jaundice  owe  their  colour,  not  merely  to  the 
absence  of  bile-pigment,  but  also  to  the  presence  of  fat.  Their  highly 
offensive  odour  used  to  be  adduced  as  evidence  that  bile  is  the  '  natural 
antiseptic  '  of  the  intestine.  It  seems  rather  to  be  due  to  the  coating 
of  the  particles  of  food  with  undigested  fat,  which  shields  the  proteins 
from  the  action  of  the  digestive  juices,  while  permitting  the  putrefactive 
bacteria  to  revel  in  them  unchecked.  As  a  matter  of  fact,  the  bile 
itself  has  little,  if  any,  power  of  hindering  the  growth  of  micro-organisms, 
although  the  free  bile-acids  are  tolerably  active  antiseptics.  In  suckling 
children  it  is  not  uncommon  to  see  the  faeces  white  with  fat.  This  is  a 
less  serious  symptom  than  in  adults,  and  perhaps  betokens  merely  that 
the  milk  in  the  feeding-bottle  is  undiluted  cow's  milk,  which  is  richer 
in  fat  than  human  milk,  and  ought  to  be  mixed  with  water. 

Bidder  and  Schmidt  found  that  the  chyle  in  the  thoracic  duct  of  a 
normal  dog  contained  3*2  per  cent,  of  fat.  In  a  dog  with  the  bile-duct 
ligatured  the  proportion  fell  to  0-2  per  cent.  It  is  an  instance  of  the 
extraordinarily  exact  adaptation  of  the  digestive  juices  to  the  nature 
of  the  food,  the  mechanism  of  which  will  present  itself  for  discussion 
later  on,  that  the  reinforcing  action  of  the  bile  upon  the  fat-splitting 
ferment  of  the  pancreatic  juice  is  said  to  be  greater  when  the  food  is 
rich  in  fat  (p.  414). 

Bile  has  been  credited  with  a  physical  power  of  aiding  the  passage 
of  fat  through  membranes  moistened  with  it  by  diminishing  the  surface 
tension,  and  it  has  been  inferred  that  this  has  an  important  bearing 
on  the  absorption  of  fat  from  the  intestine.  But  the  inference  does 
not  follow  from  the  statement,  and  the  statement  has  been  itself 
denied.  There  is  at  present  no  evidence  that  the  digestive  function 
of  the  bile  extends  beyond  the  preparation  of  the  food  for  absorption 
to  the  preparation  of  the  mucosa  for  absorbing  it. 

On  proteins  bile  has  either  no  digestive  action,  or  only  a  feeble 
one.  Fibrin  is  slightly  digested  by  the  bile  of  the  dog  and  of  man. 
But  the  addition  of  it  to  fresh  pancreatic  juice  considerably  increases 
the  proteol\i:ic  power  of  that  secretion  (Rachford),  although  not  so 
decidedly  as  in  the  case  of  the  fat-splitting  action.     The  amylol\i:ic 

24 


37©  DIGESTION 

action  of  the  pancreatic  juice  is  also  favoured  by  the  bile,  and  in 
about  the  same  degree  as  its  proteoI\-tic  effect.  Although  bile  some- 
times exerts  by  itself  a  feebly  amylol}i:ic  action,  this  is  not  to  be 
included  among  its  specific  powers,  for  a  diastatic  ferment  in  small 
quantities  is  widely  diffused  in  the  body. 

The  addition  of  bile  or  bile-salts  to  a  gastric  digest  causes  the 
precipitation  of  any  unaltered  native  protein,  acid-albumin,  albu- 
mose,  and  pepsin.  The  precipitate,  which  is  a  salt-like  compound 
of  protein  with  taurocholic  acid,  is  redissolved  when  the  liquid  is 
rendered  alkaline,  and  therefore  in  excess  of  bile,  or  of  a  solution  of 
bile-salts,  but  the  pepsin  has  no  longer  any  power  of  digesting 
proteins.  Part  of  the  bile-acids  and  bile-mucin  is  also  thrown  down 
by  the  acid  of  the  digest.  It  has  been  suggested  that  by  thus 
precipitating  the  constituents  of  the  chyme  which  have  not  been 
carried  to  the  peptone  stage  bile  prepares  them  for  the  action  of  the 
pancreatic  juice.  But  it  is  difficult  to  see  how  the  precipitation  of 
a  substance  can  prepare  the  way  for  its  digestion,  and  it  is  more 
probable  that  if  any  physiological  value  is  to  be  given  to  this  reaction, 
it  has  the  function  of  preventing  the  absorption  of  proteins  which 
have  not  been  sufficiently  split  up.  There  is  little  doubt,  however, 
that  the  rendering  of  the  pepsin  inactive  has  physiological  signifi- 
cance, for  pepsin  exerts  an  injurious  influence  upon  the  ferments  of 
the  pancreatic  juice.  In  digestion,  then,  the  bile  has  a  iuofold  func- 
tion, favouring  greatly  the  activity  of  the  pancreatic  ferments,  especially 
the  fat-splitting  ferment,  and  aiding  in  establishing  the  conditions 
necessary  for  the  transition  of  gastric  into  intestinal  digestion. 

Succus  Entericus. — This  is  the  name  given  to  the  special  secretion 
of  the  small  intestine,  which  is  supposed  to  be  a  product  of  the 
Lieberkiihn's  crypts  or  intestinal  glands.  In  order  to  obtain  it  pure, 
it  is  of  course  necessary  to  prevent  admixture  with  the  bile,  the  pan- 
creatic juice,  and  the  food."  This  can  be  done  by  dividing  a  loop  of 
intestine  from  the  rest  by  two  transverse  cuts,  the  abdomen  having 
been  opened  in  the  linea  alba.  The  continuity  of  the  digestive  tube 
is  restored  by  stitching  the  portion  below  the  isolated  loop  to  the 
part  above  it.  One  end  of  the  loop  is  sewed  into  the  lips  of  the 
wound  in  the  linea  alba,  and  the  other  being  closed  by  sutures,  the 
whole  forms  a  sort  of  test-tube  opening  externally  (Thiry's  fistula). 
Or  both  ends  are  made  to  open  through  the  abdominal  wound  (Vella's 
fistula).  Another  method  is  to  make  a  single  opening  in  the  intes- 
tine, and  by  means  of  two  indiarubber  balls,  one  of  which  is  pushed 
down,  and  the  other  up  through  the  opening,  and  which  are  after- 
wards inflated,  to  block  off  a  piece  of  gut  from  communication  with 
the  rest.  Or  several  openings  may  be  made  at  different  levels  in  the 
intestine,  each  being  allowed  to  heal  into  a  w'ound  in  the  abdominal 
wall.  When  pure  juice  is  required  it  is  collected  from  the  lower 
fistulae,  while  the  upper  fistulae  are  opened  to  permit  the  escape  of  the 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  37r 

secretions  which  enter  the  liigher  portions  of  the  alimentary  canal 
(gastric  juice,  pancreatic  juice,  and  bile).  The  intestinal  juice  so 
obtained  is  a  thin  yellowish  liquid  of  alkaline  reaction,  generally 
somewhat  turbid  from  the  presence  of  a  certain  number  of  leucocytes 
and  epithelial  cells.  Its  specific  gravity  is  about  loio,  the  total 
solids  about  1-5  per  cent.  It  contains  a  small  amount  of  proteins, 
including  serum  albumin  and  serum  globulin,  and  about  the  same 
proportion  of  inorganic  salts  as  most  of  the  liquids  and  solids  of  the 
body,  namely,  07  or  o-8  per  cent.,  chiefly  sodium  carbonate  and 
sodium  chloride;  but,  hke  the  other  digestive  liquids,  it  is  adapted 
to  the  nature  of  the  food,  and  therefore  its  composition  is  not  quite 
constant.  Like  bile,  intestinal  juice  acts  but  feebly  on  the  food 
substances  by  itself,  and  if  we  contented  ourselves  with  examining 
the  pure  and  isolated  secretion,  we  should  greatly  underestimate  its 
importance.  The  sodium  carbonate,  in  which  it  is  relatively  rich, 
will,  to  be  sure,  form  soaps  with  fatty  acids  produce!  by  the  action 
of  the  pancreatic  juice  or  of  the  fat-splitting  bacteria  in  which  the 
intestine  abounds,  and  thus  aid  in  the  digestion  of  fats.  A  lipase, 
feebler  than  that  of  the  pancreatic  juice,  or  present  in  smaller  con- 
centration, is  also  a  constituent  of  the  succus  entericus.  That  a 
great  deal  of  fat  may  be  split  up  in  the  ahmentary  canal  in  the 
absence  both  of  bile  and  pancreatic  juice  is  well  ascertained.  The 
alkah  of  the  succus  entericus  must  at  the  same  time  aid  in  neutraliz- 
ing the  original  acidity  of  the  chyme,  and  in  preserving  the  proper 
reaction  of  the  intestinal  contents.  A  ferment  called  invertase,  or 
sucrase — which  is  not  introduced  with  the  food  or  formed  by  bacterial 
action  as  has  been  suggested,  since  it  occurs  in  the  aseptic  intestine 
of  the  new-born  child — will  invert  cane-sugar.  The  ferments  maltase 
and  lactase  will  cause  a  corresponding  change  in  maltose  and  lactose 
(see  footnote,  p.  356).  It  is  worthy  of  remark  that  these  inverting 
enzymes  are  present  in  the  intestinal  mucosa  as  well  as  in  the 
intestinal  juice,  and  extracts  of  the  mucosa  are  usually  distinctly 
more  active  than  the  juice  itself.  So  that  there  is  reason  to  believe 
that  hydrolysis  of  the  disaccharides  may  take  place  both  in  the 
lumen  of  the  gut  before  absorption  and  in  the  wall  of  the  gut  during 
absorption.  Inverting  enzymes  appear  in  the  intestine  early  in 
embryonic  life.  Maltase  is  the  most  generally  distributed  of  all 
these  enzymes,  and  it  is  found  along  with  lactase  in  the  intestine  of 
the  embryo  pig,  while  invertase  is  missing  till  after  birth  (Mendel). 
On  native  proteins  and  starch  the  isolated  succus  entericus  has  little 
or  no  action.  But  it  contains  a  ferment,  crepsin,  which,  although  it 
does  not  affect  native  proteins  like  serum-  and  egg-albumin  (fibrin 
and  caseinogen  may  be  slightl}'  digested),  exerts  a  powerful  action 
on  the  first  products  of  protein  hydrolysis,  albumoses,  and  peptones, 
breaking  them  up  into  bodies  which  no  longer  give  the  biuret  re- 
action   (ammonia,    mono-amino    acids,    hexone    bases,    etc.).     It 


373 


DIoL:3TI0N 


destroys  the  diphtheria  toxin,  wiiich  is  also  rendered  innocuous  by 
trypsin.  Erepsin,  however,  is  not  specific  to  the  secreted  intestinal 
juice,  for  it  occurs  also,  not  only  in  the  mucous  membrane  of  the 
intestine,  which,  indeed,  contains  a  greater  quantity  of  it  than  the 
succus  entericus,  but  in  all  animal  tissues  hitherto  investigated.  It 
is  said  even  to  be  sometimes  present  in  pancreatic  juice,  since  in- 
activated pancreatic  juice,  which  does  not  digest  other  proteins,  will 
sometimes  digest  casein.  But  the  matter  is  far  from  being  settled, 
and  the  presence  of  erepsin  in  the  pancreatic  tissue  is  a  complicating 
circumstance.  For  under  abnormal  conditions,  most  glands  pro- 
\ided  with  artificial  fistulse  have  an  increased  liability  to  injuries 
of  various  kinds,  which  might  permit  constituents  not  normally 
present  in  the  secretion  to  pass  into  it  from  the  cells.  The  kidney  in 
mammals  is  even  richer  in  erepsin  than  the  intestinal  mucous 
membrane.  Next  to  these  come  the  pancreas,  spleen,  and  liver, 
then  at  a  long  interval  the  heart  muscle,  while  skeletal  muscle  and 
brain-tissue  are  poorest  of  all  in  the  ferment.  The  intestinal  mucosa 
varies  in  its  erepsin  content  at  different  levels  and  on  different  diets. 
In  cats  on  a  meat  or  a  mixed  diet  the  duodenum  is  about  five  times 
richer  in  the  ferment  than  the  stomach.  The  ileum  is  about  half  as 
rich  as  the  duodenum,  and  the  jejunum  occupies  an  intermediate 
position  between  the  duodenum  and  ileum  (\'ernon).  The  secretion 
of  Brunner's  glands  in  the  duodenum,  which  resemble  in  structure 
the  pyloric  glands  of  the  stomach,  digests  coagulated  albumin, 
although  its  proteohiric  powers  are  feebler  than  those  of  the  pan- 
creatic juice. 

Enterokinase. — The  most  characteristic  constituent  of  succus 
entericus  is  a  ferment,  enterokinase,  which  differs  from  all  the  fer- 
ments we  have  hitherto  described  in  acting  not  directly  upon  the 
foodstuffs,  but  upon  the  trypsinogen  of  the  pancreatic  juice,  chang- 
ing it  into  the  active  enzyme  trypsin.  It  may  therefore  be  spoken  of 
as  a  ferment  of  ferments.  It  has  been  previously  stated  that  freshly 
secreted  pancreatic  juice  is  without  action  upon  proteins.  The 
addition  of  succus  entericus  immediately  confers  upon  it  a  high 
degree  of  proteolytic  power.  In  one  experiment  pancreatic  juice, 
obtained  by  a  temporary  fistula,  required  four  to  six  hours  to  dissolve 
fibrin,  and  did  not  attack  coagulated  albumin  even  in  ten  hours. 
On  addition  of  succus  entericus,  the  same  pancreatic  juice  dissolved 
fibrin  in  three  to  seven  minutes,  and  rapidly  digested  coagulated 
albumin  (Pawlow).  In  liki-  manner  a  glycerin  extract  of  a  fresh 
pancreas  has  hardly  any  effect  on  proteins;  a  similar  extract  of  a 
stale  pancreas  is  active.  The  fresh  pancreas  contains  trypsinogen, 
which  is  soluble  in  glycerin,  for  the  inert  extract  becomes  active 
when  it  is  treated  with  dilute  acetic  acid,  or  even  when  it  is  diluted 
with  water  and  kept  at  the  body-temperature.  If  the  fresh  pancreas 
be  first  treated  with  dilute  acetic  acid,  and  then  with  glycerin,  the 


run  cii !■  mistily  oi-  the  digestive  juices  373 

extract  is  at  once  active.  The  trypsinogen  can  therefore  be  activated 
within  the  pancreatic  cells,  gradually  when  the  pancreas  is  simply 
allowed  to  stand  after  excision,  more  rapidly  in  presence  of  the  dilute 
acid.  The  ordinary  tests  for  irrnient  action  (destruction  by  boiling, 
activity  in  very  small  amounts,  etc.)  have  shown  that  this  property 
of  the  intestinal  juice  is  due  to  a  ferment,  although  it  differs  in 
certain  respects  from  most  ferments — for  instance,  in  requiring  a 
relatively  high  temperature  to  inactivate  it.  The  smallest  trace 
of  enterokinase  will  convert  a  large  quantity  of  trypsinogen  into 
trypsin  if  time  be  given.  At  the  same  time,  although  to  a  much 
smaller  extent,  the  fat-splitting  and  starch-digesting  activity  of  the 
pancreatic  juice  is  increased.  The  secretion  of  the  duodenum  causes 
a  greater  increase  in  the  proteohiiic  power  than  that  of  the  other 
portions  of  the  small  intestine,  while  no  such  difference  has  been 
made  out  in  the  case  of  the  amyloh-tic  and  hpolytic  functions.  It  is 
probable  that  the  enterokinase,  which  is  secreted  mainly  in  the  upper 
two-sevenths  of  the  small  intestine,  and  solely  by  the  intestinal 
epithelium,  acts  only  on  the  trypsinogen,  and  that  the  amj'lopsin 
and  steapsin  are  aided  in  some  other  way.  Enterokinase  is  only 
found  in  the  intestinal  juice  when  pancreatic  juice  is  present  in  the 
gut.  It  is  therefore  secreted  in  response  to  the  presence  of  tryp- 
sinogen or  of  some  other  constituent  of  the  pancreatic  juice. 

Delezenne  has  attempted  to  explain  the  interaction  of  enterokinase 
and  trj-psinogen  as  an  adaptive  phenomenon  of  the  same  kind  as  the 
formation  of  antitoxins  and  ha^molysins  (p.  31).  According  to  him, 
enterokinase  acts  Hke  a  complement  in  haemolysis,  while  trypsinogen 
plays  the  part  of  an  intermediary^  body  or  amboceptor  which  enables 
the  enterokinase  to  attack  the  protein  molecule.  He  asserts  that 
enterokinase,  or  a  substance  which  produces  a  similar  effect  on  tr^'p- 
sinogen,  is  contained  not  only  in  the  mucous  membrane  of  the  intestine, 
but  also  in  leucoc^^es,  in  fibrin  (one  of  whose  properties  it  is  to  pick 
out  ferments  from  liquids  containing  them),  in  lymph-glands,  in  snake 
venom,  and  even  in  certain  anaerobic  bacteria.  On  tliis  view  trypsin 
would  not  be  a  definite  substance  produced  by  the  interaction  of 
enterokinase  and  trypsinogen,  but  only  an  expression  for  these  two 
bodies  acting  together.  Strong  evidence  against  this  view,  and  in 
favour  of  the  independent  existence  of  trypsin,  hao  been  brought  forward 
by  Bayliss  and  Starling,  and  it  does  not  seem  to  merit  further  con- 
sideration. According  to  Mellanby,  enterokinase  is  really  a  proteolytic 
ferment,  and  trypsinogen  contains  a  protein  moiety  with  which  trypsin 
is  firmly  combined.  The  conversion  of  trypsinogen  into  trypsin 
depends  on  the  digestion  of  this  protein  moiety,  and  the  consequent 
liberation  of  trypsin.  Vernon  has  put  forward  the  view  that,  while 
enterokinase  starts  the  activation  of  trypsinogen  in  the  intestine,  and 
can  no  doubt  in  time  complete  it.  the  tn,-psin  as  it  is  formed  aids  in  the 
activation  of  more  trj'psinogen  to  trypsin,  and  so  on  by  a  process  of 
so-called  auto-catalysis  of  the  trypsinogen.  This  idea  can  be  har- 
monized with  Mellanby's  conception  by  assuming  that  the  trypsin 
formed  from  trypsinogen  can  itself  digest  the  protein  moiety  of  a  further 
portion  of  trypsinogen. 


374  DIGESTION 

According  to  P;i\vlo\v,  the  reason  wh}'  the  tr\psin  is  not  secreted 
in  the  active  form  is  that  active  trypsin  reachly  destroys  the  amylo- 
lytic  and  hpolytic  ferments.  In  the  intestine,  where  trypsin  is 
rendered  active  by  enterokinaso,  these  ferments  are  protected  from 
its  attack  by  the  proteins  of  the  food  and  by  the  bile.  Enterokinase 
is  itself  immediately  destroyed  in  the  presence  of  free  acid  (centi- 
normal  hydrochloric  acid). 

Having  now  finished  our  review  of  the  chemistry  of  the  digestive 
juices,  our  next  task  is  to  describe  what  is  known  as  to  their  secre- 
tion— the  nature  of  the  cells  by  which  it  is  effected  and  their  histo- 
logical appearance  in  activity  and  repose,  and  the  manner  in  which 
it  is  called  forth  and  controlled. 


Section  IV. — Thk  Secretion  of  the  Digestive  Juices — 
MiCROscopic.\L  Changes  in  the  Gland  Cells. 

The  digestive  glands  are  formed  originally  from  in\'olutions  of  the 
mucous  membrane  of  the  alimentary  canal,  the  salivary  glands  from 
the  ectoderm,  the  others  from  the  endoderm  (Chap.  XIX.).  Some  are 
simple  unbranchcd  tubes,  in  which  there  is  either  no  distinction  into 
body  and  duct,  as  in  I.icbcrkiilm's  cn,q:)ts  in  the  intestines,  or  in  which 
one  or  more  of  the  tubes  open  into  a  duct,  as  in  the  glands  of  the  fundus 
of  the  stomach.  Some  are  branched  tubes,  several  of  which  may  end 
in  a  common  duct ;  such  are  the  glands  of  the  pyloric  end  of  the  stomach 
and  the  Brunner's  glands  in  the  duodenum.  In  others  the  main  duct 
ramiiics  into  a  more  or  less  complex  system  of  small  channels,  into  each 
of  the  ultimate  branches  of  which  one  or  more  (usually  several)  of  the 
secreting  tubules  or  alveoli  open.  The  salivary  glands  and  the  pancreas 
belong  to  this  class  of  compound  tubular  or  racemose  glands,  and  so 
does  the  liver  of  such  animals  as  the  frog.  But  in  the  latter  organ  the 
typical  arrangement  is  obscured  in  the  higher  vertebrates  by  the  pre- 
dominance of  the  portal  bloodA  cssels  over  the  system  of  bile-channels 
as  a  groundwork  for  the  grouping  of  the  cells. 

In  every  secreting  gland  there  is  a  vascular  plexus  outside  the  cells 
of  the  gland-tubes,  and  a  system  of  collecting  channels  on  their  inner 
surface ;  and  in  a  certain  sense  the  cells  of  every  gland  are  arranged 
with  reference  to  the  bloodvessels  on  the  one  hand,  and  the  ducts  on 
the  other.  But  in  the  ordinary  racemose  gland  the  blood-supply  is 
mainly  required  to  feed  the  secretion  ;  the  cells  of  the  alveoli  have  cither 
no  other  function  than  to  secrete,  or  if  they  have  other  functions,  they 
are  not  such  as  to  entail  a  great  disproportion  between  the  size  of  the 
cells  and  the  lumen  of  the  channels  into  which  thej'  pour  their  products. 
For  both  reasons  the  relation  of  the  grouping  cf  the  cells  to  the  duct- 
system  is  vcr^'  obvious,  to  the  blood-sjstem  very  obscure.  In  the  liver, 
the  conditions  arc  precisely  reversed.  We  cannot  suppose  that  the 
manufacture  of  a  quantity  of  bile  less  in  volume  than  the  seen t ion  of 
the  salivary  glands,  though  doubtless  containing  far  more  solids, 
requires  an  immense  organ  Hke  the  liver,  and  a  tide  of  blood  like  that 
which  passes  through  the  portal  vein.  And,  as  we  shall  see,  the  liver 
has  other  functions,  some  of  them  certainly  of  at  least  equal  importance 
with  the  secretion  of  bile,  and  one  of  them  evidently  requiring  from 
its  ver>'  nature  a  bulky  organ.  Accordingly,  both  the  richness  of  the 
blood-supply  and  the  size  of  the  secreting  cells  are  out  of  proportion  to 


THE  SECRETION  OE  THE  DIGESTIVE  JUICES  375 

ihc  calibre  of  the  ultimate  channels  that  carry  the  secretion  away. 
The  so-called  bile-capillarios.  which  represent  the  lumen  of  the  secreting 
tubules,  are  mere  grooves  in  the  surface  of  adjoining  cells;  and  the 
architectural  lines  on  which  the  liver  lobule  is  built  arc:  (i)  the  inter- 
lobular veins  which  carry  blood  to  it;  (2)  the  rich  capillary  network 
whicii  separates  its  cells  and  feeds  them;  and  (3)  the  central  intra- 
lobular vein  which  drains  it.  Thus  a  network  of  cells  lying  in  the 
meshes  of  a  network  of  blood-capillaries  takes  the  place  of  a  regular 
dendritic  arrangement  of  ducts  and  tubules;  and  in  accordance  with 
this  the  bile-capillaries,  instead  of  opening  separately  into  the  ducts, 
form  a  plexus  with  each  other  within  the  hepatic  lobule  (see  also  foot- 
note, p.  14). 

The  ducts  and  secreting  tubules  of  all  glands  are  lined  by  cells  of 
columnar  epithelial  t^-pe,  but  the  type  is  most  closely  preserved  in  the 
ducts.  In  none  of  the  digestive  glands  is  there  more  than  a  single 
complete  layer  of  secreting  cells.  But  the  alveoli  of  the  mucous 
salivary'  glands  show-  here  a'.:<l  there  a  crescent-shaped  group  of  small 
deeply-staining  cells  (crescents  of  Gianuzzi)  outside  the  columnar  layer 
(Fig.  15S,  A".  B"),  and  between  it  and  the  basement  membrane,  while 
the  gland-tubes  of  the  fundus  of  the  stomach  have  in  the  same  situation 
a  discontinuous  layer  of  lart'.e  ovoid  cells,  termed  parietal  from  their 
position,  ox^mtic  (or  acid -secreting)  from  their  supposed  function 
(Figs.  155-157).  Access  to  the  lumen  of  the  glands  is  provided  for 
these  deeply-placed  parietal  cells  and  for  the  cells  of  the  crescents  by 
fine  branching  channels  which  enter  and  surround  the  cells.  The 
serous  salivary  glands,  the  pyloric  glands  of  the  stomach,  and  the 
Lieberkiihn's  crypts,  have  but  a  single  layer  of  epithelium;  and  since 
there  is  no  hepatic  cell  which  is  not  in  contact  with  at  least  one  bile 
capillar^-,  the  liver  may  be  regarded  as  having  no  more.  The  same  is 
true  of  the  pancreatic  alveoli,  except  that  in  the  centre  of  many  of  the 
acini  a  few  spindle-shaped  cells  (centro -acinar  cells),  apparently  con- 
tinued from  the  lining  of  the  smallest  ducts,  may  be  seen.  Remarkable 
histological  changes,  evidently  connected  with  changes  in  functional 
activity,  have  been  noticed  in  most  of  the  digestive  glands.  In  dis- 
cussing these,  it  will  be  best  to  omit  for  the  present  any  detailed  reference 
to  the  liver,  since,  although  there  are  histological  marks  of  secretive 
activity  in  this  gland  as  well  as  in  others,  and  of  the  same  general 
character,  they  are  accompanied,  and  to  some  extent  overlaid,  by  the 
microscopic  evidences  of  other  functions  (p.  534).  The  serous  salivary 
glands  and  the  pancreas  can  be  taken  together;  so  can  the  glands  of  the 
various  regions  of  the  stomach;  the  mucous  salivary  glands  must 
be  considered  separately. 

Changes  in  the  Pancreas  and  Parotid  during  Secretion. — The  cells 
of  the  alveoli  of  the  pancreas  or  parotid  during  rest,  as  can  be  seen 
by  examining  thin  lobules  of  the  former  between  the  folds  of  the 
mesentery  in  the  living  rabbit,  or  fresh  teased  preparations  of  the 
latter,  are  filled  with  fine  granules  to  such  an  extent  as  to  obscure 
the  nucleus.  In  the  parotid  the  whole  cell  is  granular,  in  the 
pancreas  there  is  still  a  narrow  clear  zone  at  the  outer  edge  of  the 
cell  which  contains  few  granules  or  none;  in  both,  the  divisions 
between  the  cells  are  verv  indistinct,  and  the  lumen  of  the  alveolus 
cannot  be  made  out.  During  activity  the  granules  seem  to  be 
carried  from  the  outer  portion  of  the  cell  towards  the  lumen,  and 


376 


DWESTJON 


there  discharged.  The  clear  outer  zone  of  the  pancreatic  cell  grows 
broader  and  broader  at  the  expense  of  the  inner  granular  zone,  until 
at  last  the  granular  zone  may  in  its  turn  be  reduced  to  a  narrow 
contour  line  around  the  lumen  (Fig.  153).  In  the  uniformly  clouded 
parotid  cell  a  similar  change  takes  place;  a  transparent  outer  zone 

arises;  and,  after  prolonged 
secretion,  only  a  thin  edging 
of  granules  may  remain  at 
the  inner  portion  of  the  cell 
(l-'ig.  154).  In  both  glands 
the  outlines  of  the  cells  be- 
come more  clearly  indicated, 
and  a  distinct  lumen  can 
now  be  recognized.  The 
cells  are  smaller  than  they 
are  during  rest. 

The  disappearance  of 
granules  from  without  in- 
wards during  activity  sug- 
gests that  these  are  manu- 
factured products  eUminated  in  the  secretion,  and  they  are  generally 
spoken  of  as  zymogen  granules. 

Bensley,  who  has  made  a  careful  study  i)f  the  pancreas  in  the 
guinea-pig,  has  been  able  to  distinguish,  even  in  fresh  preparation-^ 
examined  in  the  animal's  own  serum,  but  better  after  staining  with 
such  a  dye  as  neutral  red,  another  kind  of  granules,  which  he  regards 


Fig-  153. — -4.  alveolus  of  rabbit's  pancreas, 
'  loaded  '  (resting) ;  B.  '  discharged  ' 
(active),  observed  in  the  living  animal 
(Kiihne  and  Lea). 


Fig.  154.— .\lveoli  of  Parotid  Gland:  A.  at  Rest:  B,  after  a  Short  Period  of  .\ctivity: 
C,  after  a  Prolonged  PeriDd  of  .Activity  (Fresh  Preparations)  (Langley).  In  A 
and  H  tlie  nuclei  are  obscured  bv  the  granules  of  zymogen. 


as  zymogen  granules  in  the  course  of  formation,  and  therefore 
designates  prcjzymogen  granules.  The  resting  acini  show  a  clear 
basal  zone  which  is  unstained,  and  a  zone  next  the  lumen  containing 
coarse  zymogen  granules  which  are  faintly  stained.  In  the  active 
gland — e.g..  after  a  meal  or  aftrr  the  injection  of  secretin  (p.  407) — 
prozymogen  granules  which  stain  much  more  intensely  than  the 
zymogen  granules  with  neutral  red  make  their  appearance  between 
the  zymogen  granules,  now  much  reduced  in  number  jnd  size,  and 


?///:  SllCRl^TJON  OF  THE  DIGESTIVE  J  VICES 


377 


the  clear  outer  zone.  Attor  prolonged  secretion  the  zymogen  granules 
may  be  entirely'  absent  from  the  cells,  and  only  a  narrow  rim  of 
pro/.ymogen  granules  can  be  seen  around  the  lumen. 

In  one  respect  the  pancreas  differs  remirkably  from  the  salivary 
gknds — namely,  in  the  presence  of  the  islets  of  Langerhans — 
characteristic  groups  of  small 


polygonal  cells,  richly  sup- 
plied with  bloodvessels,  but 
not  arranged  in  the  form  of 
alveoli.  Some  observers  state 
that  they  are  remarkably  in- 
creased in  size,  and  even  in 
number  when  the  pancreas  is 
caused  to  secrete  actively  by 
repeated  injections  of  secretin, 
and  also  in  starvation.  But 
it  has  been  shown  that  this 
conclusion  was  based  upon 
faulty  methods  of  counting 
the  islets,  and  even  of  identi- 
fying the  islet  cells.  There 
appears  to  be  no  foundation 
for  the  view  that  they  are 
derived  from  the  ordinary 
secreting  cells,  and  that  they 
can,  in  turn,  give  rise  to  new 
alveoli  by  a  process  of  pro- 
liferation. It  is  far  more 
probable  that  they  are  inde- 
pendent structures,  with  a 
different  function  from  the 
pancreatic  alveoH  (p.  6  ,8). 

Changes  in  the  Glands  of 
the  Stomach  during  Secre- 
tion.— The  mucous  membrane 
of  the  stomach  is  covered 
with  a  single  layer  of  colum- 
nar epithelium,  largely  con- 
sisting of  mucigenous  goblet- 
cells.      It    is    studded    with 


}^ 


ll 


M 


Fig.  155-  Fig.  156. 

Fig.  155. — A  Fundus  Gland  of  Simple  Form 
from  the  Bat's  Stomach  (Osmic  Acid  Pre- 
paration) (Langley).  c.  Columnar  epithe- 
lium of  the  surface;  n,  neck  of  the  gland 
with  chief  or  central  and  parietal  cells; 
/,  base,  occupied  only  by  chief  cells,  which 
show  the  granules  accumulated  towards 
the  lumen  of  the  gland. 

Fig.  156. — A  Fundus  Gland  prepared  by 
Golgi's  Method,  showing  the  Mode  of  Com- 
munication of  the  Parietal  Cells  with  the 
Gland-Limien  (Schafer,  after  E.  MuUer). 


minute  pits,  into  which  open 
the  ducts  of  the  peptic  and  pyloric  glands,  the  ducts  being  lined 
with  cells  just  like  those  of  the  general  gastric  surface.  Three 
varieties  of  gastric  glands  have  been  distinguished:  (i)  The 
glands  of  the  cardia.  In  man  these  occupy  a  small  portion  of 
the   mucous  membrane   at  the   cardiac  end,  near  the  orifice  of 


37S  DIGESTION 

the  ousophagus.  Sonu'  ol  the  glands  are  single  tubules,  but 
others  have  two  or  more  tubules  opening  into  a  common  duct. 
Both  are  lined  by  a  single  layer  of  short  columnar  epithelium, 
which  contains  granules.  (2)  The  glands  of  the  pyloric  canal 
or  antrum.  These  consist  of  short,  branched  tubules,  which  oi)en 
by  twos  and  threes  into  long  ducts.  (3)  The  glands  of  the 
fundus  or  oxyntic  glands,  occupying  the  intermediate  and  greater 
portion  of  the  organ.  The  gland  tubules  are  long  and  seldom 
branched,  and  the  ducts,  into  each  of  which  open  from  one  to  three 
tubules,  are  relatively  short.  The  secreting  parts  of  both  kinds  of 
glands  arc  lined  by  short  columnar  granular  cells;  and  in  the  pyloric 
tubules  no  others  arc  present.  But,  as  we  have  said,  in  the  glands 
of  the  fundus  there  are  besides  large  ovoid  cells  scattered  at  intervals 
like  beads  between  the  basement  membrane  and  the  lining  or  chief 
cells.  The  cells  of  the  pyloric  glands  have  a  general  resemblance  to 
the  chief  cells  of  the  fundus  glands,  but  they  are  not  quite  the  same. 
For  example,  the  granules  are  less  distinct  in  the  pyloric  glands.  In 
the  human  stomach  it  is  only  quite  near  the  pylorus  that  the  parietal 
cells  disappear  altogether.  The  parietal  cells  also  contain  granules, 
but  they  are  smaller  and  less  numerous  than  those  of  the  chief  cells, 
so  that  the  deeper  portions  of  the  fundus  glands  are  much  darker  in 
appearance  than  the  more  superficial  portions,  since  the  oxyntic  or 
parietal  cells  are  more  numerous  in  the  neighbourhood  of  the  ducts 
(Bensley). 

The  histological  changes  connected  with  gastric  secretion  do  not 
differ  essentially  from  those  described  in  the  pancreas  and  the 
parotid,  but  there  is  much  greater  difficulty  in  making  observations 
on  the  living,  or  at  least  but  slightly  altered,  cells.  For  the  mammal 
the  best  method  is  to  use  animals  with  a  permanent  gastric  fistula, 
and  to  remove  from  time  to  time  small  portions  of  the  mucous 
membrane  for  examination  in  the  fresh  condition.  During  digestion 
the  granules  disappear  from  the  outer  part  of  the  chief  cells  of  the 
fundus  glands,  leaving  a  clear  zone,  the  lumen  being  bordered  by  a 
granular  laj'er.  Or,  more  rarely,  there  may  be  a  uniform  decrease 
in  the  number  of  granules  throughout  the  cell.  The  total  volume 
of  the  cell  is  less  than  in  the  fasting  condition.  The  parietal  cells, 
which  are  small  in  the  fasting  animal,  swell  up,  so  as  to  bulge  out  the 
mcmbrana  propria.  They  reach  their  maximum  size  (in  the  dog) 
very  late  in  digestion  (the  thirteenth  to  the  fifteenth  hour).  No 
such  definite  changes  in  their  contents  as  those  observed  in  the  other 
cells  have  been  made  out.  The  granules  in  the  ovoid  cells  during 
and  after  activity  seem  to  be  as  large  and  as  numerous  as  in  the 
resting  cell,  or  even  larger.  After  sham  feeding  in  dogs  the  histo- 
logical changes  in  the  gastric  glands  are  vcrj'  slight,  even  when  con- 
siderable amounts  of  gastric  juice  have  been  secreted  (Noll  and 
Sokoloff).  ■ 


THI-:  SECRETION  Of   I'HE  DIGESTIVE  JUICES 


379 


Tlie  chief  colls  of  the  oxyntic.  and  tlic  similar  if  not  identical  cells 
of  the  pyloric  glands,  arc  bcli(>vcd  to  manufacture  the  pepsin-form- 
ing substance.  The  ovoid  cells  of  the  former  are  supposed  to  secrete 
the  hydrochloric  acid.  The  evidence  on  which  this  belief  is  based 
is  as  follows: 

The  glands  of  the  antrum  pylori  in  the  dog,  in  which  in  most 
situations  no  ovoid  cells  are  to  be  seen,  secrete  pepsin,  but  no  acid. 
The  pyloric  end  of  the  stomach  or  a  portion  of  it  has  been  isolated, 


Fig.  157. — The  Gastric  Glands  (Ebstein). 


On  the  left,  o.xyatic;  right,  pyloric. 


the  continuity  of  the  alimentary  canal  restored  by  sutures,  and  the 
secretion  of  the  pyloric  pocket  collected.  It  was  found  to  be  alka- 
line, and  contained  pepsin.  The  glands  of  the  frog's  oesophagus, 
which  contain  only  chief  cells,  secrete  pepsin,  but  no  acid.  It  seems 
fair  to  conclude  that  the  chief  cells  of  the  fundus  glands  in  the 
mammal  secrete  none  of  the  free  hydrochloric  acid,  but  certainly 
some  of  pepsin.  But  it  does  not  follow  that  all  the  pepsin  is  formed 
by  these  cells,  although  it  would  seem  that  all  the  hydrochloric  acid 


38o  DIGESTION 

must  be  secivtod  by  the  only  other  glandular  elements  present,  the 
parietal  or  '  border  '  cells.  And,  indeed,  the  glands  in  the  fundus 
of  the  frog's  stomach,  which  are  composed  only  of  ovoid  cells,  whilst 
secreting  much  acid,  also  form  some  pepsin,  although  far  less  than 
the  oesophageal  glands.  During  winter  sleep  (in  the  marmot)  the 
production  of  hydrochloric  acid  in  the  parietal  cells  stops  altogether, 
while  the  chief  cells  continue  to  accumulate  granules  of  pepsinogen. 

That  some  pepsin  is  secreted  by  the  pyloric  end  of  the  stomach 
is  not  difficult  to  prove.  The  secretion  collected  from  the  isolated 
pyloric  portion  is,  indeed,  like  the  secretion  of  the  Brunner's  glands 
in  the  duodenum,  quite  unable  to  digest  protein  until  dilute  hydro- 
chloric acid  is  added.  But  this  is  because  in  both  cases  the  juice  as 
it  flows  from  the  glands  is  slightly  alkaline,  and,  as  we  have  already 
seen,  pepsin  only  acts  in  the  presence  of  an  acid.  The  milk-curdling 
action  of  these  two  juices  also  unfolds  itself  only  when  the  secretions 
arc  first  acidulated,  and  later  on  again  neutralized;  in  other  words, 
the  ferments  must  be  activated  by  the  addition  of  an  acid.  In  normal 
digestion  the  pepsin  of  the  (in  itself)  alkahne  secretion  of  the  pyloric 
end  of  the  stomach  becomes  a  constituent  of  the  acid  gastric  juice; 
and  it  may  perhaps  be  considered  a  morphological  accident,  so  to 
speak,  that  the  oxyntic  cells  of  the  fundus  should  mingle  their  acid 
products  with  the  (presumedly)  alkaline  secretion  of  the  chief  cells 
in  the  lumen  of  each  gland-tube,  instead  of  being  massed  as  a 
separate  organ  with  a  special  duct. 

We  are  not  without  other  examples  of  digestive  juices  fitted  or 
destined  to  act  in  a  medium  with  an  opposite  reaction  to  their  own. 
The  '  saliva  '  of  the  cephalopod  Octopus  macropus,  strongly  acid 
though  it  is,  contains  a  proteolytic  ferment  which  in  vitro  acts,  like 
trypsin,  better  in  an  alkaline  than  in  an  acid  solution.  And  trypsin, 
whose  precursor  is  a  constituent  of  the  alkaline  pancreatic  juice,  while 
the  enterokinase  which  activates  it  is  a  constituent  of  the  alkaline 
succus  entericus,  performs  a  part  at  least  of  its  work  in  an  acid 
medium. 

Attempts  made  to  demonstrate  an  acid  reaction  in  the  border  cells 
have  hitherto  failed.  Harvey  and  Bcnslcy  on  the  basis  of  experiments 
with  dyes  (cyanimin  and  neutral  red),  which  give  different  colours 
according  to  whether  the  reaction  is  acid,  alkaline,  or  neutral,  have 
concluded  that  free  acid  exists  only  on  the  internal  surface  of  the 
stomach,  or  at  most  also  in  the  necks  of  the  glands.  The  parietal  cells 
they  find  alkaline.  They  suggest  that  these  cells  form  in  some  way, 
of  course  ultimately  from  the  chlorides  of  the  blood,  a  chloride  of  an 
organic  base  which  does  not  decompose  so  as  to  yield  free  Iiydrochloric 
acid  until  it  reaches  the  mouth  of  the  gland.  Tlie  nature  of  this  decom- 
position, if  it  occurs,  is  unknown.  It  may  be  mentioned,  although  only 
as  a  matter  of  historical  interest,  that  some  observers  have  denied  that 
the  acid  is  secreted  in  the  depths  of  any  cell  from  the  chlorides  of  the 
blood,  and  have  asserted  that  it  is  formed  at  the  surface  of  contact  of 
the  stomach-wall  with  the  gastric  contents  from  the  sodium  chloride  of 
the  food  by  an  exchange  of  sodium  ions  (p.  428)  for  hydrogen  ions  from 


TUi:  SF.CRETION  01-   THI-    DIGESTIVE  JUICES  j8i 

the  blood  or  lymph.  It  wiis  pomted  out  in  favour  of  this  view  tiiat 
when,  instead  of  sodiiun  chloride,  sodium  bromide  is  given  in  the  food, 
the  hydrochloric  acid  in  the  stomach  is  to  a  large  extent  replaced  by 
hydrobromic  acid.  And  it  was  argued  that  this  cannot  be  due  to  the 
decomposition  of  the  bromide  by  hydrochloric  acid,  since  it  occurs  in 
animals  deprived  for  a  considerable  time  of  salts,  and  in  '  salt-hunger  * 
the  stomach  contains  no  acid  (Koeppc).  It  may  be,  however,  that 
even  m  '  salt-hunger  '  the  presence  of  sodium  bromide  in  the  stomach 
stimulates  the  secretion  of  hydrochloric  acid,  which  then  decomposes 
the  bromide,  with  the  formation  of  hydrobromic  acid.  The  sodium 
chloride  formed  in  the  double  decomposition  might  be  re-absorbed, 
and  the  stock  of  chlorides  in  the  blood  remain  undiminished.  It  is  in 
any  case  a  decisive  objection  to  this  now  defimct  theory  that  a  copious 
secretion  of  gastric  juice,  containing  hydrochloric  acid  in  abundance, 
can  be  obtained,  without  the  introduction  of  any  food  into  the  stomach, 
either  by  the  process  of  sham  feeding  (p.401)  or  by  psychical  st.mulation 
of  the  gastric  glands  when  food  is  shown  to  an  animal. 

Changes  in  Mucous  Glands  during  Secretion, — In  the  mucous  salivary 
and  other  mucous  glands  similar,  but  apparently  more  complex,  changes 
occur.  During  rest  the  cells  which  line  the  lumen  may  be  .seen  in  fresh, 
teased  preparations  to  be  filled  with  granules  or  '  spherules.'  After 
active  secretion  there  is  a  great  diminution  in  the  number  of  the 
granules.  Those  that  remain  are  chiefly  collected  around  the  lumen, 
although  some  may  also  be  seen  in  the  peripheral  portion  of  the  cell; 
and  there  is  no  ver^^  distinct  differentiation  into  two  zones.  That  a 
discharge  of  material  takes  place  from  these  cells  is  shown  by  their 
smaller  size  in  the  active  gland.  That  the  material  thus  discharged  is 
not  protoplasmic  is  indicated  by  the  behaviour  of  the  cells  to  proto- 
plasmic stains  such  as  carmine.  The  resting  cells  around  the  lumen 
stain  but  feebly,  in  contrast  to  the  deep  stain  of  the  demilunes,  while 
the  discharged  cells  take  on  the  carmine  stain  much  more  readily. 
Further,  when  a  resting  gland  is  treated  with  various  reagents  (water, 
dilute  acids,  or  alkalies),  the  granules  swell  up  into  a  transparent  sub- 
stance identical  with  mucin,  which  fills  the  meshes  of  a  fine  protoplasmic 
network. 

In  ordinary  alcohol-carmine  preparations  only  the  network  and 
nucleus  are  stained ;  the  nucleus,  small  and  shrivelled,  is  situated  close 
to  the  outer  border  of  the  cell.  When  a  discharged  gland  is  treated  in 
the  same  way  there  is  proportionally  more  '  protoplasm  '  (or  '  bioplasm  ') 
and  less  of  the  clear  material,  what  remains  of  the  latter  being  chiefly 
in  the  inner  portion  of  the  cell,  while  the  nucleus  is  now  large  and 
spherical,  and  not  so  near  the  basement  membrane  (Fig.  158). 

Everything,  therefore,  points  to  the  granules  in  what  we  may  now 
call  the  mucin-forming  cells  as  being  in  some  way  or  other  precursors 
of  the  fully-formed  mucin ;  manufactured  during  '  rest  '  by  the  proto- 
plasm and  partly  at  its  expense,  moved  towards  the  lumen  in 
activity,  discharged  as  mucin  in  the  secretion.  It  has  been  asserted 
that  not  only  is  the  protoplasm  lessened  in  the  loaded  cell  and  re- 
newed after  activity,  but  that  many  of  the  mucigenous  cells  may  be 
altogether  broken  down  and  discharged,  their  place  being  supplied 
by  proliferation  of  the  small  cells  of  the  demilunes.  This  conclusion, 
however,  is  not  supported  by  sufficient  evidence.  The  cells  of  the 
crescents  contain  fine  granules,  but  none  which  can  be  changed  into 


382 


DIGESTION 


mucin.  They  arc  of  serous  and  not  of  mucous  type.  But  the  fact 
on  which  \vc  would  specially  insist  is  that  the  granules  of  the  resting 
mucigenous  cell  may  be  looked  upon  as  a  mother-substance  from 
which  the  mucin  of  the  secretion  is  derived;  they  are  not  actual,  but 
potential,  mucin. 

So  in  the  pancreas,  the  serous  or  albuminous  salivary  glands,  and 
the  glands  of  the  stomach,  there  is  every  reason  to  believe  that  the 
granules  which  appear  in  tlie  intervals  of  rest,  and  are  moved 
towards  the  lumen  and  discharged  during  activity,  are  the  pre- 
cursors, the  mother-substances,  of  important  constituents  of  the 
secretion.  These  granules  are  sharply  marked  off  from  the  proto- 
plasm in  which  they  lie  and  by  which  they  are  built  up.  By  every 
mark,  by  their  reaction  to  stains,  for  instance,  they  are  non-hving 
substance,  formed  in  the  bosom  of  the  hving  cell  from  the  raw 
material  which  it  culls  from  the  blood,  or,  what  is  more  hkely. 
formed  from  its  own  protoplasm,  then  shed  out  in  granular  form  and 


Fig.  158. — Mucous  Cells  (from  Submaxillary  of  Dog)  in  Rest  and  Activity  (Langley). 

A.  B.  fresh;  A',  B',  alter  treatment  with  dilute  acetic  acid;  A",  B',  alveoli  hard- 
ened in  alcohol  and  stained  with  carmine.     A,  A',  and  A'  represent  the  loaded; 

B,  B',  and  B",  the  discharged  condition. 

secluded  from  further  change.  The  granules  in  the  ferment-forming 
glands  are  not  in  general  composed  of  the  actual  ferments,  and, 
indeed,  in  several  instances  it  has  been  shown  that  the  actual  fer- 
ments are  not  present  in  the  secreting  cells  at  all. 

We  have  already  seen  that  the  pancreas  and  even  the  fresh  pan- 
creatic juice  are  devoid  of  active  trypsin.  Similarly,  a  glycerin 
extract  of  a  fresh  gastric  mucous  membrane  is  inert  as  regards 
proteins,  or  nearly  so.  But  if  the  mucous  membrane  has  been  pre- 
viously treated  with  dilute  hydrochloric  acid,  the  glycerin  extract 
is  active,  as  is  an  extract  made  with  acidulated  glycerin.  Here  we 
must  assume  the  existence  in  the  gastric  glands  of  a  mother-sub- 
stance, pepsinogen,  from  which  pepsin  is  formed.  The  rennin  of  the 
gastric  juice,  which  is  formed  in  the  chief  cells,  also  has  a  precursor, 
which,  if  the  ferment  is  identical  with  pepsin  (p.  353),  must  be 
pepsinogen.     The  proteolytic  power  of  an  extract  of  the  pancreas, 


THE  SECRhJJON  OF  THE  DIGEST IV i:  JUICES  383 

vvhen  the  trypsinogen  has  been  activated  into  trypsin,  or  of  the 
gastric  mucous  membrane,  when  the  pepsinogen  has  been  changed 
into  pepsin,  seems  to  be,  roughly  speaking,  in  proportion  to  the 
quantity  of  granules  present  in  the  cells.  Therefore  it  is  concluded 
that  the  granules  represent  mother-substances  of  the  ferments  or 
zymogens.  Some  observers  believe  they  have  obtained  evidence  of 
stages  in  the  elaboration  of  the  ferments  still  further  back  than  the 
mother-substances,  grandmother-substances  so  to  speak,  or  pro- 
xy mogens.  Bensley,  e.g.,  concludes  that  the  nuclei  of  the  chief  cells 
in  the  fundus  glands  of  the  stomach  take  part  in  the  formation  of  a 
prozymogen,  the  precursor  of  the  zymogen  or  pepsinogen,  as  pepsino- 
gen is  the  precursor  of  the  enzyme  pepsin. 

A  glycerin  or  watery  extract  of  the  salivary  glands  always  con- 
tains active  amylolytic  ferment,  if  the  natural  secretion  is  active. 
So  that  if  ptyalin  is  preceded  by  a  zymogen  in  the  cells,  it  must  be 
very  easily  changed  into  the  actual  ferment. 

But  we  should  greatly  deceive  ourselves  if  we  supposed  that  granules 
of  this  nature  in  gland-cells  are  necessarily  related  to  the  production  of 
ferments.  The  mixigenous  granules  have  no  such  significance.  Most 
digestive  secretions  contain  protein  constituents,  with  which  the 
granules  may  have  to  do  as  well  as  with  ferments.  And  bile,  a  secretion 
which  contains  no  mucin,  no  proteins,  and  cither  no  ferments  or  mere 
traces,  as  essential  and  original  constituents,  is  formed  in  cells  with 
granules  so  disposed  and  so  affected  by  the  activity  of  the  gland  as  to 
suggest  some  relation  between  them  and  the  process  of  secretion.  In 
the  liver-cells  of  the  frog,  in  addition  to  glycogen,  and  oil-globules  small 
granules  mav  be  seen,  especiallv  near  the  lumen  of  the  gland  tubules ; 
they  diminish  in  number  during  digestion,  when  the  secretion  of  bile  is 
active  and  increase  when  food  is  withheld  and  secretion  slow.  And 
in  fasting  dogs  the  secreting  cells  of  Brunner's  glands,  the  pyloric  glands 
and  the  pr-ncreas,  as  well  as  the  lining  epithelium  of  the  bile-ducts, 
have  been  found  to  contain  many  fatty  granules.  Possibly  some  of 
these  represent  the  fat  which  is  known  to  be  excreted  into  the  alimentary 
canal  (pp.  443,  444). 

The  Nature  of  the  Process  by  which  the  Digestive  Secretions  are 
Formed. — \\"e  have  spoken  more  than  once  of  the  gland-cells  as 
manufacturing  their  secretions.  It  is  an  idea  that  rises  naturally 
in  the  mind  as  we  follow  with  the  microscope  the  traces  of  their 
functional  activity.  And  when  we  compare  the  composition  of  the 
digestive  juices  with  that  of  the  blood-plasma  and  lymph,  the 
suggestion  that  the  glands  which  produce  them  are  not  merely 
passive  filters,  but  living  laboratories,  acquires  additional  strength. 
It  is  evident  that  everything  in  the  secretion  must,  in  some  form 
or  other,  exist  in  the  blood  which  comes  to  the  gland,  and  in  the 
lymph  which  bathes  its  cells.  No  glandular  cell,  if  we  except  the 
leucocytes,  which  in  some  respects  are  to  be  considered  as  unicellular 
glands,  dips  directly  into  the  blood ;  everything  a  gland-cell  receives 
must  pass  through  the  walls  of  the  bloodvessels.     (But  see  footnote 


384  DIGESTION 

on  p.  14).  So  tliat  anything  which  we  find  in  thi'  secrt-tion  and  do 
not  find  in  tlio  blood  must  have  been  elaborated  by  the  gland 
epithelium  (or  by  the  capillary  endothelium)  from  raw  material 
brought  to  it  by  the  blood. 

Take,  for  example,  the  saliva  or  gastric  juice.  These  liquids  both 
contain  certain  things  that  also  exist  in  the  blood,  but  in  addition 
they  contain  certain  things  specific  to  themselves:  mucin  in  saliva, 
hydrochloric  acid  in  gastric  juice,  ferments  in  both.  It  is  true  that 
a  trace  of  pepsin  and  a  trace  of  a  diastatic  ferment  may  be  dis- 
covered in  blood;  but  there  is  no  reason  whatever  to  believe  that 
this  is  the  source  of  the  pepsin  of  the  gastric  juice,  or  the  ptyalin 
of  the  salivary  glands,  except,  perhaps,  in  animals  like  the  cat. 
whose  saliva  contains  a  diastase  in  still  smaller  concentration  than 
the  serum  (Carlson).  On  the  contrary,  it  is  possible  that  the  fer- 
ments of  the  blood  may  be  in  part  absorbed  from  the  digestive 
glands,  the  rest  being  formed  by  the  leucocytes  and  liberated  when 
they  break  down. 

Formation  of  Bile. — The  liver  affords  an  even  better  example  of 
this  '  manufacturing  '  activity  of  gland-cells,  and  many  facts  may 
be  brought  forward  to  prove  that  the  characteristic  constituents 
of  the  bile,  the  bile-pigments  and  bile-acids,  are  formed  in  the  liv-er, 
and  not  merely  separated  from  the  blood.  Bile-pigment  has  indeed 
been  recognized  in  the  normal  serum  of  the  horse,  and  bile-acids  in 
the  chyle  of  the  dog,  but  only  in  such  minute  traces  as  are  easily 
accounted  for  by  absorption  from  the  intestine.  Frogs  live  for  some 
time  after  excision  of  the  liver,  but  no  bile-acids  are  found  in  the 
blood  or  tissues.  But  if  the  bile-duct  be  ligatured,  bile-acids  and 
pigments  accumulate  in  the  body,  being  absorbed  by  the  hniiphatics 
of  the  hver  (Ludwig  and  Fleischl).  If  the  thoracic  duct  and  the 
bile-duct  are  both  hgatured  in  the  dog,  no  bile-acids  or  pigments 
appear  in  the  blood  or  tissues.  Wertheimer  and  Lepage  state  that 
bile  or  bilirubin  injected  into  a  bile-duct  appears  sooner  in  the 
urine  than  in  the  lymph  of  the  thoracic  duct,  and  therefore  conclude 
that  the  bloodvessels  are  the  most  important  channel  of  absorption. 
This  conclusion,  however,  cannot  be  accepted  until  it  is  shown  that 
in  these  experiments  the  injection  did  not  cause  rupture  of  some 
of  the  hepatic  capillaries  and  direct  entrance  of  the  bile-pigment 
into  the  blood.  It  is  not  improbable  that  the  pressure  attained  by 
the  bile  in  the  bile-capillaries  is  a  factor  in  determining  the  path 
by  which  it  is  absorbed,  and  that  when  the  pressure  rises  beyond 
a  certain  limit  it  may  pass  both  into  the  bloodvessels  and  into  the 
lymphatics.  In  mammals  life  cannot  be  maintained  for  any  length 
of  time  after  ligature  of  the  portal  vein,  since  this  throws  the  whole 
intestinal  tract  out  of  gear.  But  after  an  artificial  communication 
has  been  made  between  the  portal  and  the  left  renal  vein  or  th« 
inferior  cava,  the  portal  maybe  tied  and  the  animal  live  for  months 


THE  SECRETION  OF   THE  DIGESTIVE  JUICES  ,85 

(Eck).  The  liver  can  now  be  (•on)i)lctely  R'nioved,  but  death 
follows  in  a  few  hours.  A  good  method  of  establisliing  an  Feck's 
fistula  is  to  make  a  longitudinal  incision  in  the  inferior  vena  cava 
and  the  portal  or  superior  mesenteric  vein,  and  to  suture  the  edges 
of  the  two  openings  together  with  a  very  fine  sewing-needle  and 
thread  (Carrel  and  (iutlu-ie).  In  birds  tlu're  exists  a  communicating 
branch  between  the  })ortal  vein  and  a  vein  (the  renal-jiortai)  which 
passes  from  the  posterior  portion  of  the  body  to  tlie  kidney,  and 
there  breaks  up  into  capillaries:  and  not  only  may  the  portal  be 
tied,  but  the  Uver  may  be  completely  destroyed  without  immedi- 
ately killing  the  animal.  In  the  hours  of  life  that  still  remain  to  it 
no  accumulation  of  biliary  substances  (acids  or  pigments)  takes 
place  in  the  blood  or  tissues.  A  further  indication  that  bile-pig- 
ment is  produced  in  the  liver  is  the  fact  that  the  Hver  contains 
iron  in  relative  abundance  in  its  cells  (p.  21),  and  ehminates  small 
quantities  of  iron  in  its  secretion.  Now,  bile-pigment,  which  con- 
tains no  iron,  is  certainly  formed  from  blood-pigment,  which  is  rich 
in  iron.  For  haematin,  when  injected  under  the  skin,  has  been  found 
to  appear  almost  quantitatively  in  the  form  of  bile-pigment  in  the 
bile,  and  hagmatoidin  (Fig.  159),  a  crystalUne 
derivative  of  haemoglobin  found  in  old  ex- 
travasations of  blood,  especially  in  the  brain 
and  in  the  corpus  lutcum,  is  identical  with 
bilirubin.  The  fact  that  one  of  the  derivatives 
of  haematin,  haematoporphyrin  (C33H38N4O6), 
contains    no    iron,    and   is   proi)ably   nearly 

related  to    bilirubin    (C32H3gN406),    suggests  

that  haematoporphyrin  may  be  an  inter-  p^^  isg.Z^matoidin. 
mediate  step  in  the  formation  of  bile-pigrnent 

from  blood-pigment.  In  any  case,  the  seat  of  formation  of  bile- 
pigment  might  be  expected  to  be  an  organ  peculiarly  rich  in  iron. 
The  existence  of  hac m at oi din,, however,  shows  that  bile-pigment 
may,  under  certain  conditions,  be  formed  outside  of  the  hepatic 
cells.  The  occurrence  of  bihverdin  in  the  placenta  of  the  bitch 
points  in  the  same  direction.  But  the  pathological  evidence  in 
favour  of  the  pre-formation  of  the  biliary  constituents  tends  rather 
to  shrink  than  to  increase.  For  many  cases  of  what  used  to  be 
considered  '  idiopathic  '  or  '  haematogenic  '  jaundice,  i.e.,  an  accumu- 
lation of  bile-pigments  and  bile-acids  in  the  tissues,  due  to  defective 
elimination  by  the  liver,  are  now  known  to  be  caused  by  obstruction 
of  the  bile-ducts  and  consequent  re-absorption  of  bile  ('  obstructive  * 
or  '  hepatogenic  '  jaundice). 

But  if  substances  such  as  the  ferments,  mucin,  hydrochloric  acid, 
the  bile-salts  and  bile-pigments,  are  undoubtedly  manufactured  in  the 
gland-cells,  it  is  different  with  the  water  and  inorganic  salts  which 
form  so  large  a  part  of  every  secretion.     No  tissue  lacks  them;  no 


iHo 


DIGESTION 


physiological  process  got-s  on  without  them;  they  are  not  high  and 
special  j)roducts.  As  we  breathe  nitrogen  which  we  do  not  need 
because  it  is  mixed  with  the  oxygen  we  require,  the  secreting  cell 
passes  through  its  substance  water  and  salts  as  a  sort  of  by-jilay  or 
adjunct  to  its  specific  work.  But  this  is  not  the  whole  truth.  The 
gland-cell  is  not  a  mere  filter  through  which  water  and  salts  pass  in 
the  same  proportions  in  which  they  exist  in  the  Hquids  that  the 
cell  draws  them  from.  When,  e.g.,  the  salivary  glands  secrete 
against  the  resistance  of  an  abnormally  high  pressure  in  the  ducts, 
the  percentage  of  salts  in  the  sahva  increases.  The  secretions  of 
different  glands  differ  in  the  nature,  and  especially  in  the  relative 
proportions,  of  their  inorganic  constituents.  They  differ  also  in 
their  osmotic  pressure  and  electrical  conductivity,  which  depend 
so  largely  upon  those  constituents,  notwithstanding  the  fact  that 
the  osmotic  pressure  and  conductivity  of  the  blood-serum  (p.  26) 
var}'  only  within  narrow  limits.  Even  the  secretion  of  one  and  the 
same  gland  is  by  no  means  constant  in  this  respect,  as  we  shall 
have  to  note  more  especially  when  we  come  to  deal  with  the  in- 
fluence of  the  nervous  system  on  secretion  (p.  395).  The  following 
tables  illustrate  this  point : 


Dog. 

Blood-Serum.* 

Filtnte  of  Gastric  Contents.             [ 

1 

At                     KJ(5'>C.)Xio«. 

A 

KJ(s«"C.)xio*. 

I. 

II. 

III. 

0-643°                 gz-o 

0-628°                 87-6 
o-6o2°                  87-7 

0-585" 
0-585° 
0-642° 

312-5 
179-4 
351-7 

Vomit  of  man  with  complete  intes- 
tinal obstruction     -             -             - 

o-433° 

84-7 

Pancreatic  Juice  of  Dog  [Pincussohn). 


Diet. 

A 

Milk             -               -               -               - 
Cauliflower             .             _             _ 
Horseflesh               .             -             _ 

o-57»-^-63' 
0-58°— 0-63° 
0-62° — 0-63° 

*  The  blood  and  gastric  contents  were  obtained  from  the  animals  twenty- 
four  hours  after  tlie  last  meal. 

^   The  depression  of  the  freezing-point  below  that  of  distilled  water. 

I  See  footnote  on  p.  27.  The  number  in  brackets  is  the  temperature  at 
which  the  measurement  was  made. 


THE  SECRETIOi\  OF   THE  DIGESTIVE  JUICES 


387 


Gastric  Juice  from  Miniature  Stomach  in  a  Dog  in  Different 
Experiments  [Bickel). 


Milk  Diet. 

Meat  Diet. 

A 

K(asoC.)Xio*. 

A 

K(2soC.)xio*. 

0-52' 
0-65° 
o-64» 
0-69" 
o-8i° 

195-9 
402-6 

436-5 
404-2 

436-5 

0-60" 
0-71° 
1-21° 

o-79° 
0-70° 

3IO-3 

473-5 
483-3 
514-1 
514-1 

i 

A  of  Blood  and  Saliva  Compared  (Jappelli), 


A  of  Blood. 

A  of  Subma-Yillary  Saliva  of  Dog. 

1 

1 

0-570° 

0-410° 

o-6io° 

0-350° 

o-6oo° 

0-430° 

0-590° 

0-410° 

0-580° 

0-450° 

0-605° 

0-425° 

0-650' 

0-380° 

o-6io° 

0-475° 

A  of  Human  Fistula  Bile. 

A  of  Human  Bladder  Bile. 

0-56° 

o-547° 
0-615° 
0-60° 
o-545° 

0-65° 

0-865" 

0-78° 

0-92* 

A  of  Dog's 

Chorda  stimulated : 

Left  submaxillary     - 

Both    glands 
Spontaneous  secretion : 

Right  submaxillan-  - 
A  of  dog's  serum 


Submaxillary  Saliva. 


-  0-293' 

-  0-408° 

-  0-195° 

-  0-590° 


The  protein  substances,  such  as  serum-albumin  and  globuhn, 
common  to  blood  and  to  some  of  the  digestive  secretions,  take  a 
middle  place  between  the  constituents  that  are  undoubtedly  manu- 


388  DIGESTION 

factored  in  the  cell  and  those  which  seem  by  a  less  special  and 
laborious,  though  a  selective,  process  to  be  passed  through  it  from 
the  blood.  Their  practical  absence  from  bile,  and,  as  we  shall  see, 
from  urine,  their  relative  abundance  in  pancreatic  and  scantiness 
in  gastric  juice,  point  to  a  closer  dependence  upon  the  special 
activity  of  the  gland-cell  than  we  can  suppose  necessary  in  the  case 
of  the  salts. 

Although  it  is  in  the  cells  of  the  digestive  glands  that  the  power  of 
forming  ferments  is  most  conspicuous,  it  is  by  no  means  confined  to 
them.  It  seems  to  be  a  primitive,  a  native  power  of  protoplasm. 
Lowly  animals,  like  the  amoeba,  lowly  plants,  like  bacteria,  form  ferments 
within  the  single  cell  which  serves  for  all  the  purposes  of  their  life. 
The  ferment-secreting  gland-cells  of  higher  forms  are  perhaps  only  lop- 
sided amcebae,  not  so  much  endowed  with  new  properties  as  dispro- 
portionately developed  in  one  direction.  The  contractility  has  been 
lost  or  lessened,  the  digestive  power  has  been  retained  or  increased; 
just  as  in  muscle  the  power  of  contraction  has  been  developed,  and 
that  of  digestion  has  fallen  behind.  The  muscle-cell  and  the  cartilage- 
cell  are  parasites,  if  we  look  to  the  function  of  digestion  alone.  They 
live  on  food  already  more  or  less  prepared  by  the  labours  of  other  cells; 
and  it  is  a  universal  law  that  in  the  measure  in  which  a  power  becomes 
useless  it  disappears.  But  the  presence  of  pepsin  in  the  white  blood- 
corpuscles,  the  parasites  as  well  as  the  scavengers  of  the  blood,  and  of 
amylolytic,  proteolytic  and  lipolytic  ferments  in  many  tissues,  should 
warn  us  not  to  conclude  that  the  power  of  forming  ferments  belongs 
exclusively  to  any  class  of  cells.  There  is  good  and  growing  e%idence 
that  food-substances  absorbed  from  the  blood  are  further  decomposed 
and,  in  turn,  elaborated  by  ferment  action  within  the  tissues  them- 
selves; wliilc  many  facts  show  that  the  power  of  contraction  is  widely 
diffused  among  structures  whose  special  function  is  very  different, 
and  a  few  point  to  its  possession  in  some  degree  even  by  glandular 
epithelium.  On  the  other  hand,  it  must  be  remembered  that  none  of 
the  digestive  glands  absorb  food  directly  from  the  alimentarj'  canal  to 
be  then  digested  within  their  own  cell-substance ;  the  ferments  which 
they  form  do  their  work  outside  of  them ;  their  cells  feed  also  upon  the 
blood. 

Why  are  the  Tissues  of  Digestion  not  affected  by  the  Digestive 
Ferments  ? — This  is  tlie  place  to  mention  a  point  which  has  been 
very  much  debated.  Why  is  it  that  the  stomach  or  the  small  intes- 
tine does  not  digest  itself  ?  This  is  really  a  part  of  a  wider  question  : 
Why  is  it  that  living  tissues  resist  all  kinds  of  influences,  which  attack 
dead  tissues  with  success  ?  And  we  have  to  inquire  whether  the 
immunity  of  the  alimentary  canal  to  the  digestive  juices  is  an 
example  of  a  general  resistance  of  all  living  tissues  to  destructive 
agencies,  or  a  specific  resistance  of  certain  tissues  to  certain  in- 
fluences. 

That  all  living  tissues  cannot  withstand  the  action  of  the  gastric 
juice  has  been  shown  by  putting  the  leg  of  a  living  frog  inside  the 
stomach  of  a  dog;  the  leg  is  gradually  eaten  away  (Bernard). 

It  is  true  that  it  has  first  been  killed  and  then  digested,  but  the 
question   is,   why  the   stomach- wall   is  not    first    killed   and   then 


THE  SECRHTJON  OF  THE  DICES  LIVE  JUICES  ^Sq 

digested  ?     When  the  wall  has  been  injured  by  caustics  or  by  an 
embolus,  the  gastric  juice  acts  on  it.     But  the  living  epithelium 
that  covers  it  is  able  to  resist  the  action  of  the  acid  and  pepsin, 
which  destroys  the  tissues  of  the  frog's  leg.     The  explanation  is  not 
to  be  found  in  the  alkalinity  of  the  blood,  for  the  frog's  blood  is  also 
alkaline,  and  the  cells  that  line  the  intestine  are  preserved  from  the 
pancreatic  juice,  which  is  intensely  active  in  an  alkaline  medium, 
while  the  living  frog's  leg  is  not  harmed  by  a  weakly  alkaline  pan- 
creatic extract,  which  does  not  digest  the  epithelium  because  it 
cannot  kill  it.     A  certain  amount  of  protection  may  be  afforded  to 
the  walls  of  the  stomach  by  the  thin  layer  of  mucus  which  covers  the 
whole  cavity,  for  mucin  is  not  affected  by  peptic  digestion.     And 
a  mucous  secretion  seems  in  some  other  cases  to  act  as  a  protective 
covering  to  the  walls  of  hollow  viscera,  whose  contents  are  such  as 
would  certainly  be  harmful  to  more  delicate  membranes,  e.g.,  in 
the  urinary  bladder,  large  intestine,  and  gall-bladder.     Still,  how- 
ever important  such  a  mechanical  protection  may  be,  it  does  not 
explain  the  whole  matter,  and  it  is  necessary  to  suppose  that  the 
gastric  epithelium  has  some  special  power  of  resisting  the  gastric 
juice,  either  by  turning  any  of  the  ferment  which  may  invade  it 
into  an  inert  substance  and  neutralizing  any  intrusive  acid,  or  by 
opposing  their  entrance  as  the  epithelium  of  the  bladder  opposes  the 
absorption  of  urea.     There  is  reason  to  beheve  that,  as  a  matter  of 
fact,  free  hydrochloric  acid  cannot  penetrate  the  living  cells,  and 
it  is  to  be  noted  that  both  active  pepsin  and  free  acid  must  be 
present  at  the  same  point  within  the  cells  before  digestion  of  them 
can  take  place.     In  the  gland-cells  of  the  pancreas  the  protoplasm 
is,  no  doubt,  shielded  from  digestion  by  the  existence  of  the  ferment 
in  an  inert  form  as  zymogen;  and  it  is  possible  that  this  is  one  of  the 
reasons  for  the  existence  of  the  mother-substance.     But  no  such 
explanation  is,  of  course,  available  for  the  intestinal  epithelium. 
Trypsin  when  injected  below  the  skin  causes  the  tissue  to  break 
down  and  ulcerate.     And  while  an  active  solution  of  trypsin  can 
be  allowed  to  remain  a  long  time  in  an  isolated  loop  of  small  intes- 
tine without  producing  any  ill  effect,  damage  is  soon  caused  not 
only  to  the  intestinal  wall,  but  also  to  the  liver,  when  the  mucous 
membrane  of  the  loop  has  been  injured  before  the  introduction  of 
the  trypsin.     We  must  suppose,  then,  that  the  normal  mucous 
membrane  of  the  intestine  prevents  the  absorption  of  trypsin,  or, 
if  it  absorbs  any  of  it,  renders  it  harmless.     On  the  other  hand,  the 
intestinal  mucosa  is  injured  by  the  natural  gastric  juice  when  intro- 
duced directly  into  it  unless  the  animal  takes  food  simultaneously 
or  a  little  earlier.     But  for  reasons  already  given  (p.  370)  injury  to 
the  intestine  cannot  be  produced  in  this  way  in  normal  digestion. 
It  is  impossible  to  escape  the  conclusion  that  each  membrane  becomes 
accustomed,  and,  so  to  speak,  '  immune,'  to  the  secretion  normally 


390 


DIGESTION 


in  contact  with  it,  although  not   necessarily  to  other  secretions. 
It  is  easy  to  multiply  illustrations  of  this  principle. 

The  mucosa  of  the  dog's  urinary  bladder  is  digested  by  the 
natural  activated  pancreatic  juice  of  the  dog,  and  still  more  readily 
by  the  natural  gastric  juice.  Yet  few  tissues  but  the  Hning  of  the 
urinary  tract  or  of  the  large  intestine  could  bear  the  constant  contact 
of  urine  or  faeces.  When  urine  is  extravasated  under  the  skin,  or 
the  contents  of  the  alimentary  canal  burst  into  the  peritoneal 
cavity,  they  come  into  contact  with  tissues  which,  although  ahve, 
are  much  less  fitted  to  resist  them  than  the  surfaces  by  which  they 
are  normally  enclosed;  and  the  consequences,  which  are  not  wholly 
due  to  infection,  are  often  disastrous.  Leucocytes  thrive  in 
the  blood,  but  perish  in  urine.  Blood  does  not  harm  the  endo- 
thehal  cells  of  the  vessels,  but  kills  a  muscle  whose  cross-section 
is  dipped  into  it.  The  defensive  or,  in  some  cases,  offensive 
liquids  secreted  by  many  animals  are  harmless  to  the  tissues 
which  produce  and  enclose  them.  A  caterpillar  investigated 
by  Poulton  secretes  a  liquid  so  rich  in  formic  acid  that  the  mere 
contact  of  it  would  kill  most  cells.  The  so-called  saliva  of  Octopus 
macropus  contains  a  substance  fatal  to  the  crabs  and  other  animals 
on  which  it  preys.  The  blood  of  the  viper  c(jntains  an  active 
principle  similar  to  that  secreted  by  its  poison-glands,  but  its  tissues 
are  not  affected  by  this  substance,  so  deadly  to  other  animals. 

A  step  in  the  solution  of  our  problem  has  been  taken  by  Wein- 
land.  Starting  with  the  idea  that  if  special  protective  mechan- 
isms against  the  digestive  juices  were  anywhere  to  be  found,  it  would 
be  in  the  intestinal  parasites  whose  whole  existence  is  passed  among 
them,  he  has  made  the  important  discovery  that  in  these  parasitic 
worms  specific  antiferments  exist — i.e.,  substances  which  inhibit  the 
action  either  of  pepsin  or  of  trypsin  or  of  both.  These  substances  can 
be  precipitated  from  the  expressed  juice  of  the  worms  by  alcohol, 
without  completely  losing  their  activity.  Fibrin  can  be  impreg- 
nated with  them,  and  it  is  then,  just  like  the  '  hving  tissue,'  rendered 
for  a  longer  or  shorter  time  unassailable  by  the  proteolytic  ferments. 
These  facts  are  fuU  of  suggestion  for  future  work,  although  the  sup- 
posed proof  that  similar  antiferments  are  contained  in  the  cells  of 
the  mucous  membrane  of  the  stomach  and  intestines  of  the  higher 
animals  appears  to  have  broken  down.  Substances  can  indeed  be 
obtained  by  Weinland's  method  from  the  gastric  and  intestinal 
mucosa  which,  when  added  to  a  digestive  mixture,  strongly  inhibit 
the  digestion  of  proteins.  But  there  is  no  clear  proof  that  these  sub- 
stances are  specific  antiferments.  They  are  probably  merely  some 
of  the  split  products  of  protein  (Langenskjold).  There  is,  however, 
some  evidence  of  the  existence  of  an  antipepsin  in  many  tissues 
including  the  mucous  membrane  of  the  stomach.  As  already  men- 
tioned, it  is  known  that  an  antitrj^sin  exists  in  the  blood,  with  the 


hMLUh.XLL  Uh  \Ll<.VOU5  b\^iLM  0.\  DIGESTIVL  GLA.SJJb     591 

same  properties  as  tlie  antitrypsin  in  the  intestinal  worms  (Hamill). 
This  explains  the  resistance  of  blood-serum  to  the  digestive  action 
of  trypsin.  In  addition  to  this  body,  which  hinders  the  action  of 
fully-formed  trypsin,  and  has  no  effect  upon  enterokinase,  the 
serum  of  some  animals  contains  an  antikinase — i.e.,  a  substance 
which  hinders  the  action,  not  of  trypsin,  but  of  enterokinase,  pre- 
venting it  from  activating  the  trypsmogen  into  trypsin. 


Section  V. — The  Influenxe  of  the  Nervous  System 
ON  the  Digestive  Gl.\nds. 

The  Influence  of  Nerves  on  the  Salivary  Glands. — All  the  salivary 
glands  have  a  double  nerve-supply,  from  the  medulla  oblongata 
through  some  of  the  cranial  nerves,  and  from  the  spinal  cord  through 
the  cervical  sympathetic  (Fig.  160). 

In  the  dog  the  chorda  tympani  branch  of  the  facial  nerve  carries  the 
cranial  supply  of  the  sublingual  and  submaxillary  glands.  It  joins  the 
lingual  branch  of  the  fifth  nerve,  runs  in  company  with  it  for  a  little 
way,  and  then,  breaking  off,  after  giving  some  fibres  to  the  lingual, 
passes,  as  the  chorda  tympani  proper,  along  WTiarton's  duct  to  the 
siTbmaxillar\'  gland.  In  the  hilus  of  this  gland  most  of  its  fibres  break 
up  into  fibrils  around  nerve-cells  situated  there,  and  lose  their  medulla 
in  doing  so.  A  few  fibres  terminate  in  a  similar  manner  before  entering 
the  hilus,  and  a  few  deeper  in  the  gland.  The  nervous  path  is  continued 
by  the  axis-cylinder  processes  (p.  851)  of  these  nerve-ceUs,  which, 
passing  in  as  non-medullated  fibres,  end  in  a  plexus  on  the  basement 
membrane  of  the  alveoli.  From  the  plexus  fibrils  nm  in  among  the 
gland-cells,  but  do  not  seem  to  penetrate  them.  The  lingual,  the 
chorda  t^mipani  proper,  and  Wharton's  duct  form  the  sides  of  what  is 
caUed  the  chordo-lingual  triangle.  Within  this  triangle  are  situated 
many  ganglion  cells,  a  special  accumulation  of  which  has  received  the 
name  of  the  submaxillar^'  ganglion.  This,  however,  should  rather  be 
called  the  sublingual  ganglion,  since  its  cells,  as  well  as  the  others  in  the 
chordo-lingual  triangle,  are  the  cells  of  origin  of  axons  which  proceed 
as  non-medullated  fibres  to  the  sublingual  gland.  The  sublingual  gland 
receives  its  cerebral  fibres  partly  from  branches  given  off  from  the 
lingual  in  the  chordo-lingual  triangle  after  the  chorda  tympani  proper 
has  separated  from  it,  and  ending  around  the  nerve-cells  within  that 
triangle,  partly  from  the  chorda  itself  in  the  terminal  portion  of  its 
course.  These  statements  rest  on  anatomical  and  physiological  evi- 
dence.    The  latter  we  shall  return  to. 

The  cerebral  fibres  for  the  parotid  (in  the  dog)  pass  from  the  tympanic 
branch  of  the  glosso-phar^-ngeal  (Jacobson's  nerve)  through  connecting 
filaments  to  the  small  superficial  petrosal  branch  of  the  facial,  with 
this  nerve  to  the  otic  ganglion,  and  thence  by  the  auriculo-temporal 
branch  of  the  fifth  to  the  gland. 

The  sympathetic  fibres  for  all  the  salivary  glands  appear  to  arise  from 
nerve-cells  in  the  upper  dorsal  portion  of  the  spinal  cord.  Issuing 
from  the  cord  in  the  anterior  roots  of  the  upper  thoracic  nerves  (first  to 
fifth,  but  mainly  second  thoracic  for  the  submaxillary),  they  enter  the 
sympathetic  chain,  in  which  they  run  up  to  the  superior  cervical 
ganglion.     Here  they  break  up  into  terminal  twigs,  and  thus  come  into 


302 


DIGESTION 


n-Lition  with  ganglion  cells,  whose  axons  pass  out  as  non-mcdullated 
fibres,  and,  surrounding  the  external  carotid,  reach  the  salivary  glands 
along  its  branches.  Langlev  has  shown,  by  means  of  nicotine  (p.  182), 
that  the  sympathetic  fibres  for  the  submaxillary-  and  sublingual,  and, 
indeed,  for  the  head  in  general  in  the  dog  and  cat,  are  connected  with 
nerve-cells  in  this  ganglion,  b\it  not  between  it  and  their  termination, 
or  between  it  and  tlieir  origin  from  the  spinal  cord. 

Stimulation    of    the 


Cranial  Fibres. — When 
in  a  (log  a  cannula  is 
placed  in  \\  barton's 
duct,  and  the  saliva 
collected  (p.  45O),  it  is 
found  that  stimulation 
of  the  peripheral  end 
of  the  divided  chorda 
causes  a  brisk  flow  of 
watery  saliva,  and  at 
the  same  time  a  dila- 
tation of  the  vessels 
of  the  gland,  which  we 
have  already  described 
in  dealing  with  vaso- 
motor nerves  (p.  179). 
Notwithstanding  the 
vaso  -  dilatation,  the 
volume  of  the  gland 
is  in  general  dimin- 
ished, owing  to  the 
rapid  passage  of  water 
into  the  duct  (Bunch). 
The  blood  has  been 
shown  to  lose  water  in 
making  the  circuit  of 
the  submaxillary 
gland  during  excita- 
tion of  the  chorda, 
but  doubtless  some 
of  the  water  of  the 
saliva  comes  directly 
from  tlie  cells  or  from 
the  lymph.  That  the  increased  secretion  is  not  due  merely  to  the 
greater  blood-supply,  and  the  consequent  increase  of  capillary  pres- 
sure, is  shown  by  the  injection  of  atropine,  after  which  stimulation 
of  the  nerve,  although  it  still  causes  dilatation  of  the  vessels,  is  not 
followed  by  a  flow  of  saliva.  This  can  be  shown  fully  as  well  by 
injecting  a  small  quantity  of  yohimbin  into  the  subrmixillary  artery. 
Great  dilatation  of  the  vessels  is  produced,  but  no  saliva  is  secreted; 


Fig.  160  — Nerves  oi  the  Salivary  Glands.  SM  and  SL, 
submaxillary  and  sublingual  glands;  P,  parotid; 
A',  fifth  nerve;  VII.  facial;  GP,  glosso-pharyngeal; 
L.  lingual;  CT,  chorda  tympani;  CL,  chordo-lingual; 
1>.  subma.Killary  (Wharton's)  duct;  C.  ganglion  cell 
of  so-called  submaxillary  ganglion  in  the  chordo- 
lingual  triangle,  connected  with  a  nerve  fibie  going 
to  sublingual  gland;  C.  ganglion  cell  in  hilus  of  sub- 
maxillary gland:  SSP,  small  superficial  petrosal 
branch  of  the  facial;  OG.  otic  ganglion;  IM,  inferior 
maxillary  division  of  fifth  nerve:  AT,  auriculo- 
temporal branch  of  fifth:  JN,  Jacobson's  nerve: 
C,  gang'ion  cells  in  superior  cervical  ganglion  (SG) 
connected  with  sympathetic  fibres  going  to  parotid, 
submaxillarv'  and  sublingual  glands.  The  figure  is 
schematic. 


JMLLl-XCr:  Of  S'ElilUiS  SYSTEM  OS  DlGLSTIVJi  CLASDS   393 

nor  i?  ilie  amount  of  oxygen  consumed  by  the  gland  increased. 
Mere  increase  of  pressure  could  not  in  any  case  of  itself  account  for 
the  secretion,  since  it  has  been  found  that  the  maximum  pressure 
in  the  salivary  duct  when  ;iie  outflow  of  saliva  from  the  duct  is 
prevented  mav.  during  stimulaiion  of  the  chorda,  much  exceed  the 
arterial  blood-pressure  (Ludwig).  In  one  experiment,  for  example, 
the  pressure  in  the  carotid  of  a  dog  was  125  mm.,  in  Wharton's 
duct  195  mm.  of  mercury. 

Even  in  the  head  of  a  decapitated  animal  a  certain  amount  of 
sali\a  may  be  caused  to  flow  by  stimulation  of  the  chorda,  but  too 
much  may  easily  be  made  of  this.  And  since  the  blood  is  the  ultimate 
source  of  the  secretion,  we  could  not  expect  a  permanent  or  copious 
flow  in  the  absence  of  the  circulation,  even  if  the  gland-cells  could 
continue  to  live.  In  fact,  when  the  circulation  is  almost  stopped  by 
strong  stimulation  of  the  sympathetic,  the  flow  of  saUva  caused  by 
excitation  of  the  chorda  is  at  the  same  time  greatly  lessened  or 
arrested,  even  though  the  sympathetic  itself  possesses  secretory 
fibres.  So  that,  while  there  is  no  doubt  that  the  chorda  tympani 
contains  fibres  whose  function  is  to  increase  the  activity  of  the 
gland-cells,  its  vaso-dilator  action  is,  under  normal  conditions, 
closely  connected  with,  and.  indeed,  auxihary  to.  its  secretory  action, 
although  the  dilatation  of  the  vessels  does  not  directly  produce  the 
secretion.  This  is  only  a  particular  case  of  a  physiological  law  of 
wide  application,  that  an  organ  in  action  in  general  receives  more 
blood  than  the  same  organ  in  repose,  or,  in  other  words,  that  the 
tissues  are  fed  according  to  their  needs.  The  contracting  muscle,  the 
secreting  gland,  is  flushed  with  blood,  not  because  an  increased  blood- 
flow  can  of  itself  cause  contraction  or  secretion,  but  because  these 
high  efforts  require  for  their  continuance  a  rich  supply  of  what  blood 
brings  to  an  organ,  and  a  ready  removal  of  what  it  takes  away. 
Evidence  exists  that  in  the  saUvary  glands,  as  in  muscle  (p.  178), 
metabolic  products  given  off  during  functional  acti\-ity  contribute 
to  the  dilatation  of  the  vessels.  This  is  the  simplest  explanation  of 
the  fact  that  the  dilatation  caused  by  chorda  stimulation  lasts  longer 
when  saliva  is  being  secreted  than  when  the  secretion  has  been 
abohshed  by  atropine. 

The  quantity  of  blood  passing  through  the  parotid  of  a  horse 
when  it  is  actively  secreting  during  mastication  may  be  quadrupled 
(Chauveau).  The  parallel  between  the  muscle  and  the  gland  is 
drawn  closer  when  it  is  stated  that  electrical  changes  accompany 
secretion  (p.  83S),  and  that  the  rate  of  production  of  carbon  dioxide 
and  consumption  of  oxygen  (in  the  submaxillary  gland)  is  three  or 
four  times  greater  during  activity  than  during  rest .  The  temperature 
of  the  saliva  flowing  from  the  dog's  submaxillary  during  stimulation 
of  the  chorda  has  been  found  to  be  as  much  as  i^^**  C.  above  that 
of  the  blood  of  the  carotid,  although  with  the  gland  at  rest  no  con- 
stant difference  could  be  detected  between  the  arterial  blood  and 


394  DICESTIOS 

the  interior  of  Wharton's  duct.  But  such  measurements  arc  open 
to  many  fallacies;  and  while  there  is  no  doubt  that  more  heat  is 
produced  in  the  active  than  in  the  passive  ejland,  it  will  not  be 
surprising,  when  the  vastly-increased  blood-flow  is  remembered, 
that  no  difference  of  temperature  between  the  incoming  and  out- 
going blood  has  been  satisfactorily  demonstrated. 

It  has  already  been  mentioned  that  most  of  tlie  fibres  of  the  chorda 
tympani  proper  become  connected  with  ganghuu-cells,  and  lose  their 
nii-dulla  inside  the  submaxillary  gland,  only  a  few  having  already  lost 
it  by  a  similar  connection  with  ganglion-cells  in  the  chordo-Ungual 
triangle.  These  facts  have  been  made  out  by  means  of  the  nicotine 
method  previously  described  (p.  182).  Thus,  it  is  found  that,  after 
the  injection  of  nicotine  (5  to  10  mg.  in  a  rabbit  or  cat,  40  or  50  mg.  in 
a  dog),  stimulation  of  the  chorda  tj-mpani  proper  or  of  the  chordo- 
lingual  nerve  causes  no  secretion  from  the  submaxillary  gland;  but 
stimulation  of  the  lulus  of  the  gland  is  followed  by  a  copious  secretion — 
as  much,  if  the  stimulation  is  fairly  strong,  as  was  caused  by  excitation 
of  the  nerve  before  injection  of  nicotine.  That  this  is  due  neither  to 
any  direct  action  on  the  gland-cells,  nor  to  stimulation  of  the  sympa- 
thetic plexus  on  the  submaxillary  artery-,  but  to  stimulation  of  chorda 
fibres  beyond  the  hilus,  is  shown  by  the  fact  that  after  atropine  has 
been  injected  in  sufficient  amoimt  to  paralyze  the  nerve  endings  of  the 
chorda,  but  not  of  the  sympathetic,  stimulation  of  the  hilus  causes  little 
or  no  flow  of  saliva.  The  application  of  nicotine  solution  to  the  chordo- 
Ungual  triangle  does  not  affect  the  submaxillary  secretion  caused  by 
stimulation  of  the  chordo-lingual  nerve,  even  in  cases  where  a  few 
secretory  fibres  for  the  submaxillary  do  not  leave  the  chordo-lingual 
nerve  in  the  chorda  tympani  proper,  but  are  given  off  to  the  chordo- 
lingual  triangle.  This  shows  that  none  of  the  ganglion-cells  in  the 
triangle  are  connected  with  the  secreton,-  fibres  of  the  submaxillar}' 
gland.  By  observations  of  the  same  kind  they  are  kno%vn  to  be  con- 
nected with  fibres  going  to  the  sublingual.  In  a  similar  way,  by  observ- 
ing the  effects  of  stimulation  of  the  chorda  on  the  bloodvessels  before 
and  after  the  application  of  nicotine,  it  has  been  found  that  the  vaso- 
dilator fibres  are  connected  with  ganglion-cells  in  the  same  positions  as 
the  secretory  fibres  (Langley). 

Stimulation  of  the  Sympathetic  Fibres. — The  sympathetic,  as  has 
been  already  indicated,  contains  both  vaso-constrictor  and  secretory 
fibres  for  the  salivary  glands.  If  the  cervical  sympathetic  in  the 
dog  is  divided,  and  the  cephalic  end  moderately  stimulated,  a  few 
drops  of  a  thick,  viscid  and  scanty  saliva  flow  from  the  submaxillary 
and  sublingual  ducts,  while  the  current  of  blood  through  the  glands 
is  diminished.  As  a  rule,  no  visible  secretion  escapes  from  the 
parotid,  but  microscopic  examination  shows  that  many  of  the 
ductules  are  filled  with  fluid,  which  is  apparently  so  thick  as  to  plug 
them  up  (Langley) ;  while  the  cells  sliow  signs  of '  activity  '  (p.  376). 

Simultaneous  Stimulation  of  Cranial  and  Sympathetic  Fibres. — 
When  the  chorda  and  sympathetic  are  stimulated  together,  the 
former  prevails  so  far,  with  moderate  stimulation  of  the  iatter,  that 
the  submaxillary  saliva  is  secreted  in  considerable  quantity,  and  is 
not  particularly  viscid.  It  is,  however,  richer  in  organic  matter 
than  is  the  chorda  saliva  itself.     When  the  chorda  is  weakly,  and 


INFLUEi\CE  OF  NERVOUS  SYSTEM  OS  DIGESTIVE  (JLASDS  395 

the  sympathetic  strongly,  excited,  the  scanty  secretion  (if  there  is 
arty)  is  of  sympathetic  type,  thick  and  rich  in  organic  matter.  With 
strong  stimulation  of  both  nerves,  the  secretion,  at  first  plentiful 
and  watery,  soon  diminishes,  even  below  the  amount  obtained  by 
stimulation  of  the  chorda  alone,  because  of  the  diminution  in  the 
blood- flow,  and  therefore  in  the  oxygen-supply,  produced  by  the 
vaso -constrictors  of  the  sympathetic  (Heidenhain).  With  stimula- 
tion just  strong  enough  to  cause  secretion  when  apphed  separately 
to  either  nerve,  there  is  no  secretion  when  it  is  applied  simul- 
taneously to  both. 

All  this  refers  to  the  dog.  In  this  animal,  then,  there  seems  to  be 
a  certain  amount  of  physiological  antagonism  between  the  secretory 
action  of  the  two  nerves.  But  it  differs  in  one  respect  from  the 
antagonism  between  their  vaso-motor  fibres;  for  with  strong  stimu- 
lation the  constrictors  of  the  sympathetic  always  swamp  the  dilators 
of  the  chorda,  while  the  secretory  fibres  of  the  chorda  appear  upon 
the  whole  to  prevail  over  those  of  the  sympathetic.  And  in  all 
probability  this  apparent  secretory  antagonism  is  very  superficial, 
and  is  due  largely  to  the  difference  in  the  vaso-motor  effects  of  the 
two  nerves.  For  it  has  been  shown  that,  when  the  blood-flow 
through  the  submaxillary  gland  is  artificially  diminished  by  gradu- 
ated compression  of  its  artery,  stimulation  of  the  chorda  gives  rise 
to  a  thick,  viscid  and  scanty  saliva,  relatively  rich  in  organic  soHds 
(Heidenhain).  When  the  amount  of  blood  passing  through  the 
gland  is  made  approximately  the  same  as  during  stimulation  of  the 
sympathetic,  the  chorda  saliva  becomes  practically  identical  in 
composition  with  the  sympathetic  saliva.  This  is  one  reason, 
perhaps  the  chief  one,  why  the  sympathetic,  when  both  nerves  are 
stimulated  together,  without  artificial  interference  with  the  blood- 
supply,  always  appears  to  add  something  to  the  common  secretion 
when  there  is  a  secretion  at  all,  this  something  being  represented 
by  an  increase  in  the  percentage  of  organic  matter.  The  observation 
that  the  sympathetic  effect  persists  after  stimulation  has  been 
stopped,  and  that  excitation  of  the  chorda  after  previous  stimula- 
tion of  the  sympathetic  causes  a  flow  of  saliva  richer  in  organic 
matter  than  would  have  been  the  case  if  the  sympathetic  had  not 
been  stimulated,  has  long  been  considered  a  proof  that  the  secretory 
hbres  of  the  two  nerves  are  widely  different  in  function.  To  explain 
this  result,  Heidenhain  assumed  the  existence  in  the  sympathetic 
of  a  preponderance  of  fibres  concerned  in  the  building  up  in  the 
cells  of  the  organic  constituents  of  the  saUva  (so-called  '  trophic,' 
or,  better,  since  the  word  '  trophic  '  is  usually  associated  ^vith  the 
building  up  of  the  bioplasm  itself,  '  trophic-secretory  '  fibres).  It 
would  seem,  however,  that  the  increase  in  organic  constituents  is 
only  reahzed  when  a  sufficient  time  has  not  been  allowed,  after 
stimulation  of  the  S3'mpathetic,  for  the  normal  circulation  to  become 
re-established  in  the  gland.     The  saliva  obtained  by  stimulation  of 


396  DIGESTJON 

the  churda  immediately  after  a  period  of  artificially  diminished 
blood-flow,  without  any  previous  excitation  of  the  bympathetic, 
also  contains  a  surplus  of  organic  matter  (Carlson). 

Indeed,  the  distinction  between  chorda  and  sympathetic  saliva, 
which,  by  taking  account  of  the  parotid  as  well  as  the  submaxillary 
and  sublingual  glands,  has  been  generalized  into  a  distinction 
between  cerebral  and  sympathetic  saliva,  and  which,  when  the 
vaso-motor  conditions  arc  left  out  of  account,  appears  to  hold  good 
in  the  dog  and  the  rabbit,  breaks  down  before  a  wider  induction. 
For  in  the  cat  the  sympathetic  sahva  of  the  subma.xiilary  gland, 
although  more  scanty,  is  more  watery  than  the  chorda  saliva 
(Langley),  which,  however,  is  by  no  means  viscid;  and  the  two 
secretions  differ  far  less  than  in  the  dog.  The  discovery  of  Carlson 
that  the  usual  effect  of  stimulation  of  the  cat's  cervical  sympathetic 
with  a  weak  interrupted  current  is  a  marked  augmentation  in  the 
blood-flow*  through  the  submaxillary  gland  affords  an  explanation. 
In  accordance  with  this  functional  similarity,  there  is  a  much 
smaller  difference  in  the  action  of  atropine  on  the  two  sets  of  fibres 
in  the  cat  than  in  the  dog,  although  even  in  the  cat  the  sympathetic 
is  less  readily  paratyzed  than  the  chorda. 

In  their  secretory  action  there  is  not  even  an  apparent  antagonism 
in  the  cat,  with  minimal  stimulation  of  both  nerves,  which  causes 
as  much  secretion  as  would  be  produced  if  both  were  separately 
excited.  Further,  even  in  the  dog,  after  prolonged  stimulation  of 
the  sympathetic,  the  submaxillary  saliva  is  no  longer  viscid,  but 
watery-,  the  proportion  of  solids,  and  especially  of  organic  sohds, 
being  much  lessened,  as  it  is  also  in  chorda  saliva  after  long  excita- 
tion. When  the  cerebral  nerve  of  the  resting  gland  is  strongly 
excited,  it  is  found  that  up  to  a  certain  limit  the  percentage  of 
organic  matter  in  a  small  sample  of  sali\a  subsequently  collected 
during  a  brief  weak  excitation  increases  with  the  strength  of  the 
previous  stimulation ;  this  is  also  true  of  the  inorganic  solids.  But 
there  is  a  striking  difference  when  the  experiment  is  made  on  a  gland 
after  a  long  period  of  activity ;  here  increase  of  stimulation  causes 
no  increase  in  the  percentage  of  organic  material,  while  the  inorganic 
solids  are  still  increased.  In  both  cases  the  absolute  quantity  of 
water,  and  therefore  the  rate  of  flow  of  the  secretion,  is  augmented. 

All  this  points  to  the  same  conclusion  as  the  microscopic  appear- 
ances in  the  gland-cells,  that  the  cells  during  rest  manufacture  the 
organic  constituents  of  the  secretion,  or  some  of  them,  and  store 
them  up,  to  be  discharged  during  activity.  The  water  and  the 
inorganic  salts,  on  the  other  hand,  seem  rather  to  be  secreted  on 
the  spur  of  the  moment,  so  to  speak,  and  not  to  require  such 
elaborate   preparation.     And  it   has   been  stated  that   when  the 

*  The  increased  blcx)d-flow,  which  can  be  even  better  elicited  by  injection  of 
adrenalin,  immediately  succeeds  the  secretion  of  saliva,  and  seems  to  be  due 
not  to  the  presence  of  vaso-dilator  fibres  in  the  sympathetic,  but  to  metabolic 
products. 


IXFLUEXCE  OF  \ERVOUS  SYSTEM  O.V  DIGESTIVE  GEAWDS  307 

chorda  tympani  is  stimulated  with  currents  of  varying  strength, 
the  quantity  of  organic  substances  in  small  samples  of  sahva 
collected  from  a  fresh  gland  is  more  nearly  proportional  to  the  rate 
of  secretion  than  is  the  quantity  of  water  and  salts,  which  varies 
also  with  the  blood-supplv. 

Lest  the  apparently  insignificant  resuh  of  artificial  stimulation 
of  the  sympathetic  in  such  animals  as  the  dog  should  cause  its 
secretory  action  to  be  aopraised  at  too  low  a  value,  it  should  be 
remembered  that  in  tne  mtact  body  the  sympathetic  secretory  fibres, 
when  they  are  excited,  are,  it  may  be  assumed,  excited  independently 
of  the  vaso-constrictors.  and  even  in  conjunction  with  the  vaso- 
dilators of  the  salivary  glands. 

It  is  conceivable  that  such  differences  between  chorda  and 
sympathetic  saliva  as  are  not  accounted  for  by  the  differences  in 
the  blood-flow  during  their  stimulation  are  due,  not  to  the  nerve 
fibres,  but  to  the  end  organs  with  which  they  are  connected;  that 
is,  the  two  nerves  may  supply,  not  the  same,  but  different  gland- 
cells.  And  it  is  well  known  that  even  after  prolonged  stimulation 
of  the  chorda  or  chordo-lingual  alone,  some  alveoli  of  the  dog's 
submaxillary  gland  remain  in  the  '  resting  '  state ;  after  stimulation 
of  the  sympathetic  alone,  the  number  of  unaffected  alveoli  is  much 
greater;  while  after  stimulatipn  of  both  nerves,  few  alveoli  seem 
to  have  escaped  change.  If  there  is  no  essential  difference  between 
the  cranial  and  sympathetic  secretory  fibres,  it  is  easy  to  understand 
that  they  will  be  distributed  to  different  secreting  elements.  The 
supposed  proof  that  there  must  be  some  overlapping  in  the  nerve- 
supply — i.e.,  that  some  cells  must  be  suppUed  from  both  sources, 
since  excitation  of  the  sympathetic  influences  the  amount  of  organic 
material  in  the  saliva  obtained  by  subsequent  stimulation  of  the 
chorda — is,  as  we  have  just  seen,  by  no  means  so  cogent  as  has  been 
assumed.  And,  indeed,  we  know  nothing  of  a  division  of  labour 
between  the  cells  of  a  gland,  except  when  there  are  obvious  anatom- 
ical distinctions.  Thus,  the  submaxillary  gland  in  man  contains 
both  serous  and  mucous  acini,  and  mucin-making  cells  are  scattered 
over  the  ducts  of  most  glands,  and,  indeed,  on  nearly  every  surface 
which  is  clad  with  columnar  epithelium.  In  these  cases  we  cannot 
doubt  that  one  constituent — mucin — of  the  entire  secretion  is  manu- 
factured by  a  portion  only  of  the  cells.  In  the  cardiac  glands  of  the 
stomach,  too,  the  ovoid  cells,  in  all  probability,  yield  the  whole  of 
the  acid  of  the  gastric  juice.  But,  so  far  as  we  know,  every  hepatic 
cell  is  a  liver  in  little.  Every  cell  secretes  fully- formed  bile;  every 
cell  stores  up,  or  may  store  up,  glycogen.  So  it  is  with  the  secretory 
alveoU  of  the  pancreas,  if  we  consider  the  islands  of  Langerhans  as 
having  no  connection  with  the  alveoli;  one  cell  is  just  Hke  another; 
all  apparently  perform  the  same  work;  each  is  a  unicellular  pan- 
creas.   (See  p.  638.) 

Paralytic  Secretion. — When  the  chorda  tympani  is  divided,  a  slow 
'  paral^-tic  '   secretion   from  the  submaxillary   gland  begins  in   a  few 


■?q8  DIGESTION 

hours,  and  continues  for  a  long  time  accompanied  by  atrophy  of  the 
gland.  There  is  also  a  secretion  of  the  same  kind  from  the  submaxillary 
on  the  opposite  side,  but  it  is  less  copious.  This  is  called  the  '  antilytic ' 
secretion,  which  is  most  pronounced  in  the  first  few  days  after  the 
operation,  and  seems  to  be  a  transient  phenomenon.  It  can  be  at  once 
abolished  by  section  both  of  the  chorda  and  the  sympathetic  on  the 
corresponding  side,  ana  is  therefore  due  to  impulses  arising  in  the 
central  ner^•ous  system.  The  cause  of  the  paral^-tic  secretion  has  not 
been  fully  made  out.  If  within  two  or  three  days  of  division  of  the 
chorda  the  sympathetic  on  the  same  side  is  cut.  the  secretion  is  greatly 
diminished  or  stops  altogether;  and  it  is  concluded  that  up  to  this  time 
it  is  maintained  by  impulses  passing  along  the  sympathetic  to  the  gland 
from  the  salivary  centre,  the  excitability  of  which  has  been  in  some  way 
increased  by  division  of  the  chorda,  possibly  by  some  such  degenerative 
process  in  the  cells  as  the  changes  seen  in  cerebro-spinal  motor  cells 
whose  axons  have  been  divided  (p.  858).  This  may  also  account  for  the 
antilj^ic  secretion.  But  if  section  of  the  sympathetic  is  not  performed 
for  several  days,  it  has  no  effect  on  the  paralj-tic  secretion,  which  at 
this  stage  seems  to  depend  on  local  changes  in  or  near  the  gland  itself, 
leading  to  a  mild  continuous  excitation  of  those  nerve-ceUs  on  the 
course  of  the  fibres  of  the  chorda  to  which  reference  has  already  been 
made.  Section  of  the  sympathetic  alone  causes  neither  secretion  nor 
atroph}-.  nor  does  removal  of  the  superior  cervical  ganglion.  The 
histological  characters  of  the  gland-cells  during  paral}i:ic  secretion  are 
those  of  '  rest.' 

Reflex  Secretion  of  Saliva. — The  reflex  mechanism  of  salivary 
secretion  is  very  mobile,  and  easily  set  in  action  by  physical  and 
mental  influences.  It  is  excited  normally  by  impulses  v.'hich  arise 
in  the  mouth,  especially  by  the  contact  of  food  with  the  buccal 
mucous  membrane  and  the  gustatory  nerve-endings.  The  mere 
mechanical  movement  of  the  jaws,  even  when  there  is  nothing 
between  the  teeth,  or  only  a  bit  of  a  non-sapid  substance  like  india- 
rubber,  causes  some  secretion.  The  vapour  of  ether  gives  rise  to  a 
rush  of  saliva,  as  does  gargling  the  moutli  with  distilled  water. 
The  smell,  sight,  or  thought  of  food,  and  even  the  thought  of  saUva 
itself,  may  act  on  the  saUvary  centre  through  its  connections  with 
the  cerebrum,  and  make  'the  teeth  water.'  A  copious  flow  of 
saliva,  reflexly  excited  through  the  gastric  branches  of  the  vagus, 
is  a  common  precursor  of  vomiting.  The  introduction  of  food  into 
the  stomach  also  excites  salivary  secretion. 

The  researches  of  Pawlow  and  his  pupils  have  shown  that  the 
saUvary  glands  are  not  excited  indifferently  by  everything  which 
comes  into  contact  with  the  buccal  mucous  membrane.  A  remark- 
able adaptation  exists  between  the  properties  of  food  or  foreign 
bodies  introduced  into  the  mouth  and  their  effects  upon  the  secre- 
tion of  sahva.  When  solid  dry  food  is  given  to  a  dog  saliva  is 
copiously  poured  out;  much  less  is  secreted  when  the  food  is  moist. 

Acids  or  salts  induce  an  abundant  flow,  in  order  that  they  may 
be  neutralized,  diluted  or  washed  out  of  the  mouth.  In  this  case 
a  watery  liquid,  poor  in  mucin,  flows  from  the  nmcous  glands. 
Mucin  is  a  lubricant  to  facilitate  the  swallowing  of  solid  food,  and 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS  399 

here  it  could  be  of  no  use.  When  clean  pebbles  are  put  in  the  dog's 
mouth  the  animal  may  try  to  chew  them,  but  eventually  ejects 
them.  Either  no  saliva  or  very  little  is  secreted,  since  it  could 
not  aid  in  their  expulsion.  If,  however,  the  very  same  stones  are 
reduced  to  sand  and  again  introduced  into  the  animal's  mouth, 
saliva  is  plentifully  secreted  to  wash  it  out. 

The  serous  and  mucous  salivary  glands  are  not  necessarily  excited 
by  the  same  food  materials,  and  here  again  we  can  trace  an  astonish- 
ingly exact  adaptation.  A  permanent  parotid  or  submaxillary 
fistula  can  easily  be  made  in  a  dog  by  freeing  Stenson's  or  Wharton's 
duct  from  the  surrounding  mucous  membrane  for  a  little  distance, 
bringing  the  natural  orifice  of  the  duct  out  through  a  small  wound 
in  the  cheek,  and  stitching  it  in  position  there.  When  it  is  desired 
to  collect  sahva,  the  wide  end  of  a  funnel-shaped  tube,  whose  stem 
is  bent  so  as  to  hang  vertically,  can  be  attached  by  a  little  shellac 
of  low  melting-point  to  the  skin  around  the  orifice  of  the  duct  and 
at  some  distance  from  it,  and  on  the  naiTow  end  can  be  hung  a  small 
graduated  tube,  into  which  the  sahva  drops.  When  fresh  meat  is 
given  to  the  animal  little  or  no  parotid  sahva  is  secreted,  while  a 
copious  flow  takes  place  from  the  submaxillary  gland,  mucin  being 
required  to  lubricate  it  for  deglutition,  while  water  is  not  specially 
needed.  But  if  the  meat  is  in  the  form  of  a  dry  powder  the  parotid 
pours  out  a  plentiful  secretion,  while  the  submaxillary  also  secretes 
a  fluid  relatively  rich  in  mucin.  The  same  difference  is  seen  between 
fresh  moist  bread  and  dry  bread.  The  afferent  nerve-endings  from 
which  impulses  are  carried  to  the  reflex  centres  (or  the  portions  of 
the  salivary  centre)  which  preside  over  the  various  salivar\'  glands 
must  possess  the  power  of  very  delicate  selection  as  regards  the 
kinds  of  stimulation  b}'  which  they  are  affected.  The  mere  relish 
of  the  animal  for  the  different  kinds  of  food  plays  but  a  small  part. 
Most  dogs  display  a  much  livelier  interest  in  a  piece  of  meat  than 
in  a  piece  of  dry  biscuit,  yet  it  is  the  biscuit  which  excites  the  parotid 
to  activity. 

The  sight  of  dry  food  causes  an  abundant  flow  of  vi^atery  saliva 
from  the  parotid,  and  a  flow  of  fluid  rich  in  mucin  from  the  sub- 
maxillary. Various  uneatable  substances,  including  substances 
which  in  contact  with  the  mucous  membrane  of  the  mouth  produce 
strong  and  disagreeable  stimulation  of  it,  and  excite  disgust,  cause 
also,  when  viewed  from  a  distance,  secretion  by  all  the  salivary 
glands;  but  the  submaxillary  saliva,  as  ought  to  be  the  case  for 
substances  unfit  for  food,  and  therefore  not  destined  to  be  swallowed, 
is  poor  in  mucin.  When  the  animal  is  shown  pebbles  and  sand 
the  phenomena  are  qualitatively  the  same  as  when  they  are  put 
into  its  mouth — the  glands  remaining  inactive  in  presence  of 
the  pebbles,  but  secreting  plentifully  at  sight  of  the  sand.  In 
short,  the  same  adaptation  is  observed  in  the  case  of  the  so-called 
psychical  secretion  as  when  the  stimulating  substances  act  directly 


400  DIGEST  lOS 

upon  the  endings  of  the  afferent  salivary  nerves  in  the  huecal 
mucous  membrane.  It  is  further  worthy  of  note  that  when  the 
animal  is  hungry  the  psychical  secretion  is  most  copious  and  most 
easily  obtained.  Aft(;r  a  full  meal  it  cannot  be  excited  at  all. 
When  food  (or  other  exciting  sul>stance)  is  repeatedly  shown  to  a 
fasting  animal  the  reaction  Ix'comes  each  time  weaker,  and  finally 
the  glands  cease  to  respond.  All  that  is  then  necessary  to  restore 
the  reaction  is  to  put  into  the  animal's  mouth  a  little  of  the  food 
(or  other  object).  When  it  is  now  shown  it  at  a  distance  the  ordinary 
effect  follows  promptly.  This  indicatt^s  that  the  condition  of  the 
salivary  centre  exercises  an  important  inllumce  upon  the  psychical 
secretion,  its  excitability  to  the  weaker  stimulus  set  up  by  the  sight 
of  the  object  being  increased  by  the  stronger  reflex  stimulation 
coming  directly  from  the  mouth.  In  the  condition  of  satiety  the 
inexcitability  of  the  centre  may  be  du(?  to  the  action  of  food- 
products  in  the  blood. 

In  most  animals  and  in  man  the  activity  of  the  large  salivary 
glands  is  strictly  intermittent.  But  the  smaller  glands  that  stud 
the  mucous  membrane  of  the  mouth  never  entirely  cease  to  secrete, 
and  the  same  is  the  case  with  the  parotid  in  ruminant  animals. 

The  centre  is  situated  in  the  medulla  oblongata,  stimulation  of 
which  causes  a  flow  of  saliva.  The  chief  afferent  paths  to  the 
salivary  centre  are  the  Hngual  branch  of  the  fifth  and  the  glosso- 
pharyngeal; but  stimulation  of  many  other  nerves  may  cause  reflex 
secretion  of  saliva.  In  experimental  reflex  stimulation,  the  sole 
efferent  channel  seems  to  be  the  cerebral  nerve-supply  of  the  glands. 
After  section  of  the  chorda,  no  reflex  secretion  by  the  submaxillary 
gland  can  be  caused,  although  the  sympathetic  remains  intact. 

It  was  alleged  by  Bernard  that,  after  division  of  the  chordo- 
lingual,  a  reflex  secretion  could  be  obtained  from  the  submaxillary 
gland  by  stimulating  the  central  end  of  the  cut  lingual  nerve  between 
the  so-called  submaxillary  ganglion  and  the  tongue,  the  ganglion 
being  supposed  to  act  as '  centre.'  It  has  been  shown,  however,  that 
this  is  not  a  true  reflex  effect,  but  is  due  to  the  excitation  of  certain 
(recurrent)  secretory  fibres  of  the  chorda  that  run  for  some  distance 
in  the  lingual,  then  bend  back  on  their  course  and  pass  to  the  gland. 
It  may  be  in  part  a  pseudo-  or  axon-reflex  (p.  91.3),  ehcited  by 
excitation  of  efferent  fibres,  which  send  branches  to  some  of  the 
ganglion-cells. 

The  salivary  centre  can  also  be  inhibited,  especially  by  emotions 
of  a  painful  kind — for  instance,  the  nervousness  which  often  dries 
up  the  saliva,  as  well  as  the  eloquence,  of  a  beginner  in  public 
speaking,  and  the  fear  which  sometimes  made  the  medieval  ordeal 
of  the  consecrated  bread  pick  out  the  guilty. 

In  rare  cases  the  reflex  nervous  mechanism  that  governs  the 
salivary  glands  appears  to  completely  break  down;  and  then  two 
opposite  conditions  may  be  seen — xerostomia,  or  '  dry  mouth,'  in 


IKFLVENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS  401 

which  no  sahva  at  all  is  secreted,  and  chrunie  ptyaHsni,  or  hydro- 
i^iomia,  where,  in  the  absence  of  any  discoverable  cause,  the  amount 
of  secretion  is  permanently  increased.  Both  conditions  are  said 
to  be  more  common  in  women  tlian  in  men. 

The  Influence  of  Nerves  on  the  Gastric  Glands.— Like  saliva,  gastric 
juice  is  not  secreteil  continuously,  except  in  animals  such  as  the 
rabbit,  whose  stomachs  are  never  empty.  The  normal  and  most 
efficient  stinmlus  is  the  eating  of  food  and  its  presence  in  the 
stomach.  Mechanical  stimulation  of  the  gastric  mucous  membrane 
with  a  non-digestible  substance,  such  as  a  feather  or  a  glass  rod, 
causes  secretion  of  mucus,  but  not  of  gastric  juice.  But  the 
observations  mentioned  above  on  the  difference  of  response  of  the 
salivary  glands  to  different  substances  suggest  that  the  local  mechan- 
ical stimulation  of  the  food  on  the  gastric  glands  may  be  more 
effective.  There  is  also  at  first  thought  much  to  indicate  that  the 
gastric  glands  are  stimulated  chemically  in  a  more  direct  manner 
than  the  saliv^ary  glands  by  the  local  action  of  food  substances 
reaching  the  cells  by  a  short-cut  from  the  cavity  of  the  stomach, 
or  in  a  more  roundabout  way  by  the  blood.  And  it  might  be  very 
plausibly  argued  that  the  gastric  glands  are  favourably  situated 
for  direct  stimulation,  while  the  large  salivary  glands  are  not;  and 
that  the  great  function  of  saliva  being  to  aid  deglutition,  an  almost 
momentary,  and  at  the  same  time  a  perilous  act,  it  is  necessary  to 
provide  by  a  nervous  mechanism  for  an  immediate  rush  of  secre- 
tion at  any  instant,  while  it  is  not  important  whether  the  gastric 
juice  is  poured  out  a  little  sooner  or  a  little  later,  and  therefore  it  is 
left  to  be  called  forth  by  the  more  tardy  and  haphazard  method  of 
local  action.  Nevertheless,  on  looking  a  little  closer,  we  find  that 
this  does  not  exhaust  the  subject,  and  that  the  gastric  secretion 
can  be  influenced  by  events  taking  place  in  distant  parts  of  the 
body,  just  as  the  salivary  secretion  can.  In  a  boy  whose  oesophagus 
was  completely  closed  by  a  cicatrix,  the  result  of  swallowing  a  strong 
alkah,  and  who  had  to  be  fed  by  a  gastric  fistula,  it  was  found 
that  the  presence  of  food  in  the  mouth,  and  even  the  sight  or  smell 
of  food,  caused  secretion  of  gastric  juice  (Richet). 

Here  there  must  have  been  some  nervous  mechanism  at  work. 
The  secretion  cannot  have  been  excited  by  the  direct  action  of 
absorbed  food-products  circulating  in  the  blood — ^an  explanation 
which  might  be  given,  though  an  insufficient  one,  of  the  secretion 
seen  in  an  isolated  portion  of  the  cardiac  end  of  the  stomach  during 
the  digestion  of  food  in  the  rest.  The  efferent  nervous  channels 
through  which  these  effects  are  produced  have  been  defined  by 
Pawlow's  experiments  on  dogs.  He  first  made  a  gastric  fistula, 
then  a  few  days  afterwards  divided  the  oesophagus  through  a 
wound  in  the  neck,  and  stitched  the  two  cut  ends  to  the  edges  of 
the  wound.  After  the  animals  had  recovered,  it  was  observed  that 
when  meat  was  given  to  them  by  the  mouth,  a  copious  secretion  of 

<:6 


402 


DIGESTION 


Pylorus 

P/exus  gastricu. 
anterior  veg,  ' 


sophagus 

Plexus  gastricus 
oosterior  vagi 


gastric  juice  folldwrd  in  five  or  six  minutes,  notwithstanding  thi- 
fact  that  in  this  '  sham  feedinf^  '  the  food  inunechately  escaped  from 
the  opt-ning  in  the  upper  portion  of  tlie  divided  (esophagus.  Much 
the  same  result  was  seen  when  the  food  was  simply  shown  to  the 
animal.  Indeed,  when  a  hungry  animal  is  tempted  with  the  sight 
of  meat,  the  flow  of  gastric  juice,  always  occurring  after  a  latent 
period  of  five  or  six  minutes,  may  be  even  greater  than  with  sham 
feeding.  Division  of  the  splanchnic  nerves  had  no  effect  on  this 
reflex  secretion,  while  it  could  not  be  obtained  after  division  of  both 
vagi  below  the  origin  of  their  cardiac  and  pulmonary  branches,  by 
which  disturbance  of  the  heart  and  respiration  are  avoided. 
Further,  stimulation  of  the  peripheral  end  of  the  vagus  in  the  neck* 
caused  secretion.  These  experiments  show  that  secretory  fibres 
for  the  gastric  glands  run  in  the  vagi.     It  is  probable  that  the  vagi 

also  contain 
efferent  fibres 
which  inhibit 
the  gastric 
secretion.  The 
excitation  of 
the  secretory 
fibres  is  not 
produced  re- 
flexly  by  the 
processes  of 
mastication 
and  deglutition 
as  such.  Di- 
lute acid  is  the 
most  powerful 
chemical  stim- 
ulus for  the 
buccal  mucous 
membrane,  and 

when  it  is  introduced  into  the  mouth  of  a  dog  with  a  double 
oesophageal  and  gastric  fistula,  an  abundant  secretion  of  saliva  at 
once  ensues.  But  no  matter  how  long  the  animal  continues  to 
swallow  the  mixture  of  saliva  and  acid,  no  gastric  juice  is  formed. 
The  same  is  the  case  in  sham  feeding  with  salt,  pepper,  mustard, 
smooth  stones,  and  even  extract  of  meat.  It  is  the  desire  for  food 
— the  appetite,  as  we  call  it — and  the  feeling  of  satisfaction  associa- 
ated  with  eating  food  that  the  animal  relishes,  which  is  the  efficient 
cause  of  the  gastric  secretion  in  sham  feeding.  The  more  eagerly 
the  dog  eats,  the  greater  is  the  flow  of  gastric  juice. 

*  The  nerve  was  not  stimulated  till  a  few  days  after  the  section,  so  as  to 
allow  the  cardio-inhibitory  fibres  to  degenerate.  Otherwise  the  heart  would 
have  been  stopped  by  the  stimulation. 


Fig.  i6i. — Pawlow's  Stomach  Pouch.  AB,  line  of  incision; 
C,  flap  for  forming  the  stomach  pouch.  At  the  base  of  the 
flap  the  serous  and  muscular  coats  are  preserved,  and  only 
the  mucous  membrane  divided,  so  that  the  branches  of  the 
vagus  going  to  the  pouch  are  not  severed. 


Muscularis 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS    403 

Pawlow  also  performed  the  converse  experiment.  In  dogs  in 
which  a  pouch  had  been  isolated  from  the  stomach  and  made  to 
open  to  the  exterior  by  the  surgical  procedure  illustrated  in  Figs.  161 
and  162,  he  introduced  into  the  large  stomach,  without  the  animal's 
knowledge,  food  of  various  kinds.  This  is  best  done  in  a  sleeping 
dog.  The  secretion  of  gastric  juice,  both  in  the  main  stomach  and 
in  the  pouch  or  miniature  stomach,  which  is  known  in  a  great 
variety  of  conditions  to  present  an  exact  picture  of  the  process  of 
secretion  in  the  large,  is  markedly  delayed  and  scanty  when  it  does 
appear.  Bread  and  coagulated  egg-white  did  not  yield  a  single 
drop  during 
the  first  hour 
or  more.  Raw 
flesh  excited  a 
secretion,  but 
after  an  inter- 
val of  fifteen 
to  forty  -  five 
minutes,  in- 
stead of  five 
or  six  to  ten, 
as  in  sham 
feeding.  It  was 
very  scanty 
during  the 
first  hour 
(only  one- 
third  the  nor- 
mal amount), 
and  possessed 
a  very  low  di- 
gestive power. 
The  impor- 
tance of  the 
psychical  ele- 
ment is  shown  by  the  fact  that  in  one  dog,  which,  after  a  weighed 
amount  of  meat  had  been  introduced  into  its  stomach  (without  its 
knowledge) ,  received  a  sham  meal  of  meat,  the  amount  of  protein 
digested  after  one  and  a  half  hours  was  five  times  greater  than  in 
another  animal  treated  exactly  in  the  same  way,  except  that  the  sham 
meal  was  omitted.  But  even  after  division  of  the  vagi,  gastric  secre- 
tion is  still  caused  by  the  introduction  of  various  substances  into  the 
stomach,  especially  water  and  meat  extract.  The  active  substances 
in  the  meat  extract  are,  for  the  most  part,  insoluble  in  alcohol. 
Kreatin  is  inactive.  It  is  in  virtue  of  these  substances  that  raw 
meat  placed  directly  in  the  stomach  causes  some  secretion  after  a 


Fig.  162. — Pawlow's  Stomach  Pouch.     S.  the  completed  pouch; 
V,  cavity  of  stomach. 


404  DIGESTION 

time.  Milk  and  gelatin  solution  are  also  direct  excitants  of  gastric 
secretion  apart  from  the  water  in  them.  Starch,  fat,  and  egg-white 
are  totally  inert.  After  section  of  both  vagi  in  dogs,  no  marked 
qualitative  or  quantitative  changes  have  been  observed  in  the 
gastric  juice.  The  secretion  caused  by  the  presence  of  food  in  the 
stomach  is  still  obtained  when,  in  addition  to  the  vagi,  all  other 
nerves  which  can  possibly  connect  the  central  nervous  system  with 
the  organ  have  been  severed  and  the  sympathetic  abdominal 
plexuses  have  been  destroyed  (Popielski).  We  must  therefore  sug- 
pose  that  the  gastric  glands,  while  normally  under  the  control  of  a 
nervous  mechanism  in  the  upper  portion  of  the  cerebro- spinal  axis 
whose  efferent  fibres  run  in  the  vagi,  are  also  capable  of  being  locally 
stimulated  through i  the  peripheral  ganglia  in  the  stomach  walls  or 
the  chemical  action  of  the  products  of  digestion  absorbed  into  the 
blood.  Edkins  showed  that  the  injection  of  food  substances  or  the 
products  of  their  digestion  (broth,  dextrin,  peptone)  or  of  acid  into 
the  blood  caused  no  secretion  of  gastric  juice,  while  the  injection 
of  an  extract  of  the  pyloric  mucous  membrane,  made  by  boiling  it 
with  water,  acid,  or  peptone,  excited  a  certain  amount  of  secretion. 
He  therefore  concluded  that  the  secondary  secretion  of  gastric  juice 
is  determined,  not  by  local  stimulation  of  a  reflex  mechanism  in  the 
gastric  wall,  but  by  the  production  in  the  mucous  membrane  of  the 
pyloric  end  of  a  chemical  substance,  the  gastric  secretin  or  gastric 
hormone,*  which  is  absorbed  by  the  blood,  and  acts  as  an  excitant 
to  all  the  gastric  glands.  The  cardiac  mucosa  was  found  incapable 
of  forming  this  substance. 

It  is  not  to  be  imagined  that  the  '  psychical '  secretion  and  the 
secretion  called  forth  by  the  direct  action  of  the  food  or  food- 
products  in  the  stomach  perform  independent  offices.  They  can, 
in  various  instances,  be  shown  to  supplement  each  other.  For 
example,  not  more  than  one-half  or  one-third  of  the  gastric  juice 
secreted  during  the  digestion  of  bread  or  boiled  egg-albumin  can 
be  ascribed  to  the  psychic  effect.  Yet  these  substances,  when 
introduced  directly  into  the  stomach,  cause  practically  no  secretion. 
We  must  suppose  that  during  the  digestion  of  the  bread  and  albu- 
min by  the  psychically  secreted  juice  certain  products  analogous  to 
those  in  the  meat  extract  are  formed,  which  act  as  chemicd  excitants 
of  the  local  secretory  apparatus.  The  psychic  juice  is  indispensable 
in  this  case  to  start  the  process,  '  to  set  the  stove  ablaze,'  as  Pawlow 
puts  it.  In  the  case  of  meat  it  is  not  indispensable,  since  the  meat 
can  chemically  excite  the  gastric  glands;  but  it  greatly  hastens  the 
process  of  digestion.     These  facts  emphasize  the  importance  of 

*  '  Hormone  '  (from  opfiaw,  I  arouse  or  excite)  is  the  name  given  to  a  sub 
stance  which,  carried  by  the  blood  from  the  place  where  it  is  formed,  acts  a.s 
a  chemical  messenger  in  exciting  the  activity  of  some  more  or  less  distant 
organ.  The  classical  example  is  the  pancreatic  secretin  which,  manufactured 
in  the  intestinal  mucosa,  excites  the  secretion  of  the  pancreatic  juice. 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     i(05 

appetite  in  digestion,  a  truism  in  treatment  which  thus  receives 
for  the  first  time  a  rational  explanation.  The  influence  of  good- 
humour  upon  nutrition,  which  experience  has  crystallized  into  the 
proverb  '  Laugh  and  grow  fat,'  has  also  been  shown  to  depend — 
in  great  part,  at  least — upon  a  beneficial  action  on  the  digestive 
functions,  both  motor  and  chemical.  The  movements  of  a  cat's 
stomach  and  intestines  have  been  observed  to  cease  when  the 
animal  became  angry  or  excited  by  unpleasant  emotions;  and  in  a 
dog  wliose  gastric  glands  were  pouring  out  a  copious  psychical 
secretion  in  response  to  a  sham  meal,  secretion  stopped  abruptly 
when  the  animal's  wrath  was  awakened  by  what  is  probably  to  the 
normal  dog  the  most  specifically '  adequate '  stimulus  for  the  emotion 
of  anger — the  sight  of  a  cat  which  he  was  restrained  from  chasing. 

By  means  of  experiments  with  the  miniature  stomach  it  has  been 
further  shown  that  each  kind  of  food  has  its  own  characteristic 
curve  of  gastric  secretion.  With  flesh  diet  the  maximum  rate  of 
secretion  occurs  during  the  first  or  second  hour,  and  in  each  of  the 
first  two  hours  the  quantity  of  juice  furnished  is  approximately 
the  same.  With  bread  diet  we  have  always  a  sharply-indicated 
maximum  in  the  first  hour,  and  with  milk  a  similar  one  during  the 
second  or  the  third  hour  (Fig.  163).  The  juice  secreted  on  different 
chets  also  differs  in  digestive  power — i.e.,  in  the  amount  of  protein 
which  a  given  quantity  of  it  will  digest  in  a  given  time.  '  Bread 
juice  '  is  much  stronger  in  ferment  than  '  meat  juice,'  and  '  meat 
juice '  somewhat  stronger  than  '  milk  juice  '  (Fig.  164).  But 
'  meat  juice  '  has  a  higher  acidity  than  '  bread  juice,'  '  milk  juice  ' 
being  intermediate.  These  differences  do  not  necessarily  indicate 
that  the  gastric  mucous  membrane  responds  in  a  specific  way  to 
each  kind  of  food  substance,  as  suggested  by  Pawlow.  They  may 
depend  on  several  circumstances,  and  particularly  on  this — that  the 
quantity,  though  not  the  quality,  of  the  psychical  or  '  appetite  ' 
juice  is  related  to  the  relish  with  which  the  animal  eats  the  food. 
The  products  formed  in  the  digestion  of  the  different  foods  by  the 
psychical  juice  may  therefore  be  different  in  nature  and  amount, 
and  thus  the  quantity  of  the  gastric  hormone  which  determines  the 
secondary  secretion  may  vary  with  the  food. 

The  young  mammal,  like  the  adult,  secretes  gastric  juice  before 
the  food  reaches  the  stomach.  In  puppies  from  one  to  eighteen 
days  old  sham  feeding  (sucking  the  teats  of  the  mother  after  an 
oesophageal  fistula  has  been  made  in  the  younger  animals  and  a 
double  oesophageal  and  gastric  fistula  in  the  older)  causes  a  liquid 
with  the  properties  of  gastric  juice  to  gather  in  the  stomach.  This 
power,  then,  is  a  congenital  one.  The  individual  does  not  gain  it 
by  experience;  it  comes  into  the  world  with  him  (Cohnheim). 

The  Influence  of  Nerves  on  the  Pancreas. — Like  the  stomach,  the 
pancreas  receives  secretory  fibres  through  the  vagus.     These  are 


4o6 


DIGESTION 


Houra    123    4-5678    t     23456    78910123456 


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Xj 

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Flesh,  200  grm. 


Bread,  200  grm. 


Milk,  600  c.c 


Fig.  163. 


-Rate  of  Secretion  of  Gastric  Juice  with  Diets  of  Meat, 
Bread,  and  Milk  (Pawiow). 


probably  connected  with  a  reflex  centre  in  the  medulla  oblongata. 
It  has  long  been  known  that  when  the  medulla  is  stimulated  a  flow 
of  pancreatic  juice  is  occasionally  set  up,  or  is  increased  if  already 
going  on.  The  same  is  true  when  the  vagus  is  stimulated  in  the 
ordinary  way  in  the  neck.     But  the  experiment  often  failed,  for 

the  pancreas 
is  peculiarly 
susceptible 
to  circulatory 
disturbances, 
and  stimula- 
tion of  the 
bulb  or  the 
vagus  may 
interfere  with 
the  blood- 
flow  through 
the  gland  by 
exciting  its 
vaso-con- 
strictor  fibres  or  causing  inhibition  of  the  heart.  These  disturbing 
influences  may  be  avoided,  as  Pawiow  has  shown,  by  stimulating  the 
vagus,  three  or  four  days  after  dividing  it,  with  slowly-recurring 
stimuh  (induction  shocks  or  light  blows  from  a  small  hammer 
worked  by  an 
electro  -  mag- 
net at  the 
rate  of  about 
one  in  the 
second).  The 
secretory 
fibres  are  still 
susceptible  of 
excitation, 
while  the  car- 
dio-inhibitory 
fibres,  which 
degenerate 
more  rapidly, 
are  almost  or 
altogether  in- 
excitable,  and  the  vaso-constrictors  are  but  little  affected  by 
these  slow  rhythmical  stimuli,  which  excite  the  secretory  nerves 
(p.  175).  A  pancreatic  fistula  has  previously  been  established  by 
excising  a  small  portion  of  the  duodenal  wall  containing  the  open- 
ing of  the  pancreatic  duct,  closing  the  intestine  by  sutures,  and 


Hours  I    2 
10.0 


345678234     567 


I 
8    9 


2    3    4   5    6 


0.0 


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7^di 

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N-'^n — "^                / 

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-t   --^vy                     5      / 

\r                       \   ^^ 

1  1  1  1  1  1  1  1  1  1  1  1  M  1  1  1  1  1  1  1 

!•  lesh,  200  grm. 


Bread,  200  grm. 


Milk,  600  c.c. 


Fig.  164. — Digestive  Power  of  Gastric  Juice  (Pawiow).  The 
digestive  power  of  the  juice,  as  measured  by  the  length  of  the 
protein  column  digested  in  Mett's  tubes,  is  represented  hour  by 
hour,  Mth  diets  of  flesh,  bread,  and  milk. 


INFLUENCE  OF  NER VOUS  SYSTEM  ON  DIGESTI VE  GLANDS      407 


stitching  the  orifice  of  the  duct  into  the  abdominal  wound.  On 
stimulation  of  the  vagus  the  juice  will  begin  in  two  to  three  minutes 
to  drop  from  a  cannula  in  the  duct,  and  will  continue  to  flow  for 
several  minutes  after  cessation  of  the  stimulus.  The  sympathetic 
also  contains  secretory  fibres  for  the  pancreas.  Efferent  fibres 
which  inhibit  the  secretion  have  been  also  discovered  in  the  vagus. 
Their  presence  may  be  most  clearly  demonstrated  when  that  nerve 
is  stimulated  during  the  flow  of  pancreatic  juice  excited  by  the 
introduction  of  dilute  acid  into  the  duodenum.  Stimulation  of  the 
central  end  of  the  vagus  and  of  the  other  nerves  is  capable  of 
reflexly  inhibiting 
the  pancreatic  secre- 
tion. Painful  im- 
pressions have  a 
strong  inhibitory  in- 
fluence. This  is  one 
of  the  reasons  why 
many  observers 
failed  to  detect  the 
secretory  nerves. 
The  inhibition 
caused  by  vomiting 
is  probably  due  to 
impulses  ascending 
the  vagus.  It  is  pos- 
sible that  through 
these  nervous  chan- 
nels the  pancreatic 
secretion  is  affected 
by  the  psychical  con- 
ditions connected 
with  eating  and  the 
desire  for  food,  just 
as  in  the  case  of  the 
gastric  secretion ;  but 
our  information  on 
this  subject  is  scantier  and  less  precise.  A  flow  of  juice  may  un- 
doubtedly take  place  within  three  or  four  minutes  after  food  is  taken, 
but  it  is  not  quite  certain  whether  this  is  not  determined  by  the 
passage  of  some  of  the  acid  gastric  contents  into  the  duodenum. 

Secretin.— We  have  already  referred  to  the  fact  that  pancreatic 
secretion  is  excited  by  the  presence  of  acid  in  the  duodenum.  The 
mechanism  of  this  action  is  of  great  interest.  Two  or  three  minutes 
after  the  introduction  of  04  per  cent,  hydrochloric  acid  into  the 
duodenum,  pancreatic  juice  begins  to  flow.  A  similar  effect  is  seen 
when  the  acid  is  placed  in  the  jejunum,  but  not  when  it  is  injected 


Fig.  165. — Secretion  of  Pepsin.  C  shows  the  quantity 
of  pepsin(ogeii)  in  the  mucous  membrane  of  the 
cardiac  end  of  the  stomach  at  different  times  during 
digestion;  P,  the  quantity  of  pepsin(ogen)  in  the 
mucous  membrane  of  the  pyloric  end;  S,  the  quantity 
of  pepsin  in  the  secretion  of  the  cardiac  glands.  The 
numbers  marked  along  the  horizontal  axis  are  hours 
since  the  last  meal.  About  five  hours  after  the 
meal,  S  reaches  its  maximum.  From  the  very  be- 
ginning of  the  meal  C  falls  steadily  down  to  the 
tenth  hour,  and  then  begins  to  rise — i.e.,  the  gland- 
cells  of  the  cardiac  end  of  the  stomach  become 
poorer  in  pepsin(ogen)  as  secretion  proceeds. 


408  DIGESTION 

into  tlie  lower  part  of  the  iloum.  It  is  obtained  as  stronp;ly  and  as 
promptly  from  an  isolated  loop  of  intistine  when  all  the  nerves 
passing  to  it  have  been  cut,  and  the  solar  plexus  extirj)ated,  and  also 
after  the  administration  of  atropine,  wliich  paralyzes  the  endings  of 
secretory  nerves  elsewhere.  The  secretion  accor  lingly  does  not 
depend  upon  a  local  reflex  mechanism,  with  its  afferent  endings  in 
the  intestinal  mucous  membrane,  but  upon  some  substance  which  is 
carried  to  the  pancreas  by  the  blood,  and  acts  directly  upon  its  cells. 
This  substance  is  not  the  acid,  for  the  injection  of  04  per  cent, 
hydrochloric  acid  into  the  blood  produces  no  effect  upon  the  pan- 
creas. It  has  been  shown  by  Bayliss  and  Starling  that  the  exciting 
substance  is  a  diffusible  body  of  low  molecular  weight,  probably  of 
organic  natuie,  but  not  a  protein,  which  the}'  call  sccrelin.  It  is 
soluble  in  alcohol  or  alcohol  and  ether,  and  is  not  flestroyed  by 
boiling.  It  is  produced  in  the  mucous  membrane  of  the  jejunum  or 
duodenum  on  exposure  to  dilute  hydrochloric  acid.  Extracts  of 
mucous  membrane  so  treated  cause  a  copious  pancreatic  secretion, 
and  a  smaller  secretion  of  bile,  when  injected  in  small  quantities  into 
the  blood  of  animals  in  which  no  such  secretion  is  taking  place,  but 
have  no  influence  on  any  other  gland.  At  the  same  time  the  arterial 
blood-pressure  falls  somewhat.  The  substance  which  produces  the 
fall  of  blood-pressure  is  different  from  secretin,  since  acid  extracts 
of  the  lower  end  of  the  ileum,  which  have  no  effect  on  the  flow  of  pan- 
creatic juice,  diminish  the  blood-pressure.  A  precursor  of  secretin, 
called  prosecretin,  exists  in  the  intestinal  mucous  membrane,  and 
can  be  extracted  from  it  b}'  physiological  salt  solution.  It  dnes  not 
affect  the  pancreatic  secretion.  By  boiling  or  by  the  action  of  acid 
secretin  is  split  off  from  it.  Pro-secretin  is  most  abundant  in  the 
duodenum,  and  diminishes  as  we  pass  down  the  intestine. 

Secretin  is  very  widespread  in  the  animal  kingdom.  In  the 
monkey,  dog,  cat,  rabbit,  man,  ox,  sheep,  pig,  squirrel,  goose, 
tortoise,  salmon,  dog-fish,  and  skate  evidence  of  its  presence  has 
been  obtained.  The  secretin  of  one  animal  will  excite  a  flow  of  pan- 
creatic juice  in  an  animal  of  a  different  kind  as  well  as  in  one  of  the 
same  kind.  In  normal  digestion  secretin  is  formed  under  the 
influence  of  the  acid  chyme,  not  in  the  stomach,  but  after  it  has 
passed  into  the  duodenum.  The  passage  of  the  chyme  tlirough  the 
pylorus,  as  previously  mentioned  (p.  337),  is  regulated  by  the  re- 
action of  the  duodenal  contents,  as  well  as  by  the  consistence  of  the 
gastric  contents.  vSo  long  as  the  liquid  in  the  duodenum  is  acid,  the 
pylorus  remains  closed.  As  soon  as  the  first  small  portion  of  acid 
chyme  ejected  from  the  stomach  has  been  neutralized  by  the  in- 
creased secretion  of  the  pancreatic  juice  and  the  outpouring  of  bile 
from  the  gall-bladder  in  response  to  the  stimulus  of  the  acid,  the 
pylorus  opens  again. 

According  to  Pawlow,  certain  food  substances,  notably  fat,  and 


hWFLUENCE  OF  NER  VOUS  SYSTEM  O.V  DIGESTI  VE  GLA  NDS      409 

water  stimurate  the  pancreatic  secretion,  and  with  great  promptness, 
even  before  any  acid  has  been  produced  in  the  stomach,  and  there- 
fore before  any  can  have  passed  into  the  duodenum.  Possibly  this 
effect  is  ehcited  through  the  lon^  rcfiex  paths  already  described  as 
running  in  the  vagi  or  through  a  local  nervous  mechanism,  which, 
although  it  does  not  take  part  in  the  excitation  of  the  pancreatic 
secretion  by  acid,  may  yet  exist  for  the  performance  of  other  offices. 
It  is  more  probable,  however,  that  it  is  due  to  the  passage  of  some  of 
the  gastric  contents  through  the  pylorus;  for  when  oil  is  introduced 
into  the  small  intestine,  it  causes  the  production  of  secretin,  although, 
unhke  dilute  acid,  it  is  quite  ineffective  in  forming  secretin  when 
rubbed  up  with  the  scraped-off  mucous  membrane.  That  secretin 
acts  on  the  pancreatic  cells  in  a  different  way  from  the  secretory 
nerve  fibres  contained  in  the  vagus  is  indicated  by  the  difference  in 
the  characters  of  the  juice  secreted  under  the  influence  of  the  two 
mechanisms.  The  nervous  secre- 
tion is  thick  and  opalescent,  rich 
in  enzymes,  including  trypsin  in 
the  active  form,  and  proteins,  but 
its  alkaU  content  is  low.  Like 
other  secretions  excited  through 
nerves,  it  is  inhibited  by  atropine. 
The  chemical  secretion  due  to 
secretin,  is  thin  and  watery,  rich    F"ig-  166.— Rate  of  Secretion  of  Pan- 

11     1-  •  ,    •  J  creatic  Juice.     S  shows  the  variation 

in   alkalies,    poor    m    protems  and  i„  ^^e  rate  of  secretion  of  the  pan- 

in  enzymes,  and  among  the  latter,  creatic  juice  in  a  dog;  p.  the  varia- 

trypsin  occurs  only  in  the  inactive  ^io^i  i"  ^^e  percentage  of  solids  in 

r  /c       >     -ux  ^^^  juice.      It  will  be  seen  that  the 

lOrm  ^bawiTSCnj.  maxima  of  S  fall  at  the   same  time 

The  pancreatic,  like  the  gastric,  as  the  maxima  of  p.     The  numbers 

juice    is    said    to    vary    as    regards  ^lo°g  ^^^  horizontal  axis  are  hours 

.,       J-        ,  ■  ,  •  -,1     .-t  since  the  last  meal, 

its   digestive  properties  with  the 

nature  of  the  food.  On  a  diet  of  bread  the  juice  is  very  poor 
in  fat-splitting  ferment,  while  on  a  diet  of  flesh  it  is  richer,  and 
on  a  diet  of  milk  richest  of  all.  With  bread  the  juice  is  relatively 
rich  in  amylolytic  ferment.  When  we  take  the  quantity  of  the 
juice  as  well  as  its  strength  in  ferments  into  consideration,  it  is 
stated  that  bread  occasions  the  secretion  of  a  juice  with  a  greater 
quantity  of  proteolytic  ferment  than  either  milk  or  meat,  although 
it  is  relatively  dilute  (Fig.  169).  The  vegetable  proteins  require 
more  ferment  to  digest  them  than  proteins  of  animal  origin.  There 
is  no  more  evidence  that  the  adaptation  of  the  pancreatic  juice  to  the 
nature  of  the  food  is  due  to  a  specific  sensibility  of  the  duodenal 
mucosa  to  the  various  food-stuffs  than  there  is  in  the  case  of  the 
adaptation  of  the  gastric  juice.  If  the  volume  of  the  chyme  and  its 
acidity  are  related  to  the  nature  of  the  food,  then  the  amount  of 
secretin  formed,  and  therefore  the  intcnsitv  of  secretion  in  the 


410 


DIGESTION 


I  II  III  IV  V    I   II  111  IV  V  VI  vn  viii  1  n  in  IV  v  vi 


pancreas,  will  be  similarly  related.  The  one  apparently  proved 
example  of  specific  adaptation  of  the  pancreatic  juice  has  not  stood 
the  test  of  a  critical  examination.  It  was  asserted  that  in  dogs  fed 
for  some  days  with  food  containing  lactose  (milk)  the  ferment, 
lactase,  is  present  in  that  secretion,  while  the  pancreatic  juice  of 
dogs  whose  food  is  free  from  lactose  does  not  contain  lactase.  The 
adaptation  of  the  pancreas  to  lactose  was  supposed  to  be  achieved 
through  some  substance  produced  by  the  action  of  lactose  on  the 

intestinal  mucous 
membrane,  which 
plays  the  part  of 
a  specific  chemical 
stimulus  to  the 
pancreatic  cells  or 
their  secretory 
nervous  mechan- 
ism, causing  them 
Xo  form  lactase. 
But  it  has  been 
conclusively  shown 
that  when  dogs 
are  fed  with  lac- 
tose for  weeks  no 
lactase  appears  in 
the  pancreatic 
juice  (Phmmer). 

The  natural  se- 
cretion of  pan- 
creatic juice  is  by 
no  means  so  inter- 
]iiittent  as  that  of 
saliva.  In  the  rab- 
bit the  pancreatic, 
like  the  gastric, 
juice  flows  con- 
tinuously. In  the 
dog  it  begins  al- 
most as  soon  as 
a  maximum,  then 


Flesh,  loo  grm.  Bread,  250  grm. 


Milk,  600  grm. 


Fig.  167.— Secretion   of   Pancreatic    Juice  with  Different 
Diets  (Pawlow).     The  hours  are  in  roman  numerals. 


food  is  taken,  rises  in  two  or  three  hours  to  „  ...«^,,.^.„  ,,,cii 
falls  tiU  the  fifth  or  sixtli  hour,  after  which  it  may  mount 'again 
somewhat,  and  then,  gradually  diminishing,  ultimatelv  stops  (Figs 
166,  167).  During  normal  activity  the  bloodvessels  of 'the  gland  are 
dilated.  But  under  experimental  conditions  the  increased  secretion 
caused  by  secretin  is  accompanied  sometimes  by  an  increase  and 
sometimes  by  a  diminution  in  the  blood- flow,  and  secretion  may 
continue  for  some  time  after  complete  cessation  of  the  circulation 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     411 


while  the  increased  consumption  of  oxygen  which  goes  hand  in  hand 
with  the  increased  secretion  is  also  independent  of  the  blood-supply 
(May,  Barcroft  and  Starling).  This  shows  how  far  the  secretory  pro- 
cess is  from  a  mere  mechanical  filtration,  although  it  does  not  follow 
that,  under  normal  conditions,  a  decreased  blood-flow  ever  does 
accompany  an  increased  secretion.  There  is  one  difference  between 
the  normal  secretion  of  pancreatic  juice  and  of  saliva  which  may  still 
be  mentioned :  the  pressure  of  the  latter  in  the  submaxillary  duct  may, 
as  we  have  seen,  greatly  exceed  the  arterial  blood-pressure,  without 
reabsorption  and  consequent  oedema  of  the  gland  occurring;  but  the 
secretory  pressure  of  the  pancreatic  cells  is  very  low,  not  more  than 
a  tenth  of  that  of  the  salivary  glands. 
(Edema  begins  before  a  manometer  in 
the  duct  shows  a  pressure  of  20  mm. 
of  mercury,  the  secreted  fluid  passing 
very  easily  into  the  lymph  spaces. 

The  mutual  relations  of  the  spleen 
and  pancreas  have  formed  the  subject 
of  numerous  inquiries.  Some  authors 
maintain  that  the  spleen  plays  an  im- 
portant role  in  the  elaboration  of  the 
proteolytic  ferment  of  the  pancreas, 
forming  a  substance  which  we  may  call 
pro-trypsinogen,  since  it  is  supposed  to 
be  carried  in  the  blood  to  the  pancreatic 
cells,  and  changed  by  them  into  trypsin- 
ogen.  There  is  some  evidence  that 
extracts  of  the  spleen  prepared  from  it 
when  congested  during  digestion  exert  a 
favourable  influence  on  the  proteolytic 
power  of  the  pancreas  (Mendel).  And 
there  is  no  doubt  that  the  spleen,  hke 
other  organs,  contains  an  intracellular 
enzyme  which  can  aid  in  the  digestion 
of  protein.  The  products  of  the  action 
in  an  acid  medium  of  this  enzyme  are  the  same  as  those  formed  by 
trypsin  in  an  alkaline  medium  (Leathes).  But  this  is  not  enough  to 
prove  that  the  spleen  has  any  special  relation  to  pancreatic  digestion. 

The  Influence  of  Nerves  on  the  Secretion  of  Bile. — Although  bile  is 
secreted  constantly,  it  only  passes  at  intervals  into  the  intestine. 
For  the  liver  in  many  animals,  unlike  every  other  gland  except  the 
kidney,  has  in  connection  with  it  a  reservoir,  the  gall-bladder,  in 
which  its  secretion  accumulates,  and  from  which  it  is  only  expelled 
occasionally.  We  have  therefore  to  distinguish  the  bile-secretion 
from  the  bile-expelhng  mechanism.  To  study  the  rate  of  secreting 
of  bile  (Fig.  168),  a  fistula  of  the  gall-bladder  can  be  estabhshed. 


Fig.  168.— Rate  of  Secretion  of 
Bile.  S  show-s  how  the  rate  of 
secretion  of  bile  falls  in  a  dog 
when  a  biliary  fistula  is  first 
made,  and  the  bile  thus  pre- 
vented  from  entering  the  intes- 
tine ;  P  shows  the  fall  of  the  per- 
centage of  solids.  The  numbers 
along  the  horizontal  axis  are 
quarters  of  an  hour  since  bile 
began  to  escape  through  the 
fistula.  The  numbers  along 
the  vertical  axis  refer  only  to 
curve  S,  and  represent  the  rate 
of  secretion  in  arbitrary  units. 


412  DIGESTION 

But  to  learn  the  function  of  bile  in  digestion  it  is  more  important 
to  know  when  and  at  what  rate  it  enters  the  intestine.  For  tliis 
purpose  a  fistula  is  made  by  cutting  the  natural  orifice  of  the  common 
bile-duct  with  a  piece  of  the  surrounding  mucous  membrane  out  of 
the  intestine  and  transplanting  it  upon  the  serous  coat,  where  it  is 
sutured.  The  loop  of  intestine,  with  the  orifice  of  the  duct  facing 
outwards,  is  then  stitched  into  the  abdominal  wound,  where  it  is 
allowed  to  heal.  Of  course,  since  a  circulation  of  the  bile-acids 
takes  place — i.e.,  an  absorption  from  and  re-excretion  into  the 
intestine — the  formation  of  that  juice  cannot  proceed  upon  abso- 
lutely normal  lines  when  the  bile  no  longer  enters  the  duodenum. 
The  only  condition  under  which  fistula  bile  could  have  the  same 
composition  as  normal  bile  would  be  that  in  which  as  great  an 
amount  of  bile-acids  is  introduced  into  the  gut  as  escapes  through 
the  fistula.  A  circulation  of  a  smaller  proportion  of  the  bile-pig- 
ments is  also  probable.  A  circulation  of  the  biliary  cholesterin  is 
denied  by  some  observers  (Stadelmann)  but  affirmed  by  others.  It 
is  certain  that  cholesterin  is  of  importance  in  the  body,  and  if  the 
supply  of  sterins  (p.  570)  in  the  food  is  insufficient  it  is  to  be  sup- 
posed that  some  of  the  biliary  cholesterin  would  be  used  over  again. 

Of  the  direct  influence  of  nerves,  either  on  the  secretion  of  bile  or  on 
its  expulsion,  we  have  scarcely  any  knowledge,  scarcely  even  any  guess 
which  is  worth  mentioning  here.  It  is  true  the  secretion  of  bile  may 
be  distinctly  affected  by  the  section  and  stimulation  of  nerves  which 
control  the  blood-supply  of  the  stomach,  intestines,  and  spleen,  for  the 
quantity  of  blood  passing  by  the  portal  vein  to  the  liver  depends  upon 
the  quantity  passing  through  these  organs,  and  the  rate  of  secretion  is 
diminished  when  the  blood-supply  is  greatly  lessened.  In  this  way 
stimulation  of  the  medulla  oblongata,  the  spinal  cord,  or  the  splanchnic 
nerves  stops  or  slows  the  secretion  of  bile  by  constricting  the  abdominal 
vessels;  and  the  same  effect  can  be  reflexly  produced  by  the  excitation 
of  afferent  nerves. 

The  right  splanchnic  nerve  contains  inhibitory  with  some  motor 
fibres,  and  the  vagi  (especially  the  left)  contain  motor  fibres  for  the 
gall-bladder.  Probably  its  contraction  takes  place  naturally  in 
response  to  reflex  impulses  from  the  mucous  membrane  of  the  duo- 
denum, for  the  apphcation  of  dilute  acid  to  the  mouth  of  the  bile- 
duct  causes  a  sudden  flow  of  bile,*  and  the  acid  contents  of  the 
stomach,  when  projected  through  the  pylorus  into  the  intestine, 
have  a  similar  effect.  But,  in  addition,  as  we  have  seen,  the  secretin 
formed  will  cause  an  increase  in  the  rate  of  secretion  of  the  bile.  In 
studying  the  effect  of  secretin  it  is  necessary  to  obtain  it  free  from 
bile-salts,  since  these  cause  of  themselves  an  increased  secretion  of 
bile.  When  this  is  done  by  dissolving  out  with  alcohol  any  bile-salts 
which  may  be  present  in  the  extract  of  intestinal  mucous  membrane, 

♦  This  result  seems  to  be  difficult  to  realize  experimentally.  Bainbridge 
and  Dale  could  not  elicit  reflex  contraction  of  the  gall-bladder  (in  anaesthetized 
animals)  in  this  way. 


INFLUE.WCE  OF  XER  VOUS  S  YSTEM  ON  DIGESTI  VE  GLASDS     413 

a  solution  of  the  residue  containing  the  secretin  still  evokes  a  rapid 
secretion  of  bile.  The  fact  that  the  same  hormone  excites  the 
formation  both  of  pancreatic  juice  and  bile  is  obviously  related  to 
that  common  action  of  the  two  juices  in  digestion  on  which  we  have 
already  dwelt. 

When  food  passes  into  the  stomach,  there  is  at  once  a  sharp  rise  in 
the  rate  of  secretion  of  bile.  A  maximum  is  reached  from  the  fourth 
to  the  eighth  hour — that  is,  while  the  food  is  in  the  intestine.  There 
is  then  a  fall,  succeeded  by  a  second  smaller  rise  about  the  fifteenth 
or  sixteenth  hour,  from  which  the  secretion  gradually  declines  to  its 
minimum.  Upon  the  whole,  the  curves  of  secretion  of  pancreatic 
juice  and  bile  show  a  fairly  close  correspondence,  except  that  the 
latter  is  more  nearly  continuous.  But  when  we  compare  the  curves 
lepresenting  the  rate  at  which  the  bile  actually  enters  the  intestine 
with  the  curve  of  pancreatic  secre- 
tion (Fig.  169),  we  are  struck  by 
their  almost  absolute  parallelism. 
This  lends  additional  support  to 
the  conclusion  deduced  from  their 
chemical  and  physical  properties, 
that  in  digestion  they  are  partners 
in  a  common  work. 

While    the    rate    at    which    bile 
passes  into  the  intestine  seems  to  be 

influenced  by  digestion  much  in  the  Fig^ibg.-Pancreatic  juke  and  Bile 

-        '^                                       .  (Pawlow).    The  upper  curves  repre- 

Same  way  as  the  rate  of  pancreatic  sent  the  hourly  rate  of  pancreatic 

secretion,  the  details  are  as  yet  less  secretion,  and  the  lower  the  rate  ^t 

exactly      known.        In      the      fasting  which  the  bile  enters  the  intestine; 

•;          ,  .,                   ,,            ,      -^.,     '='  a,  a,  milk  diet ;  &,  6  ,  meat;  c,  c, 

animal  no  bile  enters  the  gut.    W  hen  bread.     Only  the  general  form  of 

food  is  taken,  the  flow  begins  after  the  curves  is  to  be  compared.     The 

a  definite  interval,  which  varies  for       ^""^^^  °*  ^^^  ordinates  of  the  various 

,,  ,.„  ,1-1  r    r       1  A  curves  was  not  the  same. 

the    diflerent    kinds    of   food.      As 

long  as  digestion  lasts  bile  continues  to  escape,  but  both  the 
quantity  and  quality  depend  upon  the  nature  of  the  food.  Water, 
raw  egg-white,  and  starch  paste,  whether  given  by  the  mouth  or 
introduced  directly  into  the  stomach  of  a  dog,  cause  no  flow  of  bile. 
But  fat,  the  extractives  of  meat,  and  the  products  of  digestion  of 
egg-white  produce  a  copious  discharge.  This  discharge  may  be 
determined  by  the  relatively  large  amount  of  acid  chyme  passed 
through  the  pylorus  when  proteins  are  digested  in  the  stomach  and 
the  stimulus  to  the  formation  of  secretin  occasioned  by  the  presence 
of  this  chyme  or  of  fatty  material  in  the  duodenum.  In  the  case  of 
fat  a  further  favourable  influence  on  the  secretion  of  bile  is  the 
absorption  of  bile-salts  which  accompanies  the  absorption  of  the 
fatty  acids  and  soaps  produced  in  fat  digestion.  Bile-salts  stimulate 
the  secretion  of  bile,  including  bile-salts  themselves.     An  increased 


4X4  DIGESTION 

flow  of  bile-salts  into  the  intestine  accelerates  the  splitting  of  fats  by 
the  pancreatic  juice,  and  therefore  the  absorption  of  bile-salts  acting 
as  solvents  for,  or  chemically  united  to,  the  fatty  acids  and  soaps. 
A  circle  analogous  to  the  '  vicious  circle  '  of  the  logicians,  but  con- 
stituting a  physiological  adaptation  of  most  potent  \-irtue  in  the 
digestion  of  fats,  is  thus  estabhshed.  Not  only  is  the  quantity  of 
bile  poured  into  the  intestine  increased  on  a  diet  rich  in  fat,  but  it 
is  said  that  a  given  amount  of  it  aids  the  fat-splitting  action  of  the 
pancreatic  juice  more  powerfully  than  if  the  diet  were  poor  in  fat. 
This  mav  depend  upon  an  increase  in  the  concentration  of  the  bile- 
salts  in  bile  secreted  when  a  large  amount  of  fat  is  ingested.  But  it 
is  well  to  recognize  that  we  do  not  at  present  know  with  any  great 
exactness  the  mechanism  by  which  the  rate  of  secretion  and  ex- 
pulsion of  bile  and  the  properties  of  that  juice  are  influenced  by 
digestion.  It  has  been  conjectured  that  the  first  abrupt  rise  may  be 
started  bv  reflex  nervous  action,  and  that  later  on  secretin  and,  in  the 
case  of  fat  digestion,  bile-salts  may  directly  excite  the  hepatic  cells. 

The  pressure  under  which  the  bile  is  secreted  is  higher  than  the 
pressure  of  the  portal  blood,  and  therefore  the  hver  ranges  itself  with 
the  high-pressure  salivary  glands  rather  than  with  the  low-pressure 
pancreas.  But  although  the  biliary  pressure  is  high  relatively  to 
that  of  the  blood  with  which  the  secreting  cells  are  supplied,  it  is 
absolutelv  low,  the  maximum  being  no  more  than  25  mm.  of  mer- 
curv.*  This  is  a  point  of  practical  importance,  for  a  comparatively 
slight  obstruction  to  the  outflow,  even  such  as  is  offered  by  a  con- 
gested or  inflamed  condition  of  the  duodenal  wall  about  the  mouth 
of  the  duct,  may  be  sufficient  to  cause  reabsorption  of  the  bile 
through  the  lymphatics,  and  consequent  jaundice.  Of  course, 
complete  plugging  of  the  duct  by  a  biliary  calculus  is  a  much  more 
formidable  barrier,  and  inevitably  leads  to  jaundice,  just  as  ligature 
of  a  sahvary  duct,  in  spite  of  the  great  secretory  pressure,  inevitably 
causes  oedema  of  the  inland. 

The  Influence  of  Nerves  on  the  Secretion  of  Intestinal  Juice. — As 
to  the  influence  of  nerves  on  the  secretion  of  the  succus  entericus,  our 
knowledge  is  almost  hmited  to  a  single  experiment,  and  that  an  in- 
conclusive one.  Moreau  placed  four  ligatures  on  a  portion  of  the 
small  intestine,  so  as  to  form  three  compartments  separated  from 
each  other  and  from  the  rest  of  the  gut.  The  mesenteric  nerves 
going  to  the  middle  loop  were  di\nded.  and  the  intestine  returned  to 
the  abdomen.  After  some  time  a  watery  secretion  was  found  in  the 
middle  compartment,  little  or  none  in  the  others.  This  is  a  true 
*  paral>i:ic  '  secretion,  and  not  a  mere  transudation  depending 
simply  on  the  vascular  dilatation  caused  by  section  of  the  vaso- 

•  In  the  dog,  cat,  and  monkey  the  average  maximum  pressure  at  which 
as  much  bile  is  secreted  as  is  taken  up  from  the  bile-paths  by  the  portal 
lymphatics  is  about  300  mm.  of  bile.  The  highest  pressure  recorded  was 
373  mm.  of  bile  in  a  cat  {Herring  and  Simpson). 


tNFLULSCE  OF  NER VOUS  SYSTEAf  0^'  DIGEST  1 VE  GLA SDS     41 J 

constrictor  nerves,  for  it  has  the  same  composition  and  digestive 
action  as  normal  succiis  entericus  obtained  from  a  fistula.  The 
secretion  bcfiins  about  four  hours  after  section  of  the  nerves,  goes  on 
increasing  for  about  twelve  hours,  and  then  rapidly  diminishes,  so 
that  after  about  two  days  the  middle  loop,  as  well  as  the  other 
two,  will  be  found  empty.  The  interpretation  usually  put  upon  the 
experiment  is  that  nerves  which  normally  inhibit  the  local  secre- 
tory mechanism  have  been  divided.  But  there  is  no  real  proof  of 
the  existence  of  such  nerves. 

The  same  adaptation  is  seen  in  the  secretion  of  the  succus  entericus 
as  in  the  secretion  of  the  other  digestive  juices,  and  the  adaptation 
is  naturally  most  striking  in  regard  to  those  points  in  which  the 
intestinal  juice  is  pecuhar.  While  mechanical  stimulation  of  the 
stomach  is  ineffective  as  regards  the  secretion  of  gastric  juice, 
mechanical  stimulation  of  the  intestine,  as  by  the  contact  of  a 
cannula,  produces  a  free  flow  of  succus  entericus.  The  reaction  is  a 
localized  one,  the  secretion  only  taking  place  from  the  portion  of  the 
mucous  membrane  stimulated.  This  fact  acquires  significance  when 
we  reflect  that  the  food  moves  very  slowly  in  the  intestine,  and  a 
secretion  could  be  of  use  only  at  the  points  where  the  food  happened 
to  be.  The  juice  secreted  in  response  to  mechanical  stimulation  is 
poor  in  enterokinase.  But  if  a  little  pancreatic  juice  be  put  into  the 
intestine,  and  left  there  for  some  time,  the  juice  afterwards  secreted 
is  rich  in  enterokinase. 

Summary. — Here  let  us  sum  up  the  most  important  points  relat- 
ing to  the  secretion  of  the  digestive  juices.  They  are  all  formed  hy 
the  activity  of  glmid-cells  originally  derived  from  the  epithelial  lining 
of  the  alimentary  canal-  The  organic  constituents  or  their  precursors 
{including  the  mother-substances  of  the  ferments)  are  prepared  in  the 
internals  of  rest — absolute  in  some  glands,  relative  in  others — and 
stored  up  in  the  formr  of  granules,  which  during  activity  are  moved 
towards  the  lum-en  of  the  gland  tubules,  and  there  discharged. 

The  nerves  of  the  salivary  glands  are,  as  regards  their  origin,  {a) 
cerebral,  {b)  sympathetic ;  the  former  group  is  vaso-dilator,  the  latter 
{usually)  vaso-constrictor ;  both  are  secretory.  Secretion  of  saliva 
depends  strictly  on  the  neroous  system.  That  nerves  influence  the 
gastric  and  pancreatic  secretions  is  also  made  out.  The  psychical  secre- 
tion is  of  greater  importance  for  the  saliva  and  gastric  juice  than  for 
the  pancreatic  juice.  The  direct  action  of  secretin  {produced  in  the 
intestinal  mucous  membrane  by  the  influence  of  the  chym^)  is  the  most 
characteristic  factor  in  pancreatic  secretion.  As  regards  the  intestinal 
glands  and  the  liver,  it  has  not  been  proved  that  their  secretive  activity 
is  under  the  control  of  the  nervous  system,  except  in  so  far  as  the  latter 
may  indirectly  govern  it  through  the  blood-supply,  although  various 
circumstances  suggest  the  probability  of  a  more  direct  action.  All  the 
digestive  juices  show  a  certain  adaptation  to  the  nature  of  the  food. 


4i6  DIGESTION 

although  it  hus  not  been  demonstrated  that  this  is  due  to  a  specific  sensi- 
bility of  the  niiuons  membranes  for  each  kind  of  foodstuff.  The 
action  of  one  juice  on  the  secretion  of  another  is  also  of  great  significance. 
Thus,  the  water  of  the  saliva  directly  excites  a  flow  of  gastric  juice  when 
it  reaches  the  stomach ;  the  acid  of  the  gastric  juice  excites  a  flow  of 
pancreatic  piice  when  it  reaches  the  duodenum  :  and  the  pancreatic 
juice  excites  the  intestinal  mucous  membrane  to  the  production  of 
enterokinase,  the  most  characteristic  constituent  of  the  succus  entericus. 
In  all  the  glands  the  blood-flow  is  increased  during  activity ;  in  some 
{salivary  glands)  this  is  knoivn  to  be  caused  through  vaso-motor  nerves. 
In  the  salivary  glands  electro-motive  changes  accompany  the  active 
state,  and  more  heat  is  produced.  Both  in  the  salivary  glands  and  the 
pancreas  it  has  been  shown  that  much  more  carbon  dioxide  is  given  off, 
and  much  more  oxygen  used  up.  during  secretion  than  during  rest.  In 
the  other  glands  we  may  assume  that  the  same  occurs.  This  is  one 
proof  that  work  is  done  in  the  separation  or  manufacture  of  the  con- 
stituents of  the  various  secretions. 

Section  VI. — Survey  of  Digestion  as  a  Whole. 

Having  discussed  in  detail  the  separate  action  of  the  digestive 
secretions,  it  is  now  time  to  consider  the  act  of  digestion  as  a  whole, 
the  various  stages  in  which  are  co-ordinated  for  a  common  end. 
The  solid  food  is  more  or  less  broken  up  in  the  mouth  and  mixed 
with  the  saliva,  which  its  presence  causes  to  be  secreted  in  consider- 
able quantity.  Liquids  and  small  sohd  morsels  are  shot  down  the 
open  gullet  without  contraction  of  the  constrictors  of  the  pharynx, 
and  reach  the  lower  portion  of  the  oesophagus  in  a  comparatively 
short  time  (y^y  second) ;  while  a  good-sized  bolus  is  grasped  by  the 
constrictors,  then  by  the  oesophageal  walls,  and  passed  along  by  a 
more  dehberate  peristaltic  contraction. 

Chemical  digestion  in  man  begins  already  in  the  mouth,  a  part  of 
the  starch  being  there  converted  into  dextrins  and  sugar  ^maltose), 
as  has  been  shown  by  examining  a  mass  of  food  containing  starch 
just  as  it  is  ready  for  swallowing  (p.  456).  This  process  is  no  doubt 
continued  during  the  passage  of  the  food  along  the  oesophagus. 

The  first  morsels  of  a  meal  which  reach  the  stomach  find  it  free 
from  gastric  juice,  or  nearly  so.  They  are  alkaline  from  the  ad- 
mixture of  sahva ;  and  the  juicewhich  is  now  beginning  to  be  secreted, 
in  response  to  the  psychical  e.xcitoment,  and  reflexly  through  the 
presence  of  the  food  and  the  water  of  the  saliva  in  the  stomach,  is  for 
a  time  neutralized,  and  amylolytic  digestion  still  permitted  to  go  on. 
For  20  to  40  minutes  after  digestion  has  begun  there  is  no  free 
hydrochloric  acid  in  the  stomach,  although  some  is  combined  with 
proteins,  and  during  this  period  the  ptyalin  of  the  swallowed  saliva 
will  be  able  to  act  even  better  than  in  the  mouth,  being  favoured  by 


SURVEY  OF  DIGESTION  AS  A    WHOLE  41? 

a  weakly  acid  reaction.  Indeed,  for  a  time,  as  the  meal  goes  on,  the 
successive  portions  of  food  which  arrive  in  the  stomach  will  find  the 
conditions  more  and  more  favourable  for  amylolytic  digestion.  But 
as  the  acidity  continues  to  increase,  the  activity  of  the  ptyalin  will 
first  be  lessened,  and  ultimately  abolished;  and,  upon  the  whole,  a 
considerable  proportion  of  the  starches  must  usually  escape  com- 
plete conversion  into  sugar  until  they  arc  acted  upon  by  the  pan- 
creatic juice.  This  is  particularly  tlie  case  with  unboiled  starch,  as 
contained  in  vegetables  which  are  eaten  raw;  and,  indeed,  we  know 
that  sometimes  a  certain  amount  of  starch  may  escape  even  pan- 
creatic digestion,  and  appear  in  the  faeces.  Meanwhile,  pepsin  and 
hydrochloric  acid  are  being  poured  forth;  the  latter  is  entering  into 
combination  with  the  proteins  of  the  food ;  and  before  the  end  of  an 
ordinary  meal  peptic  digestion  is  in  full  swing.  The  movements  of 
the  pyloric  end  of  the  stomach  increase,  and  eddies  are  set  up  in  its 
contents,  which  carry  the  morsels  of  food  with  them,  and  throw  them 
against  its  walls.  In  this  way  not  only  are  the  contents  thoroughly 
mixed,  and  fresh  portions  of  food  constantly  brought  into  contact 
with  the  gastric  juice  secreted  mainly  in  the  more  passive  cardiac 
end,  but  a  certain  amount  of  mechanical  disintegration  is  brought 
about.  This  is  aided  by  the  digestion  of  the  gelatin-yielding  con- 
nective tissue  which  holds  together  the  fibres  of  muscle  and  the  cells 
of  fat,  and  the  digestible  structures  in  vegetable  tissue  which  enclose 
starch  granules.  Such  nucleo-proteins  as  come  into  contact  with  the 
gastric  juice  will  be  split  up  and  the  proteins  digested  to  peptone. 
The  globin  of  the  blood  pigment  will  undergo  the  same  change,  while 
the  haematin  is  not  much  affected.  If  milk  has  formed  a  portion  of 
the  meal,  the  caseinogen  will  have  been  curdled  soon  after  its 
entrance  into  the  stomach,  by  the  action  of  the  rennet  ferment  alone 
(see  p.  353)  when  the  milk  has  been  taken  at  the  beginning  of 
digestion  before  the  gastric  contents  have  become  distinctly  acid,  by 
the  acid  and  ferment  together  when  it  has  been  taken  later.  The 
caseinogen  and  other  proteins  of  milk,  like  the  myosinogen  and  other 
proteins  of  meat,  and  the  globulins,  albumins,  and  other  proteins  of 
bread  and  of  vegetable  food  in  general,  are  acted  upon  by  the  pepsin 
and  hydrochloric  acid,  yielding  ultimately  peptones;  while  variable 
quantities  of  these  proteins  and  of  the  acid-albumin  and  proteoses 
derived  from  them  may  escape  this  final  change,  and  pass  on  as  such 
into  the  duodenum.  In  the  dog,  indeed,  a  very  large  proportion  of 
a  meal  of  flesh  has  been  found  to  be  digested  to  the  peptone  stage 
while  still  in  the  stomach,  leaving  for  the  juices  that  act  on  it  in  the 
intestine  only  its  further  hydrolysis  to  amino-acids,  etc.  But  we 
may  safely  assume  that,  in  the  case  of  a  man  li\'ing  on  an  ordinary 
mixed  diet,  a  good  deal  of  the  food  proteins  passes  through  the 
pylorus  chemically  unchanged,  or  having  undergone  only  the  first 
steps  of  hydration.     For,  even  a  few  minutes  after  food  has  been 


418  DIGESTION 

swallowed,  especially  liquid  food  or  water,  the  pyloric  sphincter 
may  relax  and  allow  the  stomach  to  propel  a  portion  of  its  contents 
into  the  intestine ;  and  such  relaxations  occur  at  intervals  as  diges- 
tion goes  on,  although  it  is  not  for  several  hours  (three  to  five)  that 
the  greater  portion  of  the  food  reaches  the  duodenum.  During  this 
period  the  acidity  has  at  first  been  constantly  increasing,  although 
for  a  time  the  hydrochloric  acid  has  combined,  as  it  is  formed,  with 
the  proteins  of  the  food.  Then  comes  a  stage  where  the  hydrochloric 
acid  has  so  much  increased  that,  after  combining  with  all  the  proteins, 
some  of  it  remains  over  as  free  acid.  After  a  time  the  total  acidity 
begins  to  fall,  the  partially  digested  proteins  continually  i)assing  on 
through  the  pylorus,  while  a  considerable  proportion  is  so  fully 
digested  as  to  be  absorbed  by  the  gastric  mucous  membrane  itself. 
Thus,  in  one  experiment  on  the  digestion  of  meat  in  a  dog,  it  was 
found  that  30  per  cent,  was  absorbed  in  the  stomach,  while  40  per 
cent,  passed  through  the  pylorus  as  peptone,  over  20  per  cent,  as 
undissolved  or  soluble  protein  (acid-albumin),  and  a  little  more  than 
8  per  cent,  as  proteose  (Tobler).  The  large  proportion  of  peptone 
is  noteworthy,  as  indicating  some  kind  of  selective  passage  of  the 
different  digestive  products  from  the  stomach  into  the  duodenum. 
For  the  gastric  contents  contain  plenty  of  proteose,  although  only 
traces  of  peptone.  The  total '  titratable  acidity  '  goes  on  diminishing 
till  the  third  or  fourth  hour,  the  proportion  of  free  to  combined  acid 
continuing,  nevertheless,  to  rise,  since  nearly  all  that  is  now  secreted 
remains  free.  In  addition  to  a  certain  amount  of  protein,  small 
quantities  of  soluble  and  easily  diffusible  substances,  like  sugars  and 
some  of  the  organic  crystalline  constituents  of  meat — e.g.,  kreatin — 
may  also  be  absorbed  into  the  blood  by  the  gastric  mucous  membrane. 
The  substances  which  reach  the  duodenum  are — (i)  The  greater 
part  of  the  fats.  The  partial  digestion  in  the  stomach  of  the  enve- 
lopes and  protoplasm  of  the  cells  of  adipose  tissue,  and  of  the  protein 
which  keeps  the  fat  of  milk  in  emulsion,  prepares  the  fats  which  are 
not  spUt  up  by  the  gastric  juice  for  what  is  to  follow  in  the  intestine. 
(2)  All  the  proteins  which  have  not  been  carried  to  the  stage  of 
peptone,  and  much  peptone.  (3)  All  the  starch  and  dextrins — and 
glycogen,  if  any  be  present — which  have  not  been  converted  into 
sugars,  and  probably  a  portion  of  the  sugars.  (4)  Nucleins,  haematm, 
cellulose,  and  other  substances  not  digestible,  or  digestible  only  with 
difficulty,  in  gastric  juice.  (5)  The  constituents  of  the  gastric  juice 
itself,  including  pepsin.  Most  of  the  pepsin  is  soon  destroyed  in  the 
unfavourable  environment  of  the  intestinal  contents.  But  it  has 
been  shown  that  a  certain  amount  of  active  pepsin  may  be  present 
for  a  time  in  the  intestine,  even  in  the  free  condition,  and  still  more 
when  enclosed  in  the  interior  of  masses  of  protein  which  protect  it, 
and  which  still  continue  to  be  digested  by  it.  This  is  particularly 
true  of  certain  materials,  like  elastin  and  connective  tissue,  which  are 


SURVEY  OF  DIGESTION  AS  A    WHOLE  419 

more  readily  hydrolysed  by  pepsin  than  by  trypsin.     The  ptyalin 
of  the  sahva  has  been  ah-eady  destroyed  in  the  stomach. 

It  must  be  remembered  that  all  this  time,  even  from  the  beginning 
of  digestion,  a  certain  amount  of  pancreatic  juice  has  been  finding 
its  way  into  the  duodenum  in  response  first  perhaps  to  the  psychical 
excitation,  and  later  to  that  action  of  the  acid  chyme  on  the  in- 
testinal mucous  membrane  which  has  been  described.  In  the 
duodenum  its  trypsinogen  is  becoming  activated  to  trypsin  by  the 
cnterokinase  of  the  intestinal  juice.  The  secretion  of  bile,  too,  has 
quickened  its  pace,  the  gall-bladder  is  getting  more  and  more  full  as 
the  meal  proceeds  and  gastric  digestion  begins,  and  some  of  the  bile 
may  very  soon  escape  into  the  intestine.  The  pylorus  opens  occa- 
sionally for  a  moment  whenever  the  small  portions  of  chyme  which 
at  this  stage  are  beginning  to  pass  through  have  been  sufficiently 
neutralized  by  the  pancreatic  juice  and  bile,  although  it  is  not 
necessary  that  the  reaction  should  become  actually  neutral.  When 
the  acid  chyme,  a  greyish  liquid,  turbid  with  the  debris  of  animal  and 
vegetable  tissues — with  muscular  fibres,  fat  globules,  starch  granules, 
and  dotted  ducts — gushes  through  the  pylorus  and  strikes  the 
duodenal  wall,  the  muscular  fibres  of  the  gall-bladder  contract,  and 
sudden  rushes  of  bile  take  place  from  the  common  duct.  By-and-by 
as  bile  and  pancreatic  juice  continue  to  be  poured  out,  the  reaction 
in  the  duodenum  becomes  less  acid  and  even  weakly  alkaline. 
The  observations  purporting  to  show  changes  in  reaction  of  the 
intestinal  contents  at  different  levels  made  with  indicators  like 
litmus,  phenolphthalein,  methyl  orange,  etc.,  have  lost  much  of 
their  value  since  the  introduction  of  physico-chemical  methods  for 
measuring  the  hydrogen-ion  concentration.  However,  properly 
chosen  colour  indicators  can  still  be  employed  for  estimating  the 
acidity  of  the  gastric  contents,  at  least  with  sufficient  accuracy  for 
most  clinical  purposes.  It  must  be  remembered  that  the  differ- 
ences in  true  reaction  at  different  stages  of  intestinal  digestion  and 
at  different  levels  of  the  gut  below  the  duodenum  are  slight.  There 
is  never  a  great  preponderance  either  of  hydroxyl  or  of  hydrogen 
ions  between  the  point  at  which  the  pancreatic  juice  and  bile  are 
mingled  with  the  gastric  chyme  and  the  lower  part  of  the  ileum. 

In  the  duodenal  contents  of  adult  human  beings  a  hydrogen-ion  con- 
centration of  000000002  (or  2X  10-')  normal  has  been  found  by  the 
gas  chain  method  (McClendon)  and  about  the  same  in  the  intestinal 
contents  of  dogs  (Auerbach  and  Pick).  This  is  a  sHghtly  alkaUne 
reaction,  the  hydrogen-ion  concentration  of  pure  water  being  about 
five  times  as  great  ^o-ooooooi,  or  i  x  10-7).  In  the  stomach,  of  course, 
a  very  different  state  of  affairs  is  found.  The  hydrogen-ion  concen- 
tration rises  in  the  course  of  i  to  3  or  4  hours  after  a  meal  to  a  maxi- 
mum which  is  very  considerable.  In  a  series  of  patients,  including  a 
number  suffering  from  gastric  disorders,  the  hydrogen-ion  concentra- 
tion ranged  from  0-03  to  0-00000007  i^^  7^  10-').     The  lowest  concen- 


420  DIGESTION 

tration  is  practically  the  same  as  that  of  water.  In  other  words,  in 
this  patient  the  gastric  contents  after  the  test  meal  were  neutral,  and 
it  would  be  impossible  for  peptic  digestion  to  proceed.  It  must  be 
distinctly  noted  that  the  acidity  of  the  gastric  contents  during  the 
digestion  of  test  meals  is  not  the  same  thing  as  the  acidity  of  the  pure 
gastric  juice.  Observations  on  juice  obtained  from  a  case  of  gastric 
fistula  without  admixture  with  saliva  showed  that  in  '  hunger  '  juice, 
where  continuous  secretion  was  going  on,  the  hydrogen-ion  concentra- 
tion varied  from  o-055  to  o-ioo  normal  in  several  samples  collected  on 
different  days  (Menten). 

This  question  of  reaction  has  significance  in  two  ways :  in  the  first 
place  the  reaction  determines  whether  a  given  ferment  shall  be 
destroyed  or  not  by  another  ferment  or  b\-  the  alkalinity  or  acidity 
of  the  medium.  Thus  pepsin  can  be  destroyed  by  the  alkali  of  the 
pancreatic  juice,  enterokinase  and  trypsin  by  the  hydrochloric  acid 
of  the  gastric  juice,  trxpsinogen  by  the  pepsin  and  hydrochloric 
acid.  Tr\^sin  has  no  destructive  effect  on  enterokinase  or  tryp- 
sinogen  (Mellanby).  Secondly,  the  reaction  affects  the  actiNuty  of 
this  or  that  ferment  on  the  food  substances.  The  optimum  hydro- 
gen-ion concentration  for  peptic  digestion  is  relatively  high  (0'02 
to  0-03  normal).  WTien  it  is  decreased  to  o«ocoi  normal  the  rate 
of  digestion  is  only  one-half  to  one-fifth  as  rapid.  The  high  con- 
centration of  hydrogen-ions  in  the  gastric  contents  of  healthy  persons 
is  clearly  advantageous,  and  the  low  concentration  in  the  gastric 
contents  in  cases  of  hypoacidity  clearly  disadvantageous.  Trypsin 
acts  best  in  a  medium  which  contains  more  hydro.xyl  than  hydrogen 
ions.  WTien  the  alkalinity  is  diminished  it  becomes  less  active, 
although  it  is  not  entirely  inhibited  even  by  an  acid  reaction  until 
the  hydrogen-ion  concentration  reaches  about  o-oooi  (or  1x10-4) 
normal.     (See  footnote,  p.  1139.) 

In  the  intestine  it  is  possible  that  trypsin  may  perform  its  work 
in  a  medium  which  is  sometimes  acid;  and  although  the  cause  of 
the  aciditv  and  the  character  of  the  medium  are  far  from  being  the 
same  as  in  the  gastric  juice,  it  is  ob\aously  an  advantage  that  the 
chief  proteolytic  ferment  should  be  able  to  act  upon  the  proteins  in 
all  parts  of  the  intestine  and  at  every  stage  of  intestinal  digestion 
whether  the  reaction  is  acid  or  alkaline.  The  proteins  of  the  chyme 
are  all  carried  by  the  trypsin  to  the  stage  of  peptone,  and  the  pep- 
tone, even  in  perfectly  normal  digestion,  is  further  spHt  up  into 
amino-  and  diamino-acids  by  the  trypsin  and  b}'  the  erepsin  of  the 
succus  entericus. 

In  the  lower  portions  of  the  small  intestine  bacteria  of  various 
kinds  are  present  and  active;  and  it  is  not  unlikely  that  even 
throughout  its  whole  length  a  certain  range  of  action  is  permitted 
to  them,  checked  by  the  acidity  of  the  chyme,  though  scarcely  by 
the  feeble  antiseptic  properties  of  the  bile. 

The  lower  end  of  the  small  intestine  is  not  cut  off  by  any  bacteria- 
proof  barrier  from  the  large  intestine,  in  which  putrefaction  is  con- 


SURVEY  OF  DIGESTION  AS  A    WHOLE  421 

stantly  going  on.  It  has  been  actually  shown  that  small  particles, 
such  as  lycopodium  spores,  suspended  in  water,  soon  reach  the 
stomach  when  injected  into  the  rectum.  So  that  micro-organisms, 
aided  by  the  antiperistalsis  of  the  colon,  may  be  able  to  work  their 
way  above  the  ileo-colic  sphincter  and  valve,  even  against  the 
downward  peristaltic  movement  of  the  small  intestine.  But  even  if 
this  were  not  the  case,  a  few  bacteria  or  their  spores,  passing  through 
the  stomach  with  the  food,  would  be  enough  to  set  up  extensive 
changes  as  soon  as  they  reached  a  part  of  the  alimentary  canal 
where  the  conditions  were  favourable  to  their  development.  In- 
deed, from  the  time  when  the  first  micro-organism  enters  the  diges- 
tive tube  soon  after  birth,  it  is  never  free  from  bacteria;  and  their 
multiplication  in  one  part  of  it  rather  than  another  depends  not  so 
much  on  the  number  originally  present  to  start  the  process,  as  on 
the  conditions  which  encourage  or  restrain  their  increase. 

A  certain  amount  of  already  emulsified  fats  is  broken  up  into 
their  fatty  acids  and  glvcerin  in  the  stomach,  unemulsified  fats 
entirelv  by  the  fat-splitting  ferment  of  the  pancreatic  juice.  The 
acids  will  form  soaps  with  alkalies  wherever  they  meet  them  in  the 
intestinal  contents,  or  even  in  the  mucous  membrane.  A  portion 
of  those  soluble  soaps  may  be  immediately  absorbed;  the  rest  will 
aid  in  the  emulsification  of  the  fats  not  yet  chemically  decomposed, 
and  thus  greatly  hasten  the  fat -splitting  action  of  the  pancreatic 
juice.  The  phosphatides  are  in  all  probability  acted  upon  in  the 
alimentary  canal  much  in  the  same  way  as  the  fats.  Lecithin  is 
decomposed  by  pancreatic  and  intestinal  juice  into  fatty  acids  and 
glyceryl-phosphoric  acid,  and  cholin  is  hberated.  As  regards  the 
beha\nour  of  the  sterins  of  the  food  little  is  known,  but  it  is  not 
unlikely  that  their  esters  are  spht  up,  and  the  sterins  thus  set  free 
as  well  as  those  originally  free  in  the  food  may  then  be  absorbed, 
in  part  at  least,  without  further  change.  The  starch  and  dextrin 
which  have  escaped  the  action  of  the  sahva  are  changed  into 
maltose  by  the  amylase  of  the  pancreatic  juice,  and  the  maltose 
into  dextrose  by  the  maltase  of  the  same  secretion  and  of  the  succus 
entericus. 

The  succus  entericus,  in  addition  to  its  important  functions 
already  mentioned,  aids  as  an  alkahne  hquid  in  lessening  the  acidity 
of  the  chyme  and  establishing  the  reaction  favourable  to  intestinal 
digestion.  It  will  convert  into  monosaccharides  any  cane-sugar, 
maltose,  or  lactose,  which  may  reach  the  intestine;  but  it  cannot 
be  doubted  that  some  cane-sugar  may  be  absorbed  by  the  stomach, 
after  being  inverted  by  ':he  hydrochloric  acid  of  the  gastric  juice 
or  by  inverting  ferments  taken  in  \uth  the  food,  or  on  its  way 
through  the  gastric  walls. 

Upon  the  whole  no  great  amount  of  water  is  absorbed  in  the  small 
intestine,  or  at  least  the  loss  is  balanced  by  the  gain,  for  the  intestinal 


422  DIGESTION 

contents  are  as  concentrated  in  the  doudenum  as  in  the  ileum.  But 
as  soon  as  they  pass  beyond  the  ileo-caecal  valve  water  is  rapidly 
absorbed,  and  the  contents  thicken  into  normal  faeces,  to  which  the 
chief  contribution  of  tlic  large  intestine  is  mucin,  secreted  by  the 
vast  number  of  gobl(;t  cells  in  its  Lieberkiihn's  crypts. 

Bacterial  Digestion.— So  far  we  have  paid  no  special  attention  to 
other  than  the  soluble  ferments  of  the  digestive  tract,  although 
we  have  incidentally  mentioned  the  action  of  the  lactic  acid  bacilli 
on  carbo-hydrates  and  of  the  fat-splitting  bacteria  on  fats.  It  is 
now  necessary  to  recognize  that  the  presence  of  bacteria  is  an 
absolutely  constant  feature  of  digestion;  and  although  their  action 
must  in  part  be  looked  upon  as  a  necessary  evil  which  the  organism 
has  to  endure,  against  the  consequences  of  which  it  has  to  struggle, 
and  to  which  in  all  probability  it  has  to  a  great  extent  adapted 
itself,  it  is  not  unlikely  that  in  part  it  may  be  ancillary  to  the  pro- 
cesses of  aseptic  digestion.  But  bacteria  are  not  essential  (in  mam- 
mals, at  any  rate,  Hving  on  milk),  as  some  have  supposed.  For  it 
has  been  shown  that  a  young  guinea-pig,  taken  by  Caesarean  section 
from  its  mother's  uterus  with  elaborate  aseptic  precautions,  and 
fed  in  an  aseptic  space  on  sterile  milk,  grew  apparently  as  fast  as  one 
of  its  sisters  brought  up  in  the  orthodox  microbic  way.  The  ali- 
mentary canal  remained  free  from  bacteria  (Nuttall  and  Thierfelder). 
On  the  other  hand,  chickens  hatched  from  sterile  eggs  and  kept  in 
a  sterile  enclosure  lived,  indeed,  for  a  time,  but  did  not  thrive  in 
comparison  with  the  control  animals,  and  died  at  latest  after  eighteen 
days  (Schottelius).  It  is  probable  that  the  difference  in  the  results 
is  to  be  attributed  to  the  difference  in  the  food,  purely  vegetable 
food  requiring  the  aid  of  bacteria  for  its  proper  digestion,  especially 
for  the  decomposition  of  the  cellulose,  v/hile  an  easily-digestible 
food  like  milk  docs  not. 

Among  the  more  important  actions  of  bacteria  on  the  protein 
food-products  in  the  intestines  may  be  mentioned  the  formation 
of  indol,  phenol,  and  skatol,  the  first  having  tyrosin  for  its  precursor, 
and  being  itself  after  absorption  the  precursor  of  the  indican  in  the 
urine;  the  second  being  to  a  small  extent  thrown  out  with  the  faeces, 
but  chiefly  absorbed  and  eliminated  by  the  kidneys  as  an  aromatic 
compound  of  sulphuric  acid;  the  third  passing  out  mainly  in  the 
faeces. 

The  view  put  forward  by  Metchnikoff,  that  in  the  putrefactive 
bacteria  of  the  intestine  the  body  carries  within  itself  the  seeds  of 
premature  decay,  owing  to  the  harmful  effects  of  absorbed  products 
of  decomposed  protein,  cannot  be  looked  upon  as  established, 
although  certainly  the  prophylaxis  suggested  by  him  (the  increase 
of  the  lactic  acid  content  of  the  intestine  by  the  addition  of  sour 
milk,  butter-milk,  etc.,  to  the  diet)  might  well  be  a  useful  modifica- 
tion of  the  dietetic  habits  of  many  persons,  especially  if  associated 


SURVEY  OF  DIGESTION  AS  A    WHOLE  423 

with  a  reduction  in  the  total  amount  of  protein  consumed.  That 
the  intestinal  contents  may  include  substances  capable  of  inducinj^ 
severe  toxic  sympton"vs  if  absorbed  unchanged  scarcely  needs  proof. 
Filtered  extracts  of  fseces  from  normal  persons  made  with  salt 
solution  cau.ic,  when  injected  in  small  amounts  into  the  circulation 
of  dogs,  a  fall  of  blood-pressure  which  may  be  speedily  recovered 
from  or  may  be  quickly  fatal  according  to  the  specimen  (Fig.  170). 
The  large  intestine  is  the  chosen  haunt  of  the  bacteria  of  the 
ahmentary  canal;  they  swarm  in  the  faeces,  and  by  their  influence, 
especially  in  the  caecum  of  herbivora,  but  also  to  some  extent  in 
man,  even  cellulose  is  broken  up,  the  final  products  comprising 
certain  fatty  acids,  such  as  but^Tic,  acetic  and  valerianic  acids, 
carbon  dioxide  and  marsh  gas.  A  cellulose-dissolving  enzyme  of 
great  activity  is, present  in  the  hepatic  secretion  of  the  snail,  which 
rapidly  produces  sugar  from  that  polysaccharide.  Dextrose  is  also 
formed  when  it  is  hydrolysed  by  dilute  acid.  Apart  from  the  im- 
portance of  solution  of  the  cellulose  in  facilitating  the  action  of  the 
digestive  juices  on  the  starch  and  other  nutrient  materials  enclosed 
by  it,  it  can  be  assumed  that  some  of  the  intermediate  products  of 
its  hydrolysis  by  the  bacteria — e.g.,  bodies  analogous  to  the  dex- 
trins  which  appear  in  the  hydrolysis  of  starch — can  be  acted  on  by 
the  ferments  of  the  succus  entericus  and  the  pancreatic  juice,  so 
as  to  form  dextrose,  which  on  absorption  then  takes  its  place  in 
the  carbo-hydrate  metabolism  just  as  if  it  had  been  derived  from 
starch.  In  the  herbivora  the  contribution  thus  made  to  the  nutri- 
tion of  the  animal  may  be  of  considerable  importance;  in  omnivora 
it  is  not  negligible.  In  man  as  much  as  40  per  cent,  of  the  cellulose 
of  young  vegetables  is  said  to  be  capable  of  assimilation.  In  car- 
nivorous animals,  however,  it  appears  that  cellulose  when  taken  in 
the  food  is  quantitatively  excreted  in  the  fsces.  In  addition  to 
the  action  of  the  intestinal  flora  on  cellulose,  certain  of  the  bacteria 
of  the  alimentary  canal  affect  some  of  the  other  carbo-hydrates  in  a 
not  unimportant  way.  Dextrose,  for  instance,  can  be  decomposed 
into  two  molecules  of  lactic  acid,  according  to  the  equation 

CgHiaOe^aCsHgOj. 

This  is  called  the  lactic  acid  fermentation^  and  is  due  to  a  special 
bacillus. 

Another  micro-organism  splits  up  dextrose  into  butyric  acid, 
carbon  dioxide  and  hydrogen,  the  so-called  butyric  acid  fermenta- 
tion, according  to  the  equation 

CfiHiaOg  =  C4H8O2  -f-  aCOj  -I-  aHg. 

The  contents  of  the  large  bowel  are  generally  acid  from  the 
products  of  bacterial  action,  although  the  wall  itself  is  alkaline. 
Faeces.— In   addition  to   mucin,   secreted   mainly   by  the   large 


424 


DIGESTION 


intestine,  the  faeces  consist  of  indigestible  remnants  of  the  food,  such 
as  clastic  fibres,  spiral  vessels  of  plants,  and  in  general  all  vegetable 
structures  chiefly  composed  of  cellulose.  They  are  coloured  with  a 
pigment,  stercobilin,  derived  from  the  bilc-pigmints.  Stercobilin 
is  identical  with  urobilin,  which  forms  a  common,  tliough  not  an 


Fig.  I/O. 


-Eflect  of  Extract  of  Faeces  on  Blood-Pressure.     The  extraot  was  injected 
at  2.     Time-trace,  seconds. 


invariable,  constituent  of  bile  itself.  A  portion  of  it  is  absorbed  by 
the  intestine  and  then  excreted  in  the  urine,  the  urobilin  in  which 
is  often  much  increased  in  fever  ('  febrile  '  urobilin).  No  bilirubin 
or  biliverdin  occurs  in  normal  faeces,  although  pathologically  they 
may  be  present.  The  dark  colour  of  the  faeces  with  a  meat  diet  is 
due  to  haematin  and  sulphide  of  iron,  the  latter  being  formed  by 
the  action  of  the  sulphuretted  hydrogen  which  is  constantly  present 
in  the  large  intestine  on  the  organic  compounds  of  iron  contained  in 
the  food  or  in  the  secretions  of  the  alimentary  canal.  A  small 
amount  of  altered  bile-acids  and  their  products  is  also  found;  and 
in  respect  to  these,  and  to  the  altered  pigments,  bile  is  an  excretion. 
And  although  its  entrance  into  the  upper  instead  of  the  lower  end 
of  the  intestine,  the  ascertained  importance  of  its  function  in  diges- 
tion, and  the  fact  that  the  greater  part  of  the  bile-salts  is  reabsorbed, 
show  that  in  the  adult  it  is  very  far  from  being  solely  a  waste  product, 
the  equally  cogent  fact,  that  the  intestine  of  the  new-born  child 
is  filled  with  what  is  practically  concentrated  bile  (meconium), 
proves  that  it  is  just  as  far  from  being  purely  a  digestive  juice. 
Skatol  and  other  bodies,  formed  by  putrefactive  changes  in  the 
proteins  of  the  food,  are  also  present  in  the  faeces,  and  are  responsible 
for  the  faecal  odour.  Masses  of  bacteria  are  invariably  present,  and 
often  make  up  a  very  considerable  proportion  of  the  total  fcccal 


SURVEY  OF  DIGESTION  AS  A    WHOLE  425 

solid:..  01  the  inorganic  substances  in  faeces  the  numerous  crystals 
ot  triple  phosphate  arc  the  most  characteristic.  When  the  diet  is 
too  large,  or  contains  too  much  of  a  particular  kind  of  food,  a  con- 
siderable quantity  of  digestible  material  may  be  found  in  the  faeces — 
eg.,  muscular  fibres  and  fat.  But  it  should  be  remembered  that 
under  all  circumstances  the  composition  of  the  faeces  differs  from 
that  of  the  food.  Tlie  intestinal  contribution  is  always  an  important 
one,  although  relatively  more  important  with  a  flesh  than  with  a 
vegetable  diet.  The  purin  bases  normally  found  in  human  faces 
come  both  from  the  food  directly  and  from  the  metabolism  of 
the  tissues.  They  arc  increased  in  amount  on  a  diet  rich  in 
purin  bodies  (such  as  meat  extract  or  thymus),  but  are  also  formed 
on  a  diet  like  milk,  from  which  purin  bases  cannot  be  obtained. 
An  interesting  constituent  of  faeces  on  which  light  has  recently  been 
thrown,  especially  by  the  researches  of  Gardner,  is  the  so-called  copro- 
sterin  (dihydrocholesterin),  which  appears  to  be  produced  from 
cholesterin  by  reduction,  j)robably  under  the  influence  of  bacteria, 
and  perhaps  also  from  the  phytosterins  of  vegetable  food. 


CHAPTER    VII 
ABSORPTION 

Section  I. — Preliminary  Physico-Chemical  Data. 

Imbibition,  or  molecular  imbibition,  is  the  term  applied  to  the  en- 
trance of  liquid  into  a  colloid,  without  the  loss  of  its  properties  as  a  solid, 
when  no  preformed  capillary  spaces  are  present.  The  entrance  of  water 
into  a  piece  of  gelatin,  or  an  epidermic  scale,  is  an  example  of  molecular 
imbibition.  IMost  animal  and  vegetable  tissues  possess  this  property, 
which  is  believed  to  be  of  importance  in  such  physiological  processes  as 
absorption,  secretion,  and  the  excretion  of  water  from  the  lungs  and 
skin.  The  process  by  which  liquid  passes  into  a  solid  with  preformed 
capillary  spaces — e.g.,  a  sponge — is  sometimes  spoken  of  as  capillary 
imbibition. 

Diffusion. — When  a  solution  of  a  sub.stance  is  placed  in  a  vessel,  and 
a  layer  of  water  carefully  run  in  on  the  top  of  it,  it  is  found  after  a  time 
that  the  dissolved  substance  has  spread  itself  through  the  water,  and 
that  the  composition  of  the  mixture  is  uniform  throughout.  The 
result  is  the  same  when  two  solutions  containing  different  proportions 
of  the  same  substance,  or  containing  different  substances,  are  placed  in 
contact.  The  phenomenon  is  called  diffusion.  The  time  required  for 
complete  diffusion  is  comparatively  short  in  the  case  of  a  substance  like 
hydrochloric  acid  or  sodium  chloride,  exceedingly  long  in  the  case  of 
albumin  or  gum.  In  both  it  is  more  rapid  at  a  high  temperature  than 
at  a  low. 

Osmosis. — If  the  solution  be  separated  from  water  by  a  membrane 
absolutely  or  relatively  impermeable  to  the  dissolved  substance,  but 
permeable  to  water,  water  passes  through  the  membrane  into  the  solu- 
tion. This  phenomenon  is  called  osmosis.  E.g.,  a  membrane  of  ferro- 
cyanide  of  copper,  nearly  impermeable  to  cane-sugar,  can  be  formed 
in  the  pores  of  an  unglazed  porcelain  pot  by  allowing  potassium  ferro- 
cyanide  and  cupric  sulphate  to  come  in  contact  there.  If  the  pot  is 
filled  with,  say,  a  i  per  cent,  solution  of  cane-sugar.  clo.scd  by  a  suitable 
stopper,  connected  to  a  manometer,  and  then  placed  in  a  vessel  of  water, 
water  passes  into  it  till  the  pressure  indicated  by  the  manometer  rises 
to  a  certain  height.  With  a  2  per  cent,  solution  it  reaches  twice  this 
height,  and  in  general  the  osmotic  pressure,  as  it  is  called,  is  in  any 
solution  proportional  to  the  molecular  concentration*  of  the  solution, 

*  The  molecular  concentration  is  strictly  defined  as  the  number  of 
grammes  of  the  dissolved  substance  in  a  litre  of  the  solution  divided  by  the 
gramme-molecular  weight.  The  gramme-molecular  weight,  or  gramme 
molecule,  is  the  number  of  grammes  corresponding  to  the  molecular  weight. 
Thus,  the  gramme-molecular  weight  of  sodium  chloride  (NaCl)  is  5S"36 
grammes,  and  of  cane-sugar  (C  121122^11) ■  34^  grammes. 

426 


PRELIMINARY  PHYSICO-CHEMICAL  DATA 


427 


or,  in  otlicr  words,  to  the  number  of  molecules  of  the  dissolved  substance 
in  a  given  volume  of  the  solution.  If  in  this  sentence  we  substitute 
'  gaseous  pressure  '  for  '  osmotic  pressure,'  and  '  gas  '  for  '  solution,' 
we  have  a  statement  of  Boyle's  law,  which  asserts  that  the  pressure  of  a 
gas  is  proportional  to  its  density.  Indeed,  it  has  been  shown  that  the 
osmotic  pressure  of  the  dissolved  substance  is  the  same  as  the  pressure 
that  would  be  exerted  by  a  gas,  say  hydrogen,  if  all  the  water  were 
removed,  and  a  molecule  of  hydrogen  substituted  for  each  molecule  of 
the  substance,  or  as  would  be  exerted  by  the  sub.stance  itself  if,  after 
removal  of  the  solvent,  it  could  be  left  as  a  gas  filling  tlie 
same  volume.  And  the  osmotic  pressure  of  a  solution  of 
one  substance  is  the  same  as  that  of  a  solution  of  any 
other  substance  which  contains  in  a  given  volume  the 
same  number  of  molecules  of  the  dissolved  substance. 
In  other  words,  the  osmotic  pressure  is  not  dependent  on 
the  nature,  but  on  the  molecular  concentration,  of  the 
substance.  The  analogy  of  the  laws  of  osmotic  to  those 
of  gaseous  pressure  becomes  still  more  obvious  when 
it  is  added  that  the  osmotic  pressure  of  a  substance  with 
any  given  molecular  concentration  is  proportional  to  the 
absolute  temperature  ;  and  that  when  a  solution  contains 
more  than  one  dissolved  substance  the  total  osmotic  pres- 
sure is  the  sum  ol  the  partial  osmotic  pressures 
vvliich  each  substance  would  exert  if  it  were 
present  alone  in  the  same  volume  of  the  solution. 
The  osmotic  pressure  of  a  solution  may  reach 
an  enormous  amount.  Thus,  a  i  per  cent,  solu- 
tion of  cane-sugar  has  a  pressure  at  0°  C.  of 
493  mm.  of  mercuiy.  A  10  per  cent,  solution 
of  cane-sugar  would  have  an  osmotic  pressure  of 
more  than  six  atmospheres,  and  a  17  per  cent, 
solution  of  ammonia  a  pressure  of  no  less  than 
224  atmospheres.  The  manner  in  which  the 
phenomenon  known  as  osmotic  pressure  is  de- 
veloped is  not  definitely  known.  One  theory 
attributes  it  to  the  attraction  between  the 
dissolved  molecules  and  the  molecules  of  the 
solvent  on  the  other  side  of  the  membrane. 
The  most  commonly  accepted  view  is  that  the 
osmotic  pressure  is  due  to  the  kinetic  energy 
of  the  moving  molecules.  Where  the  mole- 
cules are  hindered  from  passing  a  bounding 
membrane,  the  pressure  exerted  by  their  im- 
pacts on  the  boundary  is  greater  than  where 
the  membrane  is  easily  permeable,  because  in 
the  latter  case  many  of  the  molecules  pass 
through,  carrying  with  them  their  kinetic 
energy.  The  pressure  must  be  still  less  when 
a  dissolved  substance  diffuses  freely  into  water ; 
but  however  small  it  may  become,  it  is  in  the  same  force  which  gives 
rise  to  the  osmotic  pressure  of  the  molecules  of  the  dissolved  substance 
that  the  cause  of  diffusion  must  be  sought.  Recently  interest  in  the 
nature  of  the  membrane  itself  as  an  important  factor  in  osmosis  has  been 
revived  (Kahlenberg.  Armstrong,  etc.).  There  are  many  facts  which 
indicate  that  in  physiological  processes  the  affinity  of  the  dissolved  sub- 
stances for,  or  their  solubility  in,  the  cell  envelopes  or  the  cytoplasm 
plays  an  important  role. 


Fig.  171.  —  Beckmann's 
Apparatus.  For  de- 
scription, see  p,  52c. 


42  S  ABSORPTION 

It  is  as  yet  impossible  or  at  least  very  (iillitult  to  directly  measure 
the  osmotic  pressure  with  accuracy  by  means  of  a  scmi-permcablc  mem- 
brane. Recourse  is  therefore  had  to  indirect  methods,  especially  one 
which  depends  on  the  fact  that  the  freezing-point  of  a  solution  is  lower 
tiian  that  of  the  solvent,  salt  water,  c./j.,  freezing  at  a  lower  temperature 
than  fresh  water.  The  amount  by  which  the  freezing-point  is  lowered 
depends  on  the  molecular  concentration  of  the  dissolved  substance,  to 
which,  as  we  have  seen,  the  osmotic  pressure  is  also  proportional.  When 
a  gramme-molecule  of  a  substance  is  dissolved  in  water,  and  the  volume 
made  up  to  a  litre,  the  freezing-point  is  lowered  by  i86°  C. ;  the  osmotic 
jiressurc  is  22-33  atmospheres  {16,986  mm.  of  mercury).  It  is  therefore 
easy  to  calculate  the  osmotic  pressure  of  any  solution  if  we  know  the 
amount  by  which  its  freezing-point  is  lowered.  A  i  per  cent,  solution  of 
cane-sugar,  for  example,  would  freeze  at  about  —  0'054°  C.     Its  osmotic 

pressure=    .J^^^  16,986=493  mm.  of  mercury. 

A  convenient  apparatus  for  making  freezing-point  measurements  is 
shown  in  Fig.  171.  The  details  of  the  method  are  given  in  the  Practical 
I'lxcrcises,  p.  5^9. 

The  osmotic  pressure  of  different  solutions  may  also  be  compared 
by  observing  the  effect  produced  on  certain  vegetable  and  animal  cells. 
When  a  solution  with  a  greater  osmotic  pressure  than  the  cell-sap  (a 
hypcyisotonic  solution)  is  left  for  a  time  in  contact  with  certain  cells  in 
the  leaf  of  Tradcscantia  discolor,  plasmolysis  occurs — that  is,  the  proto- 
plasm loses  water  and  shrinks  away  from  the  cell-wall.  If  the  osmotic 
pressure  of  the  solution  is  lower  than  that  of  the  coloured  cell-sap 
{hypoisotonic  solution),  no  shrinking  of  the  protoplasm  takes  place.  By 
using  a  number  of  solutions  of  the  same  substance  but  of  different 
strength,  two  can  be  found,  the  stronger  of  which  causes  plasmolysis, 
and  the  weaker  not.  Between  these  lies  the  solution  which  is  isotonic 
with  the  cell-sap — that  is,  has  the  same  molecular  concentration  and 
osmotic  pressure.  The  strength  of  an  isotonic  solution  of  some  other 
substance  can  then  be  determined  in  the  same  way  with  sections  from 
the  same  leaf. 

Animal  cells  (red  blood-corpuscles)  may  also  be  employed,  the  libera- 
tion of  haemoglobin  or  the  swelling  of  the  corpuscles,  as  measured  by 
tlie  ha3matocrite  (p.  27),  being  taken  as  evidence  that  the  solution  in 
contact  with  tliem  is  hypoisotonic  to  the  contents  of  the  corpuscles. 
Here  we  may  suppose  that  the  impacts  of  the  molecules  of  the  salts  of 
the  corpuscle  on  the  inside  of  its  envelope,  not  being  balanced  by 
similar  impacts  on  the  outside,  tend  to  distend  it,  and  thus  to  create  a 
potential  vacuum  for  the  surrounding  water,  which  accordingly  enters. 
If  the  corpuscles  shrink,  the  solution  is  hyperisotonic  to  their  contents. 
But  since  the  cells  are  much  more  permeable  to  certain  substances  than 
to  others,  this  method  does  not  always  yield  trustworthy  results. 

Electrolytes. — We  have  said  that  the  osmotic  pressure  is  proportional 
to  the  concentration  of  the  solution,  but  this  statement  must  now  be 
qualified.  For  certain  compoumls,  including  all  inorganic  salts  and 
many  organic  substances,  the  osmotic  pressure  decreases  less  rapidly 
than  the  theoretical  molecular  concentration  as  the  solution  is  diluted. 
The  explanation  is  that  in  solution  some  of  the  molecules  of  these  bodies 
are  broken  up  into  simpler  groups  or  single  atoms,  called  ions.  Each 
ion  exerts  the  same  osmotic  pressure  as  the  molecule  did  before.  The 
proportion  between  the  average  number  of  these  dissociated  molecules 
and  of  ordinary  molecules  is  constant  for  a  given  concentration  of  the 
solution  and  agiven  temperature.  But  as  the  solution  is  diluted,  the 
proportion  of  dissociated  molecules  becomes  greater.     The  bodies  which 


PRELIMLWIKY  PHYSICO-CHEMICAL  DATA  419 

behave  in  this  way  are  electrolytes — that  is,  their  solutions  conduct  a 
current  of  electricity;  bodies  vvhicii  do  not  exhibit  this  behaviour  do 
not  conduct  in  solution.  And  there  arc  many  reasons  for  believing 
that  the  dissociation  of  tiie  elect rolj'les  is  the  essential  thing  in  elec- 
trolytic conduction.  We  may  suppose  that  in  a  solution  of  an  electro- 
lyte— sodium  chloride,  for  instance — a  certain  number  of  the  molecules 
fall  asunder  into  a  kation  (Na+),*  carrying  a  charge  of  positive  elec- 
tricity, and  an  anion  (CI—),  carrying  an  equal  negative  charge.  These 
electrical  charges,  it  must  be  remembered,  are  not  created  by  the 
passage  of  a  current  through  the  solution.  Wc  do  not  know  how  they 
arise,  but  the  ions  must  be  supposed  to  be  electrically  charged  at  the 
moment  when  the  molecule  is  broken  up.  And  the  ions  of  ditterent  sub- 
stances must  each  be  supposed  to  carry  the  same  quantity  of  electricity. 
But  since  they  are  all  wandering  freely  in  the  solution,  no  excess  of 
negative  or  of  positive  electricity  can  accumulate  at  any  part  of  it — in 
other  words,  no  difference  of  potential  can  exist.  When  electrodes 
connected  with  a  voltaic  battery  are  dipped  into  a  solution  of  an  elec- 
trolyte, a  difference  of  potential,  an  electrical  slope,  is  established  in  the 
liquid,  and  the  positively  charged  kations  are  compelled  to  wander 
towards  the  negative  pole,  the  negatively  charged  anions  towards  the 
positive  pole.  In  this  way  that  movement  of  electricity  which  is  called 
a  current  is  maintained  in  the  solution.  It  is  clear  that  the  greater 
the  number  of  ions,  and  the  faster  they  move  in  the  solution,  the  greater 
will  be  the  quantity  of  electricity  carried  to  the  electrodes  in  a  given 
time,  when  the  difference  of  potential  between  the  electrodes,  or  the 
steejmess  of  the  electric  slope,  remains  constant.  In  other  words,  the 
specific  conductivity  of  a  solution  of  an  electrolyte  varies  as  the  number 
of  dissociated  molecules  in  a  given  volume  and  the  speed  of  the  ions. 
It  increases  up  to  a  certain  point  with  the  concentration,  because  the 
absolute  number  of  dissociated  molecules  in  a  given  volume  increases. 
The  molecular  conductivity — that  is,  the  conductivity  per  molecule,  or, 
strictly,  the  ratio  of  the  specific  conductivity  to  the  molecular  concen- 
tration— increases  with  the  dilution,  because  the  relative  number  of 
dissociated  molecules,  as  compared  with  undissociated,  increases.  At 
a  certain  degree  of  dilution  the  molecular  conductivity  reaches  its 
maximum,  for  all  the  molecules  are  dissociated.  The  ratio  of  the 
molecular  conductivity  of  any  given  solution  to  this  maximum  or 
limiting  value  is  therefore  a  measure  of  the  proportion  between  the 
number  of  dissociated,  and  the  total  number  of  molecules.  The  molec- 
ular conductivity  of  the  salts  dissolved  in  the  liquids  of  the  animal 
body,  for  the  degree  of  dilution  in  which  they  exist  there,  is  such  that 
we  must  assume  them  to  be  for  the  most  part  dissociated. 

Surface  Tension. — This  is  a  property  of  surfaces  which  is  typically 
illustrated  in  such  instances  as  a  globule  of  mercury,  a  drop  of  water 
on  a  greasy  slide,  or  a  drop  of  oil  suspended  in  a  liquid  with  which  it 
does  not  mix.  The  tendency  of  such  drops  to  assume  the  spherical 
form  when  not  large  enough'to  be  distorted  by  gravity  is  due  to  the 
fact  that  the  surface  layer  is  under  a  certain  tension  in  virtue  of  which 
it  strives  to  contract  and  to  render  the  surface  of  the  drop  as  small  as 

*  It  has  been  shown  that  the  chemical  atoms  themselves  are  not  homo- 
geneous, but  are  all  built  up  of  simpler  particles  and  possess  a  certain  struc- 
ture. All  atoms,  e.g.,  contain  electrons,  minute  particles  charged  with  negative 
electricity.  The  number  of  electrons  in  an  atom  appears  to  be  not  far  from 
half  its  atomic  weight.  Thus  in  the  carbon  atom  there  are  6  electrons,  in  the 
oxygen  atom  8,  and  in  the  hydrogen  atom  probably  only  i.  There  is 
evidence  that  the  electrons  in  the  atom  are  divided  into  groups  or  rings 
one  within  another  (Thomson). 


430 


ABSORPTION 


possible,  just  as  if  it  were  a  stretched  elastic  membrane.  Tlie  cause 
of  this  tension  is  to  be  sought  in  the  mutual  attraction  exerted  by  mole- 
cules which  arc  very^  close  to  each  other.  This  molecular  pull  is 
enormously  strong.  It  has  been  calculated,  for  instance,  that  the 
so-called  internal  pressure  which  is  due  to  it  is  in  the  case  of  water  not 
less  than  23,000  atmospheres.  In  the  interior  of  tlie  drop  each  mole- 
cule, being  surrounded  by  other  molecules,  is  pulled  by  this  attractive 
force  equally  in  all  directions — that  is  to  say,  on  the  whole  it  is  not 
pulled  at  all,  since  the  pulls  of  all  the  surrounding  molecules  balance 
each  other.  At  the  free  surface,  on  tlie  contrary-,  the  molecules  are 
pulled  towards  the  surface,  but  not  away  from  it,  and  the  pull  of  the 
molecules  below  the  surface  layer  is  not  balanced  by  the  pull  of  mole- 
cules above  it.  The  resultant  tension  on  this  layer  is  the  surface  tension. 
Changes  in  the  amount  of  this  surface  tension  in  the  case  of  a  given 
liquid  can  be  produced  by  bringing  gases,  solids,  or  other  liquids  into 
contact  with  the  surface  layer — that  is,  by  bringing  molecules  of  other 
substances  so  near  the  surface  molecules  of  the  liquid  that  they  can 
attract  them,  and  so  to  a  greater  or  less  degree,  depending  upon  the 
nature  of  the  substances,  balance  the  attraction  of  the  molecules 
beneath  the  surface  of  the  drop.  Another  way  in  which  the  surface 
tension  can  be  altered  is  by  changing  the  temperature.  The  higher 
the  temperature,  the  greater  is  the  average  velocity  with  which  the 
molecules  of  the  liquid  are  moving,  and  the  greater  the  average  distance 
between  the  molecules  (expressed  as  the  expansion  of  the  liquid) .  Increase 
of  temperature  therefore  causes  the  molecules,  through  the  kinetic 
energy  of  heat  imparted  to  them,  say.  from  an  external  source,  to 
repel  each  other,  and  to  that  extent  counteracts  their  mutual  attrac- 
tion. Accordingly,  at  the  surface  the  tension,  which,  as  stated,  depends 
upon  the  excess  of  this  attraction  acting  towards  the  interior  of  the 
drop,  will  be  diminished.  When  the  temperature  is  diminished  the 
surface  tension  will  increase.  The  surface  tension  can  also  be  altered 
by  altering  the  electrical  charge  on  the  surface.  An  instance  of  this 
is  described  on  another  page  in  connection  with  the  capillar)-  electrom- 
eter (p.  702).  In  such  ways,  then,  the  surface  tension  at  the  inter- 
face where  the  cells  lining  the  intestine  come  into  contact  with  the 
contents  of  the  gut  or  with  the  tissue  lymph,  or  at  the  interfaces  within 
the  cells  where  solid  and  liquid  '  phases  '  come  into  contact  with  each 
other  or  where  different  liquids  touch,  may  undergo  alterations  in 
either  direction.  If  the  tension  of  the  surface  is  altered,  the  surface 
energ)^  or  power  of  doing  work  inherent  in  the  existence  of  this  tension 
will,  of  course,  be  altered  too.  In  this  way  the  energ\-,  or  a  portion  of 
it,  which  is  unquestionably  expended  in  absorption  may  be  supplied 
ultimately  at  the  expense  of  the  chemical  energy  of  cell  constituents 
or  of  food  substances  on  their  way  tlirough  the  cells,  by  means  of  which 
the  original  surface  tensions  are  restored.  It  has  been  surmised  fhat 
changes  of  surface  tension  may  also  be  concerned  in  the  secretion  of 
glands,  in  muscular  contrrxtion  (p.  744),  and  other  functions  (Macallum, 
Bernstein,  etc.). 

Adsorption. — Connected  with  the  peculiar  properties  of  surfaces 
referred  to  in  the  last  paragraph  are  certain  phenomena  spoken  of  as 
adsorption  phenomena.  Adsorption  is  typically  seen  when  a  solid  in 
such  a  form  that  the  surface  is  greatly  increased  [e.g..  a  fine  powder  or 
a  colloidal  solution  in  which  the  substance  is  suspended  in  the  form 
of  exceedingly  small  particles)  is  placed  in  contact  with  a  gas  or  a 
solution.  There  occurs  a  diminution  in  the  concentration  of  the  gas 
or  the  dissolved  substance,  and  a  corresponding  accumulation  of  it  on 
the  suvtace  of  the  solid.     Equilibrium  is  rapidly  established,  and  the 


MECHANISM  OF  ABSORPTION  43^ 

characteristic  thing  about  adsorption  is  that  at  the  equilibrium-point 
the  concentration  of  the  dissolved  substance  (or  the  ga^j  on  the  surface 
is  immensely  greater  than  in  the  general  mass  of  the  solution.  The  con- 
centration on  tlie  surface  can,  indeed,  be  increased  by  increasing  the 
concentration  of  the  solution,  but  in  a  far  smaller  proportion.  Accord- 
ing to  the  thcrmod\Tiamic  law  enunciated  by  Willard  Gibbs,  sub- 
stances wliich  diminish  the  surface  tension  must  tend  to  accumulate 
at  the  surface,  and  substances  which  increase  the  surface  tension  must 
tend  to  diminish  in  concentration  at  the  surface.  If  a  small  quantity 
of  a  substance  diminishes  the  surface  tension  at  a  given  surface  more 
in  proportion  than  a  larger  quantity,  not  only  will  there  be  an  accumula- 
tion of  the  substance  at  the  surface,  but  this  will  be  proportionally 
greater  for  small  than  for  larger  concentrations  of  the  substance  in  the 
solution.  This  characteristic  feature  of  adsorption  may  thus  depend 
entirely  on  surface  forces  due  to  the  conditions  under  which  the  attrac- 
tion of  the  molecules  for  each  other  acts  at  the  surface.  It  has  not  been 
shown,  however,  that  chemical  forces  due  to  the  interaction  of  the 
electrically  charged  ions  are  not  also  concerned.  What  is  especially 
important  to  point  out  is  that  in  the  tissues  of  the  body  there  is  a 
great  development  of  surfaces.  The  cell  walls  or  cell  envelopes  come 
into  contact  with  the  tissue  hinph  or  the  contents  of  the  digestive 
tube  or  the  secretions  in  the  alveoli  of  glands  on  the  one  side,  and  the 
cell  contents  on  the  other,  and  constitute  in  the  aggregate  an  immense 
surface.  The  surfaces  separating  the  nuclei  from  the  cytoplasm,  and. 
above  all,  the  surfaces  of  the  particles  of  the  contents  of  cytoplasm 
and  nuclei  suspended  in  colloid  solution,  offer  prodigious  opportunities 
for  such  surface  phenomena  as  adsorption. 


Section  II. — Mechanism  of  Absorption. 

In  the  preceding  chapter  we  have  traced  the  food  in  its  progress 
along  the  alimentary  canal,  and  sketched  the  changes  wrought  in 
it  by  digestion.  We  have  next  to  consider  the  manner  in  which  it 
is  absorbed.  Then,  for  a  reason  which  has  alread}^  been  explained, 
instead  of  following  its  fate  within  the  tissues,  until  it  is  once  more 
cast  out  of  the  body  in  the  form  of  waste  products,  it  will  be  best 
to  drop  the  logical  order  and  pick  up  the  other  end  of  the  clue — in 
other  words,  to  pass  from  absorption  to  excretion,  from  the  first 
step  in  metabohsm  to  the  closing  act,  and  afterwards  to  return  and 
fill  in  the  interval  as  best  we  can. 

Comparative. — And  here,  first  of  all,  it  should  be  remembered  that 
the  epithelial  surfaces,  through  which  the  substances  needed  by  the 
organism  enter  it,  and  waste  products  leave  it,  are,  physiologically  con- 
sidered, outside  the  body.  The  mucous  membranes  of  the  alimentary', 
respiratory- ,  and  urinar\-  tracts  are  in  a  sense  as  much  external  as  the 
foHrth  great  division  oi'  the  physiological  surface,  the  skin.  The  two 
latter  surfaces  are  in  the  mammal  purely  excretory.  Absorption  is 
the  dominant  function  of  the  alimentan,-  mucous  membrane,  but  a 
certain  amount  of  excretion  also  goes  on  through  it.  The  pulmonary 
surface  both  excretes  and  absorbs,  and  that  in  an  equal  measure.  But 
it  is  by  no  means  necessary-  that  the  surface  through  which  oxvgen  is 
taken  in  and  gaseous  waste  products  given  off  should  be  buried  deep  in 
the  body,  and  communicate  only  by  a  narrow  channel  with  the  exterior. 


432 


ABSORPTION 


In  the  frog  the  skin  is  largely  an  absorbing  as  well  as  an  excreting 
surface  ;  oxygen  passes  freely  in  through  it,  just  as  carbon  dioxide  passes 
freely  out.  In  most  fishes,  and  many  other  gill-bearing  animals,  the 
whole  gaseous  interchange  takes  place  through  surfaces  immersed  in 
the  surrounding  water,  and  therefore  distinctly  external.  In  certain 
forms  it  has  even  been  shown  that  the  alimentary  canal  may  serve  con- 
spicuously for  absorption  and  excretion  of  gaseous,  as  well  as  liquid 
and  solid  substances.  Still  lower  down  in  the  animal  scale,  the  surface 
of  a  single  tube  may  perform  all  the  functions  of  digestion,  absorption 
and  excretion.  Lower  still,  and  even  this  tube  is  wanting,  and  everj-- 
thing  passes  in  and  out  through  an  external  surface  pierced  by  no  per- 
manent openings. 

Indeed,  even  in  man  the  functions  of  the  various  anatomical  divisions 
of  the  phvsiological  surface  are  not  quite  sharply  marked  off  from  each 
other.  Though  gaseous  exchange  goes  on  far  more  readily  through  the 
pulmonary  membrane  than  anywhere  else,  swallowed  oxygen  is  easily 
enough  absorbed  from  the  alimentary  canal  and  carbon  dioxide  given 
off  into  it ;  and  to  a  small  extent  these  gases  can  also  pass  through  the 
skin.  Though  water  is  excreted  chiefly  by  the  skin,  the  pulmonary 
and  the  urinary  surfaces,  and  on  the  whole  absorbed  chiefly  from  the 
digestive  tract,  there  is  no  surface  which  in  the  twenty-four  hours  pours 
out  so  much  water  as  the  mucous  membrane  of  the  stomach.  Under 
normal  conditions,  it  is  true,  by  far  the  greater  part  of  this  is  reabsorbed 
in  the  intestine,  yet  in  diarrhoea,  whether  natural  or  caused  by  purga- 
tives, the  intestines  themselves  may,  instead  of  absorbing,  contribute 
largely  to  the  excretion  of  water.  Again,  although  the  solids  of  the 
excreta  are  normally  given  off  in  far  the  greatest  quantity  in  the  urine 
and  faeces  (only  part  of  the  latter  is  truly  an  excretion,  since  much  of 
the  faeces  of  a  mixed  diet  has  never  been  physiologically  inside  the 
body  at  all),  yet  salts  and  traces  of  urea  are  constantly  found  in  the 
sweat,  and  salts  and  mucin  in  the  excretions  of  the  respiratory  tract. 
Further,  although  the  solids  and  liquids  of  the  food  are  usually  taken 
in  by  the  alimentary  mucous  surface,  it  is  possible  to  cause  substances 
of  both  kinds  to  pass  in  through  the  skin ;  and  a  certain  amount  of 
absorption  may  also  take  place  through  the  urinary  bladder.  So  that 
really  it  may  be  considered,  from  a  physiological  point  of  view,  as  more 
or  less  an  accident  that  a  man  should  absorb  his  food  by  dipping  the 
villi  of  his  intestine  into  a  digested  mass,  rather  than  by  dipping  his 
fingers  into  properly  prepared  solutions,  as  a  plant  dips  its  roots  among 
the  liquids  and  solids  of  the  soil;  or  that  he  should  draw  air  into  organs 
lying  well  in  the  interior  of  his  thorax,  instead  of  letting  it  play  over 
special  thin  and  highly  vascular  portions  of  his  skin ;  or  that  the  surface 
by  which  he  excretes  urea  should  be  buried  in  his  loins,  instead  of  lying 
free  upon  his  back. 

It  has  been  already  explained  that,  although  digestion  is  a 
necessary  preliminary  to  the  absorption  of  most  of  the  solids  of 
the  food,  we  are  not  to  suppose  that  all  the  food  must  be  digested 
before  any  of  it  begins  to  be  absorbed.  On  the  contrary,  the 
two  processes  go  on  together.  As  soon  as  any  peptone,  or,  at 
least,  any  amino-acids,  have  been  formed  from  the  proteins,  or 
any  dextrose  from  the  starch,  they  begin  to  pass  out  of  the  ali- 
mentary canal ;  and  by  the  time  digestion  is  over,  absorption  is  well 
advanced. 

Even  in  the  mouth  it  has  already  begun,  although  the  amount  of 


MECHANISM  OF  ABSORPTION  433 

absorption  here  is  quite  insignificant,  and  it  is  continued  with 
greater  rapidity  in  the  stomach.  Here  a  not  inconsiderable  part 
of  the  proteins — at  k^ast,  in  the  easily  digested  form  of  animal  food — 
a  certain  amount  of  the  sugar  representing  the  carbo-hydrates  and 
diffusible  substances  like  alcohol,  and  the  extractives  of  meat, 
which  form  an  important  part  of  most  thin  soui:)S  and  of  beef-tea, 
are  undoubtedly  absorbed.  Water  is  very  sparingly  taken  up  by 
the  stomach.  It  is  in  the  small  intestine  that  absorption  reaches  its 
height.  The  mucous  membrane  of  this  tube  offers  an  immense 
surface,  nniltiplied  as  it  is  by  the  valvul?e  conniventes,  and  studded 
with  innumerable  villi.  Here  the  whole  of  the  fat,  much  sugar, 
proteose  and  peptone,  or  rather  the  products  of  the  further  action 
of  the  ferments  of  the  intestine  on  these  derivatives  of  the  native 
proteins,  and  certain  constituents  of  the  bile  are  taken  in.  In  the 
large  intestine,  as  has  been  already  said,  water  and  soluble  salts  are 
chiefly  absorbed. 

\\'hat  now  is  the  mechanism  by  which  these  various  products  are 
taken  up  from  the  digestive  tube,  and  what  paths  do  they  follow  on 
their  way  to  the  tissues  ? 

Theories  of  Absorption. — Not  so  v^ery  long  ago  it  was  supposed  by 
many  that  the  processes  of  diffusion,  osmosis  and  filtration  offered  a 
tolerably  complete  explanation  of  physiological  absorption.  At  that 
time  the  dominant  note  of  physiology  was  an  eager  appeal  to  chemistry 
and  physics  to  '  come  over  and  help  it  ' ;  and  as  new  facts  were  dis- 
covered in  these  sciences  they  were  applied,  with  a  confidence  that  was 
almost  naive,  to  the  problems  of  the  animal  organism.  The  phenomena 
of  the  passage  of  liquids  and  dissolved  solids  through  animal  membranes, 
upon  which  the  work  of  Graham  had  cast  so  much  light,  seemed  to  find 
their  parallel  in  the  absorptive  processes  of  the  alimentary  canal. 
And  when  digestion  was  more  deeply  studied,  facts  appeared  which 
seemed  to  show  that  its  whole  drift  was  to  increase  the  solubility  and 
diffusibility  of  the  constituents  of  the  food.  But  as  time  went  on,  and 
more  was  learnt  of  the  phenomena  of  absorption  and  the  powers  of 
cells,  these  crude  physical  theories  broke  down,  and  discarded  '  vital- 
istic  '  hypotheses  began  once  more  to  arouse  attention.  Then  came 
the  investigations  of  De  Vries,  Van  'T  Hoff,  and  others  in  the  domain 
of  molecular  physics,  which  gave  to  our  notions  of  osmosis  the  precision 
that  was  wanted  before  its  relation  to  many  physiological  processes 
could  be  profitably  discussed.  At  the  present  time  it  must  be  admitted 
that  we  possess  no  full  explanation  of  absorption,  none  which  is  much 
more  tnan  a  confession  of  ignorance,  and  does  not  itself  need  to  be 
explained.  Yet  some  progress  has  been  made  at  least  in  defining  the 
boundary  between  what  is  clearly  known  and  what  is  still  dark,  and 
in  showing  that  familiar  physical  processes  are  not  without  influence. 
Some  physiologists,  impressed  with  the  vast  progress  of  physics  and 
chemistry,  believe  that  it  will  eventually  become  possible  to  explain 
on  mechanical  and  chemical  principles  all  the  peculiar  phenomena  which 
we  observe  in  the  passage  of  substances  through  the  walls  of  the  ali- 
mentary canal.  As  an  aid  to  the  framing  of  practical  working  hypo- 
theses this  attitude  has  everything  in  its  favour.  Others,  taking 
account  of  the  number  and  nature  of  these  peculiarities,  oppressed  with 
the  perennial  paradox  of  vital  action,  incline  to  the  less  sanguine  view, 

28 


434  ABSORPTION 

that  after  all  physical  explanations  have  been  exhausted,  the  real  secret  of 
the  cell  will  still' lurk  in  some  ultimate  '  vital '  property  of  structure  or  of 
function  and  still  elude  our  search.  The  only  sense  in  which  thisattitude 
can  be  said  to  be  a  useful  one  is  that  it  presents  a  standing  protest  against 
the  acceptance  of  superficial '  physical '  explanations  merely  because  they 
are  physical.  Both  the  optimists  and  the  pessimists,  the  adherents 
of  the  physical  and  the  adherents  of  the  vitalistic  hypothesis,  liave. 
unfortunately,  as  a  rule  taken  up  an  extreme  position,  as  if  their  theories 
were  mutually  exclusive.  They  agree,  however,  in  adnaitting  that  the 
phenomena  of  absorption  are  essentially  connected  with  the  cells  that 
line  the  alimentar\-  canal,  and  not  with  any  more  or  less  inert  '  cement  ' 
substance  between  them.  But  the  one  school  must  confess  what  the  other 
proclaims,  that  while  the  processes  carried  on  in  these  cells  are  definite, 
well  ordered,  and  evidently  guided  by  laws,  these  laws  have  as  yet 
for  the  most  part  denied  themselves  to  the  modem  physiologist,  with 
chemistry-  in  one  hand  and  physics  in  the  other,  as  they  denied  them- 
selves to  his  predecessor,  equipped  only  with  his  scalpel,  his  sharp  eyes, 
and  his  mother-wit.  So  that  in  the  present  state  of  our  knowledge  all 
we  can  really  say  is  that,  while  absorption  is  certainly  aided  by  physical 
processes,  like  osmosis  and  diffusion,  possibly  by  physical  processes 
like  imbibition,  and  is  verj' likely  not  unrelated  to  the  molecular  proper- 
ties of  surfaces  (surface  tension,  adsorption),  it  is  at  bottom  the  work 
of  cells  with  a  selective  permeability  which  we  do  not  fully  understand, 
or  at  least  which  we  cannot  as  yet  ex:!  in  in  terms  of  known  physical 
processes  acting  through  a  membrane  of  known  physico-chemical 
structure. 

Thus,  dissolved  substances  pass  with  equal  ease  in  either  direc- 
tion through  an  ordinary  diffusion  membrane,  but  in  general  they 
pass,  with  the  water  in  which  they  are  dissolved,  more  readily  out 
of  the  intestine  than  into  it.  This  normal  direction  of  the  stream 
is  still  maintained  for  a  considerable  time  after  stoppage  of  the 
circulation,  provided  that  the  intestine  is  kept  in  good  condition — 
for  example,  by  being  suspended  in  well-oxygenated  blood.  Water 
or  solutions  of  sodium  chloride  or  sugar  disappear  from  the  lumen. 
And  this  is  not  due  to  mere  imbibition  by  the  intestinal  wall,  but 
the  liquid  is  actually  transported  across  it.  The  theory  that  liquids 
might  be  taken  up  from  the  gut  by  imbibition,  and  the  water  then 
mechanically  removed  by  the  blood  flowing  on  the  other  side  of  the 
imbibing  cells,  is  incompatible  with  this  experiment  (Cohnheim). 
Nor  is  it  necessary  that  differences  of  concentration  of  the  dissolved 
substances  on  the  two  sides  of  the  absorbing  intestinal  membrane, 
which  would  permit  osmosis  and  diffusion  to  go  on,  should  exist. 
\\'hen  the  excised  intestine  of  a  holothurian  was  filled  with  sea- 
water  and  suspended  in  the  same  sea-water,  its  contents  continued 
to  diminish  in  bulk  for  hours  or  entirely  disappeared.  Here  a  liquid 
identical  in  composition  and  concentration  with  the  external  liquid 
was  moved  in  a  definite  direction  across  the  wall  of  the  intestine 
from  the  lumen  to  the  exterior  surface.  In  like  manner,  when  a 
piece  of  intestine  from  a  newly-killed  rabbit  is  stretched  across  a 
vessel  of  salt  solution  so  as  to  divide  i«-  into  two  separate  compart- 
ments, the  solution  continues  for  ^  while  to  leave  the  compartment 


MECHANISM  OF  ABSORPTION  435 

to  which  the  mucosa  is  turned,  and  to  accumulate  in  the  other.    In 
the  cases  mentioned  the  transportation  of  the  liquid  depends  upon 
the  survival  of  those  properties  of  the  mucous  membrane  which 
characterize  its  elements  as  living  cells.     For  when  the  cells  that 
line  the  intestine  are  injured  or  destroyed,   or  subjected  to  the 
action   of  certain   poisons,    absorption   from   it   is   diminished   or 
abolished.     In  the  dead  intestine  the  characteristic  set  of  the  tide 
out  of  the  lumen  across  the  mucosa  can  no  longer  be  observed.     It 
must  be  remarked  further,  in  this  connection,  that  in  its  normal  state 
the  mucous  membrane  does  not  take  up  indiscriminately  all  kinds 
of  diffusible  substances,  or  absorb  those  which  it  does  take  up  in 
the  direct  ratio  of  their  diffusibility.     Nor  does  it  reject  everytliing 
which  does  not  diffuse.     Albumin,   for  example,  which  does  not 
pass  through  dead  animal  membranes,  is  to  a  certain  extent  taken 
up  from  a  loop  of  intestine  without  change.     Cane-sugar  (after 
inversion)    and   dextrose   are   absorbed   more   rapidly  than   their 
velocity  of  diffusion  would  indicate,  when  compared  with  inorganic 
salts.     Glauber's  salt  diffuses  in  water  fifteen  times  as  fast  as  cane- 
sugar,  but  cane-sugar  is  absorbed  from  the  intestines  ten  times  faster 
than  Glauber's  salt.     The  velocity  of  absorption  is  different  even 
for  simple  stereoisomeric  sugars — i.e.,  sugars  whose  molecule,  with 
the  same  number  of  atoms  combined  in  the  same  way,  has  a  dif- 
ferent form  (Nagano).     Nor  is  there  any  clear  relation  between  the 
rate  of  absorption  of  the  various  sugars  and  their  osmotic  pressure. 
Dextrose  and  cane-sugar  are  always  absorbed  in  greater  amount 
than  lactose  from  solutions  of  the  same  osmotic  pressure.     Indeed, 
as  we  shall  see,  lactose  is  practically  not  taken  up  at  all  as  such 
(p.  445),  and  in  concentrated  solutions  may  even  cause  a  reversal 
of  the  normal  movement  of  water,  and  act  as  a  purgative.     Even  the 
water,  organic  and  inorganic  solids  of  the  serum  of  an  animal,  are 
absorbed  from  a  loop  of  its  intestine  when  the  blood-pressure  in  the 
capillaries  of  the  intestinal  wall  is  considerably  greater  than  the 
pressure  in  the  cavity  of  the  gut.     Since  the  serum  in  the  intestine 
and  the  plasma  in  the  capillaries  must  be  isotonic,  and  practically 
identical  in  chemical  composition,  the  absorption  cannot  be  due 
to  ordinary  osmosis  or  diffusion.     Nor  can  it  be  due  to  filtration, 
since  the  slope  of  pressure  is  from  the  capillaries  to  the  lumen  of 
the  gut  (Reid).     It  is  therefore  extremely  difficult  to  reconcile  this 
experiment  with  any  purely  physical  theory  of  absorption.     The 
same  investigator,  summing  up  the  result  of  careful  experiments  on 
the  absorption  of  weak  solutions  of  glucose,  concludes  that,  '  with 
the  intestinal  membrane  as  normal  as  the  experimental  procedure 
will  permit,  phenomena  present  themselves  which  are  as  distinctly 
opposed   to   a    simple    physical   explanation    as  those   previously 
studied  in  the  absorption  of  serum.' 
There  is  also  evidence  that  even  during  the  absorption  of  fiquids 


436  ABSORPTION 

which  undergo  no  chemical  changes  in  the  gut — e.g.,  salt  solutions 
of  different  kinds  and  different  concentrations — chemical  energy 
must  be  transformed,  and  on  no  mean  scale,  in  the  intestinal 
mucosa,  for  the  consumption  of  oxygen  and  the  production  of 
carbon  dioxide  by  the  intestine  is  markedly  increased  (Brodie  and 
Vogt). 

It  may  be  taken,  then,  as  quite  certain  that  in  absorption  from 
the  ahmentary  canal  an  essential  factor  is  the  activity  of  the  hving 
cells  of  the  mucosa,  which,  in  some  way  at  present  unknown,  main- 
tain the  '  set  of  the  tide  '  from  the  lumen  to  the  bloodvessels  (or 
lymph  spaces),  whether  the  slope  of  concentration  of  the  dissolved 
substances  favours  or  opposes  it,  or  when  the  concentration  is  the 
same  on  both  sides  of  the  membrane.  It  is  even  probable  that  this 
action  of  the  cells  is  much  the  most  important  of  all  the  factors 
involved.  It  would  be  highly  misleading,  however,  to  assume  that, 
because  this  is  so,  other  factors — osmosis,  diffusion,  possibly  even 
filtration  due  to  differences  of  pressure  caused  by  the  intestinal 
movements  or  the  contractions  of  the  muscular  fibres  of  the  villi 
(p.  443) — are  of  necessity  negligible.  On  the  contrary,  these  other 
factors  cannot  be  adequately  taken  account  of,  nor  can  there  be 
any  possibility  of  assigning  to  them  their  proper  value  until  it  is 
recognized  that  their  influence  in  absorption  from  the  digestive 
tract  is  never  under  ordinary  conditions  expressed  as  a  simple  and 
uncomplicated  effect,  such  as  may  be  observed  in  experiments  with 
dead  membranes,  but,  on  the  contrary,  is  constantly  overlaid, 
thwarted,  or  totally  reversed,  by  the  special  action  of  the  cells. 
For  this  reason  the  discussion  of  the  mechanism  of  absorption  under 
the  time-honoured  captions  of  '  mechanical  or  physical  theory  ' 
versus  '  physiological  or  vital  theory,'  as  if  the  process  must  of 
necessity  be  purely  '  physical '  or  purely  '  vital,'  has  lost  interest. 
It  may  be  confidently  assumed,  indeed,  that  just  because  the 
physiological  factor  is  so  dominant,  the  famiHar  physical  forces 
must  often  appear  to  exert  a  smaller  influence  than  is  really  the 
case,  and  that,  could  we  disentangle  the  currents  which  they  create 
and  sustain  from  that  steady  drift  of  material  out  of  the  lumen  of 
the  gut  maintained  at  the  expense  of  its  chemical  energy  by  the 
still  unknown  machinery  of  the  cells,  we  should  be  impressed  with 
the  magnitude  rather  than  the  insignificance  of  their  total  effect. 

The  following  attempt  by  Hober  to  analyze  on  these  lines  an  old 
experiment  of  Heidenhain,  which  the  latter  observer  had  interpreted 
as  showing  that  diffusion  and  osmosis  play  no  essential  part  in  absorp- 
tion from  the  alimentary  canal,  is  of  interest  in  this  connection.  A 
loop  of  small  intestine  was  tied  of!  at  both  ends,  but  its  circulation  was 
not  otherwise  interfered  with.  Solutions  of  sodium  chloride  of  dif- 
ferent strengths  were  introduced  into  the  loop,  and  in  each  observation 
after  fifteen  minutes  the  contents  of  the  loop  were  recovered  and 
analyzed  for  the  chloride. 


MECHANISM  OF  ABSORPTION 


437 


Introduced. 

Recovered, 

C.C. 

Percentage  of 
NaCl. 

Total  NaCl  in 
(iraiiiines. 

C.C. 

Percentage  of 
NaCl. 

Total  NaCl  in 
Grammes. 

I20 

I20 

120 

0-30 

0-50 
I -00 
1-46 

0-36 
0-60 
I-I7 

18 
35 

75 
109 

0-60 
0-66 
0-90 
1-20 

0-108 
0-230 
0-670 
I-3IO 

Here  it  is  seen  that,  from  the  markedly  hypotonic  solutions  of  the 
first  two  observations,  sodium  chloride  was  absorbed,  of  course,  along 
with  much  water.  But  from  the  strongly  hypertonic  solution  of  the 
last  observation  some  water  was  also  taken  up,  instead  of  water  passing 
into  it  from  the  blood.  The  suggested  explanation  of  these  and  other 
data  yielded  by  the  experiment  is  that  an  osmotic  stream  of  water  out 
of  the  loop  into  the  blood  is  established  on  introduction  of  the  hypo- 
tonic solutions,  which  raises  their  percentage  of  salt,  while  in  the  case  of 
the  hypertonic  solution  a  diffusion  stream  of  sodium  chloride  is  estab- 
lished in  the  same  direction,  and  its  salt  content  falls.  The  volume  of 
the  hypotonic  solutions  in  the  loop  rapidly  diminishes  because  the 
osmotic  current  conspires  with  the  normal  '  physiological  '  drift  from 
the  lumen  outwards.  In  this  drift  both  salt  and  water  are  involved, 
as  if  the  cells  were  filters  which  maintained  through  expenditure  of 
their  own  energy  a  slope  of  hydro.static  pressure  from  free  surface  to 
depth.  The  hypertonic  solution  diminishes  only  slowly  in  bulk,  be- 
cause the  '  physiological  '  current  out  of  the  lumen  is  opposed  by  the 
osmotic  stream  of  water  into  the  lumen.  Nevertheless,  even  the  hyper- 
tonic solution  is  gradually  absorbed,  because  the  pull  of  the  cells — the 
suction,  if  it  may  be  so  expressed,  of  the  cellular  pump — is  powerful 
enough  to  overcome  the  osmotic  current  and  to  force  water  up  the 
slope  mto  the  blood  or  into  the  tissue  liquid,  whose  osmotic  pressure  is 
not  much  more  than  half  that  of  the  solution. 

Permeability  of  the  Intestinal  Epithelium  and  Lipoid-Solubility 
of  Absorbed  Substances. — If  the  cells  of  the  intestinal  mucosa  are 
to  move  materials  out  of  the  lumen  of  the  gut,  it  is  obvious  that 
these  materials  must  first  be  able  to  enter  the  cells.  The  ease  or 
difficulty  with  which  different  substances  are  absorbed  may  there- 
fore depend  upon  the  degree  in  which  the  cells  are  permeable  for 
them.  The  question  of  the  factors  on  which  the  permeabiUty  of 
cells  depends  has  already  been  discussed  to  some  extent  in  the  case 
of  the  coloured  blood-corpuscles.  A  famous  theory  attributes  the 
degree  of  permeability  of  erythrocytes  and  many  other  animal  and 
plant  cells  to  given  substances  to  the  degree  of  the  solubility  of 
these  substances  in  the  lipoids  which  are  supposed  to  form  the 
essential  constituents  in  the  outer  layer  or  envelope  of  cells  (Overton) 
Substances  which  are  readily  soluble  in  lipoids  are  supposed  to  gain 
an  easy  entrance  by  going  into  solution  in  the  envelope  ;  those  which 
are  insoluble  in  lipoids  are  checked  at  the  boundary.  Attempts 
have  been  made  to  apply  this  theory  to  the  explanation  of  selective 


438  ABSORPTION 

absorption  by  the  intestine,  but  without  much  success.  The  very 
fact  that  the  theory  is  held  to  apply  to  practically  any  cell  greatly 
circumscribes  at  the  outset  its  power  of  dealing  with  cells  like  those 
hning  the  intestine,  which  are  adapted  to  absorb  nutrient  materials 
for  all  the  body,  and  must  necessarily  differ  in  their  permeability 
from  cells  adapted  for  some  hmited  function  involving  only  a 
limited  and  specialized  nutritive  exchange.  Thus  sodium  chloride 
practically  does  not  penetrate  the  red  blood-corpuscles,  the  muscle 
fibres,  and  many  other  tissue  elements.  It  is  a  lipoid-insoluble  sub- 
stance, and  the  lipoid  theory  says  that  this  is  the  reason  why  it 
penetrates  these  cells  with  such  difficulty.  But  sodium  chloride 
must  and  does  penetrate  the  intestinal  mucosa,  and  with  consider- 
able ease,  in  order  that  the  body,  especially  its  extracellular  liquids, 
may  obtain  a  sufficient  supply  of  this  indispensable  material.  It  is 
still  a  lipoid-insoluble  substance,  and  pays  no  heed  to  the  lipoid 
theory  at  all.  It  is  perfectly  true  that  some  substances — e.g.,  ethyl 
alcohol — which  are  much  more  soluble  in  lipoids  than  sodium 
chloride,  are  also  even  more  readily  absorbed  from  the  intestine. 
It  has  been  stated  also  that,  as  regards  the  velocity  of  their  absorp- 
tion, the  three  alcohols,  glycerin,  erythrite,  and  mannite,  are  related 
to  each  other  in  the  Same  way  as  in  regard  to  their  lipoid-solubility. 
There  is,  of  course,  some  reason  for  this,  and  also  some  reason  why 
ethyl  alcohol  is  taken  up  more  easily  than  salt,  but  we  do  not  know 
that  it  has  anything  to  do  with  Upoid-solubility.  If  there  is  a 
hpoid  layer  at  the  free  ends  of  the  cells  covering  the  vilh,  it  is  very 
possible  that  a  substance  soluble  in  Hpoids  may  be  able  to  enter  cells 
which  would  otherwise  have  denied  it  entrance.  It  may  even  inflict 
temporary  or  permanent  injury  on  the  cells  in  doing  so,  and  may 
thus  be  taken  up  in  greater  amount  than  by  normal  cells,  and  this 
possibility  has  to  be  reckoned  with  in  giving  a  physiological  value 
to  experiments  with  materials  essentially  foreign  to  the  intestine, 
and  to  which  it  cannot  have  developed  any  adequate  adaptation. 
For  the  essential  food  materials  it  is  quite  certain  that,  apart  from 
any  general  relations  of  cell  envelope  and  environing  liquids  which 
are  common  to  the  intestinal  and  to  other  cells,  special  relations  of 
an  adaptive  nature  have  been  developed  between  the  intestinal  cells 
and  the  very  special  hquids,  elsewhere  unknown  in  the  body,  with 
which  they  come  in  contact  in  the  lumen  of  the  gut.  It  is  unlikely 
that  the  mucosa  has  developed  a  special  adaptation  for  lipoid- 
solublc  food  materials;  it  must  have  developed  an  adaptation  for 
such  food  materials,  lipoid-soluble  or  not,  as  have  been  offered  to 
it  through  (ountless  ages,  and  as  are  necessary  for  the  nutrition  of 
the  organism. 

But  if  it  be  true  that  the  action  of  the  columnar  epithelium  of  the 
intestinal  mucous  membrane  in  the  absorption  of  the  food  is  in  the 
main  a  process  of  selective  secretion  such  as  is  found  in  glandular 


MECHASISM  OF  ABSORPTION  435 

organs,  an  action  which  wc  may  perhaps  describe  as  making  use 
of  jMiroly  physical  processes,  hut  not  mastered  by  tliem,  the  possi- 
bihty  must  be  admitted  that  in  the  cells  of  endothelial  type  which 
line  the  serous  cavities,  the  lymphatics,  the  bloodvessels,  the  alveoli 
of  the  lungs,  and  the  Bowman's  capsules  of  the  kidney  (p.  489),  the 
element  of  secretion  may  be  less  marked,  and  more  overshadowed 
by  the  physical  factors.  And  it  may  very  plausibly  be  urged  that 
changes  of  considerable  physiological  complexity  can  only  be 
wrought  on  substances  that  have  to  pass  through  a  cell  of  con- 
siderable depth,  while  a  mere  film  of  protoplasm  suffices  for,  and 
indeed  favours,  mechanical  filtration  and  diffusion.  We  have 
already  seen  (p.  26i),  in  the  case  of  the  lungs,  that  whatever  the 
complete  explanation  may  be  of  the  gaseous  exchange  which  takes 
place  through  the  alveolar  membrane,  physical  diffusion  undoubtedly 
plays  an  important  part.  We  shall  see,  too  (p.  500),  that  in  the  case 
of  the  kidney  the  endothelium  of  the  Bowman's  capsule,  although 
by  no  means  devoid  of  selective  power,  does  seem  to  have  allotted  to 
it  a  simpler  task  than  falls  to  the  share  of  the  '  rodded  '  epithelium. 

Absorption  from  the  Peritoneal  Cavity. — Further,  it  has  been  stated 
that  interchange  between  blood-serum,  circulated  artificially  in  the 
vessels  of  dogs  and  rabbits  which  have  been  dead  for  hours,  and 
liquids  introduced  into  the  peritoneal  cavity,  is  essentiall}-  the  same 
as  in  the  living  animal,  and  can  be  explained  on  purely  physical 
principles  (Hamburger).  But  there  is  one  experiment,  at  any  rate, 
which  is  certainly  difficult  so  to  explain — viz.,  the  absorption  from 
the  peritoneal  ca\'ity  of  sodium  chloride  solution  isotonic  with  the 
blood-serum,  an  absorption  which  goes  on  with  considerable 
rapidity.  Starling  has  supposed  that  this  is  due  to  the  circum- 
stance that  the  proteins  of  the  serum  exert  osmotic  pressure,  the 
peritoneal  membrane  being  almost  or  altogether  impermeable  for 
them  in  comparison  to  its  permeability  for  the  salt  solutions.  In 
consequence,  water  passes  into  the  bloodvessels  from  the  peritoneal 
cavity.  The  solution  thus  becomes  more  concentrated  as  regards 
sodium  chloride,  some  of  which  accordingly  enters  the  blood 
by  diffusion,  and  so  on.  But  even  isotonic  serum  is  absorbed 
from  the  peritoneal  ca\nty,  and  it  seems  to  savour  of  special  pleading 
to  suggest,  as  has  been  done,  that  this  takes  place  through  the 
lymphatics,  and  not  at  all  through  the  bloodvessels. 

Up  to  a  certain  point  an  increase  in  the  intraperitoneal  pressure 
favours  absorption,  but  beyond  this  it  hinders  it  by  interfering  with 
the  circulation.  The  removal  of  a  portion  of  the  fluid  in  this  con- 
dition facilitates  the  absorption  of  the  rest — a  fact  which  has  long 
been  applied  in  the  operation  of  tapping.  Ligation  of  the  thoracic 
duct  has  little  effect  on  the  fate  of  liquids  injected  into  serous 
cavities,  since  the  bloodvessels  play  the  chief  part  in  their  absorp- 
tion, just  as  strjxhnine,  when  injected  under  the   skin — i  c,  into 


uo 


ABSORPTION 


the  lymph  spaces  of  areolar  tissue — is  taken  up  by  the  blood  and 
does  not  appear  in  the  lymph. 

But  even  if  we  admit  that  substances  can  pass,  by  physical  pro- 
cesses alone,  from  serous  cavities  into  the  blood,  and  from  the  blood 
into  serous  cavities,  this  has  little  bearing  upon  the  question  of 
intestinal  absorption.  For  we  can  hardly  put  anything  into  the 
peritoneal  cavity  which  is  not  foreign  to  it.  It  was  never  intended 
to  come  into  contact  with  the  hundred  and  one  solutions,  extracts, 
suspensions,  and  what  not,  which  the  industrious  experimenter  has 
offered  to  its  unsophisticated  endothelium.  It  cannot  possibly  have 
developed  any  high  degree  of  '  selective  '  power.  In  the  intestine 
everything  is  different.  The  mucosa  is  adapted  to  come  into 
contact  with  an  immense  variety  of  materials,  all  kinds  of  food- 
substances  mingled  with  many  kinds  of  refuse,  the  products  of 
the  action  of  numerous  digestive  ferments,  and  of  a  \agorous  and 
varied  bacterial  flora.  All  these  it  has  to  sift  and  try.  It  cannot  fail 
to  have  properties  which  suggest  a  severe  and  searching  selection. 

The  difference  between  a  serous  cavity  and  the  intestine  is  well 
illustrated  by  the  following  experiment,  in  which  the  clianges  in  the 
composition  of  a  hypotonic  (3  per  cent.)  solution  of  dextrose  introduced 
into  the  peritoneal  sac  and  into  a  loop  of  intestine  respectively  were 
compared  (Cohnheim). 


Introduced. 

After           1                              Recovered. 

1 

Peritoneum  - 
Intestine  -     - 

50  c.c. 

44    » 

f   19-5  C.C,  containing  I  percent. 
90  mins.          dextrose  and  0'55  per  cent. 

1.       XaCl. 

j    19  c.c,  containing  3-8  per  cent. 
25      „      -        dextrose  and  0-04  per  cent. 

1'      NaCl. 

J 

Here  the  water  and  sugar  are  both  taken  up  from  the  intestine  and 
the  peritoneal  cavity;  but  while  the  sugar  concentration  in  the  serous 
sac  falls  markedly,  as  ought  to  be  the  case  if  the  sugar  is  diffusing  into 
the  blood  along  the  slope  of  concentration,  the  percentage  of  sugar  in 
the  intestine  actually  increases.  Still  more  striking  is  the  fact  that 
sodium  chloride  accumulates  in  the  peritoneal  liquid  in  a  concentration 
obviously  tending  to  equality  with  that  of  the  blood,  as  would  happen 
if  the  peritoneal  lining  were  a  dead  diffusion  membrane.  On  the  other 
hand,  practically  no  sodium  chloride  passes  into  the  lumen  of  the  gut. 

Closely  connected  with  the  question  of  absorption  from  and 
secretion  (or  transudation)  into  the  serous  cavities  is  the  question 
of  the  factors  concerned  in  the  formation  of  the  lymph  (which  will 
be  considered  in  the  next  chapter),  even  although  recent  researches 
throw  grave  doubt  on  the  common  view  that  these  sacs  are  merely 
expanded  lymph  spaces,  and  indicate  that  the  liquid  found  in  them 
has  a  different  origin  from  lymph. 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTAACES       44i 


Section  III. — ^Absorption  of  the  Various  Food  Substances. 

Absorption  of  Fat — How  the  Fat  gets  into  the  Intestinal  Epithelium. 
— It  has  been  already  mentioned  that  fat  is  split  up  in  the  intestine 
into  the  corresponding  alcohols  (mostly  glycerin)  and  fatty  acids, 
but  it  has  been  a  subject  of  discussion  whether  it  all  undergoes  this 
change  or  only  a  portion  of  it.  The  common  view  has  long  been 
that  the  gi'eater  part  of  the  fat  escapes  decomposition,  and,  after 
emulsification  by  the  soaps  formed  from  the  liberated  fatty  acids, 
is  absorbed  as  neutral  fat  by  the  epithelial  cells  covering  the  villi.  If 
an  animal  is  killed  during  digestion  of  a  fatty  meal,  these  cells  are 
found  to  contain  globules  of  different  sizes,  which  stain  black  with 
osmic  acid,  are  dissolved  out  by  ether,  leaving  vacuoles  in  the  cell 
substance,  and  are  therefore  fat  (Fig.  172).  It  has  always  been 
difficult  to  explain  how  droplets  of 
emulsified  fat  could  get  into  the 
interior  of  the  epithelial  cells,  al- 
though, perhaps,  no  more  difficult 
than  to  explain  the  passage  of  living 
tubercle  bacilli  from  the  contents  of 
the  intestine  into  the  chyle  of  the 
thoracic  duct — a  fact  which  has  been 
clearly  demonstrated  (Ra  venel) .  The 
fat  is  certainly  contained  within  the 
cells,  and  not  between  them.  When 
fat  is  found  in  the  cement  sub- 
stance between  the  cells,  it  has  been 
mechanically  squeezed  out  of  them 
by  the  shrinking  of  the  villi  in 
preparation.  This  difficulty  is  obviated  if  we  suppose  that  the 
whole  of  the  fat  is  spht  up  in  the  intestine,  the  products  being 
absorbed  in  solution,  the  glycerin  as  such,  and  the  fatty  acids  either 
as  soaps  or  in  the  free  state,  or  partly  free  and  partly  saponified. 
If  this  is  the  true  theory — and  the  evidence  of  its  truth  has  of  late 
years  been  continually  growing — neutral  fat  must  again  be  built 
up  in  the  epithelial  cells  from  the  absorbed  glycerin  and  the  fatty 
acids  or  soaps.  Now,  it  has  been  shown  that  when  an  animal  is  fed 
with  fatty  acids  they  are  not  only  absorbed,  but  appear  as  neutral 
fats  in  the  chyle  of  the  thoracic  duct,  having  combined  with  glycerin 
in  the  intestinal  wall;  and  the  epithelial  cells  contain  globules  of 
fat,  just  as  they  do  when  the  animal  is  fed  with  neutral  fat.  Further, 
it  is  known  that  fat-splitting  goes  on  in  the  alimentary  canal  to  a 
much  greater  extent  than  would  be  necessary  merely  for  the  forma- 
tion of  a  quantity  of  soap  sufficient  to  emulsify  the  whole  of  the  fat 
in  the  food.     Indeed,  at  certain  stages  of  digestion  most  of  the 


Fig.  172. — Mucous  Membrane  of 
Frog's  Intestine  during  Absorp- 
tion of  Fat  (Schiifer).  ep,  epithe- 
lial cells;  str,  striated  border; 
C,  lymph  corpuscles;  /,  lacteal. 


442  ABSORPTION 

fatty  material,  both  in  the  small  and  large  intestine,  has  been  found 
to  consist  of  fatty  acids.  The  reversibility  of  tlie  reaction  under 
the  influence  of  lipase,  whicli  has  already  been  alluded  to,  does  not 
enter  into  the  question  so  far  as  fat-splitting  in  the  intestine  is  con- 
cerned, for  the  products  of  the  reaction  can  be  absorbed  as  quickly 
as  they  are  formed.  To  clinch  the  matter,  it  has  been  proved  that 
when  mixtures  of  paraffin  and  fat,  which  can  be  emulsified  in  a 
watery  solution  of  sodium  carbonate,  are  eaten,  the  paraffin  is  com- 
pletely excreted  with  the  faeces,  while  the  greater  part  of  the  fat  is 
absorbed.  And  fatty  substances  which  are  not  easily  split  up  and 
saponified  (for  example,  lanolin,  the  fat  of  sheep's  wool,  a  mixture 
of  compounds  of  fatty  acids  with  isocholesterin,  a  substance  closely 
related  to  cholesterin  and  allied  bodies)  are  not  absorbed  even  when 
they  are  easily  emulsified.  Even  fats  with  a  melting-point  far 
above  the  temperature  of  the  body  can  be  absorbed  after  being  split 
up.  The  palmitate  of  cetyl  alcohol,  the  chief  constituent  of  sper- 
maceti, melting  at  53°  C,  was  absorbed  to  the  extent  of  15  per 
cent.,  85  per  cent,  being  excreted  in  the  faeces.  It  appeared  as 
palmitin  in  the  chyle  of  a  human  being  flowing  from  a  fistula,  the 
palmitic  acid  having  been  absorbed  as  such,  or  as  a  sodium  soap,  and 
having  then  united  with  glycerin  to  form  the  neutral  fat,  palmitin. 

Some  observers  have  endeavoured  to  show  that  the  fat  is  absorbed 
without  change  by  introducing  into  the  intestine  fat  stained  with 
dyes,  such  as  alkanna  red  or  Sudan  III.,  which  are  insoluble  in 
water.  The  stained  fat  was  found  in  the  epithelial  cells  of  the  villi, 
in  the  lacteals,  and,  in  the  case  of  a  patient  suffering  from  chyluria, 
in  the  urine.  But  this  evidence  is  not  conclusive,  for  it  has  been 
shown  that  the  pigments  might  easily  have  been  absorbed  after 
decomposition  of  the  fat,  since,  although  insoluble  in  water,  they  are 
soluble  in  fatty  acids,  and  therefore  to  some  extent  in  the  intestinal 
contents,  and  readily  pass  into  the  lymph. 

As  already  pointed  out,  the  bile  plays  an  important  part  in  the 
solution  of  the  fatty  acids,  which  may  form  loose  compounds  with 
the  amide  group  of  the  bile-acids.  In  these  loose  combinations, 
soluble  in  water,  the  fatty  acids  can  be  absorbed  from  the  intestinal 
contents  (Pfliiger).  In  whatever  way  the  fat  which  can  be  seen 
in  the  epithelial  cells  during  absorption  of  fat  gets  into  them,  it 
must  be  carefully  noted  that  there  is  no  quantitative  proof  that  it 
represents  all  or  even  the  greater  part  of  the  absorbed  fat.  So  far 
as  microscopic  observations  go,  much  of  the  fat  may  pass  through 
the  mucosa  in  the  form  of  soluble  decomposition  products  without 
appearing  in  ]xirticulate  form  in  the  epithi'lium. 

How  the  Fat  gets  out  of  the  Intestinal  Epithelium. — Leucocytes 
have  been  asserted  to  be  active  agents  in  the  absorption  of  fat. 
They  have  been  described  as  pushing  their  way  between  the 
epitheUal  cells,  fishing,  as  it  were,  for  fatty  particles  in  the  juices 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES        443 

of  the  intestine,  and  then  travelling  back  to  discharge  their  cargo 
into  the  lymph.  This  view,  however,  is  erroneous.  But,  although 
the  leucocytes  do  not  aid  in  the  absorption  of  fat  from  the  intestine, 
they  may  take  up  a  certain  amount  of  it  from  the  epithelial  cells, 
and  convey  it  through  the  spaces  of  the  network  of  adenoid  tissue 
that  occupies  the  interior  of  the  villus,  to  discharge  it  into  the 
central  lacteal,  where  it  mingles  with  the  lymph  and  forms  the  so- 
called  molecular  basis  of  the  chyle.  It  has  been  supposed  that  a 
part  of  the  fat  ma}^  reach  the  lacteal  in  another  way.  The  con- 
traction of  the  smooth  muscular  fibres  of  the  villus  and  the  peristaltic 
movements  of  the  intestinal  walls,  which  alter  the  shape  of  the 
villi,  alter  as  well  the  capacity  of  the  lacteal  chamber,  and  so 
alternately  fill  it  from  the  lymph  of  the  adenoid  reticulum,  and 
empty  it  into  the  lymphatic  vessel  with  which  it  is  connected.  By 
this  kind  of  pumping  action  the  passage  of  fat  and  other  substances 
into  the  lymphatics  may  be  aided.  There  is,  however,  no  proof 
that  all  the  fat  accumulated  in  the  intestinal  epithelium  leaves 
it  without  further  change.  It  is  quite  as  probable  that  the  lipase 
which  is  known  to  be  contained  in  the  cells  again  hydrolyses  the 
fat,  or  a  portion  of  it,  and  that  the  constituents  then  pass  out  into 
the  lymph,  or  even  in  part  into  the  blood.  In  the  dog  most  of  the 
fat  goes  into  the  lacteals,  and  thence  by  the  general  lymph-stream 
through  the  thoracic  duct  into  the  blood.  And  in  man  the  chyle 
collected  from  a  lymphatic  fistula  contained  a  large  proportion  of 
the  fat  given  in  the  food  (Munk).  But  this  bare  statement  would 
be  misleading  if  we  did  not  add  that  the  fat  taken  in  can  never  be 
entirely  recovered  in  the  chyle  collected  from  the  thoracic  duct. 
A  small  fraction  of  the  deficit  might  be  accounted  for  as  fat  directly 
used  up  for  the  nutrition  of  the  intestinal  wall  itself.  But  even  after 
ligation  of  the  thoracic  and  right  lymphatic  ducts  a  large  proportion 
of  a  meal  of  fat  (32  to  48  per  cent.)  is  absorbed  from  the  intestine, 
obviously  by  the  channel  of  the  bloodvessels,  since  the  fat-content 
of  the  blood  increases  up  to,  it  may  be,  six  times  the  highest  amount 
present  in  the  blood  of  fasting  animals.  The  statement  that  only 
fatty  acids  can  be  absorbed  under  these  conditions  is  erroneous 
(Munk  and  Friedenthal). 

A  dog  normally  absorbs  g  to  21  per  cent,  of  the  fat  in  a  meal  in 
three  to  four  hours;  21  to  46  per  cent,  in  seven  hours;  and  86  per 
cent,  in  eight ieen  hours  (Harley).  After  excision  of  the  pancreas 
the  absorption  of  fat  is  hindered,  though  not  abolished.  More  fat, 
indeed,  can  be  recovered  from  the  intestine  than  is  given  in  the  food. 
This  at  first  sight  paradoxical  result  is  explained  by  the  well-estab- 
lished fact  that  a  certain  amount  of  fat  is  normally  excreted  into 
the  intestine. 

Mechanism  of  Fat  Synthesis  in  the  Intestinal  Mucosa. — As  to  the 
manner  in  which  the  synthesis  of  the  fat  in  the  intestinal  epithelium 


444  ABSORPTION 

is  accomplished,  the  most  fascinating  theory  is  that  wliicli  attributes 
it  to  the  reversed  action  of  Hpase,  possibly  the  very  same  lipase  as 
originally  split  it  up  in  the  intestine.  The  reversibility  of  the  action 
of  various  enzymes  under  changed  conditions,  especially  changes  in 
the  relative  concentration  of  the  bodies  concerned  in  the  reaction, 
has  been  previously  mentioned.  It  has  been  shown,  e.g.,  that  the 
pancreas,  intestinal  mucous  membrane,  lymph  glands,  etc.,  and 
even  cell-free  extracts  of  these  organs  have  the  power  of  synthesizing 
the  ester  ethyl  butyrate  from  butyric  acid  and  ethyl  alcohol 
(P-  338),  as  well  as  the  power  of  decomposing  the  ester  into  the 
fatty  acid  and  the  alcohol.  Moore,  however,  states  that  in  the 
case  of  ordinary  fats  the  synthesis  takes  place  in  the  intestinal  wall 
only  in  situ,  and  while  the  circulation  is  going  on.  In  the  intestinal 
mucosa  the  greater  part  of  the  fatty  acid  is  already  combined  with 
glycerin  as  neutral  fat,  although  considerable  quantities  of  free  fatty 
acid  are  also  present.  In  the  lymph  coming  directly  from  the 
mesenteric  glands  practically  the  whole  of  the  fatty  acids  are  in 
the  form  of  neutral  fat. 

An  additional,  and  in  some  respects  even  more  remarkable,  illus- 
tration of  the  synthesizing  powers  of  the  intestinal  wall  is  the  dis- 
covery of  Munk,  already  referred  to  (p.  441),  that  fatty  acids  given 
by  the  mouth  appear  in  the  lymph  of  the  thoracic  duct  as  neutral 
fats,  having  somewhere  or  other,  in  all  probability  on  their  way 
through  the  epithelium  of  the  gut,  been  combined  with  glycerin. 

Since,  however,  the  amount  of  neutral  fat  recovered  from  the 
thoracic  duct  is  not  equivalent  to  more  than  one-third  of  the  fatty 
acids  given,  it  has  been  suggested  that  this  synthesis  of  fat  is  only 
apparent,  and  that  the  whole  of  the  fat  which  appears  in  the  chyle 
after  a  meal  of  fatty  acids  comes  from  the  fat  excreted  into  the 
intestine  (Frank),  which  is  increased  when  fatty  acids  are  given  by 
the  mouth.  But  the  suggestion  is  more  ingenious  than  the  e\ndence 
advanced  in  its  support  is  convincing.  And,  as  we  have  seen 
(p.  443),  a  part  of  the  deficit  may  be  accounted  for  by  absorption 
directly  into  the  bloodvessels. 

In  concluding  our  review  of  the  absorption  of  fat,  certain  general 
considerations  which  have  a  close  relation  to  the  question  may  be 
alluded  to.  There  is  some  reason  to  think  that  the  lipises  are 
enzymes  less  finely  adjusted  to  minute  differences  in  the  structure 
of  the  fats  on  which  they  act  than  other  digestive  ferments — eg., 
maltase  or  lactase,  to  details  in  the  chemical  structure  of  their 
substrates.  If  this  be  so,  a  very  few  lipases,  or  even  a  single  one. 
may  suffice  to  accomplish  all  the  enzymatic  changes  which  occur 
in  the  fats  both  in  the  lumen  of  the  intestine  and  in  all  the  various 
tissue  cells.  At  the  same  time  the  possible  variation  in  those  decom- 
position products  which  constitute  the  '  building-stones  '  of  the  fats 
is  less  than  in  the  case  of,  say,  the  proteins.     Two  consequences 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       4^5 

follow  as  regards  the  absorption  of  fat:  (i)  Each  cell  may  be  capable 
of  dealing  with  the  original  neutral  fats  of  the  food,  and  of  adapting 
them  to  its  needs  by  decomposing  and  resynthesizing  them  so  far 
as  is  necessary  in  its  own  substance.  In  this  case  it  would  not  be 
necessiiry  for  assimilation  by  the  cells  that  the  fats  should  be  com- 
pletely split  or  even  split  at  all  in  the  alimentary  canal,  however 
important  this  might  be  for  their  absorption  from  its  lumen. 
(2)  If  it  were  necessary  for  absorption  that  decomposition  of  the 
fats  should  take  place  in  the  lumen  of  the  digestive  tube,  the  whole 
of  the  fat,  or  at  any  rate  such  portion  of  it  as  was  not  at  once  needed, 
might  without  disadvantage  for  the  tissues  be  resynthesized  after 
absorption.  It  is  not  difficult  to  see  that  it  might  even  be  advan- 
tageous that  not  only  the  relatively  fixed  reserve  in  the  fat  cells, 
but  also  what  might  be  termed  the  floating  or  circulating  reserve 
constituted  by  the  emulsified  fat  in  the  blood  should  be  in  the 
insoluble  form  of  neutral  fat. 

Absorption  of  Carbo-Hydrates. — Carbo-hydrates  are  normally 
absorbed  from  the  alimentary  canal  only  in  the  form  of  mono- 
saccharides, such  as  dextrose,  levulose  or  fructose,  and  galactose, 
but  especially  dextrose.  These  monosaccharides  are  readily 
formed  from  polysaccharides  like  starch  and  dextrin,  and  the  disac- 
charide  maltose,  which  they  yield  on  digestion  with  amylase,  as 
well  as  from  disaccharides  like  cane-sugar  and  lactose,  by  the  fer- 
ments already  studied.  That,  as  a  matter  of  fact,  the  hydrolysis 
in  the  intestine  must  convert  practically  all  the  carbo-hydrate  into 
monosaccharides  before  absorption,  can  be  shown  in  various  ways. 
The  ferment  lactase,  while  present  in  the  small  intestine  of  all 
young  mammals,  is  regularly  absent  in  some  mammalian  groups 
in  the  adult.  In  other  species,  including  man,  it  is  found  in  some 
adults,  but  not  in  all.  In  birds  and  other  animals  below  the  mam- 
mals, it  has  not  hitherto  been  found  at  any  age.  It  has  been  sur- 
mised that  these  differences  depend  upon  the  presence  or  absence 
of  lactose  (milk)  as  a  regular  constituent  of  the  food.  (But  see 
p.  410.)  If,  now,  lactose  is  introduced  into  a  loop  of  intestine  in  an 
animal  which  does  not  possess  lactase — e.g.,  an  adult  rabbit — it  is 
not  ajDsorbed,  but  remains  in  the  lumen  till  it  is  at  last  decomposed 
by  bacterial  action.  In  animals  in  which  lactase  is  present  the 
lactose  is  rapidly  absorbed.  Maltose  is  easily  taken  up  from  the 
intestine  because  of  the  action  of  the  ferment  maltase,  which  is  the 
most  widely  spread  of  all  the  inverting  ferments.  The  dextrose  formed 
by  the  maltase  is  so  rapidly  absorbed  that  none,  or  only  traces,  of  it 
can  be  detected  in  the  contents  of  the  intestinal  loop.  But  if  absorp- 
tion be  interfered  with  by  injuring  the  intestine,  maltose  disappears, 
and  the  dextrose  produced  from  it  accumulates  in  the  lumen.  The 
reason  for  the  discrimination  exercised  bj^the  intestinal  mucosa  in 
favour  of  the  monosaccharides  becomes  apparent  when  an  attempt  is 


446  ABSORPTION 

made  to  circumvent  it  by  injecting  the  sugars  parenterally — ie-,  into 
subcutaneous  or  intramuscular  connective  tissue,  into  a  serous  sac, 
or  directly  into  the  blood.  Cane-sugar  and  lactose  so  introduced 
are  excreted  unchanged  in  the  urine.  Dextrose,  levulose,  and 
galactose  are  used  u])  in  the  body,  and  some  maltose  likewise, 
thanks  to  the  presence  of  maltase  in  the  blood  and  tissues.  The  cells 
of  the  body  in  general  will  burn  only  monosaccharides,  and  not  di-  or 
poly-saccharides.  Galactose  and  fructose  are  probably  first  con- 
verted into  dextrose  before  being  utilized  by  the  tissues,  a  change 
which  can  also  be  readily  induced  in  the  test-tube.  Therefore  the 
intestine  admits  the  simple,  but  rejects  the  more  complex  sugars. 
It  is  only  in  the  presence  of  abnormally  great  quantities  or  ab- 
normally great  concentrations  of  the  sugars  which  are  not  directly 
utilizable  that  they  are  to  a  certain  extent  taken  up  unaltered, 
to  be  for  the  most  part  quickly  excreted  as  such  (p.  540).  In  like 
manner  we  have  seen  that  the  native  proteins  can,  so  to  speak, 
force  their  way  by  storm  through  the  intestinal  mucosa  when 
offered  to  it  in  exceptionally  large  a.mount.  The  sugar  absorbed 
from  the  intestine  passes  normally  into  the  rootlets  of  the  portal  vein, 
not  into  the  chyle,  for  no  increase  in  the  quantity  of  that  substance 
in  the  contents  of  the  thoracic  duct  takes  place  during  digestion, 
while  the  sugar  in  the  portal  blood  is  increased  after  a  starchy  meal. 
The  blood  of  the  portal  vein  of  a  dog  in  the  fasting  condition  con- 
tained 0-2  per  cent,  of  dextrose.  During  absorption  of  a  meal  rich 
in  carbo-hydrates  it  contained  as  much  as  0-4  per  cent.  In  the 
lymph  issuing  from  the  thoracic  duct  the  amount  was  the  same  in 
both  conditions — viz.,  o-i6  per  cent.  In  a  case  of  lymph  (chyle) 
fistula  in  a  human  being,  where  almost  all  the  lymph  from  the 
digestive  tract  escaped  through  the  fistula,  out  of  100  grammes  of 
carbo-hydrate  taken  (50  grammes  starch  and  50  grammes  sugar), 
only  ^  gramme,  or  not  i  per  cent,  of  the  sugar  corresponding  to  the 
carbo-hydrates  of  the  food,  could  be  recovered  in  the  chyle.  But 
when  a  large  amount  of  a  dilute  solution  of  sugar  is  introduced  into 
the  intestine,  some  of  it  is  taken  up  by  the  lacteals. 

Absorption  of  Water  and  Salts. — The  main  channel  for  absorption 
of  these  is  the  bloodvessels  of  the  intestine.  As  much  as  3  to  5  litres 
of  water  can  be  absorbed  in  a  day  in  the  intestine  of  a  healthy  man, 
exceptionally  even  6  to  10  litres,  without  the  faeces  altering  their 
normal  consistence.  Absorption  of  the  water  and  dissolved  salts 
may  theoretically  take  place  either  through  the  epithelial  cells  (intra- 
epithelial absorption),  or  between  the  cells  (interepithelial  absorp- 
tion). According  to  Hober,  most  metallic  salts  (silver,  mercury, 
lead,  bismuth,  copper,  manganese,  etc.)  are  absorbed  interepitheli- 
ally,  while  iron  salts  form  an  exception,  and  pass  into  the  epithelial 
cells.  The  distinction  between  interepithelial  and  intra-epithelial 
absorption  does  not  rest  upon  an  absolutely  sure  foundation.     Yet 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES 


447 


it  is  probable  that  everything  whicli  is  usiful  in  the  nutrition  of 
the  body  is  taken  up  by  the  cells,  while  such  substances  as  metaUic 
salts  which  are  foreign  to  the  organism,  and  an;  denied  entrance 
into  the  cells,  may  pass  in  small  amount  between  them,  their  passage 
being  perhaps  associated  with  more  or  less  injury  to  the  interstitial 
substance.  The  vigilant  selection  exercised  by  the  mucosa  is  well 
illustrated  by  the  facts  that,  although  manganese  and  iron  are 
chemically  so  closely  related,  iron,  which  is  necessary  for  the 
formation  of  the  blood-pigment,  is  absorbed  in  immensely  greater 
amount  than  manganese;  and  that  chlorides,  especially  sodium 
chloride,  are  readily  taken  up,  sulphates  with  difficulty.  Iron  is 
absorbed  by  the  bloodvessels,  but  also  to  some  extent  by  the  lacteals. 
From  the  blood  it  is  carried  to  various  organs,  especially  the  spleen 
and  liver.  There  is  reason  to  believe  that  the  eosinophile  leucocytes 
take  some  share  in  its  transportation. 

It  was  supposed  by  Bunge  that  only  organic  compounds  of  iron 
could  be  absorbed,  and  that  the  undoubted  benefit  derived  from 
the  administration  of  inorganic  iron  compounds,  such  zz  ferric 
chloride,  in  chlorosis,  was  due  not  to  their  direct  absorption,  but 
to  their  shielding  the  organic  compounds  from  the  attack  of  the 
sulphuretted  hydrogen  in  the  intestine  (p.  424)-  But  this  theory 
has  been  shown  to  be  inconsistent  with  the  facts.  For  instance, 
after  the  administration  of  salts  of  iron,  the  iron  in  the  blood, 
liver,  spleen,  and  other  organs  increases,  but  there  is  no  accumula- 
tion of  iron  in  the  liver  of  an  animal  to  which  salts  of  manganese 
have  been  given,  although  these  are  equally  decomposed  by  sul- 
phuretted hydrogen. 

Absorption  of  Proteins. — -The  proteins  of  the  food  or  their  digested 
products  also  pass  directly  into  the  blood-capillaries  which  feed 
the  portal  system.  For  it  has  been  shown  that  after  ligature  of 
the  thoracic  duct  protein  substances  are  still  absorbed  from  the 
intestine,  and  the  urea  corresponding  to  their  nitrogen  appears  in 
the  urine.  The  total  nitrogen  in  the  chyle  flowing  from  a  fistula 
of  the  thoracic  duct  in  a  man  was  not  found  to  be  increased  during 
the  digestion  of  protein  food.  The  quantity  of  chyle  escaping  in  a 
given  time  was  also  unaffected,  whereas  during  the  digestion  of  fats 
it  was  greatly  augmented  (-Munk). 

Although  a  certain  amount  of  egg-albumin,  serum-albumin,  alkali- 
albumin,  and  other  native  or  slightly  altered  protein  substances 
can  be  absorbed  as  such  by  the  small,  and  even  by  the  large,  in- 
testine, there  is  no  evidence  that,  under  ordinary  conditions,  this 
mode  of  absorption  is  of  any  practical  importance  in  nutrition, 
although  in  another  relation  it  may  possess  a  certain  interest  (p.  32), 
For  when  native  proteins,  with  the  possible  exception  of  the 
serum  proteins  from  an  animal  of  the  same  species,  are  introduced 
'  parenterally,'  so  that  they  do  not  reach  the  tissues  by  way  of 


448  ABSORPTION 

the  alimentary  canal,  they  behave  in  a  very  different  manner  from 
the  same  proteins  when  given  by  the  mouth.  One  notable  differ- 
ence is  that  the  parenterally  administered  proteins  give  rise  in 
general  to  the  formation  of  antiboches — e.g.,  specific  precipitins 
(p.  31).  This  is  not  the  case  when  they  are  administered  per  as, 
unless,  like  raw  egg-white,  which,  as  already  mentioned  (p.  404), 
evokes  no  secretion  of  gastric  juice,  they  remain  long  undigested 
in  the  alimentary  canal,  when  an  amount  sufficient  to  cause  the 
production  of  precipitins  may  eventually  be  absorbed  unaltered. 
Tills  has  also  been  shown  by  means  of  the  anaphylactic  reaction. 
Secondly,  they  are  not,  as  a  rule,  utilized  in  the  metabolism  of  the 
body,  or  are  utilized  very  incompletely.  Egg-albumin,  for  instance, 
when  injected  into  the  blood,  is  excreted  in  the  urine.  It  has  been 
previously  pointed  out  that  the  various  proteins  differ  remarkably 
not  so  much  in  the  kinds  as  in  the  relative  quantities  of  the  amino- 
and  diamino-acids  which  can  be  obtained  from  them  (p.  2).  This 
is  unquestionably  one  important  reason  why  the  food  proteins  are — 
for  the  most  part,  at  any  rate — so  thoroughly  hydrolysed  before 
absorption.  Another  may  be  that  it  is  easier  for  the  intestine  to 
take  up  the  small  molecules  of  the  decomposition  products  than 
the  large  colloid  aggregates  of  the  original  protein  solutions. 

So  far  as  the  first  reason  is  concerned,  the  degree  of  decomposi- 
tion need  not  be  the  same  for  all  the  food  proteins,  although  all 
must  be  decomposed,  for  even  among  the  proteins  the  products  of 
whose  hydrolysis  do  not  exhibit  qualitative  differences,  no  two 
have  hitherto  been  discovered  which  show  the  same  quantitativ.^ 
relations  among  the  '  building-stones. '  A  new  house  has  to  be  built 
fiom  the  materials  of  an  old  one.  How  far  the  work  of  demolition 
must  be  carried  will  depend  upon  the  difference  between  the  plans 
of  the  two  houses.  Sometimes  the  main  part  of  the  old  building 
may  be  saved,  and  only  the  wings  require  reconstruction.  In  like 
manner  it  is  conceivable  that  the  central  group  or  nucleus  of  the 
molecule  of  a  given  food  protein  may  be  identical  with  that  of  a 
given  body  protein,  and  that  only  the  side-chains  maybe  so  different 
that  they  must  be  broken  up  and  reconstructed.  Or,  again,  the 
whole  architectural  plan  of  the  new  house  may  be  so  distinct  from 
that  of  the  old  that  the  only  feasible  method  is  to  completely 
demolish  the  latter,  and  then  to  use  the  individual  bricks  in  the 
new  construction;  just  as  a  protein  in  the  food  may  differ  so 
radically  from  a  tissue  protein  into  which  it  is  to  be  transformed 
that  it  must  be  decomposed  into  the  simplest  products  of  proteo- 
lysis before  the  reconstruction  of  the  molecule  can  begin.  It  is  not 
known  what  the  minimum  degree  of  hydrolysis  is  which  will  permit 
of  effective  absorption  and  utilization.  But  it  would  seem  that  it 
must  be  very  complete.  Even  a  body  so  simple  in  comparison  with 
the   proteins   as  the  tripeptide  (p.    2)  alanyl-glycyl-tyrosin,  con- 


ABSORFTIUN  UF  THE   VARIOUS  FOOD  SUBSTANCES       449 

taining  only  three  '  building-stones,'  can  only  be  changed  into  the 
tripeptide  alanyl-tyrosyl-glycin  by  first  hydrolysing  it  into  its  three; 
components  and  then  synthesizing  these  afresh.  On  the  other 
hand,  in  obtaining  the  tripeptide  glycyl-tyrosyl-alanin  from  alanyl- 
glycyl-tyrosin,  the  dipcptide  group  glycyl-tyrosin  can  remain  un- 
decomposed,  and  it  is  only  necessary  to  split  alanin  off  and  link  it 
up  to  the  dipeptide  to  obtain  the  desired  glycyl-tyrosyl-alanin 
(Abderhalden).  There  can  be  no  doubt  that  by  far  the  greater 
part,  if  not  tlie  whole,  of  the  proteins  of  the  food  is  first  changed  into 
proteoses  and  peptones.  But  proteose  and  peptone  are  absent 
from  the  blood,  and,  indeed,  when  injected  into  the  blood  they 
are  excreted  in  the  urine.  When  injected  in  larger  amount,  they 
pass  also  into  the  lymph,  from  which  they  gradually  reach  the  blood 
again,  and  are  eventually,  as  before,  eliminated  by  the  kidneys. 
The  clear  inference  is  that  if  they  are  absorbed  as  such  from  the 
alimentary  canal,  they  must  be  changed  in  their  passage  through  its 
walls.  The  fact  that  a  portion  at  any  rate  of  the  peptones  and 
proteoses  is  decomposed  into  amino-acids,  etc.,  in  the  lumen 
of  the  intestine  has  been  already  alluded  to.  It  is  certain  that 
this  portion  is  a  very  large  proportion  of  the  whole,  although  the 
question  how  much,  if  any,  of  the  peptone  passes  as  such  from  the 
lumen  into  the  mucosa  must  still  be  left  undecided.  It  is  true 
that  along  with  amino-acids  peptones  are  always  found  in  the 
intestine  during  the  digestion  of  protein,  and  the  quantity  of 
amino-acids  actually  present  in  the  lumen  at  any  moment  may 
De  small  in  proportion  to  the  quantity  of  peptone.  But  this  is 
precisely  what  is  to  be  expected  if  the  peptone  as  such  is  incapable 
of  absorption.  For  the  easily  absorbed  amino-acids  will  disappear 
from  the  gut  as  fast  as  they  are  formed,  leaving  behind  the  peptone 
for  further  hydrolysis.  The  fact  that  all  the  amino-acids  which  the 
proteins  are  capable  of  yielding  can  be  detected  in  the  contents  of 
the  intestine,  including  even  those  which  appear  late  and,  as  it 
were,  reluctantly  in  artificial  digestion,  is  a  proof  that  the  decom- 
position of  the  protein  goes  fast  and  far  in  the  alimentary  canal. 
If  it  is  not  complete,  if  some  of  the  partially  hydrolysed  protein  is 
taken  up  by  the  mucous  membrane  in  the  form  of  peptones  or 
possibly  even  of  proteoses,  it  would  seem  that  this  is  similarly 
decomposed  by  the  action  of  erepsin  in  the  intestinal  wall. 

It  has  been  stated  that  during  the  digestion  of  a  protein  meal  the 
mucosa  of  the  stomach  and  intestine  contains  proteose  and  pep- 
tone, while  none  is  present  in  the  muscular  coat  or  in  any  other 
organ.  They  rapidly  disappear  from  a  portion  of  the  mucous  mem- 
brane kept  at  a  temperature  of  about  40°  C  outside  of  the  body,  and 
their  disappearance  is  due,  not  to  their  regeneration  into  serum 
proteins,  as  was  once  supposed,  but  to  their  decomposition  by  the 

erepsin.     We  must  suppose  that  the  serum  and  organ  proteins  are 

29 


450  ABSORPTION 

built  up  from  tlic  products  of  this  decomposition.  But  whether  the 
mucosa  of  the  ahmentary  tract  is  especially  a  seat  of  the  synthesis 
is  unknown  (p.  573).  On  a  priori  grounds,  it  is  at  least  equally 
probable  that  it  occurs  in  all  the  cells  of  the  body,  each  one  building 
up  for  itself  the  particular  kind  of  protein  which  it  needs.  The 
direct  way  of  testing  the  question  would  be  to  examine  the  blood 
coming  from  the  intestine  during  the  absorption  of  proteins,  and  to 
determine  quantitatively  any  changes  which  might  have  occurred  in 
the  nitrogenous  constituents.  But  the  flow  of  blood  through  the 
intestine  is  so  great,  the  absorption  of  the  digestive  products  so 
gradual,  and  their  removal  from  the  blood  by  the  tissues,  in  all 
probability,  so  rapid,  that  there  is  no  reason  for  surprise  that  till 
lately  the  results  of  such  determinations  were  ambiguous.  Leathes, 
however,  showed  some  time  ago  that  when  peptone,  proteose,  or  the 
final  products  of  trj^ptic  digestion  are  introduced  into  a  ligated 
segment  of  a  dog's  small  intestine,  there  is  always,  when  absorption 
occurs,  an  increase  in  the  nitrogenous  substances  in  the  blood,  in  the 
form  of  compounds  which  are  not  precipitated  by  tannic  acid,  and 
therefore  are  neither  native  proteins  nor  proteose.  Urea  accounts 
for  about  one-half  of  the  increase ;  the  rest  he  considered  to  represent 
probably  amino-acids  and  similar  substances.  Quite  recently  it 
has  been  conclusively  demonstrated  by  improved  methods  that  the 
digestion  of  protein  is  associated  with  an  increase  of  non-protein 
nitrogen  in  the  blood,  due,  there  is  every  reason  to  believe,  toamino- 
bodies  derived  from  the  hydrolysed  protein  (Folin  and  Denis,  Van 
Slyke,  Abel).  This  proves  for  the  mammal  what  had  been  deduced 
by  Cohnheim  for  a  much  lower  form  from  experiments  made  on  the 
intestines  of  certain  octopods,  which,  when  excised  and  suspended 
in  the  oxygenated  blood,  will  live  for  many  hours.  A  solution  of 
peptone  was  introduced  into  the  isolated  intestine,  and  after  twenty 
hours  the  crystalline  products,  leucin,  t^Tosin,  lysin,  and  arginin, 
were  found  in  the  blood.  In  the  intact  animal  none  of  these  bodies 
could  be  detected  in  the  blood  (Cohnheim).  The  inference  was 
that  protein  in  these  animals  is  absorbed  in  the  form  of  amino-acids, 
etc.,  which  are  then  carried  to  the  tissues  and  utilized  there.  In 
the  mammal  the  same  thing  appears  to  be  true.  For  the  increase 
in  the  amino-acids  during  digestion  of  proteins  occurs  not  only  in 
the  portal  blood,  but  in  the  blood  of  the  general  circulation.  So 
that,  although  a  part  of  the  absorbed  amino-bodies  may  be  removed 
by  the  liver,  a  portion  at  least  is  available  for  the  tissues  in  general. 
That  the  tissues  actually  take  up  such  decomposition  products  of 
proteins  is  indicated  by  the  fact  that  during  and  after  the  digestion 
of  protein  in  a  loop  of  intestine  the  non-protein  nitrogen  of  the 
tissues  is  increased  (Folin).  It  may  be  that  some  of  the  proteose 
and  peptone  are  regenerated  bv  a  shorter  process,  and  without 
having  been  further  split  up,  but  of  this,  too,  there  is  no  definite 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       451 

proof.  The  regeneration,  wherever  it  occurs,  must  presumably  take 
place  in  cells,  and  the  only  available  cells  in  the  digestive  mucous 
membrane  are  those  which  line  the  tube,  or  the  leucocytes  which 
wander  between  them.  Accordingly,  both  have  been  credited  with 
the  power  of  absorbing  (and  perhaps  transforming)  these  substances, 
but  the  balance  of  evidence  is  in  favour  of  the  epithelial  cells.  We 
cannot,  however,  as  in  the  case  of  the  fat,  single  out  any  particular 
tract  of  epithelium  as  alone  engaged  in  the  absorption  (and  possibly 
in  the  resynthesis)  of  the  products  of  the  digestion  of  the  proteins. 
In  all  likelihood  the  cells  covering  the  viUi  are  actively  concerned, 
but  there  is  no  valid  reason  for  den5dng  a  share  to  the  general  lining 
of  the  stomach  and  small  intestine,  even  perhaps  including  the 
iJeberkuhn's  crypts  or  intestinal  glands,  which  morphologically 
form  a  kind  of  inverted  villi.  It  is,  indeed,  true  that  the  crypts 
do  not  take  part  in  the  absorption  of  fat,  for  no  granules  blackened 
by  osmic  acid  occur  in  them  during  digestion  of  a  fatty  meal.  But 
this  is  a  ground  for  attributing  to  them  other  absorptive  functions 
rather  than  for  altogether  denying  to  them  a  share  in  absorption, 
unless,  indeed,  we  assume  that  the  secretion  of  the  succus  entericus 
engrosses  the  whole  activity  of  this  extensive  sheet  of  cells.  Even 
within  physiological  limits  distension  of  the  gut  causes  the  crypts 
to  become  shorter  and  broader,  by  a  process  of  partial  unfolding 
which  permits  a  greater  part  of  their  epithelium  to  come  into  con- 
tact with  the  intestinal  contents.  In  extreme  distension  they  may 
be  completely  smoothed  out. 

The  extraordinary  efficiency  of  the  small  intestine  in  digestion 
and  absorption  is  shown  by  the  fact  that,  after  removal  of  even 
70  to  83  per  cent,  of  the  combined  jejunum  and  ileum  in  dogs,  the 
metabolism  is  not  necessarily  much  affected.  On  a  diet  poor  in 
fat  the  animals  absorb  as  much  of  the  fat  as  a  normal  dog,  although 
a  smaller  proportion  when  the  diet  is  rich  in  fat.  It  has  been 
generally  stated  that  it  is  never  permissible  to  remov^e  more  than 
one-third  of  the  small  intestine  in  man.  But  in  one  case  2f  metres 
was  resected,  or  quite  one-half,  and  the  patient  recovered.  Even 
the  large  intestine,  which  possesses  Lieberkiihn's  crypts,  but  no  villi, 
is  able  to  absorb  not  only  peptones  and  sugar,  especially  mono- 
saccharides like  dextrose,  but  also  fats  and  native  proteins.  And 
although  these  are  powers  which  can  be  rarely  exercised  to  any  great 
extent  in  normal  digestion,  they  form  the  physiological  basis  of  the 
important  method  of  treatment  by  nutrient  enemata.  The  observa- 
tion already  mentioned  (p.  331),  that  considerable  quantities  of 
food  administered  by  the  rectum  can  pass  through  the  ileo-colic 
sphincter  and  valve  into  the  lower  part  of  the  ileum,  thanks  to  the 
antiperistaltic  movements  of  the  large  intestine,  indicates  that  an 
important  part  of  the  preliminary  digestion  and  of  the  absorption 
of  enemata  may  occur  in  the  small  intestine.  '  But  remnants  of  the 


452  ABSORPTION 

proteolytic,  amyloljrtic,  fat-splitting,  and  inverting  ferments  which 
have  done  their  work  in  the  small  intestine  are  passed  on  into  the 
large,  and  may  be  demonstrated  in  its  contents.  Doubtless  these 
are  able  to  act  upon  food  substances  which  may  have  escaped  com- 
plete digestion  and  absorption  in  the  higher  parts  of  the  alimentary 
canal,  as  well  as  upon  food  substances  injected  into  the  rectum. 

Summary. — With  the  proviso  that  in  the  case  of  the  fats  the 
statement  may  in  the  present  condition  of  our  knowledge  be  some- 
what '  diagrammatic,'  we  may  sum  up  in  a  few  words  the  chief 
points  in  the  absorption  of  the  food  materials.  All  the  fats  must  be 
split  in  order  to  he  absorbed  in  soluble  form  from  the  intestine,  but 
need  not  be  split  in  the  lumen  of  the  gut  in  order  to  be  utilized  by  the 
cells.  For  this  reason  they  are  to  a  great  extent  resynthesized  to 
neutral  fat  after  absorption,  ard  find  their  way  into  the  blood,  mainly 
by  way  of  the  lymph,  in  particulate  form.  Proteins  could  perhaps  to 
a  small  extent  be  absorbed  as  such,  but  must  be  thoroughly  hydrolysed 
in  order  to  be  utilized  by  the  tissues,  and  also  in  order  to  be  freely 
taken  up  from  the  gut.  Carbo-hydrates  in  certain  forms  {mono- 
saccharides) are  capable  without  change  of  being  both  freely  absorbed 
from  the  intestine  and  thoroughly  utilized  by  the  cells  ;  only  the  more 
complex  carbo-hydrates  need  to  be  hydrolysed  in  order  to  be  absorbed, 
but  all  above  the  monosaccharides  must  be  hydrolysed  to  tnonosac- 
charides  in  order  to  be  utilized.  The  substances  which  eventually 
circulate  in  the  blood  in  solution  reach  it  through  the  gastro-intestinal 
capillaries  ;  the  substances  which  eventually  circulate  in  the  blood  in 
particulate  form  reach  it  through  the  lymphatics. 


PRACTICAL  EXERCISES  ON  CHAPTERS  VI.  AND  VII. 

I.  Contraction  of  Isolated  Intestines  in  Ringer's  Solution. — Arrange 
a  good-sized  water-bath  (a  water-tight  garbage-can  holding  20  litres 
will  do)  so  that  the  temperature  of  the  water  is  kept  at  37°  to  38°  C. 
For  this  a  gas  regulator  is  most  convenient,  and  also  a  stirring  arrange- 
ment worked  by  a  small  motor.  But  if  neither  of  these  is  available, 
a  student,  by  a. little  care,  can  easily  keep  the  water  at  the  required 
temperature  by  raising  and  lowering  the  gas  flame  and  stirring  occasion- 
ally by  hand.  In  the  bath,  support  (a)  a  stock  bottle  of  Ringer's 
solution  (footnote,  p.  66),  {h)  a  wide-mouthed  bottle  containing  Ringer 
for  the  reception  of  the  stock  of  intestine,  (c)  a  small  cylinder  for 
segments  of  intestine  whose  contractions  are  to  be  recorded,  (c)  is 
conveniently  made  in  different  sizes  by  cutting  down  glass  T-pieces. 
One  which  holds  4  or  5  c.c.  is  convenient.  The  bottom  is  plugged  with 
a  rubber  cork  in  wliich  is  fastened  a  hook.  In  the  side-piece  is  fixed 
by  a  rubber  cork  a  glass  tube  ending  in  the  cylinder  in  a  narrow 
orifice.  This  is  connected  with  the  oxygen-supply,  conveniently  ob- 
tained under  constant  pressure  from  a  small  gas-container  which  is 
periodically  replenished  from  an  oxygen  cylinder.  A  separate  oxygen 
cylinder  is  connected  with  a  tube  passing  to  the  bottom  of  (6).  A  lever 
with  two  arms  is  arranged  on  the  same  stand  as  (c),  so  that  it  can  be 
thrown  on  and  off  a  slow-moving  drum  by  a  single  movement  of  the  stand. 

All  being  ready,  a  rabbit  is  killed  by  being  struck  on  the  back  of  the 


PRACTICAL  EXERCISES  453 

head.  Ilic  small  intestine  is  immediately  removed.  It  may  be  cut 
between  double  lif^aturcs  into  several  pieces  for  this  purjxjse.  The 
contents  arc  rapidly  washed  out  by  a  stream  of  warm  Ringer,  and 
the  pieces  placed  in  (/>),  through  which  oxygen  is  kept  bubbling.  The 
pieces  are  conveniently  supported  in  the  liquid  by  threads  fixed  by 
the  cork  of  the  bottle.  There  is  a  hole  in  the  cork  for  the  escape  of 
the  oxygen.  The  movements  of  the  intestines  in  {b)  can  be  studied 
very  well  by  inspection.  Or  a  separate  length  of  intestine  maybe  kept 
for  this  purpose,  the  contents  not  being  removed,  but  prevented  from 
escaping  by  ligatures  at  each  end.  This  can  be  mo.st  easily  observed  in  a 
shallow  dish  of  warni  Ringer.  Or  a  separate  experiment  can  be  made 
in  which  the  whole  alimentary  canal  of  a  rabbit  is  carefully  removed 
and  examined  in  oxygenated  Ringer's  solution. 

A  .segment  of  intestine  about  2  or  2^  cm.  in  length  is  now  cut  off 
one  of  the  pieces.  A  small  ring  of  platinum  or  aluminium  is  tied  to 
a  point  on  the  circumference  of  one  end  of  the  preparation  by  a  silk 
thread  passed  through  the  wall.  The  other  end  is  caught  by  a  serre- 
fine  at  a  point  exactly  corresponding  to  the  attachment  of  the  ring,  so 
that  the  pull  of  the  contracting  longitudinal  muscle  should  be  in  the 
straight  line  joining  these  two  points.  The  serre-fine  has  attached  to 
it  a  thread  with  a  hook  on  the  other  end.  In  preparing  the  intestinal 
segment  it  lies  on  a  plate  of  glass  above  a  vessel  of  warm  water.  The 
small  cylinder  (c)  is  now  partially  filled  with  warm  Ringer's  solution. 
The  ring  is  grasped  by  fine  forceps,  and  made  to  engage  with  the  hook 
at  the  bottom  of  the  c^dinder,  care  being  taken  not  to  injure  the  prepara- 
tion in  the  process.  The  cylinder  is  then  fastened  on  its  stand  and. 
lowered  into  the  bath.  The  thread  is  connected  by  its  attached  hook 
to  the  lever,  and  oxygen  allowed  to  bubble  slowly  and  regularly  through 
the  cylinder.  Very  soon  rhythmical  contractions  begin  (Fig.  173),  and 
continue  for  a  long  time.  The  effect  on  these  contractions  of  abolish- 
ing, reducing,  or  increasing  the  oxygen-supply  may  first  be  studied. 

2.  Effect  of  Blood-Serum  on  the  Contractions  of  Intestinal  Segments. 
— While  a  tracing  is  being  taken  as  in  i,  fill  a  small  bent  pipette  with 
serum  already  warmed  in  the  bath,  pass  the  point  of  the  pipette  down  to 
the  bottom  of  the  cylinder  without  interfering  with  the  preparation,  and 
allow  the  serum  to  flow  in  till  the  Ringer's  solution  is  displaced.  Almost 
at  once  the  lever  will  begin  to  rise,  indicating  strong  tonic  contraction. 
The  increase  of  tone  lasts  for  some  time,  but  can  soon  be  removed  on 
washing  the  preparation  with  Ringer.  This  is  most  easily  done,  while  the 
drum  is  stopped,  by  introducing  pipetteful  after  pipetteful  of  Ringer's 
solution  into  the  cylinder  in  the  way  described,  allowing  the  liquid  to 
overflow  into  the  bath.  The  subsequent  addition  of  serum  causes  a 
renewed  increase  of  tone,  and  this  may  be  many  times  repeated. 

Determine  the  greatest  dilution  of  the  serum  which  still  produces  a 
distinct  effect  upon  the  intestinal  segment. 

3.  Action  of  Epinephrin  (Adrenalin)  on  Intestinal  Segments. — Pro- 
ceed as  in  2,  but  use  various  dilutions  of  adrenalin  chloride  instead  of 
serum.  They  must  be  freshly  prepared.  Instead  of  increase  of  tone, 
inhibition  of  the  movements  and  decrease  of  tone  will  be  obtained 
(Fig.  173). 

This  experiment  may  be  performed  at  another  stage  in  the  course 
(p.  720). 

4.  Quantitative  Estimation  of  Ferment  Action. — For  pepsin  an  easy 
method,  although  not  a  very  accurate  one,  of  estimating  the  rate  at 
which  the  fibrin  disappears  is  to  use  fibrin  stained  with  carmine.  As 
solution  goes  on,  the  dye  colours  the  liquid  more  and  more  deeply,  and 
by  comparing  the  depth  of  colour  at  any  time  with  standard  solutions 
of  carmine,  we  get  the  quantity  of  dye  set  free,  and  therefore  of  fibrin 


454 


DIGESTION  AND   ABSORPTION 


digested.  This  mt  thod  cannot  be  used  for  trypsin.  A  mucli  better 
method  is  that  of  Mett  (p.  343).  Fluid  egg-white  is  sucked  up  into 
fine  glass  tubes  (of  i  to  2  mm.  bore).  The  tubes  are  then  heated  in  a 
bath  at  95°  C.  For  use  short  pieces  (i  or  2  cm.  long)  are  cut  off  and 
placed  in  I  or  2  c.c.  of  the  liquid  to  be  tested,  the  whole  being  kept  at 
38°  to  40°  C. 

For  amylolytic  ferments  where  rapid  work  is  required,  glass  tubes 
filled  with  tinted  starch  paste  may  be  used  in  the  same  way  as  the 
Mett's  tubes.  A  more  accurate  method,  and  yet  a  rapid  and  convenient 
one,  is  based  upon  the  time  which  is  necessary  in  order  that  the  iodine 
reaction  with  starch  may  just  disappear  when  a  standard  starch  solution 

is  digested  with  a  dilution 
of  the  ferment  solution 
at  40°  C. 

5.  Saliva — Collection 
and  Microscopic  Examina- 
tion of  Saliva. — Chew  a 
piece  of  paraffin -wax,  or 
inlir.leetherorthe  vapour 
of  strong  acetic  acid.  The 
flow  of  saliva  is  increased. 
Collect  it  in  a  porcelain 
capsule.  Examine  a  drop 
imder  the  microscope.  It 
may  contain  a  few  fiat 
epitheUal  scales  from  the 
mouth  and  a  few  round 
granular  bodies,  the  sali- 
vary corpuscles,  the  gran- 
ules in  which  often  show 
a  lively,  dancing  move- 
ment (Brownian  motion). 
Filter  the  saliva  to  free  it 
from  air-bubbles,  and  per- 
form the  following  ex- 
periments : 

(a)  Test  the  reaction 
with  litmus  paper.  It  is 
usually  alkaline.  An  acid 
reaction  may  indicate 
that  bacterial  processes 
are  abnormally  active  in 
the  mouth. 
A  precipitate  indicates  the  presence  of 


Fig.  173. — Effect  of  Scrum  and  Adrenalin  on  Con- 
tractions of  a  Segment  of  Intestine.  Rabbit's 
intestine  contracting  in  Ringer's  solution.  At 
55  the  Ringer's  solution  was  replaced  by  dog's 
serum,  and  this  at  56  by  adrenalin  {1:5,000,000) 
in  serum.  At  57  this  weak  adrenalin  solution  was 
replaced  by  a  stronger  one  (i:  500,000)  in  serum. 
Time-trace,  half-minutes.     (Reduced  to  half.) 


(b)  Add  dilute  acetic  acid, 
mucin  (p.  344).     Filter. 

(c)  Add  a  drop  or  two  of  silver  nitrate  solution  to  the  filtrate  from 
(b).  A  precipitate  insoluble  in  nitric  acid,  soluble  in  ammonia,  pro\es 
that  chlorides  ar.^  present. 

{d)  Add  to  another  portion  a  few  drops  of  dilute  ferric  chloride 
slightly  acidulated  with  dilute  hydrochloric  acid,  and  the  same  quantity 
to  as  much  distilled  water  in  a  control  test-tube.  A  reddish  coloration 
is  obtained,  due  to  the  presence  of  sulphocyanic  acid,  which  is  com- 
bined with  potassium  and  other  bases  in  the  saliva.  The  colour  is  dis- 
charged by  mercuric  chloride.  Or,  a  drop  of  saliva  may  be  allowed  to 
fall  from  the  mouth  on  a  test-paper  (prepared  by  soaking  filter-paper 
with  a  dilute  starch  solution,  containing  a  little  iodic  acid,  and  allowing 
it  to  dry  in  the  air).     The  paper  is  coloured  blue  by  the  union  of  the 


PRACTICAL  EXERCISES  453 

starch  wit  h  iodine  set  free  from  the  iodic  acid  by  the  acticn  of  the  sulpho- 
cyanic  acid. 

(e)  Take  some  boiled  starch  mucilage,  and  tist  it  for  reducing  sugar 
by  Trommer's  test  (p.  10).  If  no  sugar  is  found,  take  three  test- 
tubes,  label  them  A,  B.  C,  and  nearly  half  fill  each  with  the  boiled 
starch.  To  A  add  a  little  saliva,*  to  B  some  saliva  which  has  been 
boiled,  to  C  a  little  saliva  which  h;us  been  neutralized,  and  as  much 
0-4  per  cent,  hydrochloric  acid  as  has  been  taken  of  the  mucilage,  so  as 
to  make  the  strength  of  the  acid  iu  the  mixture  0-2  per  cent.,  a  propor- 
tion well  below  that  of  the  gastric  juice.  Put  the  test-tubes  into  a  water- 
bath  at  40°  C.  In  a  few  minutes  test  the  contents  for  reducing  sugar. 
Abundance  will  be  found  in  A,  none  in  B  or  C.  In  B  the  ferment 
ptyalin  has  been  destroyed  by  boiling;  in  C  its  action  has  been  inhibited 
by  the  acid.  If  the  test-tubes  have  been  left  long  enough  in  the  bath, 
no  blue  colour  will  be  given  by  A  on  the  addition  of  iodine,  but  a  strong 
blue  colour  by  B  and  C — i.e.,  the  starch  will  have  completely  disappeared 
from  A. 

(/)  Put  some  starch  in  a  test-tube,  add  a  little  saliva,  and  hold  in  the 
hand  or  place  in  a  bath  at  40°  C.  On  a  porcelain  slab  place  several 
separate  drops  of  dilute  iodine  solution.  With  a  glass  rod  add  a  drop 
of  the  mixture  in  the  test-tube  to  one  of  the  drops  of  iodine  at  intervals 
as  digestion  goes  on.  At  first  only  the  blue  colour  given  by  starch  will 
be  seen;  a  little  later  a  violet  colour,  due  to  the  presence  of  erythro- 
dextrin  in  addition  to  some  unaltered  starch.  A  little  later  the  colour 
will  be  reddish,  the  starch  having  disappeared  and  the  erythrodextrin 
reaction  being  no  longer  obscured.  Later  still  no  colour  reaction  will 
be  obtained,  the  erythrodextrin  having  undergone  further  changes,  and 
only  sugar  (maltose,  isomaltose,  and  perhaps  a  trace  of  dextrose)  and 
achroodextrin — a  kind  of  dextrin  which  gives  no  colour  with  iodine — • 
being  present. 

{g)  Put  two  pieces  of  glass  tube  filled  with  tinted  starch  paste  (p.  454) 
into  separate  test-tubes.  Cover  one  with  3  c.c.  and  the  other  with 
6  c.c.  of  saliva.  The  saliva  must  all  be  taken  from  the  same  stock,  and 
must  not  be  collected  separately.  Put  in  a  bath  at  38°  C,  and  when  a 
fair  amount  of  digestion  has  taken  place  in  each,  measure  the  length 
of  the  column  digested,  and  determine  the  relation  between  the  amount 
digested  in  the  two  tubes  (p.  342). 

(A)  Dilute  2  c.c.  of  saliva  with  distilled  water  up  to  20  c.c,  and  filter. 
Take  six  test-tubes  of  the  same  width,  and  label  them  A,  B,  C,  etc. 
Measure  into  A  3  c.c.  of  the  diluted  saliva,  into  B  2  c.c,  into  €1-3  c.c, 
intoD  0-9  c.c,  into  Eo'6c  c,  and  into  F  0-4  c.c.  Thus  a  series  is  obtained 
in  which  each  tube  contains  (approximately)  two-thirds  as  much  ferment 
as  the  one  it  follows.  Add  distilled  water  to  tubes  B  to  F,  sufficient  to 
make  up  the  volume  in  each  to  3  c.c.  Place  the  tubes  in  a  beaker  of 
iced  water;  add  to  each  10  c.c  of  a  i  per  cent,  solution  of  boiled  starch 
previously  cooled  in  iced  water,  and  shake  so  as  to  mix  the  contents. 
Each  tube  now  contains  starch  in  uniform  concentration,  and  ferment 
in  var^'ing  concentration.  The  low  temperature  prevents  digestion  till 
all  the  tubes  are  ready.  Now  put  the  tubes  simultaneously  into  a  water- 
bath  at  40°  C.  for  half  an  hour,  and  then  back  again  into  iced  water 
to  prevent  furlner  digestion.  Move  them  about  in  the  iced  water  to 
cool  rapidly.  Fill  up  the  tubes  with  distilled  water  nearly  to  the  top, 
add  a  drop  or  two  of  iodine  solution  to  each,  and  mix  uniformly.  The 
tubes  to  which  the  smallest  amounts  of  saliva  were  added  will  probably 

*  As  it  filters  slowly,  unaltered  saliva  may  be  used  for  Experiments  («). 
(/)  and(i). 


456 


DIGEiiTiU.\  AAL)  ABSORFTluS 


still  show  a  distinct  blue  colour,  while  those  at  the  other  end  of  the 
scries  will  be  brown  or  yellow,  and  the  intermediate  tubes  bluish -violet. 
Suppose  D  is  the  last  tube  still  showing  a  bluish  tint,  then  in  the  next 
higher  tube,  C.  all  the  starch  has  been  hydrolysed  at  least  to  dextrin — 
that  is.  i'3  c.c.  of  the  ten-times  diluted  saliva,  or  0'i3  of  the  original 
saliva,  has  been  sufficient  to  change  all  the  starch  in  lo  c.c.  of  the  i  per 
cent,  solution.  With  another  specimen  of  saliva  the  same  result  might 
be  reached  in  tube  E,  containing  an  amount  of  ferment  equal  to  that 
in  0'o6  c.c.  of  the  original  saliva.  We  could  then  conclude  that  the 
diastatic  power  of  the  second  saliva  was  about  twice  as  great  as  that 
of  the  first.  A  closer  approximation  can  now  be  made  by  setting  up 
two  fresh  tubes  (C  and  E  respectively  for  the  two  salivas)  and  deter- 
mining the  time  required  for  the  blue  reaction  with  iodine  to  disappear, 
taking  out  a  drop  from  time  to  time  and  testing  on  a  porcelain  slab. 

(t)  Put  a  little  distilled  water  into  a  porcelain  capsule,  and  bring  the 
water  to  the  boil.  Now  put  into  the  mouth  some  boiled  starch  paste, 
and  move  it  about  as  in  mastication.  After  half  a  minute  spit  the 
starch  out  into  the  boiling  water.  Divide  the  water  into  two  portions. 
Test  one  for  sugar,  and  the  other  for  starch.  Repeat  the  experiment, 
but  keep  the  starch  two  minutes  in  the  mouth.     Report  the  result. 

(;)  Starch  solution  to  which  saliva  has  been  added  is  placed  in  a 
diaiyser  tube  of  parchment-paper  for  twenty-four  hours.  At  the  end 
of  that  time  the  dialysate  (the  surrounding  water)  should  be  tested  for 
sugar  and  for  starch.  Sugar  will  probably  be  found,  but  no  starch. 
If  no  reaction  for  sugar  is  obtained,  the  dialysate  should  be  concen- 
trated on  the  w^ater-bath.  and  again  tested. 

6.  Stimulation  of  the  Chorda  Tympani. — fi)  Having  previously 
studied  the  anatomy  of  the  mouth  and  submaxillary  region  in  the  dog 
by  dissecting  a  dead  animal  (Fig.  174).  put  a  good-sized  dog  under 
morphine.  Set  up  an  induction-machim  for  a  tetanizing  current 
(p-  200),  and  connect  it  with  fine  electrodes.  Fasten  the  dog  on  the 
holder,  give  ether  if  necessary,  and  insert  a  cannula  in  the  trachea 
(p.  202).  Then  make  an  incision  3  or  4  inches  long  through  skin  and 
platysma  muscle,  along  the  iimer  border  of  the  lower  jaw,  beginning 
about  the  angle  of  the  mouth,  and  continuing  backwards  towards  the 
angle  of  the  jaw.  Such  branches  of  the  jugular  vein  as  come  in  the  way 
may  be  generally  pushed  aside,  but  if  necessary  thoy  may  be  doubly 
ligated  and  divided.  Feel  for  the  facial  arter\',  so  as  to  be  able  to 
avoid  it.  Divide  the  digastric  muscle  about  its  anterior  third,  and 
clear  it  carefully  from  its  attachments;  or,  without  dividing  it,  pull  it 
outwards  with  a  hook.  The  broad,  thin  mylo-hyoid  muscle  will  now 
be  seen  with  its  motor  nerv'e  lying  on  it.  Divide  the  muscle  about  its 
middle  at  right  angles  to  its  fibres,  and  raise  it  carefully.  The  lingual 
nerve  will  be  seen  emerging  from  under  the  ramus  of  the  jaw.  It  runs 
transversely  towards  the  middle  Une,  and  then,  bending  on  itself,  passes 
forwards  parallel  to  the  larger  hypoglossal  nerve.  In  its  transverse 
course  the  lingual  will  be  seen  to  cross  the  ducts  of  the  submaxillar\- 
and  sublingual  glands.  These  structures  having  been  identified,  the 
lingual  nerve  is  to  be  ligatured  before  it  enters  the  tongue  and  cut 
peripherally  to  the  ligature.  Then  a  glass  cannula  of  suitable  size  is  to 
be  inserted  into  the  submaxillary  duct  (the  larger  of  the  two),  just  as  if 
it  were  a  bloodvessel  (p.  63).  A  short  piece  of  narrow  rubber  tubing 
is  carefully  slipped  on  the  end  of  the  cannula.  The  lingual  is  now  to  be 
lifted  by  means  of  the  ligature,  and  traced  back  towards  the  jaw  till  its 
chorda  tympani  branch  is  seen  coming  off  and  nmning  backwards  along 
the  duct.  The  chordo-lingual  nerve  (Fig.  160,  p.  392)  is  then  to  be 
cut  centrally  to  the  origin  of  the  chorda  tjinpani,  which  can  now  be 


PRACTICAL  EXERCISES 


457 


easily  laid  on  electrodes  by  means  of  the  ligature  on  the  lingual.  On 
stimulating  the  chorda,  the  flow  of  saliva  through  the  cannula  will  be 
increased.  The  current  need  not  be  very  strong.  Jf  the  flow  stops 
after  a  short  time,  it  can  be  again  caused  by  renewed  stimulation  after 
a  brief  rest.  A  quantity  of  saliva  may  thus  be  collected,  and  the  experi- 
ments already  made  with  human  saliva  repeated. 

(2)  Expose  the  vago-sympathetic  nerv^  in  the  neck  on  the  same 
side ;  ligature  it ;  divide  below  the  ligature ;  and  note  the  effect  pro- 
duced by  stimulation  of  the  upper  end  on  the  flow  of  saliva. 

(3)  Siet  up  another  induction-machine,  and  connect  it  with  electrodes. 
Stimulate  the  chorda,  and  note  the  rate  of  flow  of  the  saliva.  Then, 
while  the  chorda  is  still  being  excited,  stimuLae  the  vago-sympathetic, 
and  observe  the  effect.  If  the  experiment  is  successful,  finish  by 
stimulating  the   chorda   for   a   long   time.      Then   harden   both   sub- 


.Mylo-hyoid 
Muscle  (cut). 


Lingual     Wharton's 
Nerve.  Duct. 


Fig.  174. — Dissection  for  Stimulation  of  Chorda  Tympani  (after  Bernard). 


maxillary"-  glands  in  absolute  alcohol,  make  sections,  stain  with  carmine, 
and  compare  them. 

7.  Effect  of  Drugs  on  the  Secretion  of  Saliva. — (i)  Proceed  as  in 
6  (i),  but,  in  addition,  insert  a  cannula  into  the  femoral  vein  (p.  218). 
On  the  cannula  put  a  short  piece  of  rubber  tubing,  filled  with  0*9  per 
cent,  salt  solution  and  closed  by  a  small  clamp,  or  a  small  piece  of 
glass  rod,  or  a  pair  of  bulldog  forceps.  While  the  chorda  is  being 
stimulated  inject  into  the  vein  10  to  15  milligrammes  of  sulphate  of 
atropine  by  pushing  the  needle  of  a  hyf)odermic  syringe  through  the 
rubber  tube.  This  will  stop  the  flow  of  saliva,  and  abolish  the  effect 
of  stimulation  of  the  chorda.  See  whether  the  sympathetic  is  also 
inactive,  and  report  the  result. 

(2)  Now  empty  the  cannula  in  the  submaxiUar}'  duct  by  means  of  a 
feather,  and  fill  it  with  a  2  per  cent,  solution  of  pilocarpine  nitrate  by 
means  of  a  fine  pipette.  Fill  also  the  short  rubber  tube  attached  to 
the  cannula,  and  close  it  again.     Compress  the  tube,  and  so  force  into 


^58  DIGESTIOX   AND  ABSORPTION 

the  duct  a  small  quantity  of  the  solution.  Open  the  tube.  Secretion 
of  Siiliva  will  again  begin,  and  stimulation  of  the  chorda  will  again  cause 
an  increase  in  tlu-  flow.  But  after  a  few  minutes  the  action  of  the 
atropine  will  reassert  itself,  and  the  flow  will  stop.  Renewed  secretion 
may  be  cau.sed  by  a  fresh  injection  of  pilocarpine. 

8.  Gastric  Juice — (a)  Preparation  of  Artificial  Gastric  Juice. — Take 
a  portion  of  the  pig's  stomach  provided,  strip  off  the  mucous  membrane 
(except  that  of  the  pyloric  end,  which  is  relatively  poor  in  pepsin),  cut 
it  into  small  pieces  with  scissors,  and  put  it  in  a  bottle  with  loo  times 
its  weight  of  0-4  per  cent,  hydrochloric  acid.  Label  and  put  in  a  bath 
at  40°  C.  for  three  hours,  and  then  in  the  cold  for  twelve  hours.  Then 
filter. 

{b)  Take  another  portion  of  the  mucous  membrane,  cut  it  into  pieces, 
and  rub  up  with  clean  sand  in  a  mortar.  Then  put  it  in  a  small  bottle, 
cover  it  with  glycerin,  label,  and  set  aside  for  two  or  three  days.  The 
glycerin  extracts  the  pepsin. 

(c)  Take  five  test-tubes,  A,  B,  C,  D,  E,  and  in  each  putfa  little  washed 
and  boiled  fibrin  or  a  small  cube  of  coagulated  egg-white.  To  A  add  a 
fv'w  drops  of  glycerin  extract  of  pig's  stomacja,  and  fill  up  the  test-tube 
with  0-4  per  cent,  hydrochloric  acid.  To  B  add  glycerin  extract  and 
distilled  water;  to  C  glycerin  extract  and  i  per  cent,  sodium  carbonate; 
to  D  0'4  per  cent,  hydrochloric  acid  alone ;  to  E  glycerin  extract  which 
has  been  boiled,  and  0*4  per  cent,  hydrochloric  acid. 

Put  np  another  set  of  five  test-tubes  in  the  same  way,  except  that  a 
few  drops  of  a  watery  solution  of  a  commercial  pepsin  are  substituted 
for  the  glycerin  extract.     Label  the  test-tubes  A',  B'.  C,  D',  E'. 

Into  another  test-tube  put  a  little  fibrin  (or  an  egg- whit?  cube),  and 
fill  up  with  the  filtered  acid  extract  from  (a).  Label  it  F.  Place  all 
the  test-tubes  in  a  tumbler,  and  set  them  in  a  water-bath  at  40°  C. 
Put  a  piece  of  a  Mett's  tube  (p.  343)  into  each  of  two  test-tubes,  and 
add  15  c.c.  of  0'4  per  cent,  hydrochloric  acid.  To  one  tube  add  5  drops 
and  to  the  other  10  drops  of  the  same  filtered  glycerin  extract  of  gastric 
mucous  membrane.  Put  the  tubes  in  the  bath,  and  when  digestion  is 
distinct  at  the  ends  of  both  tubes  measure  the  length  of  the  column 
digested  in  each.  What  is  the  relation  between  the  two  (p.  342)  ? 
The  experiment  can  be  repeated  with  the  hydrochloric  acid  extract  of 
the  mucous  membrane. 

After  a  time  the  fibrin  (or  egg-white)  will  have  almost  completely  dis- 
appeared in  A,  A',  and  F,  but  not  in  the  other  test-tubes.  Filter  the 
contents  of  A,  A',  and  F  into  one  dish. 

{d)  Test  the  fiJtiate  for  the  products  of  gastric  digestion: 

(a)  Neutralize  a  portion  carefully  with  dilute  sodium  hydrox- 
ide. A  precipitate  of  acid-albumin  may  be  thrown 
down.  Filter. 
(/3)  To  a  portion  of  the  filtrate  from  (a)  add  excess  of  sodium 
hydroxide  and  a  drop  or  two  of  very  dilute  copper 
sulphate.  A  rose  colour  indicates  the  presence  of 
proteoses  or  peptones.  The  cupric  sulphate  must  be 
very  cautiously  added,  because  an  excess  gives  a  violet 
colour,  and  thus  obscures  the  rose  reaction.  If  still 
mere  cupric  sulphate  be  added,  blue  cupric  hydroxide 
is  thrown  down,  and  nothing  can  be  inferred  as  to  the 
presence  or  the  nature  of  proteins  in  the  liquid. 
(y)  Heat  another  portion  of  the  filtrate  from  («)  to  30*  C, 
and  add  crystals  of  ammonium  sulphate  to  saturation. 
A  precipitate  of  proteoses  (albumoses)  may  be  ob- 
tained.    Filter  off. 


PRACTICAL  EXERCISES  459 

(6)  Add  to  the  filtrate  from  (y)  a  trace  of  cupric  sulj^hatc  .-i,n(l 
excess  of  sodium  hydroxide.  A  rose  colour  indicates 
that  peptones  arc  present.  More  sodium  hydroxide 
must  be  added  than  is  sufficient  to  break  up  all  the 
ammonium  sulphate,  for  the  biuret  reaction  requires 
the  presence  of  free  fixed  alkali.  A  strong  solution  of 
the  sodium  hydroxide  should  tlierefore  be  used,  or  the 
stick  caustic  soda.  The  addition  of  ammonium  sul- 
phate will  cause  the  red  colour  to  disappear;  so  will  the 
addition  of  an  acid.  Sodium  hydroxide  will  bring  it 
back.  Ammonia  docs  not  affect  the  colour. 
{e)  To  some  milk  in  a  test-tube  add  a  drop  or  two  of  rennet  extract, 

and  place  in  n  bath  at  40"  C.     In  a  short  time  the  milk  is  curdled  by 

the  rcnnin.      (Sec  p.  353) 

9.   (i)  To  obtain  Normal  Chyme.— Inject  subcutancously  into  a  dog, 

one  and  a  lialf  hours  after  a  meal  of  minced  meat  and  water,  2  mg.  of 

apomorphine.     Half  of  one  of  the  ordinary  tabloids  is  enough.     Collect 

the  vomit. 

(2)  To  obtain  Pure  Gastric  Juice. — If  the  laboratory  possesses  a  dog 
with  Pawlow's  double  oesophageal  and  gastric  fistula,  the  juice  may 
be  obtained  in  large  amount  by  sham  feeding  with  meat  (p.  402).  If 
not,  proceed  as  follows:  Put  a  fasting  dog  under  ether,  and  fasten  on 
the  holder.  Clip  the  hair  and  shave  the  skin  in  the  middle  line  below 
the  sternum.  Make  a  longitudinal  incision 
through  the  skin  and  subcutaneous  tissue 
from  the  xiphoid  cartilage  downwards  for 
3  or  4  inches.  The  linea  alba  will  now  be  seen 
as  a  white  mesial  streak.  Open  the  abdomen 
by  an  incision  through  it.  Pull  over  the 
stomach  towards  the  right,  and  stitch  it  to 
the  abdominal  wall,  open  it,  and  insert  a 
stomach  cannula  (Fig.  175).  Make  an  incision  Fig.  175. — Stomach 
through  the  serosa  and  muscularis.  Doubly  Cannula, 
ligate  and  divide  any  vessels  exposed  in  the 

submucosa.  Then  make  an  opening  in  the  mucosa  of  sufficient  size  to 
just  admit  the  gastric  cannula.  This  will  go  into  a  smaller  opening  if  it 
is  provided  with  a  nick  in  the  flange  which  enters  the  stomach.  Be 
careful  to  prevent  blood  from  getting  into  the  stomach.  Immediately 
stitch  the  wound  in  the  stomach  over  the  flange  of  the  cannula,  but 
do  not  pass  the  stitches  through  to  the  internal  surface  of  the  mucosa. 
Suture  the  muscles  and  skin  separately.  Then  stitch  up  the  wound  in 
the  abdomen.  Wash  out  any  stomach  contents  with  warm  water.  Put 
a  cork  in  the  cannula,  and  cover  the  animal  with  a  cloth.  The  follow- 
ing experiments  may  now  be  performed :  Expose  both  vagi  in  the  neck. 
Connect  two  pairs  of  electrodes  with  the  secondary  coil  of  an  induc- 
torium  arranged  for  single  shocks.  By  means  of  a  key  in  the  primary 
stimulate  the  nerves  with  slow  rhythmical  induction  shocks  at  the  rate 
of  about  one  a  second.  Continue  the  stimulation  for  fifteen  minutes, 
collect  any  juice  that  may  have  been  .secreted,  and  apply  the  tests  in  (3). 
If  secretion  is  slow,  a  little  distilled  water  may  be  put  into  the  stomach, 
and  the  vagus  stimulation  repeated.  Mechanical  stimulation  of  the 
mucous  membrane  with  a  feather  causes  no  secretion  of  acid  gastric 
juice,  but  may  cause  a  secretion  of  alkaline  mucus. 

(3)  (*)  Test  the  reaction  to  litmus  of  the  chyme  obtained  in  (i),  and 
of  the  pure  juice  obtained  in  (2). 

[b)  Test  their  proteolytic  powers  by  putting  in  a  bath  at  40°  C.  for 
two  hours  two  test-tubes  containing  respectively  filtered  chyme  and 


^f^  DIGESTION  AND  ABSORPTION 

fibrin,  and  gastric  juice  and  fibrin.     The  fibrin  will  be  digested  in  both. 
Estimate  the  proteolytic  power  quantitatively  by  Mctt's  tubes  (p.  454). 

(c)  Add  a  few  drops  of  the  chyme  and  gastric  juice  to  milk  in  two 
test-tubes,  and  place  them  in  a  bath  at  40°  C.  Repeat  (c)  after  neutral- 
izing the  liquids, 

(d)  Examine  a  drop  of  the  unfiltered  chyme  under  the  microscope. 
Partially  digested  fragments  of  the  food  will  be  seen — muscular  fibres 
or  fat  cells.     Filter,  and  proceed  as  in  8  {d)  (p.  458). 

(4)  Test  the  filtrate  from  the  chyme  and  the  gastric  juice  for  lactic 
acid  by  Uffelmann's  test  or  Hopkins's  test  (p.  821),  and  for  hydrochloric 
acid  by  Giinzburg's  reagent. 

Uffelmann's  Test  for  Lactic  Acid. — The  reagent  is  a  dilute  solution 
of  carbolic  acid  to  which  dilute  ferric  cliloride  has  been  added  till  the 
colour  is  bluish  (say  a  drop  of  a  i  per  cent,  ferric  chloride  solution  to 
5  c.c.  of  a  I  per  cent,  carbolic  acid  solution).  The  blue  colour  of  the 
mixture  is  turned  yellow  by  lactic  acid,  but  not  by  dilute  hydrochloric 
acid.  Since  Uffelmann's  test  is  given  also  by  phosphates,  alcohol,  and 
sugar,  which  may  sometimes  be  present  in  the  stomach  contents,  it  is 
best  to  shake  the  gastric  contents  with  ether,  dissolve  the  ethereal 
extract  in  water,  and  then  make  the  test  on  the  watery  solution. 

Giinzburg's  Reagent  for  Free  Hydrochloric  Acid  in  Gastric  Juice  is 
made  by  dissolving  2  parts  of  phloroglucinol  and  i  part  of  vanillin  in 
30  parts  by  weight  of  absolute  alcohol.  A  few  drops  of  the  reagent 
are  added  to  a  few  drops  of  the  filtered  gastric  juice  in  a  small  porcelain 
capsule,  and  the  whole  evaporated  to  dryness  over  a  small  bunscn 
flame.  If  free  hydrochloric  acid  is  present,  a  carmine-red  residue  is 
left.  If  all  the  hydrochloric  acid  is  united  to  proteins  in  the  stomach 
contents,  the  reaction  does  not  succeed.  It  is  also  hindered  by  the 
presence  of  Icucin. 

10.  Pancreatic  Juice. — (a)  Take  a  piece  of  the  pancreas  of  an  ox  or 
dog  which  has  been  kept  twenty-four  hours  at  the  temperature  of  the 
laboratory,  and  make  a  glycerin  extract  in  the  same  way  as  in  the 
case  of  the  pig's  stomach  in  8  (6).  Put  in  a  small  bottle,  and  set  aside 
for  a  day  or  two. 

{b)  Put  a  little  boiled  fibrin  into  each  of  six  test -tubes.  A,  B,  C,  D,  E, 
F.  To  A  add  a  few  drops  of  glycerin  extract  of  pancreas,  and  fill  up 
with  a  I  per  cent,  sodium  carbonate  solution ;  to  B  add  glycerin  extract 
and  distilled  water;  to  C  glycerin  extract  and  excess  of  005  per  cent, 
hydrochloric  acid;  to  D  i  per  cent,  sodium  carbonate  alone;  to  E  i  per 
cent,  sodium  carbonate  in  which  a  few  drops  of  glycerin  extract  of 
pancreas  have  been  previously  boiled;  to  F  glycerin  extract  and  excess 
of  0-2  per  cent,  hydrochloric  acid.* 

Set  up  six  test-tubes,  A',  B',  C,  D',  E',  F',  in  the  same  way,  but 
substitute  a  few  drops  of  a  solution  of  commercial  pancrcatin  for  the 
glycerin  extract.  Set  up  two  test-tubss  as  in  cxp:riment  8  (p.  458) 
with  Mett's  tubes.  Put  all  the  test-tubes  in  a  tumbler,  and  place  in  a 
bath  at  40°  C.  The  fibrin  will  be  gradually  eaten  away  in  A  and  A^ 
by  the  action  of  the  trypsin,  but  will  not  swell  up  or  become  clear 
before  disappearing,  as  it  does  in  dilute  hydrochloric  acid  with  glycerin 

*  With  hydrochloric  acid  of  different  strengths  the  rapidity  of  digestion 
of  boiled  fibrin  by  glycerin  extract  of  dog's  pancreas  (i  volume  of  extract 
to  25  of  acid)  was  found  about  the  same  for  o"3  and  o'ly  per  cent,  acid;  much 
less  for  o-o8  per  cent.,  while  in  0*04  per  cent,  acid  there  was  practically  no 
digestion  at  all.  In  0-4  per  cent,  acid  digestion  took  place  more  rapidly  than 
in  o-o8  per  cent.,  but  much  less  rapidly  than  in  o'lj  per  cent.  In  acid  of  all 
strengths  digestion  was  markedly  slower  than  in  i  per  cent,  sodium  car- 
bonate. 


PRACTICAL  EXERCISES  461 

extract  of  stomach.  Filter  the  contents  of  these  test -tubes.  Neutralize 
the  filtrate  witli  dilute  acid;  a  precipitate  will  consist  of  alkali-albumin. 
If  such  a  prc'cij)itatc  is  obtained,  filter  it  off  and  test  the  filtrate  for 
proteoses  and  peptones  as  in  8  [d)  (p.  438).  Some  digestion,  and  perhaps 
a  considerable  amount,  may  also  liave  taken  place  in  F  and  F';  less 
or  none  at  all  in  C  and  C ;  and  none  in  the  other  Lest -tubes  (pp.  359,  420). 

(c)  Add  a  few  drops  of  the  glycerin  extract  to  a  test-tube  containing 
starch  mucilage,  which  has  been  previously  found  free  from  reducing 
sugar.  Put  in  a  bath  at  40°  C.  After  a  short  time  abundance  of 
reducing  sugar  will  be  found,  owing  to  the  action  of  the  ferment, 
amylopsin,  or  pancreatic  amylase. 

{d)  Mince  thoroughly  a  good-sized  piece  of  fresh  pancreas,  and  shake 
up  well  with  three  or  tour  times  its  bulk  of  water.  Put  5  c.c.  of  fresh 
cream  into  a  test-tube,  then  10  c.c.  of  the  extract,  a  few  drops  of  chloro- 
form to  prevent  the  growth  of  bacteria,  a  few  drops  of  litmus  solution, 
and  if  necessary  enough  of  very  dilute  sodium  hydroxide  to  just  render 
the  colour  distinctly  blue.  Shake  up,  and  divide  the  mixture  into  two 
portions,  A  and  B.  Boil  one  portion  (B),  and  place  the  test-tubes  at 
40°  C.  Examine  from  time  to  time .  The  blue  colour  will  disappear  in 
A,  owing  to  the  formation  of  fatty  acids  from  the  neutral  fats,  and 
sodium  hydroxide  must  be  added  to  it  to  restore  the  colour.  In  B  the 
fat-splitting  ferment  has  been  destroyed  by  boiling,  and  fat-splitting 
will  not  occur.  Probably  a  distinct  result  will  not  be  obtained  for 
several  hours,  and  it  will  be  best  to  leave  the  tubes  in  the  incubator 
overnight. 

(e)  If  the  laboratory  possesses  an  animal  with  a  pancreatic  fistula, 
the  following  experiment  may  be  done  by  a  limited  number  of  students 
with  fresh  pancreatic  juice*  collected  from  the  fistula.  Take  five  test- 
tubes,  A,  B,  C,  D,  E.  Add  5  c.c.  of  pancreatic  juice  to  each  tube.  Boil 
E,  and  then  cool  it.  Put  into  A  and  B  small  pieces  of  heat-coagulated 
egg-white,  into  C  a  little  starch  mucilage,  and  into  D  and  E  5  c.c.  of 
fresh  cream.  Add  further  to  B  a  scraping  of  the  mucous  membrane  of 
the  upper  part  of  the  small  intestine  which  has  first  been  washed  free  of 
contents.  To  D  and  E  add  a  drop  or  two  of  litmus  solution,  and,  if 
necessary,  enough  of  dilute  sodium  hydroxide  to  just  establish  a  blue 
colour.  Then  put  the  test-tubes  at  40°  C,  and  examine  after  a  time. 
No  digestion  will  have  taken  place  in  A,  because  the  pancreatic  juice,  as 
secreted,  does  not  contain  active  trypsin.  In  B  digestion  may  take 
place,  because  the  entero kinase  in  the  intestinal  mucous  membrane 
will  activate  the  trypsinogen  to  trypsin.  In  C  and  D  there  will  be 
evidence  of  the  production  of  reducing  sugar  and  fatty  acids  respec- 
tively, since  the  pancreatic  juice,  as  secreted,  contains  active  amylase 
and  steapsin.     E  will  be  unchanged  unless  by  bacterial  action. 

(/)  Leucin  and  Tyrosin. — As  examples  of  amino-acids  formed  when 
pancreatic  digestion  of  proteins  (fibrin  or  casein,  e.g.)  is  allowed  to  go 
on  for  some  days, f  leucin  and  tryosin  maybe  isolated.  Add  bromine- 
water  by  drops  to  5  c.c.  of  the  digest;  a  pink  colour  indicates  trypto- 
phane. If  the  '  digest  '  be  neutralized,  then  filtered,  and  the  filtrate 
concentrated  and  allowed  to  stand,  a  crop  of  tyrosin  crystals  will 
separate  out,  since  tyrosin  is  only  slightly  soluble  in  watery  solutions 
of  neutral  salts.  These  crystals  having  been  filtered  off,  the  proteoses 
(albumoses)  and  peptones  can  be  precipitated  together  by  alcohol,  and 

*  A  considerable  flow  of  pancreatic  juice  can  be  obtained  from  a  dog  with 
a  pancreatic  fistula  by  injecting  intravenously  an  extract  of  intestinal  mucous 
membrane  containing  secretin  (p.  407). 

I  A  little  chloroform  is  added  to  prevent  bacterial  growth. 


46a  DIGESTION  AND  ABSORPTION 

afterwards  separated,  if  that  is  desired,  by  redissolving  the  precipitate 
in  water  and  throwing  down  the  proteoses  by  saturation  with  am- 
monium sulphate.  The  alcohohc  filtrate  will  contain  any  leucin  that 
may  be  present,  since  that  body  is  moderately  soluble  in  alcohol,  as 
well  as  traces  of  tyrosin,  which,  however,  is  much  less  soluble  in  this 
medium.  On  concentration,  crystals  of  both  substances  will  be  ob- 
tained. Tyrosin  crystallizes  characteristically  from  animal  liquids  in 
beautiful  silky  needles  united  into  sheaves,  leucin  in  the  form  of  in- 
distinct fatty-looking  balls,  often  marked  with  radial  striae  and  coloured 
with  pigment  (Figs.  i86  and  187,  p.  488). 

Tests  for  'Tyrosin  by  Morner's  Test. — Put  a  small  quantity  of  tyrosin 
into  a  test-tube.  Add  about  3  c.c.  of  the  reagent,*  and  heat  gradually 
and  gently  to  the  boiling-point.     A  green  colour  is  obtained. 

II.  Bile. — {a)  Test  the  reaction  of  ox  bile.     It  is  alkaline  to  litmus. 

(b)  Add  dilute  acetic  acid.  A  precipitate  of  bile-mucin  (really 
nucleo-albumin)  falls  down.  Some  of  tlie  bile-pigment  is  also  pre- 
cipitated. Filter.  (Pig's  bile  contains  more  of  the  mucin-hke  sub- 
stance than  ox  bile.) 

(c)  Put  a  little  of  the  filtrate  from  {b)  or  of  the  original  bile  into  a 
porcelain  capsule,  add  a  drop  or  two  of  a  dilute  solution  of  cane-sugar, 
and  mix  with  the  bile.  Then  add  a  few  drops  of  strong  sulphuric  acid, 
and  stir;  then  a  few  drops  more  of  the  sulphuric  acid,  stirring  all  the 
time.  A  purple  colour  appearing  at  once,  or  after  gentle  heating, 
shows  the  presence  of  bile-acids  (Pettenkofer's  reaction).  The  bile 
may  be  diluted  before  the  addition  of  the  sulphuric  acid.  In  this  case 
a  greater  amount  of  the  acid  must  be  added.  Examine  the  purple 
liquid  in  a  test-tube  with  a  spectroscope  (p.  74).  Dilute  the  liquid  with 
water,  adding  some  sulphuric  acid  to  partially  clear  up  the  precipitate 
caused  by  the  water.  Two  absorption  bands  are  seen,  one  to  the  red 
side  of  D,  and  the  other,  a  stronger  and  broader  band,  over  and  to  the 
right  of  E.  When  only  a  very  small  amount  of  bile -salts  is  present, 
the  reaction  is  made  more  sensitive  if  a  solution  of  furfuraldehyde  (i  to 
1,000)  is  used  instead  of  cane-sugar. 

(d)  Hay's  Sulphur  Test. — Sprinkle  a  little  sulphur  (in  the  form  of 
the  fine  powder  known  as  flowers  of  sulphur)  on  the  surface  of  some 
bile  in  a  small  beaker  or  deep  watch-glass.  The  sulphur  will  soon  sink 
to  the  bottom.  Repeat  with  water;  the  sulphur  will  float.  The 
reaction  is  due  to  the  diminution  of  the  surface  tension  produced  by 
the  bile-acids,  and  succeeds  also  in  a  solution  of  bile-salts.  The  test 
is  very  sensitive.  But  in  stomach  contents,  vomit,  or  stools,  it  rarely 
gives  good  results,  since  alcohol  or  acetic  acid  is  often  present  in  the 
gastric  liquid,  and  phenol  and  its  derivatives  in  intestinal  contents, 
and  all  of  these  cause  such  an  alteration  in  the  surface  tension  that  the 
sulphur  sinks.  Ether,  chloroform,  turpentine,  benzine  and  its  deriva- 
tives, anilin  and  soaps,  also  vitiate  the  test  in  the  same  way. 

{e)  Add  yellow  nitric  acid  (containing  nitrous  acid)  to  a  little  bile  on 
a  white  porcelain  slab.  A  play  of  colours,  beginning  with  green  and 
running  through  blue  to  yellow  and  yellowish-brown,  indicates  the 
presence  of  bile-pigment  (Gmelin's  reaction).  The  reaction  may  also 
be  obtained  by  putting  some  yellow  nitric  acid  into  a  test-tube,  and 
then  running  a  little  bile  from  a  pipette  on  to  the  surface  of  the  acid. 
The  play  of  colours  is  seen  at  the  surface  of  contact.  Where  the  bile- 
pigment  is  present  only  in  traces,  some  of  the  liquid  may  be  filtered 

•  The  reagent  for  this  test  is  prepared  by  mixing  thoroughly  i  volume  of 
formalin,  45  volumes  of  distilled  water,  and  53  volumes  of  concentrated 
sulphuric  acid. 


PRACTICAL  EXERCISES  463 

through  white  filter-paper,  and  the  test  apphcd  by  putting  a  drop  of 
the  nitric  acid  on  the  paper. 

(/)  Cholesterin  or  Cholesterol  (Fig.  176) — Preparation. — Extract  a 
powdered  gall-stone  (preferably  a  white  one)  with  hot  alcohol  and  ether 
in  a  test-tube.  Heat  the  test-tube  in  warm  water,  not  in  the  free  flame. 
Put  a  drop  of  the  extract  on  a  slide.  Flat  crystals  of  cholesterin,  often 
chipped  at  the  corners,  separate  out.  (a)  Carefully  allow  a  drop  of 
strong  sulphuric  acid  and  a  drop  of  dilute  iodine  to  run  under  the  cover- 
glass.     A  play  of  colours — violet,  blue,  green,  red — is  seen. 

(yS)  Evaporate  a  drop  of  the  solution  of  cholesterin  in  a  small  porce- 
lain capsule,  add  a  drop  of  strong  nitric  acid,  and  heat  gently  over  a 
flame.  A  yellow  stain  is  left,  which  becomes  red  when  a  drop  of  am- 
monia is  poured  on  it  while  it  is  still  warm. 

(7)  Dissolve  a  little  cholesterin  in  chloroform.  Add  an  equal  bulk 
of  strong  sulphuric  acid,  and  shake  gently.  The  solution  turns  red 
and  the  subjacent  acid  shows  a  green  fluorescence. 

(i^)  Put  a  drop  or  two  of  water  in  a  watch-glass,  and  add  a  drop  of  an 
ethereal  solution  of  cholesterin.  The  cholesterin  is  precipitated,  and 
will  not  dissolve  in  the  water  even  on  heating.  Repeat  the  observation 
with  bile  instead  of  water.     The  cholesterin  dissolves  in  the  bile. 

(g)  To  a  little  of  the  filtrate  from  a 
peptic  digest  {e.g.,  flbrin  which  has  been 
digested  for  twenty-four  hours  with 
pepsin  and  hydrochloric  acid)  add  some 
bile.  A  precipitate  is  thrown  down, 
which  is  redissolved  in  excess  of  the 
bile  (p.  370). 

(A)  Shake  up  a  little  bile  with  some 
rancid  olive-oil  in  a  test-tube.  An  emul- 
sion is  formed.  Repeat  the  experiment 
with  the  same  quantities  of  bile  and  oil, 
but  use  perfectly  fresh  oil.  Compare  the 
stability  of  the  two  emulsions,  allowing 
the  tubes  to  stand  together  for  a  while,      pig.  176. — Crystals  of  Cholesterin 

(t)  To  some  starch  mucilage,  shown  (Frey). 

to  be  free  from  sugar,  add  a  little  bile, 

and  place  in  a  bath  at  40°  C.     After  a  time  test  for  reducing  sugar. 
Report  the  result.     Bile  often  has  a  slight  diastatic  power. 

(/)  To  demonstrate  the  Presence  of  Iron  in  the  Liver  Cells. — Steep  sec- 
tions of  liver  in  a  solution  of  potassium  ferrocyanide,  and  then  in  dilute 
hydrochloric  acid.  Or  a  i  -5  per  cent,  solution  of  potassium  ferrocyanide 
in  0-5  per  cent,  hydrochloric  acid  may  be  used.  (The  iron  may  pre- 
viously be  fixed  in  the  tissue  by  hardening  it  in  a  mixture  of  alcohol 
and  ammonium  sulphide.)  The  sections  become  bluish  from  the 
formation  of  Prussian  blue.  A  fine-pointed  glass  rod  or  a  platinum 
lifter  should  be  used  in  manipulating  them.  A  steel  needle  cannot  be 
employed.  Mount  in  glycerin  or  Farrant's  solution,  or  (after  dehy- 
drating with  alcohol  and  clearing  in  xylol)  in  xylol-balsam.  Blue 
granules  may  be  seen  under  the  microscope  in  some  of  the  hepatic  cells. 
Sections  of  spleen  may  also  be  examined  for  this  reaction. 

12.  Microscopical  Examination  of  Faeces. — Examine  under  the  micro- 
scope the  slides  provided.  Draw,  and  as  far  as  possible  determine  the 
nature  of,  the  objects  seen  (p.  424). 

13.  Absorption  of  Fat. — (a)  Feed  a  rat  or  frog  with  fatty  food;  kill 
the  rat  in  three  or  four  hours,  the  frog  in  two  or  three  days.  Imme- 
diately after  killing  the  rat  open  the  abdomen,  carefully  draw  out  a 
loop  of  intestine,  and  look  through  the  thin  mesentery.     The  white 


464  DIGESTION  AND  ABSORPTION 

lactcals  will  probably  be  seen  ramifying  in  tlic  mesentery.  They 
appear  white  on  account  of  the  presence  of  globules  of  fat  in  the  chyle 
with  which  they  arc  filled.  Strip  off  tiny  pieces  of  the  mucous  mem- 
brane of  the  small  intestine,  and  steep  them  in  J  per  cent,  solution  of 
osmic  acid  for  forty-eight  hours.  Then  tease  fragments  of  the  mucous 
membrane  in  glycerin  and  examine  under  the  microscope.  To  preserve 
the  specimens  take  off  the  glycerin  with  blotting-paper  and  mount  in 
Farraut's  medium,  which  is  a  preservative  glycerin  mixture.  Other 
portions  of  the  mucous  membrane  may  be  hardened  for  a  fortnight  in 
a  mixture  of  z  parts  of  Miiller's  fluid  and  i  part  of  a  i  per  cent,  solution 
of  osmic  acid.  Sections  are  then  mauc  with  a  freezing  microtome  after 
embedding  in  gum.  No  process  must  be  used  by  which  the  fat  would 
be  dissolved  out  (Schafer).      (See  Fig.  172,  p.  441.) 

(6)  Feed  a  cat  with  30  grammes  of  butter  stained  a  deep  red  with  the 
dye  Sudan  III.  After  five  hours  anaesthetize  the  animal  with  ether, 
insert  a  cannula  in  the  carotid  artery,  and  obtain  a  sample  of  blood. 
Defibrinate  the  blood,  and  separate  the  serum  by  the  centrifuge.  If 
digestion  and  absorption  of  the  fat  have  proceeded  normally,  the 
serum  will  contain  numerous  fat  droplets,  and  will  be  tinged  pink  by 
the  dye,  which  can  be  dissolved  out  of  it  by  shaking  up  with  ether.  On 
opening  the  abdomen  it  will  be  seen  that  the  mucous  membrane  of  the 
small  intestine,  as  far  down  as  the  fat  has  reached,  is  stained  pink,  and 
that  the  lacteals  in  the  mesentery  are  also  pink.  Observe  whether  any 
of  the  pigment  has  passed  into  the  urine. 

14*  Time  required  for  Digestion  and  Absorption  of  Various  Food 
Substances. — Feed  three  dogs,  A,  B,  and  C",  which  have  previously  fasted 
for  twenty-four  hours,  with  a  meal  containing  starch  (proved  to  be  free 
from  sugar),  lard,  and  meat. 

(i)  After  fifteen  minutes  inject  subcutaneously  into  A  2  c.c.  of  a 
O'l  per  cent,  solution  of  apomorphine.  Note  the  time  which  elapses 
before  the  animal  vomits.     Collect  the  vomit. 

(a)  Examine  a  little  of  it  imder  the  microscope,  and  make  out  fat 
globules,  muscular  fibres  and  starch  granules.  The  latter  can  be  recog- 
nized by  their  being  coloured  blue  by  a  drop  or  two  of  iodine  solution. 

(6)  Filter  the  chyme,  mixing  it,  if  necessary,  with  a  little  water,  and 
test  it  as  in  8  (d)  (p.  458)  for  the  products  of  digestion  of  proteins.  In 
addition,  test  for  starch,  dextrin,  and  reducing  sugar. 

(2)  One  and  a  quarter  hours  after  the  meal  inject  apomorphine  into 
dog  B,  and  proceed  as  in  (i). 

(3)  Two  and  a  half  hours  after  the  meal  inject  apomorphine  into 
dog  C,  and  proceed  as  in  (i).  Compare  the  results  from  the  three 
specimens  of  chyme. 

15.*  Quantity  of  Cane-Sugar  inverted  and  absorbed  in  a  Given  Time. — 
Take  three  dogs,  A,  B.  and  C,  which  have  fasted  for  twenty-four  hours. 
The  animals  should  be  about  the  same  size.  Feed  A  and  B  with 
100  c.c.  of  a  standard  solution  of  cane-sugar  (about  a  20  per  cent,  solu- 
tion), or  as  much  more  as  they  will  take.  If  the  dogs  have  been  kept 
without  water  for  a  day  they  will  more  readily  take  the  sugar  solution. 
Or  it  may  be  given  through  a  tube  passed  into  the  stomach,  and  in 
this  case  a  larger  quantity  of  sugar  can  be  given.  A  gag  consisting  of 
a  piece  of  wood  with  a  hole  in  the  middle  of  it,  through  which  the  tube 
is  passed,   must  first  be  secured  in  the  dog's  mouth.     Feed  C  with 

*  Experiments  14  and  15  are  conveniently  done  in  a  class  by  assigning 
each  of  the  three  animals  to  a  separate  set  of  students.  The  contents  of  the 
stomach  and  intestine  are  divided  into  three  portions,  so  that  each  set  has 
a  sample  from  each  dog. 


PRACTICAL  EXhRCISES  465 

50  grammes  of  powdered  cane-sugar  mixed  with  lard,  tin-  mixture  bemg 
rolled  into  little  balls. 

(i)  After  a  quarter  of  an  hour  put  A  under  chloroform  or  the  A.C.E. 
mixture,  and  fasten  it  on  a  holder.  Kill  the  animal  witli  chloroform, 
open  the  abdomen,  tie  the  oesophagus,  place  double  ligatures  on  the 
pyloric  end  of  the  stomach  and  the  lower  end  of  the  small  intestine,  and 
divide  between  them.  Cut  out  the  stomach  imd  intestine ;  wash  their 
contents  into  separate  vessels,  and  test  th.'  reaction  with  litmus  paper. 
Add  water  and  rub  up  thoroughly.  Filter.  Wash  the  residue  re- 
peatedly with  small  quantities  of  water,  and  pass  all  the  washings 
through  the  filter.     Make  up  each  of  the  two  filtrates  to  200  c.c. 

(a)  Test  the  filtrates  from  the  contents  of  the  stomach  and  intes- 
tines qualitatively  for  dextrose  by  Trommcr's  (p.  10)  or  Fehling's 
(p.  526)  and  the  phenyl-hydrazine  test  (p.  525). 

(b)  li  no  reducing  sugar  is  present,  add  to  20  c.c.  of  each  filtrate  I  c.c. 
of  hydrochloric  acid,  boil  for  half  an  hour,  and  again  test  for  reducing 
sugar.     If  it  is  now  found,  some  cane-sugar  is  present. 

(c)  If  reducing  sugar  is  found,  estimate  its  amount  as  dextrose  bj- 
Fehling's  solution  (p.  527)  in  a  measured  quantity  of  the  original 
filtrate  of  the  gastric  or  intestinal  contents  before  and  after  boiling 
with  one-twentieth  of  its  volume  of  hydrochloric  acid. 

{d)  Estimate  in  the  same  way  the  amount  (as  dextrose)  of  the  invert 
sugar  in  the  standard  solution  of  cane-sugar  after  inversion,  and  before 
inversion  if  it  gives  the  qualitative  test  for  reducing  sugar  before  it  has 
been  boiled  with  acid. 

From  the  data  obtained  (and  taking  95  parts  of  cane-sugar  as  equal 
to  100  parts  of  dextrose)  calculate  the  amount  of  cane-sugar  absorbed, 
left  unchanged,  and  inverted,  though  not  absorbed. 

(2)  One  and  a  half  hours  after  the  meal  anaesthetize  B,  and  proceed 
as  in  (i). 

(3)  Two  hours  after  the  meal  proceed  in  the  same  way  with  C.  But 
in  addition  observe  the  lacteals  in  the  mesentery,  by  gently  lifting  up 
a  loop  of  intestine  immediately  after  opening  the  abdomen.  If  the 
absorption  of  the  fat  has  begun,  they  will  be  easily  visible,  as  a  network 
of  fine  milk-white  vessels.  Also  examine  the  gastric  and  intestinal 
contents  with  the  microscope  for  fat  globules.  Compare  your  results 
on  the  amount  of  sugar  obtained  from  the  three  animals.  Probably 
much  more  unabsorbed  sugar  will  be  found  in  C  than  in  B,  as  the  lard 
hinders  it  from  being  dissolved. 

16.  Auto-Digestion  of  the  Stomach. — In  some  of  the  previous  experi- 
ments the  stomach  of  an  animal  killed  during  digestion  should  be 
removed  from  the  body  after  double  ligation  of  oesophagus  and  duo- 
denum, and  placed  in  a  water-bath  at  40°  C.  After  several  hours  the 
contents  should  be  washed  out  and  the  mucous  membrane  examined. 
It  may  be  entirely  eaten  away  in  parts. 


30 


CHAPTER  VI IT 
FORMATION  OF  LYMPH 

Different  Kinds  of  Lymph. — We  ought  to  distinguisli  the  lymph 
as  we  collect  it  from  the  great  lymphatic  trunks,  not  only  from  the 
liquids  of  the  serous  cavities,  but  still  more  sharply  from  the  hquid 
which  fills  the  multitudinous  clefts  and  spaces  of  the  tissues.  It  is 
now  pretty  definitely  established  that  the  tissue  spaces  do  not  com- 
municate by  actual  passages  with  the  lymphatic  vessels,  but  that 
the  latter  form  everywhere  a  closed  system  like  the  blood-vascular 
system,  the  lymph  capillaries  merely  lying  in  the  tissue  spaces 
(Sabin,  etc.).  This  conception  entails  a  radical  change  in  the 
current  views  of  lymph  production.  If  the  lymphatics  form  a 
closed  system,  the  lymph  cannot  be  actual  tissue  fluid,  but  only 
tissue  fluid  modified  by  its  passage  through  the  walls  of  the  lymph 
capillaries,  just  as  tissue  fluid  is  not  actual  blood-plasma,  but  plasma 
modified  by  its  passage  thrcagh  the  walls  of  the  blood  capillaries 
as  well  as  by  exchange  with  the  tissue  elements. 

Although  it  is  customary  to  speak  of  the  lymph  obtained  from 
the  lymphatic  vessels  as  if  it  were  perfectly  homogeneous,  there  is 
no  experimental  ground  for  supposing  that  the  lymph  from  different 
tracts,  or  the  tissue  liquid  in  contact  with  the  cells  of  different 
organs,  or  even  the  tissue  liquid  in  contact  with  one  and  the  same 
cell  at  different  parts  of  its  periphery,  has  a  uniform  composition, 
or  even  a  uniform  molecular  concentration.  There  are,  indeed, 
certain  general  considerations  which  show  that  this  cannot  be  so. 
Still  less  can  it  be  assumed  that  the  serous  cavities,  although  they 
come  into  relation  with  lymphatics  and  bloodvessels  in  their  walls, 
are  analogous  to  colossal  tissue  spaces  or  even  to  expansions  of  the 
closed  lymphatic  system,  or  that  the  liquids  contained  in  them, 
normally  in  scant  amount,  are  simply  tissue,  or  if  not  tissue,  then 
simply  lymphatic  lymph.  The  cerebrospinal  fluid,  which  bathes 
the  external  surface  of  the  central  nervous  system  and  fills  its 
cavities,  and  the  special  liquids  of  the  eyeball — the  aqueous  humour 
and  the  liquid  of  the  vitreous  humour — although  no  doubt,  in 
addition  to  their  other  functions,  they  may  in  some  degree  minister 
to  the  nutrition  of  the  tissues  with  which  they  are  in  contact,  are 

466 


FACTORS  CONCERNED  IN  LYMPH  FORMATION  467 

as  regards  their  composition  and  mode  of  formation  scarcely  nnjre 
closely  allied  to  lymph  than  sweat  is.  They  are  almost  free  from 
protein,  and  are  secreted  by  special  structures — the  choroid  plexus 
and  the  uveal  epithelium — quite  different  from  any  that  can  be 
concerned  in  the  formation  of  ordinary  lymph. 

It  is  very  true  these  liquitls  are  not  blood,  but  that  is  scarcely  a 
sufficient  reason  for  calling  them  lymph,  else  we  might  classify 
sweat  or  even  milk  as  lymph  also.  If  a  term  is  desirable  to  indicate 
that  they  have  certain  relations  with  lymph,  they  might  perhaps 
be  spoken  of  as  lymphoid  secretions.  It  may  be  that  the  essentiaJ 
difference  in  the  chemical  composition  of  these  lymphoid  secretions 
and  lymph — -the  practical  absence  of  protein — -is  related  to  the 
difference  in  the  manner  of  their  formation.  The  uveal  and  choroidal 
epithelial  cells,  interposing  the  depth  of  their  columns  or  cubes 
between  the  blood  and  the  free  surface  at  which  the  liquid  escapes, 
may  well  be  suited  to  hinder  the  passage  of  the  protein  molecules 
which  find  their  way  with  greater  ease  through  the  thin  endothelium 
of  the  capillary  wall  into  the  tissue  spaces,  and  from  these  into  the 
lumen  of  the  closed  lymphatics  (see  p.  439)-  Nevertheless,  we  shall 
recognize  later  on  in  the  glomeruli  of  the  kidney  an  instance  of 
blood  capillaries  but  little  pervious  to  proteins,  and  there  are  several 
other  facts  which  show  that  the  capillaries  may  differ  considerably 
in  different  organs  in  the  readiness  with  which  the}'  permit  the 
various  constituents  of  the  plasma  to  pass  through  their  walls. 
Further,  in  discussing  the  mechanism  by  which  lymph  is  formed, 
we  shall  see  reason  to  doubt  whether  mechanical  filtration,  due  to 
differences  of  hydrostatic  pressure  on  the  two  surfaces  of  the 
capillary  endothelium,  has  much,  if  anj^thing,  to  do  with  the 
passage  either  of  protein  or  of  the  other  constituents  of  the  lymph 
from  the  lumen  of  the  capillaries  into  the  tissue  spaces.  At  first 
glance,  indeed,  such  a  process  would  seem  to  be  admirably  fitted  to 
explain  the  fact  that,  while  lymph  differs  but  little  from  blood- 
plasma  in  the  proportions  of  its  other  constituents,  it  is  at  most  no 
more  than  half  as  rich  in  protein.  For  there  are  many  filters  which 
allow  substances  in  ordinary  solution  and  their  solvent  to  pass 
through  without  alteration  in  their  relative  proportions,  while 
substances  like  proteins  in  colloid  solution  are  kept  back  to  a 
greater  or  less  extent. 

Factors  concerned  in  Lymph  Formation. — ^The  teaching  of  Ludwig, 
that  lyinph  is  formed  by  the  filtration,  and  in  a  minor  degree  by  the 
diffusion,  of  the  constituents  of  blood-plasma  through  the  walls  of  the 
capillaries  into  the  tissue  spaces,  was  based  on  such  facts  as  the 
increase  in  the  tissue  liquid  of  a  limb  or  organ  which  occurs  when 
the  exit  of  blood  from  it  by  the  veins  is  hindered,  or  when  the 
quantity  of  the  circulating  liquid  is  increased  by  the  injection  of 
blood  or  salt  solution.     It  was  first  seriously  called  in  question  by 


468  FORMATION  OF  LYMPH 

Heidenhain,  who  advanced  the  theory  that  lymph  is  secreted  by 
the  endothelium  of  the  blood  capillaries.  One  of  Heidenhain's 
strongest  arguments  in  favour  of  his  secretion  theory  was  the 
existence  of  substances  which,  when  injected  into  the  blood,  in- 
creased the  flow  of  lymph  from  the  thoracic  duct  of  the  dog  without 
affecting  appreciably  the  arterial  pressure.  He  divided  these  so- 
called  lymphagogues  into  two  classes:  (i)  Substances  like  peptone, 
extracts  of  the  head  and  liver  of  the  leech,  extract  of  crayfish 
muscle,  egg-albumin,  etc.,  which  cause  not  onh^  an  increase  in  the 
rate  of  flow,  but  an  increase  in  the  specific  gravity  and  total  solids 
of  the  lymph;  (2)  crystalloid  substances,  hke  sugar,  salt,  etc.,  which 
cause  an  increased  flow  of  lymph  more  watery  than  normal. 

Starling  has  shov.  ;i  that,  although  the  lymphagogues  of  the  second 
class  do  not  raise  the  arterial  pressure,  they  do,  by  attracting  water 
from  the  tissues  and  thus  causing  hydreemic  plethora  (an  excess  of 
blood  of  low  specific  gravity),  bring  about  a  marked  rise  of  venous, 
and  therefore,  what  is  the  important  thing  for  lymph  filtration,  of 
capillary  pressure.  But  it  can  be  demonstrated  that  vaso-dilata- 
tion  with  increase  of  capillary  pressure  is  not  in  itself  sufficient  to 
increase  the  fornicition  of  lymph.  We  have  seen,  e.g.  (p.  179),  that 
when  the  chorda  tympani  nerve  is  stimulated  in  the  dog  the  arteri- 
oles of  the  submaxillar}'  gland  are  dilated,  and  no  doubt  the  pres- 
sure in  the  capillaries  is  increased.  No  increased  flow  of  lymph, 
however,  takes  place  from  the  submaxillary  lymphatics  during  even 
prolonged  excitation  of  the  chorda,  nor  do  the  lymph  spaces  of  the 
gland  become  distended  (Heidenhain).  In  the  horse  also  the  spon- 
taneous flow  of  lymph  from  the  quiescent  parotid  is  not  appreciably 
altered  by  excitation  of  the  secretory  nerves  of  the  gland  or  by 
pilocarpine  (Carlson).  There  is  every  reason  to  believe  that  during 
active  secretion  of  saliva  tissue  liquid  is  really  formed  from  the 
blood  in  increased  amount,  and  that  it  is  from  the  tissue  spaces 
that  the  gland-cells  directly  obtain  the  increased  supply  of  water 
and  other  substances  necessary  to  sustain  the  increased  secretion. 
But  a  balance  is  maintained  between  the  production  of  tissue  liquid 
and  its  removal  by  the  gland-cells.  When  the  gland  is  quiescent, 
the  small  amount  of  tissue  liquid  normally  formed  from  the  blood 
capillaries  for  the  nutrition  of  the  cells  is  balanced  by,  upon  the 
whole,  an  equal  amount  of  lymph  secreted  from  the  tissue  spaces 
into  the  lymph  capillaries. 

We  may  say,  indeed,  that  the  closed  lymphatic  system  has  for 
its  great  function  the  regulation  of  the  quantity  and  quality  of  the 
tissue  liquid.  In  glands  with  an  external  secretion  increased  irriga- 
tion of  the  tissue  spaces  from  the  blood  does  not  as  a  rule  lead  to 
increased  flow  of  lymph,  because  the  surplus  fluid  is  required  to 
form  the  secretion.  In  other  organs,  however,  such  as  the  muscles 
and  the  ductless  glands,  it  is  probable  that  the  augmented  irriga- 


FACTORS  CONCERNED  IN  LYMPH  FORMATION  469 

tion  rendered  necessary  by  functional  activity  is  always  associated 
with  an  accelerated  flow  of  lymph,  which  carries  off  the  surplus 
liquid,  including  a  ])ortion  of  the  waste  products.  It  is  probable 
that  an  important  factor  in  the  production  of  oedema  may  be  the 
derangement  of  the  mechanism,  whatever  it  is,  through  which  the 
adjustment  of  the  rate  of  formation  of  tissue  liquid  to  that  of 
lymphatic  lymph  is  achieved.  But  it  must  be  remembered  that  in 
all  the  organs  the  blood  capillaries  not  only  supply  materials  to  the 
tissue  spaces,  but  take  up  materials  from  them.  Indeed,  there  are 
facts  which  indicate  that  in  general  water  and  dissolved  substances 
pass  more  easily  and  in  greater  amount  back  from  the  tissues  into 
the  blood  than  into  the  lymphatics.  So  that,  while  the  lymphatics 
constitute  an  accessory  drainage  system,  the  bloodvessels  irrigate 
the  tissues  and  drain  them  as  well.  A  consequence  of  this,  as  well 
as  of  the  great  difference  in  the  capacity  of  the  different  tissues  for 
storing  water,  is  that  the  amount  of  tissue  lymph  formed  can  never 
be  estimated  from  the  amount  of  lymphatic  lymph  leaving  an  organ. 
Thus  the  flow  of  lymph  from  the  limbs  at  rest  is  very  small  in  com- 
parison with  the  flow  from  the  abdominal  viscera,  which  constitutes 
the  great  bulk  of  the  lymph  passing  along  the  thoracic  duct.  This, 
however,  does  not  prove  that  very  little  liquid  passes  out  of  the 
limb  capillaries,  for  the  chief  tissue  of  the  limbs,  the  muscles,  pos- 
sesses a  far  greater  storage  capacity  for  water  than  the  intestines  and 
digestive  glands.  In  the  one  case  we  have  a  field  whose  soil  takes 
up  a  great  deal  of  water  and  is  not  easily  saturated ;  in  the  other  a 
field  whose  soil  soon  becomes  water-logged  and  refuses  to  take  up 
any  more.  With  the  same  supply  from  the  irrigating  ditch,  little 
or  no  water  may  drain  off  at  the  foot  of  the  first  field,  a  great  deal 
at  the  foot  of  the  second. 

Where  the  main  lymphatics  are  themselves  blocked  by  mechanical 
pressure  or  by  inclusion  in  a  ligature,  the  balance  is,  of  course, 
grossly  upset  by  the  failure  of  the  outflow  of  lymph  to  keep  pace 
with  its  formation.  Where  an  obstruction  on  the  course  of  the 
veins  is  responsible  for  the  oedema,  the  lymphatic  outflow,  to  be 
sure,  is  not  directly  interfered  with.  But  the  nutrition  and  the 
respiration  of  the  vascular  walls  themselves,  including  the  endo- 
thelium of  the  capillaries,  necessarily  suffers  from  the  insufficiency 
of  the  blood-flow,  and  the  crippled  capillaries  may  very  well  become 
abnormally  permeable  for  water,  salts,  and  the  other  constituents 
of  lymph.  And  while  ordinary  mechanical  filtration  may  not  be  a 
factor,  or  a  very  unimportant  one,  in  the  passage  of  Uquid  through 
the  normal  capillary  wall,  it  may  become  far  more  effective  when 
it  acts  on  a  damaged  wall.  The  tissue  cells  also  suffer  from  lack 
of  oxygen  and  nutritive  material,  and  from  the  accumulation  of 
waste  products,  including  acid  substances,  which  cause  them  to 
take  up  and  to  hold  more  water  than  normal.     Even  in  the  absence 


470  FORMATION  OF  LYMPH 

of  changes  in  the  mechanical  conditions  of  tiie  blood  and  lymph 
circulations,  alterations  in  the  tissues  must  be  recognized  as  among 
the  causes  of  cedema  (Fischer).  Thus  it  is  clear  that  the  interpre- 
tation of  such  an  apparently  simple  experiment  as  the  production 
of  oedema  by  the  ligation  of  a  vein  needs  great  care.  Whatever  it 
proves,  it  may  be  said  with  confidence  that  it  does  not  prove  that 
the  increased  capillary  pressure  is  the  direct  cause  of  the  oedema. 

A  mere  increase  in  the  capiUary  blood-pressure  does  not  of  itself 
accelerate  the  formation  of  tissue  liquid  from  the  blood  any  more 
than  that  of  lymph  from  the  tissue  liquid,  as  is  shown  by  the  fact 
that,  when  the  chorda  tympani  is  stimulated  after  injection  of  a 
dose  of  atropine  sufficient  to  prevent  all  salivary  secretion,  there  is 
neither  oedema  of  the  gland  nor  increase  in  the  flow  of  lymph  from 
it,  although  the  arterioles  are  as  widely  dilated  as  before.  When  the 
blood-pressure  is  greatly  increased  in  the  anterior  portion  of  an 
animal  by  clamping  the  aorta,  or  in  the  whole  animal  by  continued 
stimulation  of  the  cut  medulla  oblongata  or  the  splanchnic  nerves, 
the  blood  does  not  alter  in  concentration  in  the  least,  showing  that 
no  sensible  increase  in  the  passage  of  water  into  the  lymph  has 
occurred.  After  division  or  embolism  of  the  medulla  oblon- 
gata, and  consequent  paralysis  of  the  vaso-motor  centre  and 
general  vascular  dilatation,  it  is  stated  that  the  injection  of  sodium 
chloride  produces  an  increase  in  the  lymph- flow  as  great  and  as 
durable  as  in  the  normal  animal,  and  which  can  continue  even  after 
death  (Pugliese).  The  action  of  the  first  class  of  lymphagogues, 
which  cannot  be  explained  as  the  consequence  of  an  increase  of 
capillary  pressure,  because  the  pressure  in  the  capillaries  is  not 
consistently  increased,  and  may  even  in  the  case  of  some  of  these 
lymphagogues  be  diminished,  is  attributed  by  Starling  to  an  injurious 
effect  on  the  capillary  endothelium  (and  especially  on  the  endo- 
thelium of  the  capillaries  of  the  liver,  since  nearly  the  whole  of  the 
increased  13'mph-flow  comes  from  that  organ),  which  increases  its 
permeability.  But  it  is  not  easy  to  distinguish  an  increase  of  per- 
meability produced  by  lymphagogues  from  an  increase  of  secretory 
activity  of  the  endothelial  cells. 

Hamburger,  too,  has  brought  forward  results  which  it  is  difficult 
to  reconcile  with  a  theory  of  filtration  even  for  the  second  class  of 
lymphagogues.  Further,  Heidenhain  has  shown  that  some  time 
after  injection  of  a  crystalloid  substance,  like  sugar,  into  the  blood, 
a  greater  percentage  of  the  substance  may  be  found  in  the  lymph 
than  in  the  blood.  Now,  when  a  mixture  of  crystalloitls  and  col- 
loids is  filtered  through  a  thin  membrane,  the  percentage  of  crystal- 
loids in  the  filtrate  is  never,  at  most,  greater  than  in  the  original 
liquid.  And  although  Cohnstein  states  that,  if  time  enough  be 
allowed,  the  maximum  concentration  of  sodium  chloride  in  the 
lymph,   after  intravenous  injection,   becomes  approximately  the 


FACTORS  CONCERNED  IN  LYMPH  FORMATION  47X 

same  as  the  maximum  in  the  blood,  this  fact  loses  its  weight  as 
an  argument  in  favour  of  the  filtration  hypothesis  when  we  re- 
member that,  according  to  Asher,  all  the  solids  of  the  lymph  are 
inurkcdly  increased  when  even  small  quantities  of  crystalloids  are 
injected  into  the  veins.  Upon  the  whole,  tlien,  it  may  be  con- 
cluded that  up  to  the  present  it  has  not  been  shown  that  filtration 
due  to  the  excess  of  pressure  in  the  capillaries  over  that  in  the 
lymph  spaces  is  an  effective  factor  in  the  formation  of  lymph.  Nor 
is  it  at  all  easier  to  explain  lymph  formation  as  a  matter  of  pure 
osmosis  or  diffusion.  Lazarus-Barlow  found,  for  example,  that  in 
the  great  majority  of  his  experiments  the  injection  of  a  concen- 
trated solution  of  sodium  chloride,  dextrose  or  urea  into  a  vein  was 
followed,  not  by  an  initial  diminution  in  the  outflow  of  lymph  (as 
might  have  been  expected  if  the  exchange  of  water  between  the 
blood  and  the  tissue  spaces,  and  between  the  tissue  spaces  and  the 
lymph  capillaries,  was  regulated  solely  by  differences  in  osmotic 
pressure),  but  by  an  immediate  increase.  And  Carlson  has  shown 
that  the  osmotic  pressure  of  lymph  coming  from  the  active  salivary 
glands,  as  measured  by  the  freezing-point  method,  may,  under 
chloroform  or  ether  anaesthesia,  be  distinctly  less  than  that  of  the 
blood-serum.  Water  must  therefore  be  passing  from  a  liquid  of 
higher  to  one  of  lower  osmotic  concentration. 

Nevertheless,  it  would  be  erroneous  to  assume  that  because 
osmosis  and  diffusion  have  not  been  sho\NTi  to  satisfactorily  account 
for  all  the  phenomena  of  lymph  formation,  they  exert  no  influence 
upon  it.  It  is  probable,  indeed,  that  their  action  is  fully  as  im- 
portant as  in  absorption  from  the  alimentary  canal,  although,  as  in 
absorption,  it  is  often  overlaid  and  always  modified  by  the  specific 
permeability  of  the  blood-capillary  walls,  the  lymph-capillary  walls, 
and  the  tissue  cells  in  general,  in  virtue  of  which  they  exert  an 
action  upon  the  quantity  and  composition  of  the  lymph  analogous 
to  the  action  exerted  in  a  higher  degree  by  the  cells  of  the  digestive 
glands  upon  the  quantity  and  composition  of  the  liquids  passing 
into  their  ducts. 

It  is  not  difticult  to  illustrate  the  fact  that  phenomena  of  osmosis  and 
diffusion  emerge,  although  not  of  course  in  such  purity  as  in  physical 
experiments,  when  we  study  the  interchange  between  the  blood  and 
the  tissue  liquids.  If,  for  example,  a  hypertonic  solution  of  sodium 
chloride  is  injected  into  the  blood,  water  rapidly  passes  from  the  tissues 
to  the  blood  as  it  would  through  a  semipermeable  membrane,  and  the 
blood  becomes  diluted.  At  the  same  time  sodium  chloride  leaves  the 
blood  and  passes  into  the  tissues,  as  it  would  do  by  diffusion  from  a 
place  of  higher  to  a  place  of  lower  concentration.  But  after  this  has 
gone  on  for  some  time,  and  the  concentration  of  the  blood  in  salt  has 
sunk,  it  may  be,  to  that  in  the  lymph,  salt  still  continues  to  pass  out 
of  the  blood,  and  the  excess  of  water  also  leaves  the  bloodvessels  till  the 
osmotic  pressure  of  the  blood  has  again  become  normal.  When  isotonic 
and  even  hypotonic  solutions  of  sodium  chloride  are  injected,  salt  also 


472  FORMATION  OF  LYMPH 

leaves  the  blood  and  enters  the  lymph,  although  it  ought  not  to  do  so 
by  ditfusion,  while  water,  which  might  pass  from  the  hypotonic  bloo<l 
into  the  lymph  by  osmosis,  moves  in  the  same  direction  from  the  blood 
to  which  the  isotonic  salt  solution  has  been  added.  Regulative  mechan- 
isms, in  short,  exist  which  tend,  with,  but  also  without,  the  co-opera- 
tion of  diffusion  and  osmosis,  and  even,  so  to  say,  in  their  teeth, 
to  bring  back  the  quantitative  and  qualitative  composition  of  the 
blood  to  the  normal.  Exactly  similar  phenomena  are  witnessed  when 
the  equilibrium  is  upset  from  the  other  side  by  the  injection  of  salt 
solutions  into  the  subcutaneous  tissue  or  the  intramuscular  connective 
tissue.  Hypotonic  sodium  chloride  solution  injected  into  the  sub- 
conjunctival connective  tissue  quickly  loses  water  and  gains  sodium 
chloride,  as  it  ought  to  do  if  under  the  influence  of  osmosis  and  diffusion, 
and  hypertonic  salt  solutions  gain  water.  But  eventually  hypertonic, 
hypotonic,  and  isotonic  solutions,  and  even  serum  itself,  are  completely 
absorbed,  which  could  not  occur  in  the  presence  of  diffusion  and 
osmosis  alone.  Sometimes  in  dropsy  it  appears  that  the  oedema  liquid 
is  absorbed  when  the  patient  is  put  on  a  diet  free  as  far  as  possible 
from  salts.  The  suggestion  is  that  the  regulative  mechanism  which 
tends  to  keep  the  molecular  concentration  of  the  blood  and  lymph 
approximately  constant  provides  that  as  the  salt  content  of  the  body 
falls,  which  it  does  through  continued  excretion  of  salts  in  the  urine, 
water  is  eliminated  in  corresponding  amount. 

The  Contribution  of  the  Tissue-Cells  to  the  Lymph. — So  far  we 
have  considtTed  the  passage  of  the  Ij'mph  constituents,  on  the  one 
hand  through  the  endotlieUum  of  the  blood  capillaries  into  the 
tissue  spaces;  on  the  other,  from  the  tissue  spaces  through  the  endo- 
thelium of  the  lymph  capillaries.  But  it  is  not  to  be  supposed  that 
the  liquid  lying  in  clefts,  partly  bounded  by  blood  capillaries,  partly 
by  h-mph  capillaries,  partly  by  tissue-cells,  should  be  affected  solely 
by  the  first  two.  The  third  anatomical  element  must  contribute 
something  to,  or  withdraw  something  from,  the  tissue  liquid,  and 
may  thus  play  a  part  in  the  formation  of  lymph  from  the  latter. 
The  recent  researches  of  Asher  and  his  pupils  have  raised  the  ques- 
tion of  the  relation  between  the  physiological  activity  of  the  organs, 
and  especially  of  the  glands,  and  the  formation  of  the  lymph.  They 
conclude  that  the  common  doctrine  that  lymph  is  simply  a  diluted 
blood-plasma  is  erroneous.  Lymph,  they  say,  far  from  being  a 
mere  filtrate  or  even  a  secretion  from  the  blood,  is  formed  b}'  the 
activity  of  the  organs,  and  may  actually  be  absorbed  by  the  blood 
from  the  tissue  spaces.  In  fact,  according  to  their  view,  the  in- 
travenous injection  of  lymphagogues,  both  crystalloid  and  colloid, 
only  causes  an  increased  flow  of  lymph  in  so  far  as  it  leads  to  in- 
creased glandular  secretion.  But  this  generalization  has  had  only 
a  short-lived  vogue,  and  one  by  one  some  of  the  main  results  which 
seemed  to  support  it  have  been  disproved  or  shown  to  be  capable 
of  interpretation  in  a  different  sense.  For  example,  it  was  stated 
that  secretin  causes  a  flow  of  lymph  from  the  lymphatics  of  the 
pancreas,  as  well  as  a  flow  of  pancreatic  juice.  But  it  has  been 
shown  that  the  increased  production  of  lymph  is  not  due  to  the 


INFLUENCE  OF  NERVES  ON  LYMPH  FORMATION  473 

secretin  at  ull,  but  to  lymphagogue  substances,  including  proteose, 
extracted  with  the  secretin  from  the  intestinal  mucous  membrane. 
A  solution  of  secretin  can  be  prepared  which  causes  a  considerable 
increase  in  the  secretion  of  pancreatic  juice  and  bile,  but  no  augmen- 
tation whatever  in  the  flow  of  lymph  from  the  thoracic  duct. 
Again,  it  was  asserted  that  peptone,  a  noted  lymphagogue,  produces 
a  great  increase  in  the  biliary  secretion.  It  has  been  demonstrated, 
however,  that  the  action  of  the  peptone  is  merely  to  cause  expul- 
sion of  the  contents  of  the  gall-bladder  by  the  mechanical  effect  of 
the  swelling  of  the  liver,  and  not  at  all  to  stimulate  the  liver-cells 
to  form  more  bile.  For  it  produces  no  effect  on  the  flow  of  bile 
if  the  gall-bladder  be  emptied  or  the  cystic  duct  tied  before  the 
injection  (Ellinger).  That  active  salivary  secretion  is  not  accom- 
panied by  increased  lymph-flow  from  the  lymphatics  of  the  salivary 
glands  has  been  mentioned  above.  Nevertheless,  we  may  safely 
assume  that  the  activity  of  the  organs  does  make  a  contribution  to 
the  lymph — to  its  solids,  if  not  in  any  important  degree  to  its  water- 
content,  although  to  say  that  they  alone  are  concerned  in  its  forma- 
tion, to  the  exclusion  of  the  capillaries,  is  altogether  an  over-state- 
ment. The  waste-products  of  the  tissues  pass  into  the  lymph,  and 
possibly,  as  Koranyi  suggests,  may,  by  increasing  its  molecular 
concentration,  cause  the  passage  of  some  water  into  it  from  the 
blood.  Or  the  decomposition  of  the  large  protein  molecules,  which 
in  tissue  metabolism  are  breaking  down  into  numerous  smaller 
molecules,  may  entail  an  increase  of  osmotic  pressure  in  the  cells 
themselves,  which  in  turn  may  lead  to  withdrawal  of  water  by  the 
cells  from  the  tissue  liquid.  The  osmotic  pressure  of  the  liquid 
may  thus  rise,  and  water  may  pass  into  the  tissue  spaces  from  the 
blood.  The  molecular  concentration  of  lymph  (except  in  anaesthe- 
tized animals  as  mentioned  above)  is  in  general  somewhat  greater 
than  that  of  blood-serum — e.g.,  in  one  observation  A  of  serum 
was  0605°  C,  and  of  lymph  o-6io°  C.  For  the  solid  tissues,  the 
freezing-point  of  which,  however,  cannot  be  as  satisfactorily  deter- 
mined as  that  of  liquids,  the  following  values  of  A  were  obtained: 
Brain,  0-65°;  muscle,  068°;  kidney,  094°;  hver,  0-97°;  while  for 
blood  it  was  057°  (Sabbatani). 

To  sum  up,  we  may  say  that  while  the  physical  processes  of  filtra- 
tion, osmosis  and  diffusion  may  play  a  part  in  the  passage  of  water 
and  solids  through  the  walls  of  the  blood  capillaries,  as  well  as  from 
the  tissue-cells  into  the  tissue  spaces,  and  from  these  spaces  into  the 
lymph  capillaries,  there  is  much  which  they  leave  unexplained,  and 
which  at  present,  for  the  want  of  a  more  precise  term,  we  must  attribute 
to  secretory  activity. 

Influence  of  Nerves  on  Lymph  Formation. — 'In  one  instance 
it  appears  to  have  been  shown  that  lymph  may  be  formed 
under  the  influence  of  secretory  nerves.     In  the  males  of  certain 


474  FORMATION  OF  LYMPH 

aquatic  birds  erection  is  due  to  the  filling  of  the  corpus  cavernosum. 
not  \\'ith  blood,  but  with  lymph.  The  lymph  is  secreted  rapidly  by 
the  so-called  bodies  of  Tannenberg  when  certain  sympathetic  nerve- 
fibres  are  experimentally  stimulated,  and  passes  into  the  corpus 
cavernosum,  which  swells  up.  If  a  small  incision  is  made  in  the 
corpus,  a  large  quantity  of  clear  lymph,  \\  hich  clots  slowly  on  stand- 
ing, escapes.  There  is  a  simultaneous  vasodilatation.  After  erection, 
the  lymph  is  rapidly  and  completely  reabsorbed  (Eckhard,  Miiller). 

.\lthough  no  definite  lymph-secretor}^  nerve-fibres  have  as  yet 
been  discovered  in  mammals  and  for  ordinary  tissues,  it  is  possible 
that  they  exist  (Sihlen.  As  already  pointed  out,  the  same  volume 
of  liquid  as  escapes  into  the  ducts  of  the  active  submaxillary  gland 
must,  upon  the  whole,  pass  out  of  the  blood  capillaries.  On  what 
principle  shall  we  distinguish  one  only  of  these  processes  as  physio- 
logical secretion  ?  They  begin  together  when  the  chorda  tympani 
is  stimulated.  A  drug  which  paralyzes  secretory  nerve-endings 
abolishes  both  effects.  The  simplest  explanation  is  that  the  chorda 
contains  secretory  fibres  which  influence  the  formation  both  of 
saliva  and  of  the  tissue  liquid  from  which  it  is  recruited;  and,  so 
far  as  this  consideration  goes,  it  is  just  as  logical  to  consider  the 
increase  in  the  supply  of  tissue  liquid  as  the  cause  of  the  increase 
in  the  flow  of  saliva  as  to  consider  the  increased  salivary  secretion 
as  the  cause  of  the  increased  flow  of  liquid  into  the  tissue  spaces. 
The  increased  flow  of  liquid  may  be  brought  about  either  by  an 
action  of  the  nerve  on  the  gland-cells,  causing  them  to  produce  a 
hormone,  which  then  effects  the  blood  capillaries  (Carlson),  or  by 
a  direct  action  on  the  capillary  endothelium.  The  advantage  to 
cells  engaged  in  the  active  secretion  of  saliva  of  being  immersed  in 
an  abundant  bath  of  tissue  liquid  is  ob\nous. 

The  post-mortem  flow  of  l3rmph,  which  may  continue  in  some 
cases  long  after  complete  cessation  of  the  circulation — for  an  hour 
after  injection  of  dextrose  to  produce  hydremic  plethora;  for  as 
much  as  four  hours  after  injection  of  extract  of  the  strawberry, 
which  is  a . ly mphagogue  of  Heidenhain's  first  group  (Mendel  and 
Hooker) — is  a  phenomenon  whose  relation  to  normal  lymph  forma- 
tion has  not  been  definitely  settled. 

It  ought  to  be  remembered  in  this  whole  discussion  that  the 
epithelium  of  ordinary  glands  derives  its  suppHes  of  material  from 
the  tissue  lymph.  The  vicissitudes  of  blood-pressure  affect  it  only 
in  a  secondary  and  indirect  manner.  On  the  other  hand,  tho  endo- 
thelial cells  of  the  capillaries  are  in  direct  contact  with  the  blood. 
And  it  is  interesting  to  observe  that  in  this  respect  the  glomeruli 
of  the  kidney  and  the  alveoli  of  the  lungs  (if  the  endothelial  lining 
of  Bowman's  capsule  and  the  alveolar  membrane  are  assumed  to 
be  complete)  taki-  a  middle  place  between  the  glands  proper  and 
the  quasi-glandular  capillaries. 


CHAPTER    IX 
EXCRETION 

We  have  now  followed  the  ingoing  tide  of  gaseous,  liquid,  and  solid 
substances  within  the  physiological  surface  of  the  body.  There  we 
leave  them  for  the  present,  and  turn  to  the  consideration  of  the 
channels  of  outflow,  and  the  waste  products  which  pass  along  them. 
In  a  body  which  is  neither  increasing  nor  diminishing  in  mass  the 
outflow  must  exactly  balance  the  inflow;  aU  that  enters  the  body 
must  sooner  or  later,  in  however  changed  a  form,  escape  from  it 
again.  In  the  expired  air,  the  urine,  the  secretions  of  the  skin,  and 
the  faeces,  by  far  the  greater  part  of  the  waste  products  is  elimin- 
ated. Thus  the  carbon  of  the  absorbed  solids  of  the  food  is  chiefly 
given  off  as  carbon  dioxide  by  the  lungs;  the  hydrogen,  as  water 
b}'  the  kidneys,  lungs  and  skin,  along  with  the  unchanged  water 
of  the  food;  the  nitrogen,  as  urea  by  the  kidneys.  The  faeces  in 
part  represent  unabsorbed  portions  of  the  food.  A  small  and 
variable  contribution  to  the  total  excretion  is  the  expectorated 
matter,  and  the  secretions  of  the  nasal  mucous  membrane  and 
lachrymal  glands.  Still  smaller  and  still  more  variable  is  the  loss 
in  the  form  of  dead  epidermic  scales,  hairs,  and  nails.  The  dis- 
charges from  the  generative  organs  are  to  be  considered  as  excre- 
tions with  reference  to  the  parent  organism,  and  so  is  the  milk,  and 
even  the  fretus  itself,  with  respect  to  the  mother. 

Excretion  by  the  lungs  and  in  the  faeces  has  been  already  dealt 
with.  All  that  is  necessary  to  be  said  of  the  expectoration  and 
the  nasal  and  lachrymal  discharges  is  that  the  first  two  generally 
contain  a  good  deal  of  mucin,  and  are  produced  in  small  mucous 
and  serous  glands,  the  cells  of  which  are  of  the  same  general  type 
as  those  of  the  mucous  and  serous  salivary  glands.  The  lachrymal 
glands  are  serous  like  the  parotid ;  and  the  tears  secreted  by  them 
contain  some  albumin  and  salts,  but  little  or  no  mucin.  The  sexual 
secretions  and  milk  will  be  best  considered  under  reproduction 
(Chap.  XIX.),  so  that  there  remain  only  the  urine  and  the  secre- 
tions of  the  skin  to  be  treated  here. 

475 


476  EXCRETION 


Section  I. — Excretion  by  the  Kidneys— The  Chemistry  of 

THE  Urine. 

Normal  urine  is  a  clear  yellow  liquid  acid  to  litmus  and  similar 
indicators,  but  nearly  neutral  or  very  weakly  acid  in  the  physico- 
chemical  sense  (p.  24).  The  average  specific  gravity  is  about  1020, 
the  usual  limits  being  1015  and  1025,  although  when  water  is  taken 
in  large  quantities,  or  long  withheld,  the  specific  gravity  may  fall 
to  1005,  or  even  less,  or  rise  to  1035,  or  even  more.  The  quantity 
passed  in  twenty-four  hours  is  very  variable,  and  is  especially 
dependent  on  the  activity  of  the  sweat-glands,  being,  as  a  rule, 
smaller  in  summer  when  the  skin  sweats  much,  than  in  winter  when 
it  sweats  little.  The  average  quantity  for  an  adult  male  is  1,200  to 
1,600  c.c.  (say,  40  to  50  oz.).* 

Composition  of  Urine. — This  is  very  closely  related  to  the  quantity 
and  quality  of  the  food.  Hence  it  is  impossible  to  speak  of  a 
definite  normal  composition  of  the  urine.  It  is  essentially  a  solu- 
tion of  urea  and  inorganic  salts,  the  proportion  of  the  latter  being 
generally  about  15  per  cent.,  or  double  the  usual  amount  of  physio- 
logical liquids.  Besides  urea,  there  are  other  nitrogenous  bodies 
in  much  smaller  quantity,  such  as  ammonia,  uric  acid,  and  the 
allied  purin  bases,  hippuric  acid,  and  kreatinin.  Some  of  these  at 
least  are  products  of  the  metabolism  of  proteins  within  the  tissues. 
And  besides  the  inorganic  salts  there  are  certain  organic  bodies — 
indoxyl,  phenyl,  pyrokatechin',  skatoxyl — united  with  sulphuric 
acid,  which  are  primarily  derived  from  the  products  of  the  putre- 
faction of  proteins  within  the  digestive  tube. 

Folin  has  published  analyses  of  '  normal '  urines  from  six  persons, 
weighing  from  56-6  to  70-9  kilos  (average  63-4  kilos),  who  were  kept 
for  seven  days  on  one  standard  uniform  diet.  The  diet  consisted  of 
500  c.c.  of  milk,  300  c.c.  of  cream  (containing  18  to  22  per  cent,  of  fat), 
'450  grammes  of  eggs,  200  grammes  of  Horlick's  malted  milk,  20  grammes 
of  sugar,  6  grammes  of  sodium  chloride,  water  enough  to  make  the 
whole  up  to  two  litres,  and  900  c.c.  of  additional  water.  The  ingredients 
contained  119  grammes  of  protein,  about  148  grammes  of  fat,  and 
225  grammes  of  carbo-hydrates.  The  average  results  of  all  the  deter- 
minations are  given  in  the  following  table : 

*  The  average  quantity  of  urine  varies  not  only  with  the  season,  but  also 
with  the  habits  of  the  person,  especially  as  reganls  the  amount  of  liquid 
taken.  The  average  for  seventeen  healthy  (American)  students,  whose  urine 
was  collected  for  six  to  eight  successive  days  in  winter,  was  1,166  c.c.  The 
highest  average  in  any  one  individual  for  the  observation  period  was  1,487  c.c. 
(for  seven  days),  and  the  lowest  743  c.c.  (for  eight  days).  The  greatest  quan- 
tity passed  in  any  one  perio<l  of  twenty-four  hours  was  2,286  c.c.  (by  the  in- 
dividual whose  average  was  the  highest).  The  smallest  quantity  passed  in 
twenty-four  hours  was  650  c.c.  (by  the  individual  whose  average  was  the 
lowest. 


CHEMISTRY  OF  URINE 


477 


Grammes. 

Containing 

Nitrogen 

(Grammes). 

Percentage 
of  Total 
Nitrogen. 

Urea  ----- 
Ammonia        -             -             .             - 
Kreatinin        -             -             -             - 
Uric  acid         -             -             -             - 
Nitrogen  in  other  compounds 

29-8 

1-55 
0-37 

13-9 
0-70 
0-58 

0-I2 

o-6o 

87-5 

4-3 
3.6 
0-8 
3-75 

~        i 

Total  nitrogen         -             -             - 

— 

i6-oo 

Inorganic  SO3              _             _             - 
Ethereal  SO3  -             -             -             - 
'  Neutral  '  SO3 

Total  sulphur  as  SO3 

Total  phosphates  as  P20g   - 
Chlorine      .              -              -              - 

2 '92 
0'22 
0-17 

3-31 

3-87 

6-1 

Percentage  of  Total 
Sulphur. 

87-8 

6-8 
5-1 

Titratable  acidity  in  c.c.  of  decinormal  acid  -  617  \  „-._JL:„'  ^,t' 


Indican  (Fehling's  solution  =  100*) 
Volume  of  urine 


77 
1430  c.c. 


The  great  influence  of  diet  on  the  composition  of  the  urine  is  illus- 
trated in  the  following  table.  Urine  I.  was  obtained  from  a  man  weigh- 
ing 87  kilos  on  the  standard  protein-rich  diet  described  above.  Urine  II. 
was  obtained  from  the  same  person  on  a  diet  very  poor  in  protein 
(400  grammes  of  starch  and  300  c.c.  of  cream),  containing  only  about 
I  gramme  of  nitrogen,  as  against  19  grammes  in  the  first  diet. 


I. 

II. 

Volume  of  urine 

1170  c.c. 

385  c.c. 

Grammes.       Per  Cent. 

Grammes.     Per  Cent. 

Total  nitrogen   -             -             - 

i6-8 

3-60 

Urea-nitrogen     -             -             - 

1470   =    87-5 

2-20    =     6l«7 

Ammonia-nitrogen 

0-49   =      3-0 

0-42    =    II«3 

Uric  acid-nitrogen 

o-i8   =      I'l 

0-09    =       2'5 

Kreatinin -nitrogen 

0-58   =      3-6 

o-6o   =    I7'2 

Nitrogen  in  other  compounds    - 

0-85    =      4-9 

0-27  =      7-3 

Total  SO3            -             -             - 

3-64 

Inorganic  SO3    .             -             - 

3-27   =    90-0 

0-46  =    6o'5 

Ethereal  SO,       .             -             - 

0-19    =       5-2 

o-io   =    13-2 

Neutral  SO3 

o-i8   =      4-8 

0-20    =     26'3 

Total  phosphates  as  P.2O5 

4-1 

I'O 

Chlorine 

6-1 

1-6 

Titratable  acidity  in  c.c.  ^^  acid  -  Sosj^/g^^'^'f^^;  \f^  324{^rgan?c:  201' 

Indican  (Fehling's  solution  =  100)  -      120         -         -         -     o 

*  The  indican  is  given  in  arbitrary  units,  the  indigo  blue  being  obtained 
from  the  urine  and  then  estimated  colorimetrically,  using  Fehling's  solu- 


47S 


EXCRETION 


The  titrable  acidity  of  urine  (see  p.  25)  is  chiefly  due  to  the  acid  (mono- 
basic) phosphates,  such  as  acid  sodium  phosphate  (Nai^l2P04),  but  in 
an  important  degree  also  to  organic  acids.  According  to  Fohn.  indeed, 
the  organic  acidity  may  be  more  than  lialf  the  total  acidity.  Normally 
the  acidity  diminishes  distinctly,  or  even  gives  place  to  alkalinity, 
during  digestion,  when  the  acid  of  the  gastric  juice  is  being  secreted. 
'J1iis  is  sometimes  fancifully  denominated  the  alkaline  tide.  After  a 
fast,  as  before  breakfast,  the  opposite  condition,  the  acid  tide,  occurs. 

The  acidity  varies  with  the  quantity  of  vegetable  food  in  the  diet. 
The  urine  of  herbivora  and  vegetarians  is  alkaline,  and  is  either  turbid 
when  passed,  or  on  standing  soon  becomes  turbid  from  precipitated 
carbonates  and  phosphates  of  earthy  bases,  while  that  of  camivora 
and  of  fasting  herbivora,  which  arc  living  on  their  own  tissues,  is 
strongly  acid  and  clear.  Normal  human  urine  may  deposit  urates  soon 
after  discharge,  as  they  are  more  soluble  in  warm  tiian  in  cold  water. 
They  carry  down  some  of  the  pigment,  and  therefore  usually  appear  as 
a  pink  or  brick-red  sediment.  When  urine  is  alloyved  to  stand  after 
being  voided,  what  is  generally  described  as  '  acid  fermentation  '  occurs. 
The  acidity  gradually  increases;  acid  sodium  urate  is  produced  from 
the  neutral  urate,  and  comes  down  in  the  form  of  amorphous  granules, 
while  the  liberated  uric  acid  is  deposited  often  in  '  whetstone  '  crystals, 
coloured  yellow  by  the  pigment  (Fig.  177).     Calcium  oxalate  may  also 


Uric  Acid. 


Fig.  178. — Calcium  Oxalate 


be  thrown  down  as  '  envelope,'  a.  b,  or  less  frequently,  '  sand-glass  ' 
crystals,  c  (Fig.  178).  If  the  urine  is  allowed  to  stand  for  a  few  days, 
especially  in  a  warm  place,  or  in  a  place  where  urine  is  decomposing, 
the  reaction  becomes  ultimately  strongly  alkaline ,^  owing  to  the  forma- 
tion of  ammonium  carbonate  from  urea  by  the  action  of  micro-organ- 
isms {Micrococcus  iirece.  Bacterium  urecB,  and  others)  which  reach  it 
from  the  air,  and  produce  a  soluble  lennent  urease,  in  whose  presence 
the  urea  is  split  up  with  assumption  of  water.     Thus: 


C.^ 


NH2 

o 

NNHj 

Urea. 


+  2H2O 


/O.NH4 

c=o 

NO.NH^, 

Amiiiontum  carbonate. 


This  is  a  reaction  of  considerable  interest,  for  the  reverse  reaction 
occurs  when  blood  containing  ammonium  carbonate  is  circulated 
tlirough  the  liver,  the  ammonium  carbonate  being  converted  into  urea 
with  loss  of  water.  The  enzyme  urease  is  present  in  higher  plants  than 
ba-cteria  and  fungi.  A  solution  containing  it,  conveniently  prepared 
from  the  soy  bean,  can  be  used  for  the  quantitative  estimation  of  urea, 
and  this  is  probably  the  easiest  and  most  accurate  method. 

tion  as  a  standartl.  Fehling's  solution  is  employed  because  it  is  a  blue  liquid 
of  a  definite  depth  of  tint  already  prepared  in  every  physiological  laboratory. 


CHEMISTRY  OF  innxE 


479 


The  substances  insoluble  in  alkaline  urine  are  tlirowii  'lown.  the 
deposit  containing  atiimonio-magnesic  or  trif^le  phosphate,  iormed  by 
the  union  of  ammonia  with  the  magnesium  phosphate  present  in  friish 
urine,  and  precipitated  as  clear  crystals  of  '  knife-rest  '  or  '  coffin-lid  ' 
shape  (Fig.  179),  along  with  amorphous  earthy  phosphates,  and  often 
acid  ammonium  urate  in  the  form  of  dark  balls  occasionally  covered 
with  spines  (Fig.  i8j).  Calcium  phosphate  (CaHP04)  is  another  phos- 
phate found  in  sediments  deposited  from  alkaline  or  faintly  acid  urine. 
It  is  usually  amorphous,  but  sometimes  in  the  form  of  long  prismatic 
crj'stals  arranged  in  star  fasldon,  and  hence  spoken  of  as  stellar  phos- 
phate (Fig.  181).     It  is  not  pigmented. 

It  is  only  in  pathological  conditions  that  the  alkaline  fermentation 
takes  place  within  the  bladder.     The  reaction  of  the  uruie  can  readily 


i^ 


#  o 


Kig.  179. — Triple  Phosphate.  Fig.  180. — Cystin.        Fig.  181. — Stellar  Phos- 

phate Crystals. 

be  niadc  alkaline  by  the  administration  of  alkalies,  alkaline  carbonates, 
or  the  salts  of  vegetable  acids  like  malic,  citric,  and  tartaric  acid,  which 
are  broken  up  in  the  body  and  form  alkaline  carbonates  with  the  alkalies 
of  the  blood  and  lymph.  It  is  not  so  easy  to  increase  the  acidity  of  the 
urine,  although  mineral  acids  do  so  up  to  a  certain  limit.  If  the  admin- 
istration of  acid  be  pushed  farther,  ammonia  is  split  off  frona  the  pro- 
teins, and  is  excreted  in  the  urine  as  the  ammonium  salt  of  the  acid. 

Determination  of  the  Acidity. — A  titration  method  is  described  in 
the  Practical  Exercises  (p.  ^15).  In  speaking  of  the  reaction  of  blood, 
it  has  already  been  mentioned  (p.  25)  that  we  can- 
not determine  by  titration  the  true  acidity  or  alka- 
linity of  a  liquid  in  the  physico-chemical  sense — i.e., 
the  concentration  of  the  dissociated  hydrogen  and 
hydro xyl  ions  respectively.  E.g..  when  we  titrate 
equal  quantities  of  decinormal*  acetic  acid  and  deci- 
normal  hydrochloric  acid  with  decinormal  potassium 
hydroxide,  using,  say,  phenolphthalein  as  the  indi- 
cator, nearly  the  same  volume  of  the  potassium 
hydroxide  solution  will  be  needed  to  neutralize  each 
acid.  Yet  it  can  be  shown  by  physico-chemical 
methods  that  the  acetic  acid  in  the  strength  used  is 
only  dissociated  to  the  extent  of  a  little  more  than  i  per  cent.,  while 
about  80  per  cent,  of  the  hydrochloric  acid  is  dissociated.  The  concen- 
tration of  the  hydrogen  ions  is  therefore  eighty  times  as  great  in  the 
hydrocliloric  as  in  the  acetic  acid  solution.  What  we  determine  by  the 
titration  is  not  the  true  acidity,  but  the  total  amount  of  hydrogen  which 
can  be  replaced  by  metal.  The  concentration  of  the  hydrogen  ions  in 
normal  urine  is  very  small,  on  the  average  only  about  0'003  mUli- 

*  A  normal  solution  of  a  substance  contains  in  a  litre  a  number  of  grammes 
of  the  substance  equal  to  the  number  wliich  expresses  its  equivalent  weight 
— a  decinormal  (usually  written  -^)  solution  one-tenth  of  this  amount,  a 
centinormal  one-hundredth,  etc.  Thus,  a  normal  solution  of  potassium 
hydroxide  contains  56  grammes  of  KOH,  and  a  decinormal  solution  5*6 
grammes  in  1,000  c.c. 


Ammo- 


nium Urate  (after 
Milroy). 


48o  EXCRETION 

graiiiiue  in  tli<'  litre,  or  about  thirty  times  as  much  as  is  present  in  the 
purest  distilled  water.  Urine  departs  about  as  much  from  neutrality  in 
the  one  direction  as  blood  does  in  the  other. 

Urea,  CO(NH2)2'  '^  ^^^^  form  in  which  by  far  the  greater  part  of  the 
nitrogen  is  under  ordinary  conditions  discharged  from  tlic  body.  Its 
amount  is  as  important  a  measure  of  protein  metabolism  as  the  quantity 
of  carbon  dioxide  given  out  by  the  lungs  is  of  the  oxidation  of  carbon- 
aceous material.  Yet  a  glance  at  the  table  on  p.  477  shows  that,  when 
the  total  protein  metabolism  is  greatly  reduced  by  diminishing  the 
protein  in  the  food,  the  relative  as  well  as  the  absolute  amount  of 
nitrogen  eliminated  as  urea  sutlers  a  great  diminution.  The  relative 
amount  of  the  other  nitrogenous  urinary  constituents,  especially  of 
the  kreatinin,  is  markedly  increased.  The  significance  of  this  difference 
is  alluded  to  in  speaking  of  the  kreatinin  content  of  urine,  and  will  have 
to  be  again  considered  under  Protein  Metabolism.  Urea  is  soluble  in 
water  and  in  alcohol,  and  crystallizes  from  its  solutions  in  the  form  of 
long  colourless  needles,  or  four-sided  prisms  with  pyramidal  ends.  It 
can  be  easily  prepared  from  urine.  Urea  can  also  be  obtained  artificially 
by  heating  its  isomer,  ammonium  cyanate  (NH4  — O— CN),  to  100"  C. 
This  reaction  is  of  great  historical  interest,  as  it  forms  the  final  step 
in  Wohlcr's  famous  synthesis  of  urea,  the  first  example  of  a  complex 
product  of  the  activity  of  living  matter  being  formed  from  the  ordinary 
materials  of  the  laboratory.  Heated  in  watery  solution  in  a  sealed 
tube  to  180°  C,  urea  is  entirely  split  up  into  carbon  dioxide  and  am- 
monia, a  change  which  can  also  be  brought  about,  as  already  mentioned, 
by  the  action  of  micro-organisms.  Nitrous  acid,  hypochlorous  acid,  and 
salts  of  hypobromous  acid  carry  the  decomposition  still  farther,  carbon 
dioxide,  nitrogen,  and  water  being  the  products  of  their  oxidizing  action 
on  urea.  Thus:  C0.2(NH2) +3NaBrO-3NaBr  +  2H20-i- COg-f- No. 
This  reaction  is  the  basis  of  the  h^^pobromite  method  of  estimating  the 
quantity  of  urea  in  urine  (Practical  Exercises,  p.  519). 

Ammonia. — The  ammonia  in  urine  is  united  with  acids  in  the  form 
of  salts.  Its  formation  from  proteins  is  determined,  as  w-e  shall  see 
later  on,  by  the  necessity  of  neutralizing  certain  acids  produced  in 
metabolism — e.g.,  those  derived  from  the  sulphur  and  phosphorus  of  the 
proteins,  or  acids  administered  experimentally.  According  to  some 
observers,  the  percentage  amount  of  the  total  nitrogen  in  the  urine 
in  the  form  of  ammonia  remains  the  same  whether  the  food  be  rich  or 
poor  in  protein  (Schittenhelm.  etc.),  but  others  state  that  when  the 
protein  is  reduced  there  is  a  relative  increase  in  the  ammonia-nitrogen 
(see  tabic  on  p.  477)  (Folin). 

Uric  acid  (C5H4N4O3)  exists  in  large  amount  in  the  urine  of  birds. 
The  excrement  of  serpents  consists  almost  entirelj^  of  uric  acid.  In 
both  cases  it  is  mainly  in  the  form  of  acid  ammonium  urate.  In  con- 
trast to  urea,  uric  acid  is  very  insoluble,  requiring  1.900  parts  of  hot 
and  15,000  parts  of  cold  water  to  dissolve  it.  In  man  and  mammals 
the  quantity  is  comparatively  small  in  health,  but  is  increased  after 
a  meal  containing  material  {e.g.,  thymus  gland)  rich  in  nucleins, 
from  the  nucleic  acid  of  which  purin  bodies  are  derived,  or  sub- 
stances containing  purin  bases  in  the  free  state — e.g..  hypoxanthin 
in  meat.  In  mammals  the  amount  of  uric  acid  excreted  depends 
little,  if  at  all,  upon  the  quantity  of  protein  in  the  food,  but  a  great  deal 
upon  the  quantity  of  purin  bodies,  whether  free  or  combined.  When 
nitrogenous  food  is  omitted  altogether,  the  absolute  quantity  of  uric 
acid  is  diminished,  but  the  proportion  of  the  total  nitrogen  of  the  urine 
eliminated  rs  uric  acid  is  increased,  since  the  '  endogenous  '  uric  acid 
(p.  596)  still  continues  to  be  formed  and  excreted. 


CHEMISTRY  OF  URINE 


481 


Tlic  purin  bases  (somitimcs  called  the  nuclcin  bases,  the  ulioxuric 
bases,  or  the  xanthiu  bases)  are  a  group  of  substances  allied  to  uric 
acid,  and  including,  besides  xanthin  itself,  hypoxanthin,  guanin,  adenin, 
and  other  bodies.  Thev  exist  in  very  small  amount  in  urine,  but,  like 
uric  acid,  are  increased  in  amount  by  the  ingestion  of  nuclcin-contain- 
ing  substances.  Tlie  greater  part  of  the  purin  bases  produced  in  the 
body  is  transformed  into  uric  acid  ;  it  is  only  the  untransformed  residue 
which  appears  in  the  urine.  An  interesting  fraction  of  the  purin  bases 
in  the  urine  which  is  not  related  to  the  nuclein  metabohsm  is  composed 
of  the  so-called  heteroxanthin.  derived  from  caffeine  in  the  coffee  and 
tea.  /-methylxauthin,  derived  from  theobromine  in  the  cocoa,  and  para- 
xanthin,  derived  from  theophyllin  in  the  tea,  consumed  as  beverages. 

Hippuric  acid  (C9H9NO;,)  occurs  in  considerable  quantity  in  the  urine 
of  herbivora  (Practical  Exercises,  p.  324);  in  the  urine  of  carnivora  and 
of  man  only  in  traces;  in  that  of  birds  not  at  all.  Its  amount  is  much 
more  dependent  on  the  presence  of  particular  substances  in  the  food 
than  that  of  the  other  organic  constituents  of  urine.  Anything  which 
contains  benzoic  acid,  or  substances  which  can  be  readily  changed  into 
it  (such  as  cinnamic  and  quinic 
acids),  causes  an  increase  of  the 
hippuric  acid  in  urine.  In  fact 
one  of  the  best  ways  of  obtaining 
the  latter  is  from  the  urine  of  a 
person  to  whom  benzoic  acid  is 
given  by  the  mouth;  the  sweat 


Fig.  183.— Creatin. 


Great  inin-Zinc-C!iloride. 


may  also  in  this  case  contain  a  trace  of  hippuric  acid.  Chemically  it 
is  a  conjugated  acid  formed  by  the  union  of  benzoic  acid  and  glycin. 

Amino-Acids. — The  only  amino-acid  hitherto  detected  with  certainty 
in  normal  urine  is  glycin. 

Oxalic  acid  is  always  present,  although  in  very  small  amount.  Some 
of  it  comes  from  the  oxalates  of  the  food,  but  a  portion  of  it  arises  in 
the  metabolism  of  the  tissues,  probably  from  the  decomposition  of  uric 
acid.  It  is  known  that  outside  of  the  body  uric  acid  may  be  made  to  yield 
oxalic  acid.  Calcium  oxalate  crystals  are  often  seen  in  urinary  sediments. 

Creatinin  (C4H7N3O). — Creatinin  is  the  anhydride  of  creatin 
(Fig.  183).  Its  formula  differs  from  that  of  creatin  only  in  possessing 
the  elements  of  one  molecule  of  water  less ;  and  creatinin  can  be 
obtained  by  boiling  creatin  with  dilute  sulphuric  acid.  From  its 
alcoholic  solution  it  crystallizes  in  colourless  prisms.  Creatinin  forms 
crystalline  compounds  with  various  acids  and  salts.  One  of  the  best 
known  of  these  is  creatinin-zinc-chloride,  formed  on  the  addition  of 
zinc  chloride  to  an  alcoholic  or  watery  solution  of  creatinin,  often  in 
the  shape  of  beautiful  thick-set  rosettes  of  needles  (Fig.  184).     A  por- 

31 


482  EXCRETION 

tion  of  the  urinary  creatinin  is  derived  from  the  creatin  of  the  meat 
taken  as  food.  But  this  is  not  its  only  source,  for  on  a  meat-free  diet 
and  in  starvation  creatinin  is  still  excreted.  The  absolute  c|uantity  in 
the  urine  on  a  meat-free  diet  is  constant  for  one  and  the  same  individual, 
although  different  in  different  persons,  and  independent  of  the  total 
amount  of  nitrogen  eliminated.  Hence  on  a  diet  poor  in  protein  the 
percentage  of  the  total  nitrogen  excreted  as  creatinin  is  much  greater 
than  on  a  protein-rich  diet,  as  shown  in  the  table  on  p.  477.  So  constant 
is  the  quantity  that  a  determination  of  the  creatinin  may  be  used  as  a 
check  upon  the  complete  collection  of  the  urine. 

Carbo-hydrates  are  normally  present  in  human  urine,  but  only  in 
ver>'  small  amounts.  Three  arc  knowTi  with  certainty — dextrose, 
isomaltose,  and  the  so-called  animal  gum  or  urine  dextrin.  Glycuronic 
acid  (CgHioO;),  a  body  which  can  be  derived  from  dextrose,  is  con- 
stantly present  in  small  amount  as  a  conjugated  acid,  paired  with 
phenol  or  indoxyl.  It  gives  Fehling's  test,  and  thus  may  easily  be 
mistaken  for  sugar.  Glycuronic  acid  becomes  coupled  ver^'  easily  with 
a  large  variety  of  substances,  including  many  drugs,  and  care  must  be 
taken  after  the  administration  of  camphor,  chloral  hydrate,  chloro- 
form, nitrobenzol,  etc.,  not  to  confound  the  largely  increased  excretion 
of  conjugate  glycuronates  in  the  urine  with  glycosuria.  The  yeast  test 
will  turn  out  negative  if  the  reduction  is  due  to  glycuronic  acid,  and 
the  polarimetcr  will  show  rotation  to  the  right  if  it  is  due  to  dextrose. 
The  total  quantity  of  carbo-hydrates,  including  glycuronic  acid, 
excreted  in  the  urine  of  the  twenty-four  hours  has  been  estimated  at 
2  to  3  grammes.  The  quantity  of  dextrose  in  normal  human  urine  is 
about  0-02  per  cent.,  or  about  one-fifth  of  the  proportion  in  blood. 

Proteins,  mainly  serum-albumin,  are  also  found  in  normal  urine  in 
minute  quantities,  on  the  average  about  0-0036  per  cent.  (Momer). 

Pigments  of  Urine. — The  pigments  of  urine  have  not  hitherto  been 
exhaustively  studied ;  but  we  alreadv  know  that  normal  urine  contains 
several,  and  pathological  urines  probably  additional,  pigmentary  sub- 
stances. The  best-known  pigments  in  normal  urine  are  urochrome, 
the  yellow  substance  which  gives  the  liquid  its  ordinary  colour; 
uroerythrin.  the  pink  pigment  which  often  colours  the  deposits  of  urates 
that  separate  even  from  healthy  urine ;  and  urobilin,  which,  as  has  been 
already  stated,  is  identical  with  the  fa;cal  pigment  stercobilin,  and  occurs 
not  only  in  many  febrile  conditions,  but  also  in  cases  with  no  fever,  such 
as  functional  derangements  of  the  liver,  dyspepsia,  chronic  bronchitis, 
and  valvular  diseases  of  the  heart.  The  urobilin  of  urine  represents, 
mainly  at  least,  the  portion  of  the  stercobilin  which  is  not  excreted  with 
the  faeces,  but  absorbed  from  the  intestine  into  the  blood.  The  urobilin 
in  normal  urine  only  exi.sts  in  small  amount  in  the  fully-formed  con- 
dition, most  of  it  being  present  as  a  chromogen  or  mother-substance 
(urobilinogen),  which  by  oxidation,  as  on  standing  exposed  to  the  air, 
is  converted  into  urobilin.  On  the  addition  of  ammonia  and  zinc 
chloride  to  a  solution  of  urobilin  a  beautiful  green  fluorescence  is 
obtained,  and  the  solution  now  shows  an  absorption  band  between 
b  and  F.  Urobilin  and  urochrome  are  related  substances,  bat  the  exact 
nature  of  the  relation  has  not  been  settled.  There  is  some  evidence 
that  a  portion  of  the  urobilin  of  urine  is  not  derived  from  the  intestine, 
but  manufactured  probably  in  the  liver.  In  hunger  urobihn  is  still 
excreted  in  the  urine,  although  in  greatly  reduced  amount.  During 
menstruation  it  is  markedly  increased,  both  in  fasting  and  in  normally 
fed  individuals.  Urorosein  is  a  red  pigment  which  is  produced  from 
its  chromogen  by  the  action  of  mineral  acids — e.g.,  strong  hydrochloric 
acid — in  the  presence  of  an  oxidizing  agent,  especially  nitrites. 


CHEATISTRY  OP  TJRINE 


48.^ 


The  pigments  of  the  blood  and  bile  and  some  of  their  derivatives  are 
of  common  occurrence  in  the  urine  in  disease.  Hcvmatoporphyrin  has 
not  only  been  found  in  some  pathological  conditions,  but  is  constantly 
present  in  minute  traces  in  normal  urine.  Certain  drugs — e.g.,  sulphonal 
— cause  an  increase  in  its  amount.  In  paroxysmal  haemoglobinuria, 
victhcBmoglobin .  mixed  with  some  oxyhaemoglobin,  is  found  in  the  urine  in 
large  amount;  and  it  is  worthy  of  note  that  it  is  not  formed  in  the  urine 
after  secretion,  but  is  already  present  as  such  when  it  reaches  the  bladder. 

In  the  rare  condition  termed  alkaptonuria,  a  body,  alkapion,  now 
known  to  be  identical  with  homogentisinic  acid,  CfiH3.(OH)2CH2.COOH, 
a  dioxyphenylacetic  acid,  is  present.  The  urine  becomes  dark  brown 
on  the  addition  of  an  alkali,  or  simply  on  exposure  to  air.  It  gives 
Fehling's  test  for  sugar.  The  substance  has  relations  to  the  aromatic 
amino-acids  tyrosin  and  phcnyl-alanin,  and  when  either  of  these  is 
given  to  a  person  suttcring  from  alkaptonuria,  the  amount  of  alkapton 
excreted  is  increased.  We  may  suppose,  therefore,  that  in  this  con- 
dition the  normal  decomposition  of  these  products  of  proteolysis  is 
interfered  with. 

Ferments. — The  urine  contains  traces  of  proteolytic  cmd  amylolytic 
ferments  (Fig.  185).  These  may  be  easily  separated  from  it  by  putting 
a  little  fibrin,  which  has  the  power  of  fixing  (adsorbing)  enzymes,  into 
the  urine. 

Of  the  inorganic  constituents  of  urine  the  most  important  and 
most  easily  estimated  are  the  chlorine,  phosphoric  acid,  and  sul- 
phuric acid. 


Fig. 


185. — Pepsin  in  Urine.     Diastatic  Ferment  in  Urine. 
At  Different  Times  of  the  Day  (Hoffmann). 


Chlorine. — IMuch  the  greater  part  of  the  chlorine  is  united  with 
sodium,  a  smaller  amount  with  potassium.  The  chlorides  of  the  urine 
arc  undoubtedly  to  a  great  extent  derived  directly  from  the  chlorides 
of  the  food,  and  have  not  the  same  metabolic  significance  as  the  organic, 
and  even  as  some  of  the  other  inorganic  constituents.  But  it  is  note- 
worthy that  in  certain  diseased  conditions  the  chlorine  may  disappear 
entirely  from  the  urine,  or  be  greatly  diminished — e.g.,  in  pneumonia, 
and  in  general  in  cases  in  which  much  material  tends  to  pass  out  from 
the  blood  in  the  form  of  effusions  (p.  515). 

Phosphoric  Acid. — The  phosphoric  acid  of  the  urine  is  chiefly  derived 
from  the  phosphates  of  the  food,  but  must  partly  come  from  the  waste 
products  of  tissues  rich  in  phosphorus-containing  substances,  such  as 
lecithin  and  nuclein.  The  phosphoric  acid  is  united  partly  with  alkalies, 
especially  as  acid  sodium  phosphate,  and  partly  with  earthy  bases,  as 
phosphates  of  calcium  and  magnesium.  The  earthy  phosphates  are 
precipitated  by  the  addition  of  an  alkali  to  urine,  or  in  the  alkaline 


484 


LXLHETIUN 


'icrmcntation.  In  some  pathological  urines  they  come  down  when  the 
carbon  dioxide  is  driven  off  by  heating;  a  precipitate  of  this  sort  differs 
from  heat-coagulated  albumin  in  being  readily  soluble  in  acids  (Practical 
Exercises,  p.  524).  A  small  amount  of  phosphorus  may  appear  in  the 
urine  in  a  less  oxidized  form  than  phosphoric  acid. 

Sulphuric  Acid. — Tliis  is  only  to  a  slight  extent  derived  from  ready- 
formed  sulphates  in  the  food.  The  greater  part  of  it  is  formed  by 
oxidation  of  the  sulphur  of  proteins.  About  nine-tenths  of  the  sulphur 
in  normal  urine  is  present  as  inorganic  sulphates,  mainly  those  of 
potassium  and  sodium.  Of  the  other  tenth,  a  portion  is  represented 
by  ethereal  sulphates,  and  the  remainder  by  the  so-called  '  neutral  ' 
sulphur,  including  the  sulphur  associated  with  the  pigment  urochrome. 
A  small  amount  of  sulphur  occurs  in  less  oxidized  forms  than  sul- 
phates in  such  compounds  as  the  sulphocyanide ,  which  is  probably, 
in  part  but  not  entirely,  derived  from  that  of  the  saliv^a,  and  ethyl 
sulphide,  a  substance  with  a  penetrating  odour,  which  appears  to  be  a 
constant  constituent  of  dog's  urine  (Abel). 

Thiosulphuric  acid  (H2S2O3)  occurs  almost  constantly  in  cat's  urine, 
often  in  dog's.     It  is  not  free,  but  combined  with  bases. 

The  ethereal  sulphates  are  compounds  in  which  the  sulphuric  acid  is 
united  with  aromatic  bodies  (indol,  phenol,  etc.).  Such  are  potassium- 
phenyl-sulphate  (CeH5KS04),  potassium-kresyl-sulphate  (C7H7KSO4), 
potassium-indoxyl-sulphate  (QHgN  KSO4) ,  potas.=?ium-skatoxyl-sulphate 
(C9H8NKSO4),  and  two  double  sulphates  of  potassium  and  pyrocatechin. 
The  formation  of  potassium  indoyxl  sulphate  may  be  thus  represented : 

Indol,  QH4C  ^tt'  on  absorption  from  the  intestine  is  changed  into 
mdoxyl,   C6H4/^-2^'^^'    which   +   ^^z(^i    (potassium   hydrogen 

sulphate)   yields    S02<  qj^    '       (potassium   indoxyl   sulphate) -h  HgO. 

The  '  pairing  '  of  these  aromatic  bodies  with  sulphuric  acid  renders 
them  innocuous  to  the  organism.  Most  of  the  compounds  are  present 
in  greater  amount  in  the  urine  of  the  horse  than  in  the  normal  urine  of 
man.  But  in  disease  the  quantity  of  indican  in  the  latter  may  be  much 
increased ;  and  to  a  certain  extent  it  must  be  looked  upon  as  an  index 
of  the  intensity  of  putrefactive  processes  in  the  intestine  and  of  absorp- 
tion from  it.  Munk  made  the  observation  that  in  the  urine  of  a  starving 
dog  the  phenol-forming  substances  are  absent,  while  in  the  urine  of  a 
starving  man  they  are  present  in  abnormally  large  amount.  The 
indigo-forming  substances  (indican),  on  the  other  hand,  are  in  hunger 
excreted  in  considerable  quantity  by  the  dog,  and  not  at  all  by  man 
(Practical  Exercises,  p.  518).  According  to  Folin,  the  indoxyl  potassium 
sulphate  or  indican  of  the  urine  is  not  to  any  appreciable  extent  related 
to  protein  metabolism,  but  for  the  most  part  to  the  putrefaction  of 
protein  in  the  intestine.  The  indoxyl-potassium  sulphate  taken  by  itself 
may  therefore  afford  a  rough  index  of  the  intensity  of  the  intestinal 
putrefactive  processes.  On  the  other  hand,  the  total  ethereal  sulphuric 
acid  cannot  be  taken  as  an  index  of  the  extent  of  the  putrefaction,  for, 
although  absolutely  diminished,  it  is  increased  relatively  to  the  total 
excretion  of  sulphur  on  a  diet  poor  in  protein,  or  even  protein-free 
(see  tables  on  p.  477). 

Phenol  and  kresol  can  easily  be  obtained  from  horse's  urine  by 
mixing  it  with  strong  hydrochloric  acid  and  distilUng.  These  aromatic 
bodies  pass  over  in  the  distillate.  Pyrocatechin  remains  behind,  and 
can  be  extracted  by  ether.  It  gives  a  green  colour  with  ferric  chloride, 
which  becomes  violet  on  the  addition  of  sodium  carbonate. 


CHEMISTRY  OF  URINE 


485 


The  sulphur  of  the  inorganic  sulphates  is  the  fraction  of  the  total 
sulphur  which  fluctuates  in  proportion  to  the  total  protein  metabolism. 
In  this  regard  it  follows  the  variations  in  the  urea.  It  represents 
'  exogenous  '  metabolism.  The  neutral  sulphur  occupies  a  position 
analogous  to  that  of  the  creiatinin :  the  smaller  the  amount  of  protein 
in  the  food,  and  the  smaller  therefore  the  total  protein  decomposed,  the 
larger  is  the  fraction  which  the  neutral  sulphur  forms  of  the  total 
sulphur.  The  neutral  sulphur  accordingly  represents  endogenous 
metabolism.  The  ethereal  sulphur  takes  an  intermediate  position  in 
this  regard,  but  upon  the  whole  it  also  becomes  a  more  prominent 
fraction  of  the  total  sulphur  when  the  food  contains  little  or  no  protein. 
The  ethereal  sulphates  are  therefore  not  entirely  derived  from  the 
putrefaction  of  protein. 

Carbonates  of  sodium,  ammonium,  calcium,  and  magnesium  occur 
in  alkaline  urine.  Their  source  is  the  carbonates  and  the  vegetable 
organic  acids  of  the  food.  In  acid  urine  a  certain  amount  of  carbon 
dioxide  is  present,  although  not  firmly  united  with  bases,  so  that  most 
of  it  can  be  pumped  out. 

So-called  Physico-Chemical  Analysis  of  Urine. — The  freezing-point 
of  urine  has  often  been  determined  to  obtain  a  measure  of  the  mole- 
cular concentration,  which  with  the  total  quantity  of  urine  secreted 
in  a  given  time  was  erroneously  assumed  to  afford  an  index  of  the 
work  done  by  the  kidney.  Clinically  the  method  is  of  little  use,  but 
for  certain  physiological  questions  freezing-point  determinations  are 
of  value  and  are  sometimes  combined  with  determinations  of  the 
electrical  conductivity,  by  which  we  obtain  an  approximate  measure 
of  the  number  of  dissociated  ions  in  unit  volume,  mainly  the  inorganic 
salts.  Normally,  A  has  a  higher  value  for  urine  than  for  blood — i.e., 
the  molecular  concentration  of  the  urine  is  higher  than  that  of  the 
serum.  But  when  large  draughts  of  water  are  taken  a  may  be  lower 
for  urine  than  for  blood,  and  in  general  it  varies  within  far  wider 
limits  (from  0'ii5**  to  2'54t)°  C,  according  to  Koppe).  The  following 
table  from  Kovesi  and  Roth-Schulz  shows  the  changes  in  A  under  the 
influence  of  water: 


Time. 

Urine  in  C.C. 

A 

10  to  2 

240 

I -So 

2  to  6 

255 

172 

6  to  ID 

l6i 

1-93 

10  to  2 

131 

2-l8 

2  to  6 

160 

2*23 

6  to  I* 

120 

I -91 

II  to  12 

I'S  litres  '  Salvator  '  water  taken 

— 

12  to  12.30 

500 

0'12 

12.30  to  I 

444 

O'll 

I  to  1.30 

442 

O'lO 

1.30  to  2 

46 

078 

2  to  2.30 

45 

I -30 

1 

The  Urine  in  Disease. — Although,  strictly  speaking,  a  truly  patho- 
logical urine  has  no  place  in  physiology,  the  line  which  separates  the 
urine  of  health  from  that  of  disease  is  often  narrmv,  sometimes  invisible; 
while  the  study  of  abnormal  constituents  is  not  only  of  great  importance 
in  practical  medicine,  but  throws  light  upon  the  physiological  processes 


486  EXCRETION 

takinj^  place  in  the  kidney,  and  upon  the  j,'cncral  problems  of  metabolism. 
Even  in  health  the  (|aantity  of  the  urine,  its  specific  gravity,  its  acidity, 
may  vary  within  wide  limits.  A  hot  day  may  increase  the  secretion 
of  sweat,  and  correspondingly  diminish  the  secretion  of  urine,  and  the 
deficiency  of  water  may  lead  to  a  deposit  of  brick-red  urates.  A  meal 
rich  in  fruit  or  vegetables  may  render  the  urine  alkaline,  and  its  alkalinity 
may  determine  a  precipitate  of  earthy  phosphates.  But  neither  the 
scanty  acid  urine  with  its  sediment  of  urates,  nor  the  alkaline  urine 
with  its  sediment  of  phosphates,  comes  into  the  category  of  pathological 
urines;  the  deviation  from  the  normal  does  not  amount  to  disease. 
The  maximum  deviation  from  the  line  of  health  is  the  total  suppression 
of  the  urine.  If  this  lasts  long,  a  train  of  symptoms,  oi  which  con- 
vulsions may  be  one  of  the  most  prominent,  and  which  are  grouped 
under  the  name  of  uraemia,  appears.  At  length  the  patient  becomes 
comatose,  and  deatffctoses  the  scene.  Suppression  of  urine  may  be 
the  consequence  of  many  pathological  conditions,  but  there  is  one  case 
on  record  in  the  human  subject  which,  in  effect,  though  not  in  intention, 
belongs  to  experimental  physiology.  A  surgeon  diagnosed  a  floating 
kidney  in  a  woman.  With  a  natural  impatience  of  loose  odds  and 
ends  of  this  sort,  he  offered  to  remove  it,  and  in  an  evil  hour  the  patient 
consented.  The  surgeon,  a  perfectly  skilful  man,  who  acted  for  the 
best,  and  to  whom  no  blame  whatever  attached,  carried  the  kidney  to 
a  well-known  pathologist  for  examination.  The  latter,  to  the  horror 
of  the  operator,  suggested,  from  the  appearance  of  the  organ,  that  it 
was  the  only  kidney  the  woman  possessed.  This  turned  out  to  be  the 
fact.  Not  a  drop  of  urine  was  passed.  Apart  from  this  ominous 
symptom,  all  went  well  for  seven  or  eight  days;  but  then  uraemic 
troubles  came  on,  and  the  patient  died  on  the  eleventh  or  thirteenth 
day  after  the  operation.  The  necropsy  showed  that  her  only  kidney 
had  been  taken  away. 

In  disease  the  urine  may  contain  abnormal  constituents,  or  ordinary 
constituents  in  abnormal  amounts.  Of  the  normal  constituents  which 
may  be  altered  in  quantity,  the  most  important  are  the  water,  the  inor- 
ganic salts,  the  urea,  the  uric  acid,  and  the  aromatic  substances. 

Water. — A  marked  and  persistent  diminution  in  the  quantity  of 
urine — ^that  is  to  say,  practically  in  the  water,  with  or  without  an 
increase  in  the  specific  gravity — is  suggestive  of  disorganization  of  the 
renal  epithelium.  In  some  infective  diseases  the  kidney  is  liable  to 
be  secondarily  involved,  its  secreting  cells  being  perhaps  crippled  in  the 
attempt  to  eliminate  the  bacterial  poisons.  In  the  form  of  paren- 
chymatous or  tubal  nephritis  wliich  so  frequently  complicates  scarlet 
fever,  the  quantity  of  urine  has  in  some  cases  fallen  to  50  or  60  c.c.  in 
the  twenty -four  hours. 

In  chronic  interstitial  nephritis  ('  granular  kidney  '),  on  the  other 
hand,  where  the  structural  changes  in  the  tubules  are,  for  a  long  time 
at  least,  comparatively  circumscribed,  the  quantity  of  urine  is  often 
increased  and  of  low  specific  gravity.  In  chese  cases  the  incpcasc  in 
the  blood -pressure,  associated  with  hypertrophy  of  the  hearf^'may  be 
a  factor  in  the  exaggerated  renal  secretion.  In  diabetes  mellitus  the 
quantity  of  urine  is  greatly  increased,  perhaps  in  some  cases  because 
more  urea  is  excreted  than  normal,  and  urea  acts  as  a^iuretic,  perhaps 
also  because  the  elimination  of  sugar  draws  withlfan  increased  excretion 
of  water  to  hold  it  in  solution.  Although  a  specific  gravity  as  low  as 
1002  has  been  seen  in  healthy  persons  (after  copious  potations),  the 
persistence  of  a  density  below  loio  shoukl  suggest  hydruria.  Watson 
mentions  the  case  of  a  boy  with  diabetes  insipidus,  who  voided  in 
twenty-four  hours  9  or  10  pints  (5  to  6  Utres)  of  urine  with  a  specific 
gravity  of  1002.     On  the  other  hand,  while  the  specific  gravity  has  been 


CIII-MISTRY  ni-   rRI\E  487 

occasionally  observed  tu  mounl  111  health  toal  least  1036,  its  persistence 
at  1025  or  10  ^o  cr  anytiiing  above  this,  especially  if  the  urine  is  pale 
and  a^parcutly  dilute,  should  suggest  diabetes  niellitus. 

Inorganic  Salts. — -The  changes  in  the  (juantity  of  the  inorganic  con- 
stituents of  the  urine  in  disease  are  not,  in  the  present  state  of  our 
knowledge,  of  as  mlich  importance  as  the  changes  in  the  organic  con- 
stituents. The  chlorides  are  diminished  in  most  acute  febrile  diseases 
and  may  even  totally  disappear  from  the  urine,  and  their  reappearance 
after  the  crisis  is,  so  far  as  it  goes,  a  favourable  symptom.  In  most 
cases  in  which  the  quantity  of  the  urine  is  markedly  lessened,  all  the 
inorganic  substances  are  diminished  in  amount. 

Urea. — The  quantitj-  of  urea  is,  as  a  rule,  increased  in  fever,  either 
absolutely  or  in  proportion  to  the  amount  of  nitrogen  in  the  food.  In 
the  interstitial  varieties  of  kidney  disease  the  urea  is  usually  not 
diminished,  but  when  the  stress  of  the  change  falls  on  the  tubules 
(parenchymatous  nephritis),  it  is  distinctly  decreased — it  may  be  even 
to  one-twentieth  of  the  normal. 

Uric  acid  is  diminished  in  the  urine  in  gout  (perhaps  to  one-ninth  of 
the  normal),  not  only  during  the  paroxysms,  but  in  the  intervals.  It 
accumulates  in  the  blood  and  tissues,  and,  as  sodium  urate,  may  form 
concretions  in  the  joints,  the  cartilage  of  the  ear,  and  other  situations. 
Watson  relates  the  case  of  a  gentleman  who  used  to  avail  himself  of  his 
resources  in  this  respect  by  scoring  the  points  at  cards  on  the  table  with 
his  chalky  knuckles.  In  leukaemia  the  quantity  of  uric  acid  and  purin 
bases  in  the  urine  is  greatly  increased,  not  only  absolutely,  but  also  in 
proportion  to  the  urea.  As  much  as  4^  grammes  of  free  uric  acid,  in 
addition  to  about  i  J  grammes  of  ammonium  urate,  has  been  found  in  a 
urinary  sediment  in  a  case  of  leukaemia. 

The  aromatic  bodies,  of  which  indoxyl  may  be  taken  as  the  type, 
are  increased  when  the  conditions  of  disease  favour  the  growth  of 
bacteria  in  the  intestine — e.g.,  in  cholera,  acute  peritonitis,  and  carci- 
noma of  the  stomach.  A  marked  increase  in  the  amount  of  the  indican 
in  the  urine  may,  as  far  as  it  goes,  be  taken  as  an  indication  that  the 
bacteria  are  gaining  the  upper  hand  in  the  intestinal  tract;  a  marked 
diminution  is  usually  a  sign  that  the  battle  has  begun  to  turn  in  favour 
of  the  organism  (Practical  Exercises,  p.  517).  Tryptophane,  a  sub- 
stance which  we  have  already  recognized  among  the  products  of  the 
tryptic  digestion  of  proteins,  has  been  showm  to  be  a  precursor  of  indol, 
which  is  formed  from  it  under  the  influence  of  bacteria.  When  trypto- 
phane is  injected  into  the  caecum  of  rabbits,  the  indican  in  the  urine 
is  markedly  increased.  Putrefactive  processes  in  other  parts  of  the 
body  than  the  intestine  may  also  increase  the  indican  in  the  urine — • 
e.g.,  a  collection  of  putrid  pus  in  the  pleural  cavity. 

Abnormal  Substances  in  Urine. — Sugar,  proteins,  the  pigments  of  bile 
and  blood,  or  their  derivatives,  are  the  most  important  abnormal  sub- 
stances found  in  solution  in  the  urine.  Normal  urine,  as  has  been 
stated,  contains  a  trace  of  dextrose,  but  so  little  that  it  cannot  be 
detected  by  ordinary  tests,  and  for  practical  purposes  it  may  be  con- 
sidered absent.  Dextrose  is  the  sugar  found  in  the  urine  in  diabetes. 
In  the  urine  of  nursing  mothers  lactose  may  be  present.  Pentoses, 
sugars  with  five  carbon  atoms  in  the  molecule  (instead  of  six,  as  in  the 
hexoses,  of  which  group  dextrose  is  a  member),  may  also  occasionally 
occur  in  urine.  Pentoses  give  the  ordinary  reduction  tests  for  sugar, 
and  yield  osazones,  but  do  not  ferment  with  y-east.  Various  plants 
contain  pentoses,  and  when  these  are  eaten  the  pentoses  are  excreted 
in  the  urine,  but  in  cases  of  true  pentosuria  they  originate  in  the  body, 
possibly  from  nuclco-proteins.  The  condition  has  not  the  same  sinister 
significance  as  diabetes.     Specific  toxic  substances  produced  by  bac- 


488  KXCRIiTlON 

tcrial  aclidii  ha\c  bcon  dcmonslratccl  in  tlic  urine  in  certain  diseases. 
Red  blood-corpuscles  and  leucocytes  (pus  corpuscles,  white  blood- 
corpuscles,  mucous  corpuscles)  are  the  chief  organized  deposits;  but 
spermatozoa  may  occasionally  be  found,  as  well  as  pathogenic  bacteria — 
e.g.,  the  typhoid  bacillus;  and  in  disease  of  the  kidney  casts  of  the  renal 
tubules  arc  not  uncommon.  These  tube-casts  may  be  composed  chiefly 
of  red  blood-corpuscles,  or  of  leucocytes,  or  of  the  epithelium  of  the 
tubules,  sometimes  fattily  degenerated,  or  of  structureless  protein, 
or  of  amyloid  substance.  Abnormal  cr^'stallinc  substances,  such  as 
the  amino-acids,  leucin  (Fig.  i86),  tyrosin  (Fig.  187),  and  cystin 
(Fig.  180),  may  be  on  rare  occasions  found  in  urinary  sediments;  but 
generally  the  unorganized  deposits  of  pathological  urine  consist  of 
bodies  actually  contained  in,  or  obtainable  from,  the  normal  secretion, 
but  present  in  excess,  cither  absolutely,  or  relatively  to  the  solvent 
power  of  the  urine.  Cystin  is  of  interest  because  of  its  relations  to  the 
sulphur  of  the  protein  molecule  (p.  360)-  It  is  not  found  in  the  normal 
organism.  It  very  occasionally  formfe  calculi  in  the  bladder.  There 
are  individuals  who  constantly  pass  as  much  as  one-fourth  of  all  the 
sulphur  in  the  form  of  cystin,  without  any  other  symptoms. 

Various  amino-acids  are  present  in  solution  in  the  urine  in  man  3' 
pathological  conditions.  Of  these  the  least  soluble  are  leucin  and 
tyrosin,  and  this  is  the  reason  why  they  are  most  easily  detected.  A 
general  reaction  for  amino-acids  is  their  precipitation  as  sparingly 
soluble  compounds  (/^-naphthalinsulphones)  by  /3-naphthalinsulpho- 
chloride  in  the  presence  of  an  alkali  (sodium  hydroxide).  In  acute 
yellow  atrophy  of  the  liver  leucin  and  tyrosin  have  been  found  in  large 
amounts  in  the  liver  itself,  as  well  as  in  the  urine.  In  phosphorus 
poisoning  these  amino-acids,  as  well  as  glycocoll,  have  been  detected  in 
the  urine,  and  there  is  no  doubt  that  other  amino-acids,  arising  from 
the  decomposition  of  proteins,  are  also  present  in  such  conditions. 

Sugar. — In  diabetes  mellitus,  although  the  quantity  of  urine  is  usually' 
much  increased,  its  specific  gravity  is  above  the  normal;  and  this  is  due 
cliiefly  to  the  presence  of  sugar  (dextrose),  which  generally  amounts 
to  I  to  5  per  cent.,  but  may  in  extreme  cases  reach  10  or  even  15  per 
cent.,  more  than  half  a  kilogramme  being  sometimes  given  off  in  twenty- 
four  hours. 

The  name  of  the  tests  for  dextrose  is  legion.  They  are  mostly 
founded  on  its  reducing  action  in  alkaline  solution.  Hydrated  oxide  of 
bismuth  (Boettcher),  salts  of  gold,  platinum  and  silver,  indigo  (Mulder), 
and  a  host  of  other  substances,  are  reduc-d  by  dextrose,  and  may 
be  used  to  show  its  presence.     The  reduction  of  cupric  salts  (Trommer), 


Fig.  186.— Leucin  Crystals.  Fig.  187.— Tyrosin  Crystals 


fermentation  by  yeast,  and  the  formation  of  crj'stals  of  phenyl-gluco- 
sazone  are  the  best  established  tests.  (See  Practical  Exercises,  p.  517.) 
Proteins. — Serum-albumin  and  scrum-globulin  arc  the  proteins  most 
commonly  found  in  pathological  urine.  Both  arc  coagulated  by  heating 
the  urine,  slightly  acidulated  if  it  is  not  already  acid,  or  by  the  addition 


CHEMISTRY  OF  URINE  489 

of  strong  nitric  acid  in  the  cold.  Proteoses  (albumoses)  are  also  occa- 
sionally present,  e.g..  in  the  diseiisc  called  '  osteomalacia  '  and  in  con- 
ditions associated  with  the  formation  and  especially  with  the  decom- 
position of  pus.  They  may  be  recognized  by  the  tests  given  in  the 
Practical  Exercises  (p.  525).  It  is  doubtful  whether  the  presence  of 
true  peptone  has  as  yet  been  satisfactorily  made  out. 

The  presence  of  bile-salts  may  be  shown  by  Hay's  test  or  Petten- 
kofer's  test  (p.  40^). 

The  pigments  of  blood  and  bile  may  be  detected  by  the  characters 
described  in  treating  of  these  substances ;  the  spectrum  of  oxyhaemo- 
globin,  or  methaemoglobin,  or  any  of  the  other  derivatives  of  haemoglobin, 
with  the  formation  of  hasmin  crystals,  would  afford  proof  of  the  presence 
of  the  former,  and  Gmelin's  test  of  the  latter.  The  red  blood-corpuscles, 
seen  with  the  microscope ,  are  the  most  decisive  evidence  of  the  presence  of 
blood,  as  leucocv-tes  in  abundance  arc  of  the  presence  of  pus.  It  should 
be  remembered  that  pus  in  the  urine  of  women  has  sometimes  no  signifi- 
cance except  as  showing  that  there  has  been  an  admixture  of  leucorrhcal 
discharge  from  the  vagina.     (See  Practical  Exercises,  pp.  74,  531-) 

Section  II. — The  Secretion  of  the  Urine. 

We  have  now  to  consider  the  mechanism  by  which  the  urine  is 
formed  in  the  kidney  from  the  materials  brought  to  it  by  the  blood. 
And  here  the  same  questions  arise  as  have  already  been  discussed 
in  the  case  of  the  salivary  and  other  digestive  glands:  (i)  Are  the 
urinary  constituents,  or  any  of  them,  present  as  such  in  the  blood  ? 
(2)  If  they  do  exist  in  the  blood,  can  they  be  shown  to  be  separated 
from  it  by  processes  mainly  physical  or  mainly  '  vital ' — in  other 
words,  by  ordinary  filtration,  diffusion  and  osmosis,  or  by  the  selec- 
tive action  of  living  cells  ?  In  the  case  of  the  digestive  juices  it 
has  been  seen  that  some  constituents  are  already  present  in  the 
blood,  but  that  physical  laws  alone,  so  far  as  we  at  present  under- 
stand them,  cannot  explain  the  proportions  in  which  they  occur  in 
the  secretions,  or  the  conditions  under  which  they  are  separated; 
while  other  constituents — and  these  the  more  specific  and  important 
— are  manufactured  in  the  gland-cells. 

In  the  kidneys  the  conditions  seem  at  first  sight  favourable  to 
physical  separation,  as  opposed  to  physiological  secretion.  Urine 
has  been  described  as  essentially  a  solution  of  urea  and  salts,  and 
both  are  ready  formed  in  the  blood.  The  arrangement  of  the  blood- 
vessels, too,  suggests  an  apparatus  for  filtering  imder  pressure. 

Bloodvessels  and  Secreting  Tubules  of  Kidney. — The  renal  arter>'  splits 
up  at  the  hilus  into  several  branches,  which  pass  in  between  the  Mal- 
pighian  pyramids,  and  form  at  the  boundary  of  the  cortex  and  medulla 
vascular  arches,  from  which  spring,  on  the  one  side,  interlobular  arteries 
running  up  into  the  cortex  between  the  pyramids  of  Ferrein,  and,  on 
the  other,  vasa  recta  running  down  into  the  boundary  layer  of  the 
medulla  (Fig.  18S).  The  interlobular  arteries  give  ofi  at  intervals 
afferent  vessels.  Each  of  these  soon  breaks  up  into  a  glomerulus  or  tuft 
of  vascular  loops,  which  gather  themselves  up  again  into  a  single 
efferent  vessel  of  somewhat  smaller  calibre  than  the  afferent.  The 
glomerulus  is  fitted  into  a  cup  or  capsule  (of  Bowman),  which  is  closely 


490 


EXCRETION 


Fig.  1 88.— Diagram  of  Blood- 
vessels of  Kidney  {Klein,  after 
Ludwig).  at,  interlobular  ar- 
tery; vi,  interlobular  vein; 
g,  glomerulus,  to  which  an 
afferent  artery  is  seen  coming 
from  the  interlobular  artery, 
and  from  which  an  efferent 
artery  proceeds  to  break  up 
into  a  capillary  network  sur- 
rounding the  renal  tabules; 
vs,  vena  stellata;  ar,  artcria 
rect.TC ;  vb,  leash  of  vena;  rcctae ; 
;•/',  vascular  network  round 
ducts  at  apex  of  a  papilla. 


Fig.  189. — Diagram  of  Renal  Tubule  (Klein). 
A,  corte.x;  a,  layer  of  cortex  immediately  under 
capsule  containing  no  Malpighian  corpuscles; 
a' ,  inner  layer  of  corte.x  devoid  of  Malpighian  cor- 
puscles; B,  boundary  layer;  C,  papillary  zone  of 
medulla;  i.  Bowman's  capsule;  2.  neck  of  cap- 
sule; 3,  proximal  convoluted  tubule;  4,  spiral 
tubule;  5,  descending  part  of  Henle's  loop- 
tubule;  6,  the  loop;  7,  8,  and  9,  ascending  limb 
of  loop-tubule;  10,  irregular  tubule;  ir,  distal 
convoluted  tubule;  12,  junctional  tubule;  13, 
collecting  tubule  in  a  medullarv'  ray  or  pyra- 
mid of  Ferrein;  14,  collecting  tubule  in  the 
boundary  layer;  15.  large  collecting  tubule 
ending  in  a  duct  of  Belliai. 


THE  SECRET  IDS  OF  THE  VRINE  491 

reflected  over  it,  except  where  the  afferent  and  efferent  vessels  pass 
through,  and  forms  the  beginning  of  a  urinaiy  tubule.  If  wc  suppose 
tlic  tuft  pi'slicd  into  the  bhnd  end  of  the  tubule  so  as  to  indent  it,  it  will 
be  easily  understood  that  the  single  layer  of  flattened  epithelium  reflected 
on  the  glomerulus  is  continuous  with  that  lining  the  capsule,  which  in 
its  turn  is  continuous  with  the  epithelial  layer  of  the  rest  of  the  urinary 
tubule.  This  has  been  divided  by  histologists  into  a  number  of  parts 
which  it  is  unnecessary  to  enumerate  here,  further  than  to  say  that  the 
urinarA'  tubule  proper  begins  in  the  cortex  in  Bowman's  capsule  and 
the  proximal  convoluted  tubule  (with  its  continuation,  the  spiral  tubule), 
and  ends  in  the  cortex  with  the  distal  convoluted  tubule,  the  connection 
between  the  two  being  made  by  a  long  loop  (Henle's)  with  a  descending 
and  an  ascending  limb  (Fig.  189).  Between  the  ascending  limb  and 
the  distal  convoluted  tube  is  interposed  the  zigzag  tubule.  The  tubule 
throughout  its  length  is  bounded  by  a  basement  membrane  lined  by  a 
single  layer  of  epithelium,  which  differs  in  its  character  in  different 
parts  of  the  tubule 

The  distal  convoluted  tube  joins  by  means  of  the  short  connecting 
tubule  one  of  the  straight  tubules  which  form  the  pyramids  of  Fcrrein 
or  medullary  rays  in  the  cortex,  and  which  run  down  into  the  medulla, 
always  uniting  into  larger  and  larger  tubes  as  they  go.  until  at  length 
they  open  as  ducts  of  Bellini  on  the  apex  of  a  papilla.  The  two  convo- 
luted tubules  (with  the  spiral  and  zigzag  tubules)  are  lined  by  similar 
epithelial  cells  with  granular  contents,  and  the  tendency  of  the  granules 
to  be  arranged  in  rows  perpendicular  to  the  basement  membrane  gives 
them  a  striated  or  '  rodded  '  appearance  (Fig.  190).  The  granules  arc 
eosinophile  (p.  17),  which  is  also  a  character  of  the  granules  of  other 
secreting  cells.  Towards  the  lumen  the  cells  may  show  a  brush  of  pro- 
cesses, looking  like  cilia,  but  in  mammals  these  are  not  motile.  The 
ascending  part  of  Henle's  loop  also  has  cells  of  the  same  general  char- 
acter, with  numerous  granules,  although  the  '  rodding  '  may  not  be  so 
distinct.  We  shall  see  directly  that  the  morphological  resemblance  is 
the  index  of  a  functions!  likeness.  The  blood-supply  of  the  tubules, 
especially  of  the  convoluted  portions,  is  exceedingly  rich,  the  efferent 
vessels  of  the  glomeruli  breaking  up  around  them  into  a  close-meshed 
network  of  capillaries,  from  which  the  blood  is  collected  into  inter- 
lobular veins  running  parallel  to  the  interlobular  arteries  between  the 
pyramids  of  Ferrein.  The  straight  tubules  of  the  medulla  are  also 
surrounded  by  capillaries  given  off  from  straight  arteries  (arteriae 
rectae)  running  down  into  it  partly  from  the  arterial  arches  and  partly 
from  efferent  vessels  of  the  glomeruli  nearest  the  boundary  layer,  the 
blood  passing  away  by  straight  veins  (venae  rectae)  which  join  the  larger 
veins  accompanying  the  arterial  arches.  The  greater  part  of  the 
blood  going  through  the  kidney  has  to  pass  through  two  sets  of  capil- 
laries, one  in  the  glomeruli,  the  other  around  the  tubules.  Even  the 
portion  of  it  which  does  not  go  through  the  glomeruli  has  for  the  most 
part  a  long  route  to  traverse  in  narrow  arterioles  and  venules  to  and 
from  its  capillary  distribution.  And  the  mean  circulation-time  through 
the  kidney  has  been  found  to  be  longer  thari  that  through  most  other 
organs  (p.  137). 

Theories  of  Renal  Secretion. — To  come  back  to  our  problem  of 
the  nature  of  renal  secretion,  the  anatomical  structure  of  the  kidney 
might  be  expected  to  throw  light  upon  the  question.  And,  indeed, 
it  was  on  a  purely  liistological  foundation  that  Bowman  established 
his  famous  *  vital  '  theory  of  renal  secretion.     Impressed  \\At\\  the 


492 


EXCRETION 


resemblance  between  the  renal  epithelium  and  the  epithelial  cells 
of  otht-r  glands,  and  with  the  distribution  of  the  bloodvessels  in  the 
kidney,  he  came  to  the  conclusion  that  the  characteristic  con- 
stituents of  urine,  including  urea,  were  secreted  from  the  blood  by 
the  tubules.  To  the  Malpighian  bodies  he  assigned  what  he  doubt- 
less considered  the  humbler  office  of  separating  water  from  the 
blood  for  the  solution  of  the  all-important  solids.  To  Ludwig,  on 
the  other  hand,  with  iiis  whole  attention  fastened  on  the  mechanical 
factors  by  which  the  flow  of  urine  could  be  influenced,  the  tubules 


Fig.  190. — From  a  Vertical  Section  of  Dog's  Kidney  to  show  the  Structure  of  Different 
Portions  of  the  Renal  Tubule  (Klein),  a.  Bowman's  capsule  enclosing  glomerulus, 
the  capillaries  of  which  are  arranged  in  lobules  separated  by  a  little  coimective 
tissue.  The  capsule  and  glomerulus  together  constitute  a  Malpighian  body  or 
corpuscle;  n,  neck  of  capsule;  c,  c,  convoluted  tubules,  cut  in  various  directions; 
b,  irregular  or  zigzag  tubule;  i,  e,  and/ are  straight  tubules,  which  take  part  in  the 
formation  of  a  medullary  ray  or  pyramid  of  Ferrein ;  d.  collecting  tubule ;  e,  e,  spiral 
tubule;  /,  narrow  part  of  ascending  limb  of  Henle's  loop-tubule;  b,  c,  and  e  are 
lined  with  rodded  epithelium. 

seemed  of  secondary  importance,  while  the  glomeruli  appeai'ed  a 
complete  apparatus  for  filtering  urine  from  the  blood  into  Bow- 
man's capsule.  He  saw  that  the  efferent  vessel  was  smaller  than 
the  afferent ;  that  it  was  therefore  easier  for  blood  to  come  to  the 
glomerulus  than  to  get  away  froiii  it,  and  that  the  pressure  in  the 
capillaries  of  the  tuft  must  be  higher  than  in  ordinary  capillaries, 
because  the  resistance  beyond  them  in  the  comparatively  narrow 
efferent  vessel,  and  especially  in  the  second  plexus,  is  greater  than 
the  resistance  beyond  a  single  capillary  network.  And  experi- 
mental investigation  soon  showed  him  that  the  rate  at  which  urine 


THE  SECRETION  OF  THE   UETNE  493 

was  fornu'd  could  be  greatly  influenced  by  changes  in  the  blood- 
pressure. 

On  such  considerations,  Ludwig  founded  the  '  mechanical  '  theory 
of  urinary  secretion,  which,  although  in  a  much  modified  form,  still 
divides  with  the  '  vital  '  theory  the  allegiance  of  physiologists. 
It  is  impossible  here  to  enter  in  detail  into  a  controversy  that  has 
extended  over  more  than  half  a  century  and  produced  an  extensive 
literature.  The  result  of  the  discussion  has  been,  in  our  opinion, 
to  establish  in  its  essential  principles  the  '  vital '  theory  of  Bowman, 
or  at  least  to  show  that  no  purely  physico-chemical  theory  as  yet 
constructed  will  account  for  all  the  facts. 

Ludwig  supposed  that  the  urine,  qualitatively  complete  in  all  its 
constituents,  was  simply  filtered  through  the  glomeruli,  the  work 
done  in  this  filtration  being  performed  entirely  at  the  expense  of 
the  energy  of  the  heart-beat  represented  as  lateral  pressure  in  the 
vessels  of  the  tufts.  But  as  the  proportion  of  salts,  and  especially 
of  urea,  is  very  far  from  being  the  same  in  urine  as  in  blood,  it  had 
further  to  be  assumed  that  the  liquid  which  passes  into  Bowman's 
capsule  is  exceedingly  dilute,  and  that  absorption  of  water,  and 
perhaps  of  other  constituents,  takes  place  in  its  passage  along  the 
renal  tubules.  This  process  of  reabsorption  he  pictured  as  a  purely 
physical  diffusion  between  the  dilute  urine  in  contact  with  the  free 
ends  of  the  epithelial  cells  lining  the  tubules  and  the  much  more 
concentrated  lymph  with  which  their  deep  ends  are  bathed.  The 
great  length  of  these  tubules,  as  compared  with  those  of  most  other 
glands,  might  indeed  seem  to  indicate  a  long  sojourn  of  the  urine 
in  them,  and  the  probability  of  important  changes  being  caused  in 
its  passage  along  them.  But  if  we  consider  the  immense  length 
(60  to  70  cm.)  of  the  seminal  tubules  and  of  their  gigantic  ducts 
(epididymis  6  metres),  where,  of  course,  absorption  of  water  on  a 
large  scale  is  out  of  the  question,  it  will  be  granted  that  little  can 
be  built  upon  the  mere  length  of  the  renal  tubules.  On  the  other 
hand,  the  sahvary  glands,  where  there  are  no  glomeruli,  secrete  as 
much  water  as  the  kidneys  are  supposed  to  filter;  and  the  pancreas, 
whose  capillaries  form  the  first  of  a  double  set,  and  therefore  in  this 
respect  correspond  to  the  renal  glomeruli,  secretes  less  water  than 
the  liver,  whose  capillaries  correspond  to  the  low-pressure  plexus 
around  the  convoluted  tubules  of  the  kidney.  So  that  deductions 
drawn  from  the  anatomical  relations  of  the  bloodvessels  are  not  in 
this  case  of  much  value,  unless  supported  by  physiological  results. 

It  is  somewhat  unfortunate  that  systematic  writers  have  fallen 
into  the  habit  of  discussing  the  mechanism  of  urinary  secretion  as 
if  the  Ludwig  theory  and  the  Bowman  theory  presented  an  exact 
antithesis,  as  if  the  one  offered  a  complete  '  mechanical  '  explana- 
tion of  a  process,  which  the  other  viewed  as  entirely  '  vital,'  and 
therefore  withdrawn  from  physical  explanation. 

We  need  not  concern  ourselves  here  with  the  historical  develop- 


494  EXCRETION 

ment    of    tliis    discussion.      Three    main    questions   require   our 
attention : 

1.  Is  there  any  evidence  that  reabsorption  actually  occurs  in  the 
tubules  ?  If  reabsorption  on  an  important  scale  does  take  place,  it 
follows  at  once  that  there  must  be  a  difference  of  function  between 
the  two  parts  of  the  renal  apparatus,  through  which  urinary  con- 
stituents pass  in  opposite  directions. 

2.  But  if  there  is  no  reabsorption,  or  none  of  im])ortance,  it  may 
still  be  asked  whether,  the  direction  of  movement  of  the  urinary 
constituents  through  the  glomeruli  and  the  tubular  epithelium  being 
the  same,  some  quantitative  or  qualitative  difference  in  their 
activity  may  not  exist,  certain  constituents,  e.g.,  passing  mainly  or 
exclusively  through  the  one  or  the  other. 

3.  When  these  questions  have  been  settled,  we  are  in  a  position 
to  consider  the  nature  of  the  process  by  which  the  urinary  con- 
stituents find  their  way  from  the  blood  into  the  lumen  of  the 
capsules  and  the  tubules,  or,  if  there  is  reabsorption,  out  of  the 
tubules  into  the  lymph  and  blood  again,  and  to  see  whether  or  no 

-it  can  be  entirely  explained  on  mechanical  and  physico-chemical 
principles. 

The  Question  of  Reabsorption  from  the  Tubules. — That  some 
absorption  can  take  place  from  the  kidney  wlu-n  the  pressure  in 
the  ureter  is  abnormally  raised  need  not  be  doubted,  and  when 
substances  like  potassium  iodide  or  strychnine  are  introduced  into 
the  ureter  or  the  pelvis  of  the  kidney  untler  these  circumstances, 
they  can  speedily  be  detected  in  the  blood.  When  the  ureter 
pressure  (in  dogs)  is  only  slightl}^  increased,  instead  of  evidence  of 
reabsorption,  we  obtain  evidence  of  increased  secretion.  The 
volume  of  urine,  the  total  quantity  of  sulphate  in  the  urine  when 
sodium  sulphate  is  injected  into  the  blood  as  a  diuretic,  and  the 
total  amount  of  reducing  sugar  when  phlorhizin  is  injected,  are  all 
greater  on  the  obstructed  than  on  the  normal  side.  These  facts  are 
quite  opposed  to  the  idea  that  filtration  and  reabsorption  are  im- 
portant factors  in  the  preparation  of  normal  urine  (Brodie  and 
CuUis) .  Changes  in  the  blood- flow  through  the  kidney  have  nothing 
to  do  with  the  results,  since  the  small  increase  in  pressure  in  the 
ureter  was  shown  not  to  affect  the  rate  of  flow  of  the  blood.  The 
attempt  has  been  made  to  decide  whether  absorption  normally 
occurs  by  removing  as  much  of  the  tubules  as  possible,  and  seeing 
whether  the  character  of  the  urine  is  altered.  In  rabbits  the  whole 
or  a  large  portion  of  the  medulla  has  been  excised  from  one  kidney 
and  the  other  then  extirpated.  From  the  mutilated  kidney  two  or 
three  times  as  much  urine  was  said  to  flow  as  was  secreted  by  a 
control  rabbit  operated  on  in  the  same  way,  except  for  the  removal 
of  the  renal  medulla  (Ribbert).  The  conclusion  was  drawn  that 
the  greater  quantity  of  urine  escaping  was  due  to  the  smaller 
opportunity  for  reabsorption  of  the  water.     But  experiments  men- 


THE  SECRETION  Ob'  THE   URINE 


493 


tioned  in  Chapter  XI.  suggest  a  different  interpretation  of  these  ob- 
servations. And  Boyd,  who  repeated  Ribbcrt's  work,  ol)tained  quite 
•  iilierent  results  after  ]Kutial  removal  of  the  medulla.  He  found 
.it  impossible  to  remove  the  whole.  So  that  hitherto  the  direct 
method  of  eliminating  the  tubules  has  left  the  matter  where  it  was. 
Some  hght  has  been  thrown  on  this  question,  by  taking  advantage 
of  the  anatomical  fact  that  the  kidney  of  batrachians,  and,  indeed, 
that  of  fishes  and  ophidia  as  well,  has  a  double  blood-supply.  The 
renal  artery  gives  oft  afferent  vessels  to  the  glomeruli;  the  vena 
advehens.  or  renal  portal  vein,  breaks  up,  like  the  portal  vein  in  the 
liver,  into  a  plexus  of  capillaries  surrounding  the  tubules,  and  there 
seems  to  be  no  communication  between  the  two  vascular  systems. 
By  tying  all  the  arteries  going  to  the  kidneys  in  frogs  the  circula- 
tion through  the  glomeruli  can  be  completely  cut  off,  while  ligation 
of  the  renal  portal  vein  does  not  affect  the  blood-supply  of  the 
glomeruli,  though  markedlj^  interfering  with  that  of  the  tubules. 
Gurwitsch  has  found  that,  after  ligation  of  the  renal  portal  vein  of 
one  kidney  in  (male)  frogs,  the  flow  of  urine  from  that  kidney  is 
much  diminished  as  compared  with  the  other.  He  argues  that  if 
reabsorption  of  dilute  urine  filtered  through  the  glomeruli  takes 
place  in  the  tubules,  the  opposite  result  ought  to  be  obtained,  since 
the  glomeruli  are  not  affected,  while  any  absorptive  power  of  the 
tubules  must  be  crippled  or  abolished. 

Experiments  on  the  Excretion  of  Pigments  by  the  Kidney. — In 
connection  with  the  second  question,  and  also  incidentally  with  the 
first,  the  results  of  experiments  on  the  distribution  of  pigments  in 

the  kidney  after  their  injection  into 
the  blood  have  often  been  appealed  to. 
Heidenhain  injected  indigo  -  carmine 
into  the  blood  of  rabbits,  and  after  a 
variable  time  killed  them,  cut  out  the 
kidneys,  and  flushed  them  with  alcohol, 
in  which  the  pigment  is  insoluble.  His 
results  were  as  follows:  (i)  When  the 

"t^'oV^Sme^™  "f/id^eyaft";    ^P™="  ^°'\''^^  ^"^  h<:lore  the  injec 

Injection  into  Blood.  The  cor-  tion  m  order  to  reduce  the  blood- 
te.x  between  a  and  b  and  be-    pressure,  the  blue  granules  were  found 

tween  c  and  d  was  cauterized  j^  the  '  rodded  '  epithelium  of  the 
before    the   injection.      In  the  ^.^J^^^■,^^  ■,. 

blank  wedge-shaped  portions,  i,  convoluted  tubules  and  the  ascendmg 
there  was  no  pigment.  In  the  limb  of  Henle's  loop,  and  in  the  lumen 
zones  shaded  like  2  there  was    ^f    ^he    tubules,    but    nowhere    else. 

some  pigment,  but  no<  so  much      „  , 

as  in  the  areas  shaded  like  3.  Bowman  s  capsules  contamed  no  pig- 
ment. The  renal  cortex  was  coloured 
blue.  (2)  When  the  spinal  cord  was  not  cut,  the  pigment  was  found 
in  the  medulla  and  pelvis  of  the  kidney,  as  well  as  in  the  cortex, 
but  always  in  the  lumen  of  the  tubules,  and  not  in  the  epithelium, 
except  in  the  situations  mentioned.     (3)  If  a  portion  of  the  cortex 


496  EXCRETIO>J 

of  the  kidney  liad  been  cauterized  with  nitrate  of  silver  before  in- 
jection of  the  pigment,  the  spinal  cord  being  left  intact,  a  wedge  of 
the  renal  substance,  corresponding  to  this  area,  remained  coloured 
only  in  the  cortex,  although  the  rest  was  blue  in  the  medulla 
also.  The  '  rodded  '  epithelium  was  filled  with  blue  granules  as 
before  (Fig.  191). 

(i)  shows  that  the  epithelium  is  capable  of  excreting  some  sub- 
stances at  least.  (2)  appears  to  show  that  when  the  bkjod-pressure 
is  normal  water  is  poured  out  from  some  part  of  the  tubule,  and 
washes  the  pigment  separated  by  the  '  rodded  '  epithelium  down 
towards  the  papillae.  (3)  suggests  that  it  is  through  the  glomeruli 
that  most  of  the  water  passes.  For  cauterization  has  not  destroyed 
the  power  of  the  epithelium  to  excrete  pigment,  and  therefore, 
presumably,  would  not  have  destroyed  its  power  to  excrete  water 
if  it  possessed  this  power  in  any  great  degree;  and  the  glomeruli 
and  their  capsules  are  the  only  other  part  of  the  renal  mechanism 
which  can  have  been  affected.  It  must  be  carefully  noted  that 
these  experiments  do  not  prove  that  urea  is  secreted  by  the  tubular 
epithelium.  Indeed,  after  section  of  the  cord  no  accumulation 
of  urea  takes  place  in  the  kidney  (Cushny).  It  would  be  equally 
erroneous  to  conclude  from  this  that  the  cells  of  the  tubules  do  not 
secrete  urea.  For  the  reduction  of  the  blood-supply  may  have 
rendered  them  incapable  of  doing  so. 

When  pigments  are  injected  into  the  dorsal  lymph-sac  of  a  frog 
without  interference  with  the  renal  circulation,  they  are  found 
pl^tifuUy  in  the  lumen  of  the  convoluted  tubules,  and  also  in  the 
epithelial  cells  hning  them.  The  suggestion  has  been  made  that 
the  pigments  have  been  absorbed  by  the  cells  from  the  lumen,  and 
not  excreted  by  them  into  it.  And  certainly  pigments  soluble  in 
the  cytoplasm  or  in  the  substances  that  form  the  envelopes  of  cells, 
and  therefore  capable,  like  methylene  blue,  of  staining  them  during 
Hfe,  might  be  taken  up  by  the  renal  epithelium  if  excreted  into  the 
tubules  by  the  glomeruli,  and  might  cause  staining  of  them,  par- 
ticularly, of  course,  of  the  free  ends  of  the  cells  next  the  lumen. 
But  this  suggestion  is  inadmissible,  since,  on  injection  of  the  same 
pigments  after  ligation  of  the  renal  portal  vein,  the  convoluted 
tubules  contain  little  or  no  pigment  in  their  lumen.  And  when  the 
urinary  flow  is  stopped  on  one  side  in  mammals  by  temporary  com- 
pression of  the  renal  artery,  the  corresponding  kidney  takes  up  fully 
as  much  carmine  as  its  fellow  (Carter).  There  is  no  doubt  that  not 
only  pigments  capable  of  '  vital  staining,'  like  methylene  blue,  but 
also  pigments  which  do  not  stain  living  cells,  are  taken  up  from 
the  blood  (or  lymph)  by  the  epithelial  cells,  and,  lying  in  vacuoles 
in  their  cytoplasm,  are  transported  towards  the  lumen,  and  there 
extruded.  It  is  not  the  solubility  of  the  pigments  in  lipoids,  and 
therefore  their  solubility  in  the  supposed  lipoid  envelope  of  the  cells, 
which  determines  whether  they  shall  be  excreted.     The  degree  in 


THE  SECRETION  OF  THE  URINE  4$7 

which  they  are  capable  of  being  presented  to  the  cells  in  non-colloid 
solution  appears  to  some  extent  to  be  a  determining  factor.  The 
pigments  not  taken  up  are  highly  colloidal  (Gurwitsch,  Hober). 
Shafer  has  recently  confirmed  Heidenhain's  statements  as  to  the 
place  of  excretion  of  indigo-carmine.  When  leuco-indigo-carmine 
(a  colourless  reduction-product  of  indigo-carmine)  was  injected,  the 
blue  oxidized  substance  was  found  in  the  lumen  of  the  convoluted 
tubules  and  in  the  collecting  tubules,  but  not  at  all  in  the  Bow- 
man's capsule.  The  cells  of  the  convoluted  tubules  were  colour- 
less, because  they  kept  the  pigment  in  its  reduced  condition,  and  it 
only  became  oxidized  in  the  lumina  of  those  parts  of  the  tubules 
whose  contents,  according  to  Dreser,  show  an  acid  reaction.  On  oxi- 
dation by  peroxide  of  hydrogen  the  cells  of  the  convoluted  tubules 
became  faintly  green,  but  the  Bowman's  capsule  remained  colourless. 
This  can  only  be  explained  on  the  assumption  that  the  lenco-product 
of  the  pigment  was  excreted  by  the  cells  of  the  convoluted  tubules. 

But  these  cells  are  far  from  taking  up  all  pigments  indifferently. 
Some  pigments  are  extruded  mainly  by  one  part,  others  mainly  by 
another  part,  of  the  renal  tubule,  and  some  even  by  the  glomeruli, 
as  shown  long  ago  for  ammonium  carminate.  The  glomeruli,  how- 
ever, are  in  general  far  less  active  in  this  regard  than  the  epithelial 
cells,  and  the  fact  that  the  latter  pick  out  from  the  blood  such  sub- 
.stances  as  these  foreign  pigments,  which  pass  through  the  Mal- 
pighian  tufts  unchallenged,  renders  it  likely  that  the  tubules  also 
exercise  a  special  function  in  the  secretion  of  the  normal  con- 
stituents of  urine.  More  direct  evidence  of  this  is  not  wanting, 
for  Bowman  saw  crystals  of  uric  acid  in  the  epithelium  of  the 
convoluted  tubules  of  birds.  Heidenhain  found  that  urate  of  soda 
injected  into  the  blood  of  a  rabbit  is  excreted  by  the  epithelium  of 
the  convoluted  tubules  and  the  ascending  part  of  Henle's  loop, 
just  as  is  the  case  with  indigo-carmine.  And  Nussbaum's  experi- 
ments, although  not  quite  conclusive,  have  made  it  probable  that 
in  the  frog  urea  is  actually  separated  by  the  epithelium  of  the 
tubules.  They  were  founded  on  the  anatomical  peculiarity  in  the 
renal  circulation  of  the  frog  already  mentioned.  By  tying  the  renal 
arteries  in  that  animal,  he  thought  he  could  at  will  stop  the  circula- 
tion in  the  glomeruli,  and  he  found  that  after  this  was  done  there 
was  no  further  spontaneous  secretion  of  urine.  But  when  urea  was 
injected  intravenously  the  secretion  of  urine  again  began,  urea 
being  ehminated  by  the  kidneys,  and  water  along  with  it.  Sugar, 
peptone,  and  egg-albumin,  injected  into  the  blood,  no  longer  passed 
into  the  urine,  even  when  the  secretion  was  excited  by  simultaneous 
injection  of  urea,  although  they  readily  did  so  when  the  arteries 
were  not  tied.  He  concluded  that  the  Malpighian  corpuscles  have 
the  power  of  excreting  water,  sugar,  peptone,  and  albumin,  while 
the  epithelium  of  the  tubules  excretes  urea  as  well  as  water. 

Beddard  has  confirmed  Nussbaum's  statement  that  when  all  th(? 

32 


49S  EXCRETION 

arteries  going  to  the  kidney  are  tied  the  glomeruli  are  completely 
and  permanently  deprived  of  blood.  The  spontaneous  secretion 
of  urine  is  totally  stopped,  as  Nussbaum  found,  but  only  in  three 
experiments  out  of  eighteen  was  it  possible  to  start  the  secretion 
by  injection  of  urea.  The  epithelium  of  the  tubules  degenerated 
and  desquamated  after  complete  ligation  of  all  the  renal  arteries, 
showing  that  it  requires  some  arterial  blood  as  well  as  the  venous 
blood  from  the  n-nal  portal  to  maintain  its  vitality-  The  degenera- 
tion of  the  epithelium  can  be  prevented  by  keeping  the  frogs  in  an 
atmosphere  of  oxygen  after  ligation  of  the  arteries.  In  six  such 
frogs,  in  which  the  complete  elimination  of  the  glomeruli  was  con- 
trolled by  subsequent  injection,  secretion  of  urine  followed  the 
injection  of  urea,  alone  or  in  combination  with  dextrose,  phlorhizin, 
or  di -sodium  hydrogen  phosphate  (Xa2HP04).  In  all  the  cases  the 
urine  contained  urea,  chlorides,  and  sulphates,  and  was  acid  to 
phenolphthalein.  In  one  case  after  injection  of  urea  and  dextrose, 
and  in  another  after  urea  and  phlorhizin,  the  urine  reduced  Fehling's 
solution,  and  therefore  presumably  contained  dextrose  (Beddard 
and  Bainbridge).  When  the  frog's  kidney  is  perfused  in  situ  with 
oxygenated  salt  solution  a  certain  flow  of  urine  takes  place.  Sub- 
stitution of  non-oxygenated  sahne  markedly  slows  the  flow  (Cullis). 

Apparently,  then,  the  tubules  have  the  capacity  to  secrete  prac- 
tically all  the  constituents  of  urtne,  and  when  the  flow  of  urine  is 
small,  probably  most  of  it  comes  from  the  tubules.  When,  as  in 
the  diuresis  produced  by  salt  solutions,  large  quantities  of  water 
and  salts  have  to  be  rapidly  excreted,  the  bulk  of  the  liquid  comes 
from  the  glomeruli,  but  also  by  a  process  of  secretion. 

Lindemann  has  endeavoured  to  exclude  the  glomeruli  in  mam- 
mals by  injecting  oil  through  the  renal  artery.  After  a  short  time, 
according  to  him,  the  oil  emboh  clear  away  from  practically  all 
parts  of  the  kidney  except  the  glomeruU,  which  remain  plugged. 
If  indigo-carmine  be  subsequentlv  injected  into  the  blood,  it  is  not 
only  taken  up  from  it  by  the  embolizcd  kidney  as  well  as  by  a  normal 
one,  but  is  excreted.  The  quantity  of  urine  is  much  diminished, 
and  its  specific  gravity  increased,  but  its  composition  is  not  essen- 
tially altered.  He  infers  that  the  tubules  are  in  a  high  degree 
independent  of  the  glomeruli  as  an  apparatus  for  the  secretion  of 
urine.  More  conclusive  observations  have  lately  been  reported  in 
which  the  tubules  were  eliminated  by  producing  an  artificial  nephritis 
in  rabbits  bv  the  subcutaneous  injection  of  sodium  tartrate.  Tar- 
trates act  mainly  upon  the  tubules,  causing  no,  or  a  much  smaller, 
effect  upon  the  glomeruli.  After  the  intravenous  infusion  of  a 
solution  containing  sodium  chloride  and  urea  during  pronounced 
tartrate  nephritis,  all  the  chlorine  appears  in  the  urine  within  forty- 
eight  hours,  but  little,  if  any,  of  the  urea.  In  the  light  of  the 
histological  findings,  this  is  interpreted  to  mean  that  under  normal 
conditions  chlorides  and  water  are  passed  through  the  glomerular 


THE  SECRETION  OF  THE   URINE  409 

mechanism,  and  urea  througli  the  convoluted  tubules  (Uiidcrhill, 
WVUs,  and  Goldschmidt).  These  results  constitute  a  direct  and 
striking  confirniation  of  the  Bowman  hypothesis. 

As  regards  our  first  two  questions,  we  may  rom  lude  thai  there  is 
no  good  evidence  that  reahsorplion  of  xcater  oy  other  constituents  of  the 
urine  in  the  renal  tubules  plays  an  important  part  in  the  preparation 
of  that  secretion.  Manx  facts  favour  the  conclusion  that  the  glomeruli 
and  the  renal  epithelium  act  as  distinct,  although,  of  course,  mutually 
supplementary  mechanisms,  the  glomeruli  separating  the  larger  portion 
of  the  water  and  salts,  the  epithelium  the  larger  portion,  if  not  the 
whole,  of  the  characteristic  organic  constituents. 

As  regards  the  third  question,  it  is  now  generally  admitted,  even 
by  those  who  uphold  a  modified  '  mechanical  '  theory,  that  if 
the  urine  is  originally  separated  from  the  blood  by  filtration  at  the 
expense  of  the  energy  of  the  heart-beat  represented  by  the  pressure 
of  the  blood  in  the  glomeruli,  the  reabsorption  in  the  tubules  cannot 
be  attributed  to  simple  diffusion,  but  must  be  a  selective  process 
analogous  to  absorption  in  the  intestine  and  entailing  the  expendi- 
ture of  a  large  amount  of  work  at  the  expense  of  the  food  materials 
or  the  protoplasm  of  the  epithelial  cells.  Every  attempt  at  a 
strictly  mechanical  explanation  breaks  down  for  the  kidney,  as  for 
other  glands. 

The  practical  absence  from  urine  of  the  proteins  and  sugar  of  the 
blood  under  normal  circumstances,  and  the  elimination  by  the 
kidney  of  egg-albumin,  peptone,  and  other  bodies  when  injected 
into  the  veins,  show  a  selective  permeability  inexplicable  by  refer- 
ence to  any  known  structural  or  physico-chemical  property  of  the 
renal  epithelium  or  the  glomeruli,  but  precisely  the  kind  of  thing 
which  the  physiologist  has,  without  being  hitherto  able  to  explain 
it,  learnt  to  associate  with  the  activity  of  living  cells.  Urea  and 
dextrose,  both  highly  diffusible  substances,  circulate  side  by  side 
in  the  bloodvessels  of  the  kidney.  The  one  is  taken  and  the  other 
left.  The  urea  is  a  waste-product  of  no  further  use  in  the  economy. 
The  sugar  is  a  valuable  food-substance.  The  kidney  selects  with 
unerring  certainty  the  urea,  of  which  only  4  parts  in  10,000  are 
present  in  the  blood,  but  rejects  the  sugar,  of  which  there  is  three 
times  as  much.  The  theory  that  the  dextrose  of  the  blood  or  a 
part  of  it  is  combined  with  substances  in  the  colloid  state,  and  not 
in  ordinary  solution,  has  been  advanced  from  time  to  time  as  an 
explanation  of  the  practical  impermeability  of  the  kidney  for  this 
sugar  under  normal  conditions.  But  no  proof  of  the  truth  of  this 
hypothesis  has  ever  been  given.  On  the  contrary,  there  is  good 
evidence  that  all  the  dextrose  which  is  estimated  in  blood  by 
analytical  methods  is  in  the  free  condition.  For  instance,  dextrose 
easily  escapes  from  blood  circulating  in  the  vivi-diffusion  apparatus 
previously  described  (p.  48).  And  when  the  plasma  of  shed  blood  is 
placed  in  a  dialyser  tube  of  animal  membrane  surrounded  by  a  liquid 


500  EXCRETION 

in  which  dextrose  is  dissolved  in  exactly  the  safrie  concentration  a.s 
that  determined  in  the  plasma  by  the  ordinary  chemical  methods, 
the  contents  of  the  dialyser  neither  lose  nor  gain  dextrose.  Now, 
the  plasma  ought  to  gain  sugar  by  diffusion  if  a  portion  of  the 
dextrose  in  it  exists  in  a  combination  which  prevents  its  diffusion, 
just  as  it  does  gain  dextrose  when  the  liquid  outside  the  dialyser 
contains  sugar  in  greater  concentration  than  the  plasma  (Michaelis 
and  Rona). 

Egg-albumin  injected  into  the  blood  passes  through  the  renal 
circulation  side  by  side  with  the  serum-albumin  of  the  plasma. 
Both  are  indiffusible  tlirough  membranes,  and  to  the  physical 
chemist  the  differences  between  them  may  appear  superficial  and 
minute.  But  the  kidney  does  not  hesitate  for  an  instant.  A  large 
part  of  the  egg-albumin  is  promptly  excreted  as  a  foreign  substance; 
the  serum-albumin  passes  on  untouched. 

Not  only  does  the  kidney  exercise  a  power  of  qualitative  selec- 
tion; it  also  takes  cognizance  of  the  quantitative  composition  of 
the  blood.  So  long  as  there  is  less  sugar  in  the  plasma  than  about 
1-5  to  2  parts  in  1,000,  it  is  refused  passage  into  the  renal  tubules. 
But  when  this  limit  is  passed,  and  the  proportion  of  sugar  in  the 
blood  becomes  excessive,  the  kidney  begins  to  excrete  sugar,  and 
continues  to  do  so  till  the  balance  is  redressed. 

The  advocates  of  the  theory  of  filtration  tlirough  the  glomeruli 
under  the  influence  of  the  difference  of  hydrostatic  pressure  in  the 
capillaries  and  in  the  lumen  of  the  capsules  have  made  their  firmest 
stand  on  the  excretion  of  the  inorganic  constituents  of  the  urine. 
Thev  have  laid  stress  particularly  on  the  fact  that  the  hydraemic 
plethora  caused  by  intravenous  injection  of  salts  is  accompanied 
by  diuresis.  It  is  true  that  the  direct  introduction  of  water  into 
the  blood,  or  its  attraction  from  the  lymph-spaces  when  the  osmotic 
pressure  of  the  blood  is  increased  by  the  injection  of  substances  like 
urea,  sugar,  and  sodium  chloride,  may  cause  a  condition  of  hydrcemic 
plethora,  and  that  this  plethora  may  sometimes  be  associated  with 
an  increase  of  pressure  in  the  capillaries  in  general,  and  therefore 
in  the  vessels  of  the  Malpighian  tuft.  It  may  also  be  admitted  that 
such  an  increase  of  pressure  might  be  accompanied  by  an  increased 
filtration  of  water  and  salts  into  Bowman's  capsule.  Even  in  the 
excised  kidne}',  after  the  vital  activity  of  its  cells  may  be  presumed 
to  have  ceased,  filtration  of  the  most  varied  solutions  occurs  when 
the  organ  is  perfused  with  them  through  the  renal  artery.  The 
liquid  which  escapes  from  the  ureter  always  has  the  same  composi- 
tion as  the  perfusion  fluid  (SoUmann).  It  would  certainly  appear 
unlikely  that  the  glomerular  epithelium  should  make  no  use  what- 
ever for  the  furtherance  of  its  task  of  the  difference  of  hydrostatic 
pressure  on  its  two  surfaces.  It  is  in  taking  advantage  of  such 
circumsta  ces  for  the  promotion  of  its  specific  work  up  to  the 
point  at  which  they  cease  to  favour  it  that  a  great  part  of  the  true 


THE  SECRETION  OF  THE   URINE  501 

secretory  activity  of  cells  may  be  supposed  to  consist.  When  we 
see  a  barge  passing  through  a  lock,  and  bt-ing  gradually  lifted  to 
the  proper  level  by  the  inrush  of  water,  wt-  never  dream  of  saying 
that  the  whole  thing  is  an  affair  of  the  laws  of  hydrostatics.  We 
know  that  the  part  played  by  the  lock-keeper,  the  opening  and 
closing  of  the  gates  and  sluices  at  the  proper  time,  is  all-important, 
although  he  does  not  lighten  by  one  ounce  the  weight  which  the 
water  must  lift.  He  uses  the  head  of  water  for  a  specific  purpose 
— namely,  to  lift  the  barge.  In  like  manner  it  is  to  be  expected 
that  the  glomerular  epithelium,  when  the  difference  of  pressure 
on  its  two  surfaces  is  increased  by  hydraemic  plethora,  will  use  the 
increased  facility  of  filtration  to  rapidly  excrete  a  portion  of  the 
water.  But  who  will  believe  that  the  addition  of  a  tumbler  of 
water,  absorbed  from  the  alimentary'  canal,  to  4  or  5  litres  of  blood 
circulating  in  a  system  of  vessels  whose  capacity  can  and  does  vary 
within  wide  limits,  should  cause  in  the  capillaries  of  the  kidney 
an  increase  of  pressure  exactly  proportional  to  the  increase  in  the 
elimination  of  water  in  the  urine,  lasting  for  the  same  time  and 
disappearing  at  the  moment  when  the  normal  composition  of  the 
blood  is  restored  ?  Nor  is  it  easier  to  explain  on  any  mechanical 
hypothesis  how  it  is  that  in  a  starving  animal  the  quantity  of 
inorganic  substances  eliminated  in  the  urine  drops  almost  to  zero, 
while  the  proportional  amount  in  the  blood  and  tissues  is  little,  if 
at  all,  affected.  In  a  rabbit  rendered  poor  in  sodium  chloride  by 
feeding  it  with  salt-free  food,  the  injection  of  a  solution  of  sodium 
chloride  isotonic  with  the  blood  produces  no  diuresis  for  a  con- 
siderable time,  but,  on  the  contrary,  a  diminished  flow  of  urine, 
while  a  similar  solution  injected  into  the  veins  of  a  rabbit  previously 
fed  with  salted  food  causes  an  immediate  and  considerable  diuresis. 
When  small  quantities  of  isotonic  solutions  of  various  salts  are 
injected,  those  not  normally  present  in  the  blood  produce  a  greater 
diuresis  than  normal  constituents.  Sodium  chloride,  which  is 
present  in  normal  plasma  in  greater  amount  than  any  other  salt, 
causes  the  smallest  diuresis  of  all  (Haake  and  Spiro). 

Such  facts  suggest  that  the  secreting  cells  of  the  kidney  are  stimu- 
lated or  inhibited  by  the  contact  of  blood  or  lymph  in  which  the 
normal  constituents  are  present  in  too  great  or  in  too  small  amount, 
and  that  the  intensity  of  the  action  is  proportional  to  the  degree  of 
deficiency  or  excess.  The  greater  the  velocity  of  the  circulation 
in  the  kidney,  the  more  effective  will  be  the  stimulation  produced 
by  any  given  substance  present  in  excess,  and  therefore  the  greater 
the  total  amount  of  it  eliminated  in  a  given  time.  For  in  making 
the  round  of  the  renal  circulation  the  concentration  of  the  sub- 
stance in  any  given  portion  of  blood  will  fall  less,  and  therefore  the 
average  stimulation  exerted  by  it  during  the  round  will  be  greater 
the  faster  the  blood  flows.  It  is  quite  in  agreement  with  this  that 
when  plethora  is  occasioned  by  transfusion  of  blood  there  is  little 


502  EXCRETION 

or  no  diuresis,  although  the  increase  of  arterial,  capillary,  and 
venous  })ressure,  and  the  dilatation  of  the  kidney,  arc  evident. 
For  the  rapid  passage  of  liquid  out  of  the  \essels  would  lead  to  a 
great  increase  in  the  relative  proportion  of  corpuscles  to  i^lasma — 
that  is  to  say,  to  an  abnormal  condition  of  the  blood.  On  the  other 
hand,  when  plethora  is  produced  by  injection  of  serum  diuresis 
occurs  (Cushny).  This,  again,  is  what  we  should  expect,  since  the 
elimination  of  the  superfluous  liquid  will  restore  the  normal  pro- 
portion. The  diminished  viscosity  of  the  blood  (p.  23)  produced 
by  the  excess  of  scrum  will  aid  the  flow  through  the  kidney  and 
therefore  increase  the  diuresis,  while  in  the  case  of  the  plethora 
produced  by  injection  of  blood  the  elimination  of  liquid  will  at  once 
increase  the  viscosity,  diminish  the  velocity  of  the  renal  flow,  and 
tend  to  lessen  diuresis. 

There  is,  then,  little  more  reason  to  assume  that  the  copious  flow 
of  urine  which  follows  the  absorption  of  a  large  quantity  of  water 
is  due  to  a  mere  process  of  filtration  than  there  is  to  beheve  that 
filtration,  and  not  selective  secretion,  is  the  cause  of  the  gush 
of  saliva  which  precedes  vomiting,  or  the  sudden  outburst  of 
sweat  on  sudden  and  severe  exertion.  In  addition,  there  are  the 
positive  proofs  already  mentioned  that  the  '  rodded  '  epithelium 
of  the  tubules,  which  no  one  supposes  to  be  abandoned  more 
to  mere  physical  influences  than  the  epitheUum  of  the  salivary 
glands,  plays  a  part  in  the  secretion  of  some  of  the  urinary 
constituents. 

Cushny  has  recently  stated  more  clearly  than  had  previously  been 
done  a  theory  which  he  designates  as  the  '  modern  theory  '  of  urine 
formation.  He  assumes  that  blood-plasma  is  filtered  through  the 
glomeruli  under  the  hydrostatic  pressure  of  the  blood,  only  the  colloid 
proteins  being  kept  back.  The  filtrate  contains  the  non-colloid  con- 
stituents approximately  in  the  proportions  in  which  they  exist  in 
plasma.  It  is  therefore  very  poor  in  urea  and  very  rich  in  sugar  as 
compared  with  urine.  In  the  tubules  some  of  the  constituents,  which 
he  terms  '  threshold  bodies  '  are  reabsorbed.  These  are  the  sub- 
stances like  sugar,  the  sodium  and  chlorine  ions,  etc.,  which  are  only 
excreted  when  they  exceed  a  certain  threshold  value  in  the  plasma. 
Other  constituents  of  the  filtrate,  like  urea,  are  not  reabsorbed.  These 
are  called  'no-threshold  bodies,'  and  are  excreted  in  proportion  to 
their  absolute  amount  in  the  plasma.  The  cells  of  the  tubules  are 
supposed  in  some  way  at  present  unknown  to  take  up  from  the  filtrate 
the  threshold  bodies, 'and  always  in  a  definite  concentration — namely, 
that  in  w^hich  they  normally  exist  in  blood.  As  Cushny  puts  it,  the 
filtrate  is  deproteinized  plasma,  from  which  '  Locke's  fluid  '  (p.  66) 
is  reabsorbed  by  the  tubule  cells.  Apparently  he  thinks  it  simpler  to 
make  the  assumption  that  the  renal  cells  are  organized  to  absorb  from 
the  lumen  of  the  tubules  a  solution  of  invariable  composition,  leaving 
a  variable  residue  to  be  excreted,  than  to  make  the  assumption,  under- 
lying the  Bowman-Heidenhain  theory,  that  they  are  organized  to 
leave  behind  in  the  blood  or  lymph  an'invariable  residue  by  absorbing 
from  them  a  solution  of  variable  composition.  In  reality,  however,  the 
two  assumptions  are  precisely  on  the  same  footing  :  they  are  equally 


THE  SECRETION  OF  THE  URIXE  503 

simple  or  ecjually  abstruse.  For  a  cell  wliich  is  able  to  take  up 
'  Locke's  fluid  '  from  a  deprotcinized  plasma  is  able  in  that  very  act 
to  reject  any  constituent  which  does  not  belong  to  '  Locke's  fluid,' 
as  well  as  an  excess  of  any  constituent  which  docs  belong  to  it.  What  is 
rejected  and  its  amount  are  quite  as  important,  if  the  final  product  is 
to  be  constant,  as  what  is  accepted  and  its  amount.  If  we  are  willing 
to  attribute  a  power  of  this  kind  to  the  free  end  of  a  tubule  cell  we 
need  not  shrink  on  the  ground  of  added  complexity  from  investing 
the  attached  end  of  the  cell  with  the  power  of  refusing  passage  to 
'  Locke's  fluid  '  from  the  plasma  or  the  lymph  while  accejjting  crys- 
talloid constituents  like  urea  which  do  not  belong  to  it,  as  well  as  an 
excess  of  any  constituent  which  does  belong  to  it.  There  is  nothing 
more  '  occult  '  about  a  cell  which  bars  out  sodium  chloride  till  it 
exceeds  0-9  per  cent,  in  the  fluid  offered  to  it,  and  then  lets  the  surplus 
through,  than  there  is  about  a  cell  which  takes  up  sodium  chloride 
from  the  fluid  offered  to  it  till  it  has  amassed  a  concentration  of  o-c) 
percent.,  and  then  bars  out  the  surplus.*  In  like  manner,  the  financial 
organization  required  by  a  Government  to  take  from  a  citizen  in  taxes 
the  surplus  of  his  income  above  one  hundred  pounds  would  be  of  the 
same  general  nature  as  that  required  to  take  from  him  his  whole  income, 
returning  him  one  hundred  pounds  to  live  on.  If  a  machine  could 
manage  the  one  operation,  a  mandarin  would  not  be  needed  for  the  other. 
It  is  impossible  in  this  place  to  go  further  into  the  discussion  of  the 
reabsorption  theory  so  ably  presented  by  Cushnj'.  In  the  absence  of 
definite  evidence  of  reabsorption  on  the  great  scale  required  by  the 
theory,  it  remains  simply  a  working  hypothesis,  which  is  all  that  can 
be  claimed  at  present  for  any  theory  of  urine  formation.  One  of  the 
objections  always  urged  against  filtration  (with  reabsorption)  theories 
has  been  the  enormous  amount  of  liquid  which  must  under  certain  con- 
ditions be  poured  into  the  renal  tubules.  Heidenhain  calculated  that 
in  a  man  no  less  than  70  litres  of  liquid  per  day  must  be  filtered  through 
the  glomeruli  in  order  that  the  urea  found  in  the  urine  may  be  obtained 
from  a  glomerular  filtrate  containing  0-05  per  cent,  of  urea.  This  is 
probably  a  moderate  estimate,  and  considerably  larger  amounts  of 
filtrate  in  proportion  to  body  and  kidney  weight  have  been  deduced 
from  data  obtained  in  animals.  It  has  been  argued  by  advocates  of 
the  reabsorption  theory  that  equally  great  quantities  of  lymph  con- 
taining urea  in  the  small  concentration  in  which  it  exists  in  the  plasma 
must  be  poured  out  around  the  attached  ends  of  the  tubule  cells  on 
the  hypothesis  of  direct  secretion.  This  argument,  however,  is  based 
upon  an  erroneous  conception  of  the  manner  in  which  exchange  between 
the  blood  and  the  tissues  proceeds.     There  is  no  reason  to  suppose 

*  The  reabsorption  theory  is  perhaps  inferior  to  the  '  direct  secretion  ' 
theory  in  one  point.  If  a  solution  of  constant  composition  is  always  absorbed 
from  the  glomerular  filtrate,  the  smaller  the  concentration  in  the  filtrate  of 
any  substance  capable  of  being  taken  up  by  the  cells,  the  greater  will  be  the 
proportion  of  it  absorbed;  and  the  greater  its  concentration  in  the  filtrate, 
the  smaller  will  be  the  proportion  of  it  absorbed.  On  the  direct  secretion 
theory,  the  greater  the  concentration  of  a  substance  in  the  blood  or  lymph 
in  contact  with  the  cells,  the  more  of  it  will  pass  into  the  cells  and  be  ex- 
creted by  them.  The  '  modern  '  theory  which  sets  out  by  saj-ing  to  the 
Bowman-Heidenhain  theory.  '  Stand  by  thyself,  come  not  near  to  me,  for  I 
am  more  physical  than  thou,'  thus  abandons  a  physical  process,  diffusion, 
which  its  rival  utilizes.  The  fact  is  that  the  simphfication  attained  by  postu- 
lating filtration  as  the  first  stage  in  urine  formation  has  to  be  paid  for  in 
the  reabsorption.  The  boat  having  shot  the  rapids  in  the  glomeruli  with 
next  to  no  physiological  expense  has  straightway  to  be  more  or  less  painfully 
locked  a  certain  distance  upstream. 


504  EXCRETION 

that  the  exchange  between  blood  and  tissue  lymph  is  mainly  accom- 
plished by  filtration  from  the  capillaries  of  vast  quantities  of  liquid 
containing  the  crystalloid  constituents  and  the  gases  in  the  concen- 
tration in  which  they  exist  in  plasma.  On  the  contrary,  the  dissolved 
substances  are  currently  antl  no  doubt  correctly  assumed  to  move  to 
a  great  extent  by  diffusion  through  the  capillary  walls  (perhaps  with 
a  certain  amount  of  active  intervention  of  the  endothelial  cells)  and 
across  the  thin  sheets  of  tissue  lymph  on  their  way  to  and  from  the 
cells.  In  other  words,  they  move  mainly  through  the  water  and  not 
with  the  water.  An  attempt  to  explain  the  gaseous  exchani^e  between 
the  blood  and  the  tissues  as  a  matter  purely  of  filtration  of  plasma 
containing  dissolved  gases,  and  not  at  all  of  diffusion  of  the  gases, 
would  lead  to  curious  results.  There  is  no  more  reason  to  believe  that 
urea  passes  from  the  blood  to  the  boundary  of  the  tubule  cells  by  a 
filtration  process  independent  of  diffusion,  and  therefore  entailing  the 
irrigation  of  the  cells  with  a  very  large  amount  of  lymph,  than  there 
is  to  believe  that  when  loo  c.c.  of  arterial  blood  loses  lo  c.c.  of  oxygen 
in  passing  through  the  capillaries,  this  is  accomplished  by  filtration 
into  the  Ivmph  spaces  of  4,000  c.c.  of  plasma  containing  0-25  c.c.  of 
oxygen  in  100  c.c.  (p.  252). 

As  to  the  nature  of  tiie  mechanism  set  in  motion,  and  the  series 
of  events  that  take  place  as  the  constituents  of  the  urine  journey 
from  the  interior  of  the  bloodvessels  to  the  lumen  of  the  tubules, 
we  know  no  more  than  in  the  case  of  other  glands.  This  alone 
is  clear,  that  the  separation  of  the  urine  from  the  blood  implies  the 
performance  of  a  large  amount  of  work  by  the  kidney.  A  token  of 
the  intensity  of  the  metabolic  effort  required  is  the  marked  increase 
in  the  absorption  of  oxygen  which  occurs  during  diuresis.  In  one 
experiment  the  oxygen  absorbed  by  a  dog's  kidneys  was  11  per  cent, 
of  what  would  have  been  used  up  by  the  entire  animal  under  normal 
conditions. 

The  mere  fact  that  urine  differs  in  its  quantitative  composition 
from  blood-plasma  is  sufficient  to  show  that  work  must  be  done  in 
its  separation  from  the  blood.  Although  the  amount  of  work 
cannot  be  calculated  from  the  difference  in  the  osmotic  pressures 
of  the  two  liquids,  a  comparison  of  the  freezing-points  affords  quali- 
tative evidence  of  the  performance  of  work  by  the  kidney.  For 
average  urine,  the  value  of  A  is  several  times  as  great  as  for  the 
plasma.  Blood-plasma  freezes  at  -0-55°  to  -  o>t)5°  C.  (average, 
-  0-6°,  corresponding  to  an  osmotic  pressure  of  5,662  mm.  of  mercury, 
or  about  75  metres  of  water).  Human  urine  has  been  found  to 
freeze  at  -i'38°  to  -2«ii°C.  (average,  -  i-8°C.,  corresponding  to 
an  osmotic  pressure  of  about  17,000  mm.  of  mercury,  or  225  metres 
of  water).  For  highly  concentrated  urines,  the  depression  of  the 
freezing-point  mav  be  considerably  greater.  Even  when  the 
freezing-point  is  foimd  in  ver>'  dilute  urines  to  be  approximately 
the  same  as  in  the  blood-plasma,  work  may  still  have  been  done  in 
the  separation  of  the  urine,  because  although  the  total  molecular 
concentration  may  be  the  same  in  the  two  liquids,  the  concentra- 
tion of  each  of  the  substances  in  solution  mav  be  different.     For 


TUF.   SFCRFTWX  OF  I'HF  URINE  503 

example,  cvtn  in  tlie  most  dilute  urine,  the  concentration  of  urea 
will  in  general  be  much  greater  than  in  the  blood.  It  is  of  interest 
in  connection  with  the  work  performed  by  the  kidney  that  when 
the  flow  of  urine  is  increased  by  diuretics  like  caffeine  or  sodium 
sulphate,  whicli  cause  the  secretion  of  urine  with  a  very  different 
crystalloid  composition  from  that  of  the  plasma,  more  oxygen  is 
used  up,  whereas  the  diuresis  caused  by  the  injection  of  Ringer's  solu- 
tion where  the  urine  and  plasma  do  not  differ  materially  in  the  amount 
or  kind  of  the  non-protein  constituents,  is  accomplished  practically 
without  change  in  the  oxygen  consumption  of  the  kidney. 

Significance  of  the  Glomeruli. — What  is  the  significance  of  the 
peculiar  arrangement  of  the  glomerular  bloodvessels,  if  the  epithelium 
of  the  capsules  has  secretive  powers  like  that  of  ordinary  glands  ? 
It  is  difficult  to  believe  that  these  unique  vascular  tufts  have  not  a  near 
and  important  relation  to  the  renal  function:  but  it  is  b}'  no  means 
clear  what  that  relation  is.  The  secretion  of  water,  and  even  its  rapid 
secretion,  is  not  at  all  bound  up  with  any  set  arrangement  of  blood- 
vessels. Gland-cells  all  over  the  body  secrete  water  under  the  most 
varied  conditions  of  blood-pressure,  although  a  comparatively  liigh 
pressure  is  upon  the  whole  favourable  to  a  copious  outiiow. 

But    the    kidney    has    perhaps     other    functions    than    excretion 
(Chapter  XI.).     And  it  may  be  that  the  simplest  part  of  the  latter 
process,  the  elimination  of  water  and  salts,  is  largely  thrown  upon  the 
Malpighian  corpuscles,  as  a  physiologically  cheaper  machine  than  the 
epithelium  of  the  tubules,  which  is  left  free  for  more  complex  labours. 
These  may  include  not  only  the  separation  of  nitrogenous  metabolites, 
but  also  synthetic   processes  possibly  concerned  in  the  regulation  of 
protein  metabolism.     One  characteristic  synthesis,  the  union  of  benzoic 
acid  and  glycin  to  hippuric  acid,  has  already  been  referred  to.     As  will 
be  shown  later  (p.  380),  it  takes  place  mainly,  in  some  animals  perhaps 
exclusively,  in  the  kidney.     The  epithelium  of  the  glomerulus,  being  a 
less  highly  organized  and  less  delicately  selective  mechanism  than  that 
of  the  convoluted  tubules,  may  more  easily  respond  to  increase  of  blood- 
pressure  by  increased  secretion.     At  the  same  time,  placed  as  it  is  at 
the  last  flood-gate  of  the  circulation,  where  the  escape  of  anything 
valuable  means  its  total  loss,  the  glomerular  epithelium  may  be  endowed 
with  a  general  power  of  resistance  to  transudation,  which  renders  a 
comparatively  high  blood-pressure  a  necessary  condition  of  its  acting 
at  all.     And  as  a  matter  of  fact  water  ceases  to  be  secreted  by  the 
kidney  long  before  the  blood-pressure  in  the  glomeruli  can  have  fallen 
below  that  which  suffices  for  the  highest  activity  of  the  liver.     Perhaps, 
however,  the  high  minimum  pressure  required  (30  to  40  mm.  of  mercury 
in  the  dog)  is  merely  the  necessary  consequence  of  the  long  and  difficult 
path  which  most  of  the  blood  going  through  the  kidney  has  to  take,  and, 
that  a  sufficient  blood-fiow  cannot  be  kept  up  with  less.     It  may  be, 
too,  that  the  comparatively  small  surface  of  the  glomeruli,  restricted 
in  order  to  leave  room  for  the  more  highly  organized  parts  of  the  renal 
mechanism,  entails  the  more  intense  and  concentrated  activity  which 
the  high  blood-pressure  renders  possible,  and  the  simplicity  of  work 
and  organization  renders  harmless. 

An  obvious  result,  and  perhaps  an  important  one,  of  the  peculiar 
arrangement  of  the  bloodvessels  of  the  kidney  is  that  the  renal  tubules 
proper  are  shielded  from  an  excessive  blood-pressure  by  the  inter- 
position of  the  glomeruli  as  a  block.  This  may  be  either  because  the 
epithelium  of  the  tubules  would  not  perform  its  work  so  well  under  a 


5o6  EXCRETION 

Jiigh  blood -prcs.su re,  or  because  there  would  be  a  danger  of  substances 
which  ought  to  be  retained  being  cast  out  into  the  urine.  In  this  con- 
nection it  is  interesting  to  note  that  the  specific  constituents  of  urine 
are  separated  by  epithelium  surrounded  by  capillaries  of  the  second 
order,  and  therefore  with  a  smaller  blood-pressure. than  exists  in  the 
capillaries  of  most  glands,  while  the  same  is  true  of  bile,  another 
(practically)  protein-free  secretion. 

The  maximum  secretory  pressure  in  the  kidney,  as  shown  by  a 
manometer  tied  into  tlie  divided  ureter,  is  about  60  mm.  of  mercury 
in  the  dog,  or  less  than  half  that  of  saliva.  If  the  escape  of  the 
urine  is  opposed  by  a  greater  pressure  than  this,  or  if  the  ureter  is 
tied,  the  kidney  becomes  u.'dematous.  Whether  the  oedema  is  due 
to  reabsorption  of  urine  or  to  the  pouring  out  of  lymph  owing  to 
the  pressure  of  the  dilated  tubules  on  the  veins  has  not  been  de- 
finitely settled.  It  has  been  already  pointed  out  that  there  is  no 
necessary  relation  between  the  blood-pressure  in  the  capillaries  of 
a  gland  and  its  secretory  pressure;  and,  so  far  as  this  goes,  water 
might  just  as  well  be  secreted  at  a  pressure  of  60  mm.  of  mercury 
from  the  low-pressure  blood  of  the  second  set  of  renal  capillaries 
as  from  the  high-pressure  blood  of  the  glomeruli.  By  obstruction 
the  molecular  concentration  of  the  urine  is  diminished  to  half  or 
three-quarters  of  the  normal. 

The  Influence  of  the  Circulation  on  the  Secretion  of  Urine. — 
Although  the  activity  of  no  organ  in  the  body  is  governed  more 
by  the  indirect  effects  of  nervous  action  than  that  of  the  kidney, 
no  proof  has  been  given  of  the  existence  of  secretory  fibres  for  it 
comparable  to  those  of  the  salivar}'  glands.  All  the  changes  in  the 
rate  of  renal  secretion  which  follow  the  section  or  stimulation  of 
nerves  can  be  explained  as  the  consequences  of  the  rise  or  fall  of 
local  or  general  blood-pressure,  and  of  the  corresponding  variations 
in  the  velocity  of  the  blood  in  the  renal  vessels. 

The  best  way  to  study  variations  in  the  calibre  of  the  renal  vessels  is 
the  plethysmographic  method,  and  the  oncometer  of  Roy  is  a  pkthysmo- 
graph  adapted  to  the  kidney  (Fig.  192).  It  consists  of  a  metal  capsule 
lined  with  loose  membrane,  between  which  and  the  metal  there  is  a 
space  filled  with  oil.  The  two  halves  of  the  capsule  open  and  shut  on  a 
hinge;  and  the  kidney,  when  introduced  into  it,  is  surrounded  on  all 
sides  by  the  membrane,  the  vessels  and  ureter  passing  out  through  an 
opening.  The  oil-space  is  connected  with  a  cylinder  also  filled  with  oil, 
above  which  a  piston,  attached  to  a  lever,  moves.  The  lever  registers 
on  a  drum  the  changes  in  the  volume  of  the  kidney — i.e.,  practically  the 
changes  in  the  quantity  of  blood  in  it,  and  therefore  in  the  calibre  of 
its  vessels.  A  still  better  oncometer  is  that  of  Schafer,  in  which  air  is 
employed  instead  of  oil. 

Nerves  of  the  Kidney. — Both  vaso-constrictor  and  vaso-dilator  fibres 
for  the  renal  vessels,  but  most  clearly  the  former,  have  been  shown 
to  leave  the  cord  (in  the  dog)  by  the  anterior  roots  of  the  sixth  thoracic 
to  second  lumbar  nerves,  and  especially  of  the  last  three  thoracic. 
They  run  in  the  splanchnics,  and  then  through  the  renal  plexus — around 
the  renal  artery — into  the  kidney.     The  vaso-constrictors  predominate, 


THE  SECRETION  OF  THE  URINE 


507 


so  that  the  general  effect  of  stimulation  of  the  nerve-roots,  the  splanch- 
nics,  or  the  renal  nerves  is  shrinking  of  the  kidney,  with  diminution  or 
cessation  of  the  secretion  of  urine.  But  slow  rhythmical  stimulation 
of  the  roots  causes  increase  of  volume,  the  scanty  dilators  being  by  this 
method  excited  in  preference  to  the  constrictors. 

The  renal  nerves,  entering  at  the  liilum,  branch  repeatedly,  so  as  to 
form  a  wide-meshed  plexus  around  the  arteries,  and  accompany  them 
even  to  their  finest  ramifications  in  the  cortex.  Coming  off  from  the 
nerves  surrounding  the  arteries  are  fine  fibres  which  are  distributed  to 
the  convoluted  tubules.  Some  of  them  terminate  in  globular  ends, 
others  in  fine  threads  that  pass  through  the  membrana  propria  (Berkely)- 

Section  of  the  renal  nerves  is  followed  by  relaxation  of  tlie  small 
arteries  in  the  kidney,  and  consequent  swelling  of  the  organ.  The 
flow  of  urine  is  greatly  increased,  and  sometimes  albumin  appears 
in  it,  the  excessive  pressure  in  the  capillaries  (particularly  in  those 

of  the  glomeruli)    being 
supposed  to  favour   the 
escape   of   substances  to 
which  a  passage  is  refused 
under  normal  conditions. 
An  experiment  which  is 
sometimes  quoted  as  a  de- 
cisive test  of  the  relative 
importance  of  changes  in 
the  rate  of  flow,  and  in 
the  pressure  of  the  blood 
within  the  glomeruli,  is 
that    of  tying  the  renal 
vein.      This  undoubtedly 
does  not  lower  the  intra- 
glomerular  pressure  —  on 
the  contrary,  it  must  in- 
crease it — but  the  secretion  of  urine  stops.     If  the  venous  outflow 
from  the  kidnej^  is  only  partially  interfered  with,  the  flow  of  urine  is 
immediately  diminished,  but  the  administration  of  a  diuretic  like 
potassium  nitrate  causes  an  increase.     It  is  more  than  likely  that 
in  these  experiments  the  secretion  stops  or  slackens  not  because  a 
high  blood- pressure,  but  because  an  active  circulation  is  its  necessary 
condition.     When  the  blood  stagnates  in  the  kidney  the  natural 
stimulus  to  the  renal  apparatus  speedily  disappears  owing  to  the 
elimination  of  the  urinary  constituents  to  the  neutral  or  indifferent 
point  (p.  501).     The  experiment,  however,  is  not  perfectly  conclu- 
sive.    For  few  glands  can  go  on  performing  their  function  after  the 
circulation  has  ceased.     The  kidney  must  be  able  to  feed  itself  in 
order  to  continue  its  work.     Above  all,   it  needs  oxygen;  and  it 
might  be  urged  that  if  the  blood  in  the  glomeruli  could  be  kept  at 
the  normal  standard  of  arterial  blood,  secretion  might  still  go  on 
after  ligation  of  the  renal  vein. 


Fig.  192. — Diagram  of  Organ-Plethysmograph  or 
Oncometer.  B,  metal  box  in  two  halves  open- 
ing on  the  hinge  H ;  M,  thin  membrane ;  A,  space 
filled  with  oil;  O,  organ  enclosed  in  oncometer; 
V,  vessels  of  organ;  /,  tube  for  filling  instrument 
with  oil;  T,  tube  connected  with  D,  which  opens 
into  cylinder  C;  C  is  also  filled  with  oil;  P,  pis- 
ton attached  by  E  to  a  writing  lever. 


So8  EXCRETION 

According  to  Ludwig,  indeed,  the  flow  of  urine  stops,  in  spite 
of  continued  filtration  through  the  glomeruli,  because  the  swelling 
of  the  veins  in  the  boundary  layer  compresses  the  tubules,  and  may 
even  obliterate  their  lumen.  There  is  no  conclusive  experimental 
evidence,  however,  and  no  a  priori  probability,  that  the  obstruction 
so  produced  is  sufficiently  sudden  or  sufficiently  complete  to  cause 
instant  and  total  cessation  of  the  flow.  It  is  even  less  justifiable 
to  conclude  from  the  experiment  that  the  liquid  part  of  the  urine 
is,  at  any  rate,  not  separated  by  the  epithelium  of  the  tubules,  since 
the  blood-pressure  in  the  capillaries  around  the  tubules  must  rise 
very  greatly  after  ligature  of  the  vein,  and  yet  secretion  is  stopped. 
It  might  equally  well  be  argued  that  the  renal  epithelium  normally 
secretes  water  under  a  low  blood-pressure,  but  is  disorganized  under 
the  excessive  and  entirely  unaccustomed  pressure  which  follows  the 
closure  of  the  vein. 

It  is  not  only  through  nerves  directly  governing  the  calibre  of  the 
vessels  of  the  kidney  that  the  rate  of  urinary  secretion  can  be 
affected.  Any  change  in  the  general  blood-pressure,  if  not  counter- 
acted by,  still  more  if  conspiring  with,  simultaneous  local  changes 
in  the  renal  vessels,  may  be  followed  by  an  increased  or  diminished 
flow  of  urine ;  and  the  law  which  explains  all  such  variations,  or  at 
least  serves  to  sum  them  up,  is  that  in  general  an  increase  in  the 
rate  of  the  blood- flow  through  the  kidney  is  followed  by  an  increase  in 
the  rate  of  secretion.  It  will  be  remarked  that  this  is  the  converse 
of  the  great  law,  of  which  we  have  already  seen  so  many  illustra- 
tions, that  functional  activity  increases  blood-flow.  It  is  probable 
that  this  law  holds  for  the  kidney  as  well  as  for  other  organs,  but 
that  the  influence  of  activity  on  blood-supply  is  subordinated  to 
that  of  blood-supply  on  activity,  while  in  most  tissues,  as  in  the 
muscles,  the  opposite  is  the  case.  It  is  evident  that  an  increase  in 
the  blood-flow  would  favour  the  secretory  activity  of  the  renal  cells, 
since  the  average  concentration  of  the  blood  presented  to  them  as 
regards  those  constituents  which  they  select  would  remain  relatively 
high  in  its  circuit  through  the  kidney.  The  '  stimulus  '  to  secretion 
would,  therefore,  be  relatively  intense. 

Destruction  of  the  medulla  oblongata  {i.e.,  of  the  vaso-motor 
centre),  or  section  of  the  cord  below  it,  diminishes  the  secretion  of 
urine,  because  the  arterial  pressure  is  lowered  so  much  as  to  over- 
compensate  the  dilatation  of  the  renal  vessels,  which  the  operation 
also  brings 'about.  If  the  blood-pressure  falls  below  40  mm.  of 
mercury,  the  secretion  is  abolished.  Stimulation  of  the  medulla  or 
cord  also  lessens  the  flow  of  urine  by  constricting  the  arterioles  of 
the  kidney  so  much  as  to  over-compensate  the  rise  of  general  blood- 
pressure,  caused  by  the  constriction  of  small  vessels  throughout  the 
body. 

If  the  renal  nerves  have  been  cut,  stimulation  of  the  medulla 


THE  SECRETION  OF  THE  URINE  je? 

oblongata  increases  the  urinary  secretion,  because  now  the  rise  of 
general  blood-pressure  is  no  longer  counterbalanced  by  constriction 
of  the  renal  vessels.  An  increase  in  the  urinary  flow  can  be  pro- 
duced in  the  rabbit  by  a  lesion  in  a  part  of  the  funiculi  teretes, 
which  can  be  reached  in  the  floor  of  the  fourth  ventricle  (Eckhard), 
perhaps  by  destroying  the  portion  of  the  vaso-motor  centre  governing 
the  renal  nerves,  while  the  rest  remains  uninjured,  or  is  even  stimu- 
lated, and  thus  keeps  up  or  even  increases  the  general  blood- 
pressure.     There  is  either  no  glycosuria,  or  it  is  very  slight. 

Section  of  the  splanchnic  nerves  causes  a  fall  of  arterial  pressure, 
which  is,  however  (in  animals  like  the  dog,  in  which  compensation 
soon  takes  place),  more  than  balanced  by  the  simultaneous  dilata- 
tion of  the  renal  vessels,  and  therefore  for  some  time  the  flow  of 
urine  is  increased,  but  not  so  much  as  when  the  renal  nerves  alone 
are  cut.  In  the  rabbit  there  is  no  increase.  On  the  other  hand, 
stimulation  of  the  splanchnics  stops  the  urinary  secretion,  because 
the  general  rise  of  pressure  is  not  enough  to  make  up  for  the  con- 
striction of  the  renal  vessels. 

Diuretics  are  substances  that  increase  the  flow  of  urine.  Some  of 
them  act  mainly  on  the  circulation,  as  by  increasing  the  general  blood- 
pressure,  others  mainly  by  a  direct  influence  on  the  secreting  mechanism. 
Digitalis  is  a  representative  of  the  first  class ;  urea  and  caffein  belong  to 
the  second.  The  action  of  digitalis  is  to  strengthen  the  beat  of  the 
heart,  which  is  at  the  same  time  somewhat  slowed,  and  to  constrict  the 
arterioles.  Both  eftects  contribute  to  the  increase  of  pressure.  The 
accompanying  diuresis,  seen  practically  only  in  cardiac  disease  with 
dropsical  effusions,  is  due  to  the  improvement  of  the  renal  circulation 
and  the  absorption  of  the  oedema  fluid.  Caffein,  when  injected  into  the 
blood,  affects  the  pressure  but  little.  It  causes  dilatation  of  the  renal 
vessels  after  a  passing  constriction,  and  an  increase  in  the  flow  of  urine 
after  a  temporary  diminution.  The  vascular  dilatation  is  not  the 
chief  reason  for  the  diuretic  effect,  for  the  latter  is  still  obtained  when  the 
vaso-motor  mechanism  has  been  paralyzed  by  chloral  hydrate,  and 
even  after  the  secretion  of  urine  has  been  stopped  by  the  fall  of  pressure 
consequent  on  section  of  the  spinal  cord.  Caffein,  therefore,  acts 
directly  on  the  renal  epithelium.  When  these  cells  are  asphyxiated  by 
temporary  clamping  of  the  renal  artery,  caffein  after  removal  of  the 
clamp  causes  no  diuresis,  while  the  injection  of  Ringer's  fluid  still 
causes  a  secretion  of  urine  possessing  the  same  crystalloid  composition 
as  the  plasma,  just  as  it  would  have  done  if  perfused  through  the  excised 
kidney.  The  action  of  urea,  potassium  nitrate,  and  saline  diuretics 
such  as  sodium  sulphate  is  probably  also  a  direct  action  on  the  secret- 
ing structures,  although  some  have  supposed  that  their  primary  effect 
is  to  cause  vaso-dilatation  in  the  kidney. 

Summary. — Our  knowledge  of  renal  secretion  may  be  thus 
summed  up:  The  water  and  salts  of  the  urine  are  chiefly  separated 
by  the  glomeruli  ;  the  process  is  not  a  mere  physical  filtration,  but 
a  true  secretion.  Substances  like  sugar,  peptone,  egg-albumin,  and 
hcemoglobin,  when  injected  into  the  blood,  are  probably  excreted  mainly 
by  the  glomeruli  ;  and  so  is  the  sugar  of  diabetes.  Urea,  uric  acid, 
and  presumably  the  other  organic  constituents  of  normal  urine,  with 


5^0  EXCRETION 

<(  portion  of  the  li-'aler  and  satts,  are  excreted  by  the  physiological 
activity  of  the  '  redded  '  epithelium  of  the  renal  tubules.  The  rate  of 
secretion  of  urine  rises  and  falls  ivith  the  pressure,  and  still  more  with 
the  velocity,  of  the  blood  in  the  renal  vessels.  No  secretory  nerves  for 
the  kidney  have  been  found ;  the  effects  of  section  or  stimulation  of 
nerves  on  the  secretion  can  all  be  explained  by  the  changes  produced  in 
the  renal  blood-flow.  Some  diuretics  act  by  increasing  the  blood-flow, 
others  directly  on  the  epithelium  of  the  tubules  or  the  glomeruli. 

Section  III. — Expulsion  of  the  Urine. 

Micturition. — The  urine,  like  the  bile,  is  being  constantly  formed; 
although  scMTction  varies  in  its  rate  from  time  to  time,  it  never 
ceases.  Trickling  along  the  collecting  tubules,  the  urine  reaches 
the  pelvis  of  the  kidney,  from  which  it  is  propelled  along  the  ureters 
by  peristaltic  contractions  of  their  walls,  and  drops  from  their  valve- 
like orifices  into  the  bladder.  When  this  becomes  distended,  rhyth- 
mical peristaltic  contractions  are  set  up  in  it,  and  notice  is  given 
of  its  condition  by  a  characteristic  sensation,  which  is  perhaps  aidetl 
by  the  squeezing  of  a  few  drops  of  urine  past  the  tonically  con- 
tracted circular  fibres  that  form  a  sphincter  round  the  neck  of  the 
bladder,  and  into  the  first  part  of  the  urethra.  The  desire  to  empty 
the  bladder  can  be  resisted  for  a  time,  as  can  the  desire  to  empty 
the  bowel.  If  it  is  yielded  to,  the  smooth  muscular  fibres  in  the 
wall  of  the  viscus  are  thrown  into  contraction.  This  is  aided  by  an 
expulsive  effort  of  the  abdominal  muscles.  The  sphincter  vesica; 
is  relaxed;  and  the  urine  is  forced  along  the  urethra,  its  passage 
being  facilitated  by  discontinuous  contractions  of  the  ejaculator 
urinae  muscle,  which  also  serve  to  squeeze  the  last  drops  of  urine 
from  the  urethral  canal  at  the  completion  of  the  act. 

Regurgitation  into  the  ureters  is  to  a  great  extent  prevented  by 
their  compression  between  the  mucous  and  muscular  coats  of  the 
bladder,  where  they  run  for  more  than  half  an  inch  before  opening 
at  the  posterior  angle  of  the  trigone.  But  it  has  been  shown  that 
a  certain  amount  of  back  flow  can  take  place.  Small  bodies  like 
(hatoms  suspended  in  water  and  pigments  dissolved  in  it  have  been 
found  in  the  pelvis  of  the  kidney,  the  renal  tubules,  and  even  the 
circulation  after  being  injected  into  the  bladder. 

The  pressure  in  the  bladder  of  a  man  may  be  made  as  high  as 
10  cm.  of  mercury  during  the  act  of  micturition;  about  half  this 
amount  is  due  to  the  contraction  of  the  vesical  walls  alone,  the 
rest  to  the  contraction  of  the  abdominal  muscles.  A  pressure  of 
i6  to  26  mm.  of  mercury  is  required  to  open  the  sphincter  of  a 
rabbit's  bladder  in  life. 

Although  the  whole  performance  seems  to  us  to  be  completely 
voluntary,  there  are  facts  which  show  that  it  is  at  bottom  a  reflex 


EXPULStOM  OF  THE   J' RISE  511 

series  of  co-ordinated  movements,  that  can  be  started  by  impulses 
passing  to  a  centre  in  the  spinal  cord  from  above  or  from  below — 
from  the  brain  or  from  the  bladder.  In  dogs,  with  the  spinal  cord 
divided  at  the  upper  level  of  the  lumbar  region,  micturition  takes 
place  regularly  when  the  bladder  is  full,  and  can  be  excited  by  such 
slight  stimuli  as  sponging  of  the  skin  around  the  anus  (Goltz). 
Here,  of  course,  the  act  is  entirely  reflex;  and  the  centre  is  situated 
at  the  level  of  the  fifth  lumbar  nerves.  The  efferent  nerves  of  the 
bladder,  like  those  of  the  rectum,  come  partly  from  the  cord  directly 
through  the  sacral  nerves,  and  partly  through  the  lumbar  sympa- 
thetic chain  (second  to  sixth  ganglia).  The  sacral  fibres  are  con- 
nected with  nerve  cells  in  the  hypogastric  plexus,  and  the  sympa- 
thetic, partly  at  least,  in  the  inferior  mesenteric  ganglia.  This 
anatomical  coincidence  acquires  interest  in  view  of  the  striking 
physiological  similarity  between  the  processes  of  micturition  and 
defsecation,  a  similarity  which  is  emphasized  by  the  fact  that  the 
latter  is  almost  invariably  accompanied  by  the  former.  An  im- 
portant difference,  however,  is  that  the  will  can  far  more  readily 
set  in  motion  the  machinery  of  micturition  than  that  of  defsecation; 
a  man  can  generally  empty  his  bladder  when  he  likes,  but  he  cannot 
empty  his  bowels  when  he  likes. 

Sometimes  in  disease,  and  especially  in  disease  of  the  spinal  cord, 
the  mechanism  of  micturition  breaks  down;  the  bladder  is  no 
longer  emptied ;  it  remains  distended  with  urine,  which  dribbles 
away  through  the  urethra  as  fast  as  it  escapes  from  the  ureters. 
To  this  condition  the  term  incontinence  of  urine  is  properly 
applied. 

Reflex  emptying  of  the  bladder,  without  an  act  of  will  or  during 
unconsciousness,  is  not  true  incontinence.  The  involuntary  mic- 
turition of  children  during  sleep,  for  example,  is  a  perfectly  normal 
reflex  act,  although  more  easily  excited  and  less  easily  controlled 
than  in  adults.  Section  either  of  both  nervi  erigentes,  or  of  both 
hypogastrics,  is  never  followed  by  more  than  quite  temporary  dis- 
turbance of  function  of  the  bladder  in  clogs,  both  male  and  female. 
In  a  few  days  the  urine  is  normally  passed.  In  bitches  the  same 
is  true  when  both  pairs  of  nerves  are  divided.  But  in  male  dogs 
true  incontinence  of  urine  follows  section  of  the  four  nerves,  as  well 
as  intense  tenesmus  due  to  paralysis  of  the  lower  part  of  the  large 
intestine. 

Section  IV. — Excretion  by  the  Skin. 

Besides  permitting  of  the  trifling  gaseous  interchange  already 
referred  to  (p.  299),  the  skin  plays  an  important  part  in  the  ehmina- 
tion  of  water  by  the  sweat-glands. 

Sweat  is  a  clear  colourless  liquid  of  low  specific  gravity  (1003  to 
1006),  consisting  chiefly  of  water  with  small  quantities  of  salts, 


jtl  EXCRETIOH 

neutral  fats,  volatile  fatty  acids,  and  the  merest  traces  of  proteins 
and  urea.  It  is  acid  to  litmus  except  in  profuse  sweating,  when  it 
may  become  neutral  or  even  alkaline.  It  is  secreted  by  simple 
gland-tubes,  which  form  coils  lined  with  a  single  layer  of  columnar 
epithelium,  in  the  subcutaneous  tissue,  with  long  ducts  running  up 
to  the  surface  through  the  true  skin  and  epidermis.  Unless  col- 
lected from  the  parts  of  the  skin  on  which  there  are  no  hairs,  such 
as  the  palm,  it  is  apt  to  be  mixed  with  sebum,  a  secretion  formed 
by  the  breaking  down  of  the  cells  of  the  sebaceous  glands,  which 
open  into  the  hair  follicles,  and  consisting  chiefly  of  glycerin  and 
cholesterin  fats,  soaps,  and  salts.  Sebum  is  probably  of  consider- 
able importance  for  maintaining  the  normal  condition  of  the  hair 
and  skin. 

Although  it  is  only  occasionally  that  sweat  collects  in  visible 
amount  on  the  skin,  water  is  always  being  given  off  in  the  form  of 
vapour.  This  invisible  perspiration  leaves  behind  it  on  the  skin, 
or  in  the  glands,  the  whole  of  the  non-volatile  constituents,  which 
may  be  to  some  extent  reabsorbed ;  and  since  even  the  visible  per- 
spiration is  in  large  part  evaporated  from  the  very  mouths  of  the 
glands  in  which  it  is  formed,  the  sweat  can  hardly  be  considered  a 
vehicle  of  solid  excretion,  even  to  the  small  extent  indicated  by  its 
chemical  composition. 

The  total  quantity  of  water  excreted  by  the  skin,  and  the  relative 
proportions  of  visible  and  invisible  perspiration,  vary  greatly.  A 
dry  and  warm  atmosphere  increases,  and  a  moist  and  cold  atmo- 
sphere diminishes  the  total,  and,  within  limits,  the  invisible  per- 
spiration. Visible  sweat — given  the  condition  of  rapid  heat-produc- 
tion in  the  body  as  in  muscular  labour — is  more  readily  deposited 
on  freely  exposed  surfaces  when  the  air  is  moist  than  when  it  is  dry. 
The  air  in  contact  with  surfaces  covered  by  clothing  is  never  far 
from  being  saturated  with  watery  vapour.  Here,  accordingly,  a 
comparatively  slight  increase  in  the  activity  of  the  sweat-glands 
suffices  to  produce  more  water  than  can  be  at  once  evaporated; 
and  the  excess  appears  as  sweat  on  the  skin,  to  be  absorbed  by 
the  clothing  without  evaporation,  or  to  be  evaporated  slowly,  as 
the  pressure  of  the  aqueous  vapour  gradually  diminishes  in  con- 
sequence of  diffusion.  The  power  of  imbibition  (p.  426)  of  water 
by  the  various  layers  of  the  skin  diminisJies  as  we  pass  outwards, 
and  the  cells  of  the  epidermis  are  characterized  by  the  rapidity  with 
which  they  return  from  a  condition  of  excessive  imbibition  to  their 
normal  state.  This  constitutes  a  protective  mechanism  against 
excessive  loss  of  water.  When  the  skin  is  thoroughly  moistened,  its 
degree  of  imbibition  is  three  times  the  normal. 

The  quantity  of  sweat  given  off  by  a  man  in  twenty-four  hours 
varies  so  much  that  it  would  not  be  profitable  to  quote  here  the 
numerical  results  obtained  under  different  conditions  of  tempera- 


l:xcri:tio\  b)    iiii.  skin  513 

tiire  ami  lnmiidity  o{  the  air  (hut  sec  p.  691).  It  is  eiKMit^h  to  say 
that  the  excretion  of  water  from  the  skin  is  of  tlie  same  order  of 
magnitude  as  that  from  the  kidneys:  a  man  loses  upon  tlie  whole 
as  much  water  in  sweat  as  in  urine.  But  it  is  to  be  carefully  noted 
that  these  two  channels  of  outfiovv  are  complementary  to  each 
other;  when  the  loss  of  water  by  the  skin  is  increased,  the  loss  by 
the  kidneys  is  diminished,  and  vice  versa. 

The  Influence  of  Nerves  on  the  Secretion  of  Sweat. — The  sweat- 
glands  are  governed  directly  by  the  nervous  system ;  and  though 
an  actively  perspiring  skin  is,  in  health,  a  flushed  skin,  the  vascular 
tlilatation  is  a  condition,  and  not  the  chief  cause  of  the  secretion. 
Stimulation  of  the  peripheral  end  of  the  sciatic  nerve  causes  a 
copious  secretion  of  sweat  on  the  pad  and  toes  of  the  corresponding 
foot  of  a  young  cat,  and  this  although  the  vessels  are  generally 
constricted  by  excitation  of  the  vasomotor  nerves.  Not  only  so, 
but  when  the  circulation  in  the  foot  is  entin^ly  cut  off  by  compres- 
sion of  the  crural  artery  or  by  amputation  of  the  limb,  stimulation 
of  the  sciatic  still  calls  forth  some  secretion.  As  in  the  case  of  the 
salivary  glands,  injection  of  atropine  abolishes  the  secretory  power 
of  the  sciatic,  while  leaving  its  vaso-motor  influence  untouched;  and 
pilocarpine  increases  the  flow  of  sweat  by  direct  stimulation  of  the 
endings  of  the  secretory  nerves  in  the  glands. 

That  the  sweating  caused  by  a  high  external  temperature  is 
normally  brought  about  by  nervous  influence,  and  not  by  direct 
action  on  the  secreting  cells,  is  shown  by  the  following  experiments. 
One  sciatic  nerve  is  divided  in  a  cat,  and  the  animal  put  into  a  hot- 
air  chamber.  No  sweat  appears  on  the  foot  whose  nerve  has  been 
cut,  but  the  other  feet  are  bathed  in  perspiration.  Similarly,  a 
venous  condition  of  the  blood  (in  asphyxia)  causes  sweating  in  the 
feet  whose  nerves  have  not  been  divided,  but  none  in  the  other 
foot;  and  stimulation  of  the  central  end  of  the  cut  sciatic  has  the 
same  effect.  All  this  points  to  the  existence  of  a  reflex  mechanism ; 
and  it  is  certain  that  asphyxia  acts  by  direct  stimulation  of  the 
centre  or  centres.  The  vaso-motor  centre  is  at  the  same  time 
stimulated,  and  the  bloodvessels  constricted,  as  in  the  cold  sweat 
of  the  death  agony.  Fear  may  also  cause  a  cold  sweat,  impulses 
passing  from  the  cerebral  cortex  to  the  vaso-motor  and  sweat 
centres. 

It  is  probable  that  a  general  sweat  -  centre  exists  in  the  medulla 
oblongata,  but  its  position  has  not  been  exactly  determined  nor  even 
its  existence  definitely  proved.  On  the  other  hand,  it  is  known  that 
in  the  cat  there  are  at  least  two  spinal  centres,  one  for  the  fore-limbs 
in  the  lower  part  cf  the  cervical  cord,  and  another  for  the  hind-limbs 
where  the  dorsal  portion  of  the  cord  passes  into  the  lumbar.  That  this 
latter  centre  docs  not  exist  or  is  comparatively  inactive  in  man  is 
indicated  by  the  following  case :  A  man  fell  from  a  window  and  fractured 
his  backbone  at  the  fifth  dorsal  vertebra.  The  lower  half  of  tlic  liody 
was  paralyzed  for  a  time,  but  recovered.     Ultimately,  however,  the 

33 


514  EXCRETION 

paralysis  returned;  and  shortly  before  his  death  (twenty-one  years  after 
the  aecident)  it  was  noticed  tliat  a  copious  perspiration  broke  out 
several  times  on  the  upper  part  of  the  body,  while  tlic  lower  portion 
remained  perfectly  dry.  If  there  is  any  functional  spinal  centre  in  man, 
it  appears  to  lie  above  the  fifth  spinal  segment.  For  it  was  seen  in  a 
professional  diver  who  fractured  his  neck  at  that  level,  and  lived  three 
months  after  the  accident,  that  sweat  frequently  appeared  on  parts  of 
the  body  above  the  lesion,  but  never  below.  At  the  autopsy  the  whole 
thickness  of  the  cord,  except  perhaps  a  small  portion  of  tlic  anterior 
columns,  was  found  destroyed.  Of  course,  it  may  be  that  in  man  the 
spinal  centres,  although  normally  active,  lose  their  function  for  a  long 
time  after  such  severe  injuries  to  the  cord,  owing  to  the  condition  known 
as  shock. 

The  secretory  fibres  for  the  fore-limbs  (in  the  cat)  leave  the  cord  in 
the  anterior  roots  of  the  fourth  to  ninth  thoracic  nerves.  They  pass  by 
white  rami  communicantes  to  the  sympathetic  chain,  in  which  they 
reach  the  ganglion  stellatum,  where  they  are  all  connected  with  nerve- 
cells.  Then,  as  non-meduUated  fibres,  they  gain  the  brachial  plexus 
by  the  grey  rami,  and  run  in  the  median  and  ulnar  to  the  pads  of  the 
feet.  The  fibres  for  the  hind-limbs  leave  the  cord  in  the  anterior  roots 
of  the  twelfth  thoracic  to  the  third  or  fourth  lumbar  nerves ;  pass  by  the 
white  rami  to  the  sympathetic  ganglia,  in  which  they  form  connections 
with  ganglion  cells;  then,  as  non-meduUated  fibres,  run  along  the  grey 
rami,  and  are  distributed  to  the  foot  in  the  sciatic. 

The  evidence  of  the  direct  secretory  action  of  nerves  on  the  sweat- 
glands  is  singularly  striking  and  complete,  in  contrast  to  what  we 
know  of  the  kidney.  In  the  latter,  blood-fiov;  is  the  important 
factor;  increased  blood-flow  entails  increased  secretion.  In  the 
former,  the  nervous  impulse  to  secretion  is  the  spring  which  sets 
the  machinery  in  motion;  vascular  dilatation  aids  secretion,  but 
does  not  generally  cause  it.  It  would,  however,  be  easy  to  lay  too 
much  stress  on  this  distinction,  for  in  the  horse  the  mere  dilatation 
of  the  bloodvessels  of  the  head  after  section  of  the  cervical  sympa- 
thetic has  been  found  to  be  accompanied  by  increased  secretion  of 
sweat,  and  urinary  secretion  can  certainly  be  affected  by  the  direct 
action  of  various  substances  on  the  secretory  mechanism,  indepen- 
dently of  vascular  changes.  But  the  broad  difference  stands  out 
clearly  enough,  and  the  reason  of  it  lies  in  the  essentially  different 
purpose  of  the  two  secretions.  The  water  of  the  urine  is  in  the 
main  a  vehicle  for  the  removal  of  its  solids;  the  solids  of  the  sweat 
are  accidental  impurities,  so  to  speak,  in  the  water.  The  kidney 
eliminates  substances  which  it  is  vital  to  the  organism  to  get  rid 
of;  the  sweat-glands  pour  out  water,  not  because  it  is  in  itself 
hurtful,  not  because  it  cannot  pass  out  by  other  channels,  but 
because  the  evaporation  of  water  is  one  of  the  most  important 
means  by  which  the  temperature  of  the  body  is  controlled.  In 
short,  urine  is  a  true  excretion,  sweat  a  heat-regulating  secretion. 
No  hurtful  effects  are  produced  when  elimination  by  the  skin  is 
entirely  prevented  by  varnishing  it,  provided  that  the  increased 
loss  of  heat  is  compensated.     A  rabbit  with  a  varnished  skin  dies 


PRACTICAL  EXERCISES 


515 


of  cold,  as  a  rabbit  with  a  closely-clippod  or  shaven  skin  does; 
suppression  of  the  secretory  function  of  the  si<in  has  nothing  to  do 
with  death  in  the  first  case  any  more  than  in  the  second  (p.  299). 


PRACTICAL  EXERCISES  ON  CHAPTER  IX. 

Urine. 

For  most  of  the  experiments  human  urine  is  employed — in  the 
quantitative  work  the  mixed  urine  of  the  twenty-four  hours.  Urine  may 
also  be  obtained  from  animals.  In  rabbits  pressure  on  the  abdomen 
will  usually  empty  the  bladder.  Dogs  may  be  taught  to  micturate  at 
a  set  time  or  place,  or  kept  in  a  cage  arranged  for  the  collection  of  urine. 
Or  a  catheter  may  be  used  (p.  716). 

I.  Specific  Gravity, — Pour  the  urine  into  a  glass  cylinder,  and  remove 
froth,  if  necessary,  with  filter-paper.     Place  a  urinometer  (Fig.   193) 
in  the  urine,  and  see  that  it  does  not  come  in  contact 
with  the  side  of  the  vessel.     Read  off  on  the  graduated 
,0  stem  the  division  which  corresponds  with  the  bottom 

,Q  of  the  meniscus.     This  gives  the  specific  gravity. 

,g  2.  Reaction. — (a)  Test  with  litmus-paper.    Generally 

,g  the  litmus  is  reddened,  but  occasionally  in  health  the 

urine  first  passed  in  the  morning  is  alkaline.  Some- 
times urine  has  an  amphicroic  reaction — i.e.,  affects 
both  red  and  blue  litmus-paper.  This  is  the  case  when 
there  is  such  a  relation  between  the  bases  and  acids 
that  both  acid  and  '  neutral  '  (dibasic)  phosphates  are 
present  in  certain  proportions.  The  acid  phosphate 
reddens  blue  litmus,  and  the  '  neutral '  phosphate 
turns  red  litmus  blue. 

(b)   Titratable  Acidity. — To  25  c.c.  of  urine  add  15 
to  20  grammes  of  powdered  potassium  oxalate,  and 
one  or  two  drops  of  a  i  per  cent,  solution  of  phenol- 
phthalein.     Shake  the  mixture  rapidly  for  a  minute 
Fig.    193. — Urin-     or  two,  and  then  titrate  with  decinormal  sodium  hy- 
ometer.  droxide  at  once  (while  still  cold  from  the  solution  of  the 

oxalate)  till  a  faint  pink  colour  remains  permanent  on 
shaking.  The  potassium  oxalate  is  added  to  counteract  the  tendency 
of  the  calcium  present  in  urine  to  form  basic  phosphates,  which  would 
be  precipitated,  and  the  acidity  of  the  urine  thus  increased  (Folin). 

3.  Chlorides — (a)  Qualitative  Test. — Add  a  drop  of  nitric  acid  and  a 
drop  or  two  of  silver  nitrate  solution.  The  nitric  acid  is  added  to 
prevent  precipitation  of  silver  phosphate.  A  white  precipitate  soluble 
in  ammonia  shows  the  presence  of  chlorides.  The  precipitate  appears 
to  be  incompletely  soluble  in  ammonia,  since  the  ammonia  brings  down 
a  small  precipitate  of  earthy  phosphates. 

[b]  Quantitative  Estimation. — The  quantitative  estimation  of  the 
chlorine  in  urine  without  previous  evaporation  and  incineration  is  best 
made  by  one  of  the  modifications  of  Volhard's  method.  It  depends  upon 
the  complete  precipitation  of  the  chlorine  combined  with  the  alkaline 
metals,  and  also  of  sulphocyanic  acid,  by  silver  from  a  solution  con- 
taining nitric  acid  in  excess ;  and  avoids  the  error  introduced  into  simpler 
methods,  like  Mohr's,  by  the  imion  of  some  of  the  silver  with  other 
substances  than  chlorine.     A  given  quantity  of  a  standard  solution  of 


5i6  EXCRETION 

silver  nitrate  (more  than  suf&cient  to  combine  with  all  the  chlorine)  is 
added  to  a  given  volume  of  urine.  The  excess  of  silver  is  now  estimated 
by  means  of  a  standard  solution  of  ammonium  sulphocyanide,  which 
precipitates  the  silver  as  insoluble  silver  sulphocyanide.  A  fairly  strong 
solution  of  the  double  sulphate  of  iron  and  ammonium  (known  as  iron- 
ammonia-alum)  is  taken  as  the  indicator,  since  a  ferric  salt  does  not 
give  the  usual  red  colour  with  a  sulphocyanide  so  long  as  any  silver  in  the 
solution  is  uncombined  with  sulphocyanic  acid.  The  iron-ammonia- 
alum  forms  the  red  salt,  ferric  sulphocyanide,  when  any  excess  of 
ammonium  sulphocyanide  is  present,  but  it  does  not  react  with  silver 
sulphocyanide. 

The  standard  solution  of  silver  nitrate  can  be  made  by  dissolving 
29'o63  grammes  of  pure  fused  silver  nitrate  in  distilled  water  and  making 
up  the  volume  of  the  solution  accurately  to  i  litre.  The  solution  should 
be  kept  in  the  dark.  One  c.c.  of  this  solution  corresponds  to 
o-oi  gramme  NaCl  or  0-00607  gramme  CI. 

The  standard  solution  of  ammonium  sulphocyanide  is  prepared  as 
follows:  Dissolve  13  grammes  of  pure  ammonium  sulphocyanide 
(NH4CNS)  in  a  litre  of  distilled  water.  Measure  with  a  pipette  into 
a  beaker  20  c.c.  of  the  standard  silver  nitrate  solution,  and  add  5  c.c. 
of  the  iron  alum  solution  and  4  c.c.  of  pure  nitric  acid  (specific  gravity 
I -2).  Fill  a  burette  with  the  sulphocyanide  solution,  and  run  it  into 
the  silver  nitrate  solution  until  a  faint  permanent  red  tinge  is  obtained. 
Note  the  number  of  c.c.  of  the  sulphocyanide  solution  required,  and 
then  dilute  the  solution  till  2  c.c.  of  the  sulphocyanide  solution  corre- 
spond exactly  to  i  c.c.  of  the  silver  solution,  so  as  just  to  allow  of  the 
end  reaction  with  the  iron  solution  being  seen,  and  no  more. 

To  carry  out  the  method,  put  10  c.c.  of  urine,  which  must  be  free 
from  albumin,  in  a  stoppered  flask,  with  a  mark  corresponding  to  100  c.c. 
or  a  graduated  cylinder.  Add  50  c.c.  of  water,  4  c.c.  of  pure  nitric  acid 
(specific  gravity  1-2),  and  15  c.c.  of  the  standard  silver  solution;  shake 
well,  fill  with  water  to  the  mark,  and  again  shake.  After  the  precipitate 
has  settled,  filter  it  off.  Take  50  c.c.  of  the  filtrate,  add  5  c.c.  of  the 
solution  of  iron-ammonia-alum,  and  run  in  from  a  burette  the  standard 
solution  of  ammonium  sulphocyanide  until  a  weak  but  pennanent  red 
coloration  appears. 

Suppose  X  c.c.  of  the  sulphocyanide  solution  are  required,  then  the 
chlorine  in  10  c.c.  of  urine  evidently  corresponds  to  (15  —x),  o'oi  gramme 
NaCl 

4.  Phosphates — (i)  Qualitative  Tests. — (a)  Render  the  urine  alkaline 
with  ammonia.  A  precipitate  of  earthy  phosphates  (calcium  and  mag- 
nesium phosphates)  falls  down.  Filter.  The  filtrate  contains  the 
alkaline  phosphates.  To  the  filtrate  add  magnesia  mixture.*  The 
alkaline  phosphates  (sodium,  potassium,  or  ammonium  phosphates) 
are  precipitated  as  ammonio-magnesic  or  triple  phosphate,  (fe)  Add  to 
urine  half  its  volume  of  nitric  acid  and  a  little  molybdate  of  ammonium, 
and  heat.  A  yellow  precipitate  of  ammonium  phospho-molybdate 
shows  that  phosphates  are  present.  This  test  is  given  both  by  alkaline 
and  earthy  phosphates. 

(2)  Quantitative  Estimation. — The  quantitative  estimation  of  phos- 
phoric acid  in  urine  is  best  done  volumetrically,  by  titration  with  a 
standard  solution  of  uranium  nitrate,  using  fcrrocyanide  of  potassium 
as  the  indicator.  Uranium  nitrate  gives  with  phosphates,  in  a  solution 
containing  free  acetic  acid,  a  precipitate  with  a  constant  proportion  of 

*  Magnesium  chloride  no  grammes,  ammonium  chloride  140  grammes, 
ammonia  (specific  gravity  0*91)  250  c.c,  and  water  1,750  c.c. 


PRACTICAL  EXERCISES  517 

phosphoric  acid.  As  soon  as  there  is  more  uranium  in  the  solution  than 
is  required  to  combine  with  all  the  phosphoric  acid,  a  brown  colour  is 
given  with  potassium  Icrrocyanidc,  due  to  the  formation  of  uranium 
ferrocyanide.  In  carrying  out  the  method,  5  c.c.  of  a  mixture  of  acetic 
acid  and  sodium  acetate  (there  are  10  grammes  of  sodium  acetate  and 
10  grammes  of  glacial  acetic  acid  in  100  c.c.  of  the  mixture)  are  added 
to  50  c.c.  of  urine,  which  is  then  heated  in  a  beaker  on  the  water-bath 
almost  to  boiling.  The  standard  uranium  solution  (which  contains 
35 '5  grammes  of  uranium  nitrate  in  the  litre,  and  i  c.c.  of  which  corre- 
sponds to  0-005  gramme  P2O5)  is  now  run  in  from  a  burette,  until  a  drop 
of  the  urine  gives,  with  a  drop  of  potassium  ferrocyanide  solution,  on  a 
porcelain  slab,  a  brown  colour.  Uranium  acetate  may  be  used  instead 
of  uranium  nitrate,  but  the  latter  keeps  best.  When  uranium  acetate 
is  employed  it  is  not  necessary  to  add  the  sodium  acetate  mixture. 

5.  Sulphates — (i)  Qualitative  Test. — Add  to  urine  a  drop  of  hj'^dro- 
chloric  acid  and  then  a  few  drops  of  barium  chloride.  A  white  pre- 
cipitate comes  down,  showing  that  inorganic  sulphates  are  present. 
The  hydrochloric  acid  prevents  precipitation  of  the  phosphates. 

(2)  Quantitative  Estimation  of  the  Sulphates  {Inorganic  and  Ethereal). 
— Add  to  50  c.c.  of  albumin-free  urine  in  a  200-c.c.  Erlenmeyer  flask 
5  c.c.  of  a  4  per  cent,  potassium  chlorate  solution  and  5  c.c.  of  strong 
hydrochloric  acid,  and  boil  the  mixture  to  break  up  the  ethereal  sul- 
phates. In  five  to  ten  minutes  it  becomes  perfectly  colourless.  While 
it  continues  to  boil,  25  c.c.  of  a  10  per  cent,  solution  of  barium  chloride 
are  added  by  drops,  at  such  a  rate  that  it  takes  about  five  minutes  to 
add  this  quantity.  The  flask  is  now  put  on  the  water-bath  for  one-half 
to  one  hour,  till  the  precipitate  has  settled.  Then  filter  through  an 
ash-free  filter.  Wash  the  precipitate  on  the  filter  for  half  an  hour  with 
hot  water.  During  the  first  twenty  minutes  of  the  washing,  at  intervals 
of  a  few  minutes,  substitute  hot  5  per  cent,  ammonium  chloride  solution 
for  the  water.  At  the  end  of  the  half-hour's  washing,  as  soon  as  the 
water  has  run  through  the  filter,  fold  up  the  latter  and  press  it  gently 
between  drj^  fiJter-papers  to  remove  a  portion  of  the  water.  Then  place 
the  filter  in  a  weighed  porcelain  crucible.  Pour  into  the  crucible  3  or  4 
c.c.  of  alcohol,  and  ignite  it,  to  dry  and  partially  bum  the  filter-paper. 
Then  incinerate  till  all  the  carbon  is  burned  off,  cool,  and  weigh.  From 
the  weight  of  the  barium  sulphate,  the  sulphuric  acid  in  50  c.c.  of  urine 
is  easily  calculated  (SO4  in  i  gramme  of  barium  sulphate,  0-41 187 
gramme)  (Folin). 

(3)  Quantitative  Estimation  of  the  Sulphuric  Acid  united  with  Aromatic 
Bodies  {Aromatic  or  Ethereal  Sulphates). — Put  200  c.c.  of  the  same  urine 
as  used  in  (2)  into  a  beaker.  Add  100  c.c.  of  10  per  cent,  barium 
chloride  solution  in  the  cold.  Let  stand  for  twenty -four  hours.  Then 
decant  off  the  clear  supernatant  liquid,  and  filter  it.  Measure  150  c.c. 
of  the  clear  filtrate,  corresponding  to  100  c.c.  of  the  urine,  into  a  400-c.c. 
Erlenmeyer  flask.  Add  10  or  15  c.c.  of  concentrated  hydrochloric  acid 
and  10  to  15  c.c.  of  4  per  cent,  potassium  chlorate.  Heat  the  mixture 
to  boiling,  and  proceed  as  in  (2).  From  the  weight  of  the  barium  sul- 
phate, the  ethereal  sulphuric  acid  in  100  c.c.  of  urine  can  be  calculated. 
Deducting  this  from  the  quantity  per  100  c.c.  of  urine  obtained  in  (2), 
we  get  the  amount  of  inorganic  sulphuric  acid  per  100  «.c.  (Folin). 

6.  Indoxyl  (contained  in  the  urine  as  indican,  the  potassium  salt  of 
indoxj-l-sulphuric  acid)  can  be  oxidized  into  indigo,  and  so  detected 
and  estimated. 

A  qualitative  test  is  the  following:  Ten  c.c.  of  horse's  urine  is  mixed 
with  10  c.c.  of  Obermayer's  reagent  (pure  concentrated  hydrodhloric 
acid  containing  2  to  4  parts  of  ferric  chloride  in  1,000),  and  shaken  well 


51 8  EXCRETION 

for  a  minute  or  two;  a  bluish  colour  appears  if,  as  is  generally  the  case, 
indoxyl  is  present,  indigo  (Ci6HioN'2^2)  being  formed  by  the  oxidizing 
action  of  the  ferric  chloride  on  the  indoxyl,  the  compound  of  which 
with  sulphuric  acid  has  been  broken  up  by  the  hydrochloric  acid.  The 
urine  must  be  free  from  albumin.  In  performing  the  test  in  human 
urine,  which  contains  a  smaller  quantity  of  the  indigo-forming  sub- 
stance, the  faint  blue  liquid  should  be  shaken  up  with  a  few  drops  of 
chloroform.  The  latter  takes  up  the  colour,  which  is  thus  rendered 
more  evident.  If  there  is  difficulty  in  obtiiining  the  reaction,  the  urine 
may  first  be  decolorized  by  precipitating  it  with  acetate  of  lead, 
avoiding  excess.  The  precipitate  is  filtered  off,  and  the  test  then 
applied  to  the  clear  filtrate.  The  skatoxyl  of  urine  can  also  be  oxidized 
to  indigo,  but  it  is  present  in  far  smaller  amount.  The  average  quantity 
of  indigo  obtained  from  a  litre  of  horse's  urine  is  about  150  milligrammes ; 
from  a  litre  of  human  urine,  not  a  twentieth  of  that  amount. 

For  comparative  quantitative  determinations  the  method  of  Folin 
may  be  used.  One-hundredth  of  the  twenty-four  hours'  urine  is  taken. 
In  this  the  indigo  is  developed  by  the  addition  of  an  equal  volume  of 
Obermayer's  reagent  (p.  5i'7),  and  the  indigo-blue  dissolved  by  means 
of  5  c.c.  of  chloroform.  The  chloroform  solution  is  then  compared 
colorimetrically  with  Fehling's  solution.  This  can  be  done  by  putting 
the  indigo  solution  and  5  c.c.  of  the  Fehling's  solution  respectively  into 
small  test-tubes  of  equal  calibre,  and  comparing  the  depth  of  tint. 
If  the  Fehling's  solution  is  stronger  than  the  indigo  solution,  run  water 
into  the  former  from  a  pipette,  graduated  in  tenths  of  a  c.c,  shaking 
up  after  each  addition,  till  equality  of  tint  has  been  reached.  If  the 
indigo  solution  has  a  stronger  blue  colour  than  the  Fehling's  solution, 
dilute  a  measured  amount  of  it  first  of  all  with  such  a  quantity  of 
chloroform  (say  an  equal  volume)  as  will  make  its  tint  distinctly  weaker 
than  that  of  the  Feliling's  solution.  Then  dilute  the  Fehling's  solutmn 
with  water,  as  before,  till  the  tint  is  the  same.  From  the  amount  of 
dilution  the  quantity  of  indigo  can  be  expressed  in  arbitrary  units, 
taking  Fehling's  solution  as  100.  Thus,  if  i  c.c.  of  water  must  be 
added  to  the  5  c.c.  of  Fehling's  solution,  the  indican  can  be  expressed 

as  =  5^  =  83.     The  comparison  can  be  made  more  accurately  by 

a  colorimeter,  if  one  is  available.  To  determine  the  absolute  amount 
of  indigo  obtained,  comparison  must  be  made  with  a  standard  solution 
of  indigo. 

7.  Urea — (i)  Decomposition  of  Urea. — Heated  dry  in  a  test-tube,  it 
gives  off  ammonia.  The  residue  contains  biuret,  which,  when  dissolved 
in  water,  gives  a  rose  colour  with  a  trace  of  cupric  sulphate  and  excess 
oi  sodium  hydroxide  (or  of  the  hydroxides  of  certain  other  metals  of 
the  alkalies  and  alkaline  earths  (p.  8).  Some  proteins — peptones  and 
alb  imoses — in  the  presence  of  the  same  reagents,  give  a  similar  colour, 
the  so-called  biuret  reaction. 

(2)  Quantitative  Estimation — Marshall's  Urease  MetJiod.  (According 
to  Van  Slyke). — One-half  c.c.  of  urine  is  measured  into  the  bottom  of 
tube  A  (Fig-  194).  Five  c.c.  exactly  of  a  0-6  per  cent,  solution  of 
KH2PO4  is  then  run  in  from  a  burette,  and  i  c.c.  exactly  of  a  10  per 
cent,  watery  solution  of  the  dry  urease  powder.  The  phosphate  is 
added  as  a  '  buffer  '  to  maintain  the  enzyme  action  near  its  maximum 
rate,  by  preventing  the  development  of  alkalinity  as  the  production  of 
ammonium  carbonate  goes  on.     The  solutions  in  the  tube  are  well 


PRACTICAL  KXERCISES 


519 


mixet-l,  2  drops  of  caprylic  alcohol  are  added  to  prevent  foaming  during 
the  subsequent  aeration  (by  Folin's  method,  p.  521),  and  the  stopper 
bearing  the  ;u  rating  tubes  is  put  into  place.     Let  stand  twenty  minutes 
at  room  temperature  of  15',  or  fifteen  minutes  at  20°  ('.  or  above,  for 
complete  decomposition   of  urea.     This  time   must  not  be  shortened 
unless  more  enzyme  is  used,  but  no  harm  is  done  if  it  is  longer.     Mean- 
while measure  into  tube  B  25  c.c.    ?J,  hydrochloric  or  sulphuric  acid, 
I    drop   of    I    per  cent,   sodium    alizarine   sulphonate    indicator,    and 
1  drop  caprylic  alcohol,  and  connect  the 
tubes   as   shown   in  I'Mg.   i{)4.      After  the 
twenty  minutes  for  decomposition  of  urea 
has  elapsed,  the  air  current  is  passed  for 
half  a  minute  to  sweep  into  B,  a  small 
amount  of  ammonia  which  has  escaped 
into  the  air  space  of  A  during  the  decom- 
position.    Then    A   is   opened,  and   4  to 
5  grammes  potassium  carbonate  added  to 
liberate  the  ammonia  from  the  ammonium 
carbonate  formed.     Now  let  the  air  cur- 
rent  pass    gently  through  the  tubes  for 
the  first  mmute   and   then   rapidly  until 
all  the  ammonia  has  been  brought  into 
the  acid  in   B.     The  time  necessary  for 
this  will  depend   upon  the  speed  of  the 
air  current  (varying  from  five  minutes  to 
half  an  hour,  according  to  the  efhciency 
of  the  pump  or  vacuum  by  which  the  air 
is  moved)  and  should  be  determined  once 
for  all.      The   excess   acid   in   B   is   now 
titrated  with  |L  sodium  hydroxide.     The 
weight   of  nitrogen    contained   in   the    urea   of    100   fc.c.    of   urine    is 
(25  -  *•)  X  0-056,  where  x  is  the  number  of  c.c.  of  the  sodium  hydroxide 
solution    necessary  to   neutralize    the    acid.      Included    in    the    urea 
nitrogen  is   the   nitrogen  of  any  ammonia   originally  present   in    the 
urine.      This   can   be    determined   separately,   if   desired,    by  putting 
5  c.c.  of  urine  into  A  without  urease,  adding  the  carbonate  at  once, 
and  then  aerating  through  the  acid  in   B.     The  acid  neutralized  in 
this  case  is  multiplied  by  0'0056  to  give  the  ammonia  nitrogen  in  100  c.c. 
of  urine,  and  this  being  deducted  from  the  previous  result,  the  net  urea 
nitrogen  is  obtained. 

The  method  as  above  described  is  adapted  for  urine  containing  not 
more  than  3  per  cent,  urea,  which  is  about  the  maximum  found  in  human 
urine.  Cat's  or  dog's  urine  should  first  be  diluted  to  reduce  the  urea 
below  3  per  cent. 

Clinical  Urease  Method  by  Direct  Titration  of  Urine. — Two  5  c.c. 
portions  of  urine  are  put  into  flasks  a  and  b  of  200  to  300  c.c.  capacity, 
and  diluted  with  distilled  water  to  about  100  to  125  c.c.  One  c.c.  of 
10  per  cent,  urease  is  added  to  flask  a,  and  a  few  drops  of  toluene  to 
each.  The  flasks  are  allowed  to  remain,  w-ell  stoppered,  at  room  tempera- 
ture over  night,  then  titrated  to  a  distinct  pink  colour  with  ^^  hydro- 
chloric acid,  using  methyl  orange  as  indicator.  From  the  amount  of 
hydrochloric  acid  needed  for  a  is  deducted  the  amount  needed  for  b; 
and  also  the  amount  previously  determined  to  be  necessary  to  neutra- 
lize the  alkalinity  of  the  enzyme  solution.  The  remaining  number  of 
c.c.  multiplied  by  0-6  gives  the  urea  in  grammes  per  litre  of  urine,  since 


Fig.  194- — Apparatus  for  deter- 
mining Urea  Content  by  means 
of  Urease.    (After  Van  Slyke.) 


5^0 


EXCRETION 


I  c.c.  of  N  hydrochloric  acid  is  equivalent  to  3  miiligrainmcs  of  urea. 
Instead  of  the  drictl  urease  preparation,  an  extract  of  finely  powdered 
soy  beans  can  be  made  by  mixing  25  grammes  of  the  powder  with 
250  c.c.  of  distilled  water,  and  allowing  it  to  stand  with  occasional 
shaking  for  an  hour.  Twenty-five  c.c.  of  ^^  hydrochloric  acid  are  then 
added,  and  the  mixture  allowed  to  remain  a  few  minutes  longer  (best 
at  about  35"  C).  The  mixture  is  filtered,  treated  with  a  few  drops  of 
toluene,  and  preserved  for  use  in  a  stoppered  bottle.     It  must  be  made 

up  fresh  after  a  few  days  as  it  does 
not  keep  long.  The  solution  is  alka- 
line to  methyl  orange,  and  2  c.c.  (the 
quantity  used  in  the  above  clinical 
determination  of  urea)  generally  re- 
(juircs  about  0*3  c.c.  of  .N.  hydro- 
chloric acid  for  neutralization. 

A  less  exact  method  which  is  very 
rapid,  and  is  therefore  much  used  in 
clinical  determinations,  is  the  Hypo- 
bromite  Method.  The  urea  is  split  up 
by  sodium  hypobromite  (p.  480),  and 
the  carbon  dioxide  being  absorbed  by 
the  excess  of  sodium  hydroxide  used 
in  preparing  the  hypobromite,  the 
nitrogen  is  collected  over  water  in  an 
inverted  burette.  It  is  easy  to  calcu- 
late the  weight  of  urea  corresponding 
to  a  given  volume  of  nitrogen  measured 
at  a  given  temperature  and  pressure. 
The  nitrogen  of  urea  is  j^Jj,  or  ^^  of  the 
whole  molecular  weight.  Now,  i  c.c. 
of  N  weighs,  at  760  millimetres  of 
mercury  and  0°  C,  0'00i23  gramme. 
Therefore,  i  c.c.  of  N  corresponds  to 
0-00125  X  J^  =  0*00268  gramme  urea. 
Suppose,  now,  that  i  c.c.  of  urine  was 
found  to  yield  10  c.c.  of  N  measured 
at  i7°C.  and  750  millimetres  barome- 
tric   pressure.     Since    a    gas    expands 


Fig.  195. — Hypobromite  Method 
of  estimating  Urea.  A,  glass 
thimble;  B,  bottle,  through  the 
rubber  cork  of  which  pass  two 
short  glass  tubes,  one  connected 
by  the  rubber  tube  C  with  a 
burette  D,  and  the  other  armed 
with  a  short  piece  of  rubber  tube 
F.  F  is  provided  with  a  pinch- 
cock.  The  burette  is  supported 
on  a  stand,  and  immersed  in 
water  contained  in  the  glass 
cylinder  E. 


^i.,  part  of  its  volume  at  0°  for  every 


degree  above  0°,  we  must  correct  the 
apparent  volume  of  nitrogen  by  multi- 
plying by  'il^.  Since  the  volume  of  a 
gas  is  inversely  proportional  to  the 
pressure,  we  must  further  multiply 
by  l^.  Thus  we  get  10  x  |^  x  i^%  ^ 
-.V.^,^f- =9*29  c.c.  as  the  volume  of  the 
nitrogen  reduced  to  0°  C.  and  760  milli- 
metres of  mercury.  Multiplying  this  by  0'00268,  we  get  0-0249  gramme 
urea  for  i  c.c.  urine,  which  for  a  daily  yield  of  1,200  c.c.  would  corre- 
spond to  2Q-88  grammes  urea. 

A.s  a  matter  of  fact,  however,  it  has  been  found  that  there  is  always 
a  deficiency  of  nitrogen^that  is,  a  gi^•en  quantity  of  urea  yields  less 
than  the  estimated  amount  of  gas.  .\  gramme  of  urea  in  urine,  instead 
of  giving  off  373  c.c.  of  nitrogen,  gi\es  only  354  c.c.  at  o^  C.  and  760 
millimetres  pressure.     We  must  therefore  take  i  c.c.  of  N  as  correspond- 


PRACTICAL  EXERCISES  521 

ing  to  0-00282  gramme,  instead  of  o'oo2()8  gramme  urea.  But  it  is 
affectation  to  make  this  correction  if,  as  is  selclom  done  in  hospitals,  the 
temperature  is  not  taken  into  account. 

A  convenient  apparatus  is  shown  in  Fig.  195.  In  B  place  10  c.c. 
of  a  solution  made  by  adding  bromine  to  ten  times  its  volume  of  40  per 
cent,  sodium  hydroxide  solution.  Mix  5  c.c.  of  urine  with  5  c.c.  of 
water.  Put  3  c.c.  of  the  mixtnre  into  the  thimble  A,  which  is  then  set 
in  the  small  bottle  B.  The  cork  is  now  carefully  fixed  in  B,  and  the 
tube  F  being  open,  the  level  of  the  water  in  the  burette  is  read  off. 
The  pinchcock  having  been  closed,  the  bottle  B  is  now  tilted  so  that 
the  urine  in  the  thimble  is  gradually  mixed  with  the  hypobromite  solvi- 
tion,  and  the  nitrogen  given  off  is  added  to  the  air  in  the  burette  and 
its  connections.  The  level  of  the  water  in  the  burette  is  therefore 
depressed.  When  gas  ceases  to  be  given  off,  and  a  short  time  has  been 
allowed  for  the  whole  to  cool,  the  tube  is  raised  till  the  level  of  the 
water  is  once  more  the  same  inside  and  out.  The  level  is  again  read 
off;  the  difference  of  the  two  readings  gives  the  volume  of  nitrogen  at 
the  temperature  of  the  air  and  the  barometric  pressure.  In  order  that 
the  temperature  of  the  water  may  be  the  same  as  that  of  the  air,  the 
cylinder  should  be  filled  a  considerable  time  before  the  observations 
are  begun. 

8.  Estimation  of  the  Ammonia  in  Urine  (Folin's  Method).— Ammonia 
is  liberated  by  addition  of  a  weak  alkali  (sodium  carbonate).  Then 
the  ammonia  is  driven  out  at  ordinary  temperature  by  a  strong  current 
of  air  and  taken  up  in  decinormal  acid,  which  is  then  titrated  with 
decinormal  alkali. 

The  apparatus  employed  consists  of — (i)  A  cylinder  of  about  45  cm. 
diameter,  with  a  rubber  stopper  through  which  pass  two  glass  tubes. 
One  of  the  tubes  goes  nearly  to  the  bottom  of  the  cylinder,  and  the 
other  end  is  connected,  through  a  U-tube  filled  with  cotton,  with  a  tube 
containing  sulphuric  acid.  The  second  tube  is  cut  off  short  below  the 
rubber  cork,  and  its  other  end  is  connected,  through  a  U-tube  con- 
taining cotton,  with  a  sulphuric  acid  tube  (or  with  two  in  series).  (2)  A 
water-pump  to  draw  or  force  air  through  the  apparatus  (600  to  700 
litres  in  an  hour). 

Put  into  the  first  svdphuric  acid  tube  25  c.c,  into  the  second  10  c.c. 
decinormal  acid  and  some  water;  into  the  cylinder  25  c.c.  of  filtered 
urine,  8  to  10  grammes  sodium  chloride,  5  to  10  c.c.  of  petroleum  or 
toluol  to  prevent  foaming,  and  last  of  all  i  gramme  dried  sodium 
carbonate.  At  once  close  the  cylinder  and  allow  a  strong  stream  of  air 
to  pass  through  the  apparatus.  At  a  temperature  of  20°  to  25°  (room 
temperature),  and  using  600  to  700  litres  of  air  an  hour,  all  the  ammonia 
is  in  the  sulphuric  acid  in  one  to  one  and  a  half  hours.  The  contents 
of  the  sulphuric  acid  tubes  are  put  into  a  beaker  and  titrated  with 
decinormal  alkali,  using  lacmoid  (litmoid)  or  rosolic  acid  as  indicator. 
Deduct  the  number  of  c.c.  of  alkali  used  from  the  number  of  c.c.  of  the 
decinormal  acid  originally  taken,  and  multiply  the  remainder  by  1*7034 
to  get  the  quantity  of  ammonia  in  milligrammes.  The  method  can  be 
employed  also  for  albuminous  urine. 

9.  Estimation  of  the  Total  Nitrogen. — It  is  sometimes  more  important 
to  determine  the  total  nitrogen  of  the  urine  than  the  urea  alone.  This 
IS  conveniently  done  by  Kjeldahl's  method  (or  some  modification  of 
it),  which  can  also  be  applied  to  the  estimation  of  the  nitrogen  in  the 
faeces,  or  in  any  of  the  solids  or  liquids  of  the  body.  It  depends  on  the 
oxidation  of  the  nitrogenous  matter  (or,  rather,  in  the  case  of  urine, 
mainly  its  hydrolysis)  in  such  a  way  that  the  nitrogen  is  all  represented 


52  2  EXCRETION 

as  ammonia.     The  ammonia  is  then  distilled  over,  collected  and  esti- 
mated, and  from  its  amount  the  nitrogen  is  easily  calculated.     In  urine 
the  method  can  be  carried  out  by  adding  to  a  measured  quantity  of  it 
(say  5  CO.)  four  times  its  volume  of  strong  sulphuric  acid,  and  boiling 
in  a  long-necked  flask  (capacity  200  c.c).  after  the  addition  of  a  globule 
of   mercur>'    (about   o-i    c.c), 'which   hastens  oxidation   and   obviates 
bumping.     A  part  of  the  mercuric  sulphate  formed  remains  in  solution  ; 
the  rest  forms  a  crystalline  deposit.     The  heating  should  continue  for 
half  an  hour,  or  until  the  liquid  is  decolourized.      It  should  be  kept 
gently  boiling.     This  completes  the  process  of  oxidation  ;  and  the  next 
step  is  to  liberate  the  ammonia  from  the  substances  with  which  it  is 
united  in  the  solution,  and  to  distil  it  over.     Dilute  the  liquid  with 
water,  after  cooling,  up  to  about  150  c.c,  and  pour  into  a  larger  long- 
necked  flask.     Add  enough  of  a  solution  of  sodium  hydroxide  (specific 
gravity  about  1-25)  to  render  the  liquid  alkaline,  avoiding  excess,  as 
this  favours  bumping.     The  proper  quantity  can  be  found   by  deter- 
mining beforehand  how  much  of  the  alkali  is  needed  to  neutralize  the 
acid  used  for  oxidation,  and  a  little  more  than  this  amount  should  be 
added.     Twenty  c.c.  of  strong  sulphuric  acid  needs  about  75  c.c.  of 
40  per  cent,  sodium  hydroxide  to  neutralize  it.     Bumping  mav  further 
be  prevented  by  the  addition  of  a  little  granulated  zinc.     Shake  the 
flask  two  or  three  times.     Add  also  about  12  c.c.  of  a   concentrated 
solution  of  potassium  sulphide  (i  part  to  i^  parts  water),  which  favours 
the  setting  fiee  of  the  ammonia  from  the  amino-compounds  of  mercury 
that  have  been  formed  during  oxidation .     Commercial '  liver  of  sulphur'' 
will  do  quite  well.     Immediately  connect  the  distilling-flask  with  a 
worm  or  Liebig's  condenser,  and  distil  the  ammonia  over  into  50  c.c. 
of    standard    (decinormal)  sulphuric  acid   (see  footnote,   p.  473)  con- 
tained in  a  flask  into  which  a  glass  tube  connected  with  the  lower  end 
of  the  \yorm  dips.    Heat  the  distilling-flask  at  first  gentlv,  then  strongly, 
and  boil  for  three-quarters  of  an  hour,  or  until  about  t'wo-thirds  of  the 
liquid  has  passed  over.     Then  lift  the  tube  out  of  the  standard  acid,  and 
continue  the  distillation  for  two  or  thiee  minutes  longer.     The  ammonia 
is  now  all  united  with  the  standard  acid,  a  certain  amount  of  which  is 
left  over.     By  determining  this  amount  we  arrive  at  the  quantity  com- 
bined with  ammonia,  and  therefore  at  the  quantity  of  ammonia.     Fill 
a  burette  with  a  decinormal  solution  of  potassium  or  sodium  hydroxide. 
Add  a  little  methyl-orange  solution  to  the  standard  sulphuric  acid,  to 
serve  as  indicator.     Then  run  in  the  potassium  or  sodium  hydroxide 
till  the  pink  tinge  gives  place  to  a  permanent  but  just  recognizable 
yellow.     Let  x  be  the  number  of  c.c.  run  in.     Since  i  c.c.  of  any  deci- 
normal solution  is  equivalent  to  i  c.c.  of  any  other,  x  represents  also  the 
number  of  c.c.  of  the  standard  sulphuric  acid  left  uncombincd  with 
ammonia;  and  50  — jt,  the  quantity  combined  with  ammonia.     Then, 
I  c.c.  of  decinormal  sodium  or  potassium  hydroxide  being  equivalent 
to  I  c.c.  of  decinormal  ammonium  hydroxide,  and  i  c.c.  of  decinormal 
ammonium   hydroxide    containing   0-0014    gramme    nitrogen,    we    get 
{50 -  x)x  0-0014  ^s  the  quantity  of  nitrogen  in  5  c.c  of  urine. 

Instead  of  mercury,  potassium  sulphate  and  copper  sulphate  may  be 
added  to  the  sulphuric  acid  in  order  to  aid  the  decomposition  in  the 
first  stage  of  the  estimation.  About  3  grammes  of  potassium  sulphate 
and  I  gramme  of  copper  sulphate  are  added  to  p  c.c  of  urine,  and  then 
5  c.c.  of  sulphuric  acid.  The  liquid  is  gently  boiled  for  an  hour,  or  until 
it  is  quite  clear.  The  neutralization  and  distillation  are  conducted  as 
before,  the  proper  quantity  of  sodium  hydroxide  being  determined  in 
advance.     No  potassium  sulphide  is  added,  but  a  small  quantity  of 


PRACTICAL  EXERCISES  523 

talc  may  be  put  in  to  prevent  bumping.  Instead  of  methyl  orange, 
'  alizarin  red,'  which  is  bright  red  in  the  presence  of  the  slightest  trace 
of  alkali,  mav  be  used. 

10.  Uric  Acid — (i)  Qualitative  Test  for  Uric  Acid — Murexide  Test. — 
A  small  quantity  of  uric  acid  or  one  of  its  salts  is  heated  with  a  little 
dilute  nitric  acid.  The  colour  of  the  residue  left  by  evaporation 
becomes  yellow,  and  then  red.  and  on  the  addition  of  ammonia  changes 
to  deep  purple-red.  Potassium  or  sodium  hydroxide  changes  the 
yellow  to  violet.  In  the  reaction  alloxantin  is  formed  by  oxidation  of 
the  uric  acid.  When  ammonia  acts  on  alloxantin  it  is  changed  into 
purpuric  acid,  and  this  into  its  ammonium  purpurate,  the  purple-red 
substance  called  murexide.     Thus: 

CsHeN^Og-l-  NH3  =C8H5N508-h  2H2O. 

Alloxantin.  Purpuric  Acid. 

The  reaction  is  also  given  by  theobromine  (dimethylxanthin),  an  alkaloid 
in  cocoa,  and  thcine  or  caffeine  (trimethylxanthin),  an  alkaloid  in  tea 
and  coffee,  which  are  also  purin  derivatives  (p.  481')- 

(2)  Quantitative  Estimation  —  Folin's  Modification  of  Hopkins's 
Method. — The  chief  reagent  is  a  solution  of  500  grammes  ammonium 
sulphate,  5  grammes  uranium  acetate,  and  60  c.c.  10  per  cent,  acetic 
acid,  in  650  c.c.  of  water. 

One  hundred  and  fifty  c.c.  of  urine  is  measured  into  a  tall,  narrow 
beaker  or  a  cylinder,  and  37I  c.c.  of  the  reagent  added.  If  enough 
urine  is  available,  200  c.c.  of  urine  and  50  c.c.  of  reagent  are  to  be  used. 
Allow  the  mixture  to  stand  without  stirring  for  about  half  an  hour. 
The  uranium  precipitate  has  then  settled,  and  the  clear  supernatant 
liquid  is  removed  by  siphoning  or  decantation.  One  hundred  and 
twenty-five  c.c.  of  this  liquid  is  measured  into  another  beaker,  5  c.c. 
of  strong  ammonia  added,  and  the  mixture  set  aside  till  next  day.  The 
precipitate  is  then  filtered  off,  and  washed  with  10  per  cent,  ammonium 
sulphate  solution  until  the  filtrate  is  quite  or  nearly  free  from  chlorides. 
The  filter  is  then  removed  from  the  funnel,  opened,  and  the  precipitate 
rinsed  back  into  the  beaker.  Enough  water  to  make  about  100  c.c.  is 
added,  and  the  precipitate  is  then  dissolved  by  means  of  15  c.c.  con- 
centrated sulphuric  acid,  and  at  once  titrated  with  ^^  (one -twentieth 
normal)  potassium  permanganate  solution  (made  by  dissolving 
i'58i  grammes  of  the  permanganate  in  a  litre  of  water),  each  c.c.  of 
which  corresponds  to  375  milligrammes  of  uric  acid.  The  very  first 
pink  coloration,  extending  through  the  entire  liquid  on  the  addi- 
tion of  two  drops  of  permanganate  solution,  marks  the  end  point. 
A  correction  of  3  milligrammes,  owing  to  the  solubility  of  ammonium 
urate,  is  added  to  the  result. 

11.  Creatinin. — Qualitatively,  creatinin  may  be  recognized  in  very 
small  amounts  by  Weyl's  test.  A  few  drops  of  a  dilute  solution  of 
sodium  nitro-prusside  are  added  to  urine,  and  then  dilute  sodium 
hydroxide  drop  by  drop.  A  ruby-red  colour  appears,  which  soon  turns 
yellow.  If  the  urine  is  now  strongly  acidified  with  acetic  acid  and 
heated,  it  becomes  first  greenish  and  then  blue.  Enough  acid  must  be 
added  to  more  than  neutralize  the  alkali. 

Another  test  which  has  been  made  the  basis  of  a  quantitative  method 
by  Folin  is  Jake's  test.  A  little  urine  (say  5  c.c.)  is  put  in  a  test-tube, 
and  then  a  solution  of  picric  acid  in  water.  The  mixture  is  rendered 
alkaline  by  the  addition  of  potassium  or  sodium  hydroxide  solution, 
and  a  reddish  colour  is  produced,  which  turns  yellow  on  the  addition  of 


52  4  EXCRETION 

acid.     A  similar  red  colour  is  given  by  dextrose,  but  not  unless  the 
solution  is  heated. 

Quantitative  Estimation  of  Creatinin  by  Folin's  Method. — It  depends 
upon  the  comparison  of  the  colour  which*  creatinin  gives  with  picric 
acid  in  an  alkaline  solution  with  that  of  a  standard  solution  of  potassium 
bichromate.  Ten  c.c.  of  urine  is  measured  into  a  500  c.c.  measuring- 
flask;  15  c.c.  of  a  saturated  picric  acid  solution  (containing  about 
12  grammes  per  litre)  and  5  c.c.  of  a  10  per  cx»nt.  solution  of  sodium 
hydroxide  are  added.  The  mixture  is  allowed  to  stand  for  five  minutes. 
Then  water  is  added  up  to  the  500  c.c.  mark,  and  the  flask  shaken  to 
mix  uniformly.  Samples  of  the  liquid  are  then  at  once  compared 
colorimetrically  with  a  half-normal  solution  of  potassium  bichromate 
containing  24*55  grammes  per  litre.  The  colour  of  the  urine  does  not 
introduce  a  sensible  error  on  account  of  the  great  dilution.  For  exact 
work  the  comparison  must  be  made  with  a  good  colorimeter.  It  has 
been  found  experimentally  that,  when  10  milligrammes  of  creatinin 
arc  present  in  500  e.g.  of  a  solution  made  as  described,  a  layer  of  the 
solution  8*1  millimetres  in  thickness  has  the  same  depth  of  tint  as  8  milli- 
metres of  the  bichromate  solution.  Suppose  it  takes  9  millimetres  of 
the  urine-picrate  solution  to  equal  8  millimetres  of  the  bichromate, 

8*1 
then    the    10    c.c.    of    urine    contains    10  x  —  =9-0    milligrammes    of 

creatinin . 

12.  Hippuric  Acid. — From  horse's  or  cow's  urine  hippuric  acid  is 
prepared  by  evaporating  to  a  small  bulk,  and  adding  strong  hydrochloric 
acid.  The  crystalline  precipitate  is  washed  with  cold  water,  then 
dissolved  in  hot  water,  and  filtered  hot.  Hippuric  acid  separates  out 
from  the  filtrate  in  the  cold  in  the  form  of  long  four-sided  prisms  with 
pyramidal  ends.  Heated  dry  in  a  test-tube,  the  crystals  melt,  and 
benzoic  acid  and  oily  drops  of  benzonitrilc,  a  substance  with  a  smell 
like  that  of  oil  of  bitter  almonds,  are  formed. 

ABNORMAL    SUBSTANCES    IN    URINE, 

13.  Proteins — (i)  Qualitative  Tests. — {a)  Boil  and  add  a  few  drops 
of  nitric  acid.  A  precipitate  on  boiling,  increased  or  not  affected  by 
the  acid,  shows  the  presence  of  coagnlable  proteins  (scrum-albumin  or 
globulin).  A  precipitate  of  earthy  phosphates  sometimes  forms  on 
boiling.  It  is  distinguished  from  a  precipitate  of  proteins  by  dissolving 
on  the  addition  of  acid. 

(b)  Heller's  Test. — Put  some  nitric  acid  in  a  test-tube.  Pour  care- 
fully on  to  the  surface  of  the  acid  a  little  urine.  A  white  ring  at  the 
junction  of  the  liquids  indicates  the  presence  of  albumin  or  globulin. 
If  much  albumose  is  present,  a  white  precipitate,  which  disappears  on 
heating,  may  be  formed.  When  this  test  is  performed  with  undiluted 
urine,  uric  acid  may  be  precipitated  and  cause  a  brown  colour  at  the 
junction.  A  similar  ring  may  be  found  in  the  absence  of  proteins  when 
the  test  is  made  on  the  urine  of  a  patient  who  has  been  taking  copaiba. 
In  very  concentrated  urine  a  white  ring  of  nitrate  of  urea  may  be 
formed.  A  coloured  ring  is  frequently  seen,  owing  to  the  oxidation  of 
certain  chromogens  of  urine. 

(c)  Filter  some  urine,  and  add  to  the  filtrate  its  own  volume  of  acetic 
acid.  A  precipitate  mav  indicate  mucin  or  nucleo-albumin.  If  any  is 
formed,  filter  ft  off,  and  add  to  the  filtrate  a  few  drops  of  potassium 
ferrocyanide.     A  white  precipitate  shows  the  presence  of  proteins. 

{d)   Test  for  Globulin   in    Urine.  —  Serum-globulin    probably    never 


PRACTICAL  EXERCISES  525 

occurs  in  iiniic  apart  from  serum-albumin.  It  may  be  detected  thus: 
Make  the  urine  alkahne  with  ammonia,  let  it  stand  for  an  hour,  and 
filter.  Half  saturate  the  filtrate  with  ammonium  sulphate — i.e.,  add 
to  it  an  equal  volume  of  a  saturated  solution  of  ammonium  sulphate. 
Serum-globulin  is  precipitated,  serum-albumin  is  not. 

{e)  Test  for  Albiiniose  in  Urine  {Albumosuria). — Coagulable  proteins 
are  removed  by  boiling  the  urine  (acidulated  if  necessary),  and  filtering 
off  the  precipitate  if  any.  The  filtrate  is  neutralized.  If  a  further 
precipitate  falls  down  it  is  filtered  off,  the  clear  filtrate  is  heated  in  a 
beaker  placed  in  a  boiling  water-bath,  and  there  saturated  with  crystals 
of  ammonium  sulphate.  A  precipitate  indicates  that  albumoses 
(proteoses)  are  present.  A  slight  precipitate  might  possibly  be  due  to 
the  formation  of  ammonium  urate.  A  further  test  may  be  performed 
on  the  original  urine  if  it  is  free  from  coagulable  proteins,  or  on  the 
filtrate  after  their  removal.  Add  a  drop  or  two  of  pure  nitric  acid. 
If  albumoses  are  present,  a  precipitate. is  thrown  down  which  disappears 
on  heating,  and  reappears  on  cooling  the  test-tube  at  the  cold-water  tap. 

(2)  Quantitative  Estimation  of  Coagulable  Proteins  {Serum- Albumin 
and  Globulin) — {a)  Gravimetric  Method. — Heat  50  to  100  c.c.  of  the 
urine  to  boiling,  adding  a  dilute  solution  (2  per  cent.)  of  acetic  acid  by 
drops  as  long  as  the  precipitate  seems  to  be  increased.  Filter  through 
a  weighed  filter.  Wash  the  precipitate  on  the  filter  with  hot  water, 
then  with  hot  alcohol,  and  finally  with  ether.  Dry  in  an  air-bath  at 
110°  C,  and  weigh  between  watch-glasses  of  known  weight. 

{b)  Esbach's  Method. — Esbach's  reagent  is  made  by  dissolving 
10  grammes  of  picric  acid  and  20  grammes  of  citric  acid  in  boiling 
water  (800  or  900  c.c),  and  then  making  up  the  volume  to  a  litre.  The 
so-called  albuminimeter  is  simply  a  strong  glass  tube  graduated  and 
marked  in  a  certain  way.  Fill  the  tube  up  to  the  mark  U  with  the 
urine.  Then  add  the  reagent  up  to  the  mark  R.  Close  the  tube  with 
the  rubber  cork,  and  invert  it  a  dozen  times  without  shaking.  Set  the 
tube  aside  for  twenty -four  hours,  then  read  off  the  graduation  on  the 
tube  which  corresponds  with  the  top  of  the  precipitate.  The  figures 
indicate  the  number  of  grammes  of  dry  protein  in  a  litre  of  the  urine. 
Suppose  the  top  of  the  sediment  is  at  4 ,  this  will  indicate  4  grammes  per 
litre,  or  0-4  per  cent.  The  method  is  of  some  clinical  importance,  owing 
to  its  simplicity,  although  it  is,  of  course,  not  very  accurate. 

14.  Sugar — (i)  Qualitative  Tests — (a)  Trammer's  Test  (p.  10). — It  is  to 
be  remarked  that  some  substances  present  in  small  amount  in  normal 
urine  reduce  cupric  sulphate — e.g.,  uric  acid  (present  as  urates)  and 
kreatinin — but  although  a  normal  urine  may  thus  decolourize  the 
copper  solution,  it  rarely  causes  so  much  reduction  that  a  yellow  or  red 
precipitate  is  formed,  as  is  the  case  in  diabetic  urine.  Glycuronic  acid 
(p.  4S2)  also  reduces  cupric  salts,  as  does  alcapton  or  homogentisinic 
acid,  a  substance  found  in  rare  cases  in  disease  (p.  483)- 

{b)  Fehling's  Test. — Fehling's  solution  (p.  526)  is  brought  to  the  boil  iu 
a  test-tube,  a  little  of  the,  urine  then  added,  and  the  change  of  colour 
noted.  Benedict's  modification  of  Fehling's  solution  may  also  be  used. 
It  has  the  advantage  that  it  keeps  indefinitely,  and  therefore  is  always 
ready  for  use,  and  is  also  said  to  be  more  delicate. 

(c)  Phenyl-Hydrazine  Test. — This  test  depends  upon  the  fact  that 
phenyl-hydrazine  forms  with  sugars  such  as  glucose  (dextrose),  maltose, 
isomaltose,  etc.,  but  not  with  cane-sugar,  characteristic  cr^'stalline 
substances  (phenyl-glucosazone,  phenyl-maltosazone,  etc.)  which  can 
be  recognized  under  the  microscope,  and  are  distinguished  from  each 
other    by     melting    at    different    temperatures.      Phenyl-glucosazone 


526 


EXCRETION 


(C18H22N4O4)  melts  at  205°  C.  To  perform  the  test  for  dextrose  m  the 
unnc.  proceed  thus:  Put  5  c.c.  of  urine  in  a  test-tube,  add  i  decigramme 
of  hydrochlorate  of  phenyl-hydrazine  and  2  decigrammes  of  sodium 
acetate.  It  is  sufi&ciently  accurate  to  add  as  much  phenyl-hydrazine 
as  will  lie  on  a  sixpence  (or  a  dime)  and  twice  as  much  sodium  acetate. 
Heat  the  test-tube  in  a  boiling  water-bath  for  half  an  hour.  Then  cool 
at  the  tap  and  examine  the  deposit  under  the  microscope  for  the  yellow 
phenyl-glucosazone  crystals  (Fig.  196).  Sometimes  the  osazone  pre- 
cipitate is  amorphous.  If  this  should  be  the  case,  the  precipitate,  if  no 
crj'stals  can  be  seen,  must  be  dissolved  in  hot  alcohol.  The  solution  is 
then  diluted  with  water  and  the  alcohol  boiled  off,  when  the  osazone. 

if  any  be  present,  will  crystallize  out. 
Very  minute  traces  of  sugar  can  be 
detected  in  this  way  (as  little  as  O'l  per 
cent,  in  urine).  Often  in  normal  urine 
yellow  crystals  are  deposited  during 
the  first  fifteen  minutes'  heating. 
They  must  not  be  mistaken  for  gluco- 
sazonc.  They  probably  consist  of  a 
compound  of  glycuronic  acid  and 
phenyl-hydrazine.  They  are  changed 
as  the  heating  goes  on  into  an  amor- 
phous brownish  -  yellow  precipitate 
(Abel). 

{d)  The  Yeast  Test  is  an  importanl 
confirmatory  test  for  distinguishing 
the  fermentable  sugars  from  other  re- 
ducing substances,  but  it  is  not  very 
delicate,  and  will  with  difficulty  detect 
sugar  when  less  than  0-5  per  cent,  is 
present.  It  can  be  performed  thus: 
A  little  yeast  (the  tablets  of  com- 
pressed yeast  do  very  well)  is  added 
to  a  test-tube  half  filled  with  urine. 
The  test-tube  is  then  filled  up  with 
mercury,  closed  with  the  thumb,  and 
inverted  over  a  dish  containing  mer- 
cury. The  dish  may  be  placed  on  the 
top  of  a  water-bath  whose  temperature 
is  about  40°  C.  After  twenty-four 
hours  the  sugar  will  have  been  broken 
up  into  alcohol  and  carbon  dioxide.  The  latter  will  have  collected 
above  the  mercurj^  in  the  test-tube,  and  the  former  will  be  present  in 
the  urine.  The  tests  for  sugar  will  either  be  negative  or  will  be  less 
distinct  than  before.  A  control  test-tube  containing  water  and  yeast 
should  also  be  set  up,  as  impurities  in  the  yeast  sometimes  j-ield  a  small 
amount  of  carbon  dioxide.  Specially-constructed  tubes  are  also  often 
used  for  performing  the  test. 

(2)  Quantitative  Estimation  of  Sugar  in  Urine. — (a)  V olumetrically , 
the  sugar  can  be  estimated  by  titration  with  Fehling's  solution.  As 
this  does  not  keep  well,  two  solutions  containing  its  ingredients  should 
be  kept  separately  and  mixed  when  required.  Solution  I.:  Dissolve 
34-64  grammes  pure  cupric  sulphate  in  distilled  water,  and  make  up  the 
volume  to  500  c.c.  Solution  II.:  Dissolve  173  grammes  Rochelle  salt 
in  400  c.c.  of  water,  add  to  this  51-6  grammes  sodium  hydroxide,  and 
make  up  the  volume  with  water  to  500  c.c.     Keep  in   well-stoppered 


Fig.  196. — Phenyl-Glucosazone  and 
Phenyl-Maltosazone  Crystals  (Mac- 
leod).  The  phenyl  -  glucosazone 
crystals  are  in  the  upper  part  of 
the  figure,  the  phenyl-maltosazone 
in  the  lower. 


PRACTICAL   EXERCISES  527 

bottles  in  the  dark.  For  use,  mix  together  equal  volumes  of  the  two 
solutions.  Ten  c.c.  of  this  mixture  is  reduced  by  0-05  gramme  dextrose. 
To  estimate  the  sugar  in  urine,  put  10  c.c.  of  the  mixture  into  a  porcelain 
capsule  or  glass  flask,  and  dilute  it  four  or  five  times  with  distilled  water. 
Dilute  some  of  the  urine,  say  ten  or  twenty  times,  according  to  the 
quantity  of  sugar  indicated  by  a  rough  determination.  Run  the 
diluted  urine  from  a  burette  into  the  Fchling's  solution,  bringing  it  to 
the  boil  each  time  urine  is  added,  until,  on  allowing  the  precipitate 
to  settle,  the  blue  colour  is  seen  to  have  entirely  disappeared  from  the 
supernatant  liquid.  The  observation  of  the  colour  must  be  made  while 
the  liquid  is  still  hot.  Benedict's  modification  of  Fehling's  solution* 
may  also  be  employed. 

Suppose  that  10  c.c.  of  Fehling's  solution  is  decolourized  by  20  c.c. 
of  the  ten-times  diluted  urine.  Then  2  c.c.  of  the  original  urine  contains 
0-3  gramme  dextrose.  If  the  urine  of  the  twenty-four  hours  (from 
which  this  sample  is  assumed  to  have  been  taken)  amounts  to  4,000  c.c, 
the  patient  will  have  passed  0-05  x  2,000=  100  grammes  sugar,  in 
twenty-four  hours. 

{b)  The  polarinieter  affords  a  rapid  and,  with  practice,  a  delicate 
means  of  estimating  the  quantity  of  sugar  in  pure  and  colourless  solu- 
tions, but  diabetic  urine  must  in  general  be  first  decolourized  by  adding 
lead  acetate  and  filtering  off  the  precipitate.  What  is  measured  is  the 
amount  by  which  the  plane  of  polarization  of  a  ray  of  polarized  light  of 
given  wave-length  (say  sodium  light)  is  rotated  when  it  passes  through 
a  layer  of  the  urine  or  other  optically  active  solution  of  known  thickness. 
Let  a  be  the  observed  angle  of  rotation,  I  the  length  in  decimetres  of 
the  tube  containing  the  solution,  w  the  number  of  grammes  of  the 
optically  active  substance  per  c.c.  of  solution,  and  (a)n  the  specific 
rotation  of  the  substance  for  light  of  the  wave-length  of  the  part  of  the 
spectrum  corresponding  to  the  D  line  {i.e.,  the  amount  of  rotation 
expressed  in  degrees  which  is  produced  by  a  layer  of  the  substance 
I  decimetre  thick,  when  the  solution  contains  i  gramme  of  it  per  c.c). 

Then   {a)o=±—,.     In  this  equation  a  and  /  are   known    from  direct 

measurement;  {a)o  has  been  determined  once  for  all  for  most  of  the 
important  active  substances,  and  therefore  w  is  easily  calculated.  For 
dextrose  {a)o  may  be  taken  as  52-6°.  It  varies  somewhat  with  the 
concentration,  but  for  most  investigations  on  the  urine  these  variations 
may  be  neglected. 

It  is  not  possible  to  describe  here  the  numerous  forms  of  polarimeter 
that  are  in  use.  Those  constructed  on  what  is  called  the  '  half -shadow  ' 
system  (Fig.  197)  give  sufficiently  satisfactory  results.  A  half-shadow 
polarimeter  consists,  like  other  polarimeters,  of  a  fixed  Nicol's  prism 
(the  polarizer),  and  a  nicol  capable  of  rotation  (the  analyzer).  In 
addition,  there  is  an  arrangement  which  rotates  by  a  definite  angle  the 
plane  of  polarization  in  one-half  of  the  field,  but  not  in  the  other — 
e.g..  a  small  nicol  occupying  only  half  of  the  field.  In  the  zero  position 
of  the  analyzer,  both  halves  of  the  field  are  equally  dark.  The  solution 
to  be  investigated  is  placed  in  a  tube  of  known  length,  the  ends  of  which 

♦  It  contains  i7"3  grammes  of  cupric  sulphate,  i73'o  grammes  of  sodium 
citrate,  loo'o  grammes  of  anhydrous  sodium  carbonate  made  up  with 
distilled  water  exactly  to  one  litre.  In  making  the  solution  the  citrate  and 
carbonate  are  dissolved  with  the  aid  of  heat  in  about  600  c.c.  ot  water,  and 
then  made  up  to  about  800  c.c.  The  cupric  sulphate  is  dissolved  in  about 
100  or  150  c.c.  of  water  and  added  to  the  other  solution,  the  whole  being  then 
made  up  to  a  litre. 


52  i> 


EXCRETION 


arc  closed  by  glass  discs  secured  by  brass  screw  caps.  The  glass  discs 
must  be  slid'  on,  so  as  to  exclude  all  air.  The  tube  having  been  intro- 
duced between  the  polarizer  and  analyzer,  the  sharp  vertical  line  which 
indicates  the  division  between  the  two  half-fields  is  focusscd  with  the 
cyc-piece,  and  then  the  analyzer  is  rotated  till  the  two  lialves  are  again 
equally  shadowed.  The  angle  of  rotation,  a,  is  read  off  on  the  graduated 
arc.  which  is  provided  with  a  vernier. 

Pentoses  reduce  Fehling's  solution,  but  do  not  give  the  yeast  test. 
Tliey  give  the  following  characteristic  tests,  which  may  be  performed 
with  gum  arable,  a  substance  containing  arabinose,  one  of  the  pentoses: 

(i)  Phloioglucin  Reaction. — -Warm  in  a  test-tube  some  pure  concen- 
trated hvdrochloric  acid  to  which  an  equal  volume  of  distilled  water 
has  been  added.     Add  phloroglucin  until  a  little  remains  undissolved. 


Fig.  197. — Mitscherlich's  Polarimeter.      (Half-shadow  instrument.)     (Simple  form.) 

Add  a  small  quantity  of  gum  arable,  and  keep  the  test-tube  in  a  water- 
bath  at  100°  C.  The  solution  becomes  cherry-red,  and  a  precipitate 
gradually  separates,  which  may  be  dissolved  in  amyl  alcohol.  The 
solution  shows  with  the  spectroscope  a  band  between  D  and  E. 

(2)  Orcin  Reaction. — Use  orcin  instead  of  phloroglucin  in  (i).  The 
solution  becomes  reddish-blue  on  warming,  and  shows  a  band  between 
C  and  D,  near  D.  The  colour  quickly  changes  from  violet  to  blue,  red, 
and  finally  green.  A  bluish-green  precipitate  separates,  which  is 
soluble  in  amyl  alcohol.  Glycuronic  acid  gives  all  the  above  reactions 
of  pentoses. 

Bile-Salts  [Hay's  Test). — Put  a  little  finely-divided  sulphur,  m  the 
form  of  flowers  of  sulphur,  on  the  top  of  a  glass  of  urine.  If  bile-salts 
are  present  the  sulphur  will  sink  to  the  bottom.     If  there  are  no  bile- 


PRACTICAL  EXERCISES  5^9 

salts  il  will  float  on  the  top.  The  difference  is  due  to  an  alteration  in 
the  surface  tension  of  the  urine  produced  by  the  bile-salts.  We  must 
exclude  the  presence  of  acetic  acid,  alcohol,  ether,  chloroform,  turpen- 
tine, benzine  and  its  derivatives,  piienol  and  its  derivatives,  anilin  and 
soaps,  all  of  which  also  cause  such  an  alteration  in  the  surface  tension 
of  urine  tluit  the  sulphur  sinks  to  the  bottom.  The  urine  should  be 
fresh,  and  if  it  has  to  be  kept  it  should  be  preserved  from  decomposition 
by  cyanide  of  mercury,  which  does  not  alter  the  surface  tension.  The 
reaction  has  the  great  advantage  over  other  tests  of  being  easily  carried 
out  at  the  bedside. 

Acetone — (i)  Legal' s  Test  (Rothera's  modification). — To  5  to  10  c.c. 
of  the  acetone-containing  urine  add  enough  ammonium  sulphate  crystals 
to  form  a  layer  at  the  bottom  of  the  test-tube,  then  2  or  3  drops  cf 
a  fresh  5  per  cent,  solution  of  sodium  nitro-prusside  and  i  to  2  c.c.  of 
strong  ammonia.  The  development  of  a  colour  like  that  of  perman- 
ganate of  potassium,  often  in  the  form  of  a  ring  a  little  above  the 
undissolved  salt,  indicates  the  presence  of  acetone.  The  reaction  must 
not  be  declared  negative  till  half  an  hour  has  elapsed.  The  colour 
slowly  fades. 

{2)  Where  there  is  doubt  as  to  the  presence  of  acetone,  it  is  best  first 
to  distil  it  over.  Put  250  to  500  c.c.  of  the  urine  suspected  to  contain 
acetone  into  a  litre  flask.  Add  a  few  c.c.  of  phosphoric  acid;  connect 
the  flask  with  a  worm,  and  distil  over  the  urine  into  a  small  flask. 
For  qualitative  tests  it  is  best  to  collect  only  the  first  20  to  30  c.c, 
as  most  of  the  acetone  is  contained  in  this.  Test  the  distillate  for 
acetone  by  (i)  or  by 

Lieben's  Test. — To  a  few  c.c.  of  the  distillate  in  a  test-tube  add  a  few 
drops  of  solution  of  iodine  in  potassium  iodide,  and  then  sodium  or 
potassium  hydroxide.  A  precipitate  of  yellow  iodoform  crystals  (six- 
sided  tables)  is  thrown  down  if  acetone  be  present.  Examine  them 
under  the  microscope.  On  heating,  the  odour  of  iodofonn  may  be 
recognized.  If  the  precipitate  is  amorphous  it  may  be  dissolved  in 
ether  (free  from  alcohol),  which  is  allowed  to  evaporate  on  a  slide, 
when  crystals  may  be  obtained. 

Determination  of  the  Freezing-Point  of  Urine.* — Study  Beckmann's 
apparatus  shmvn  in  Fig.  171,  p.  427.  Note  the  large  thermometer  D 
graduated  in  hundredths  of  a  degree  centigrade.  It  is  inserted  through 
a  rubber  cork  into  the  inner  test-tube  A.  A  platinum  wire,  F,  bent 
at  the  lower  end  into  a  circle  or  a  spiral,  which  passes  easily  up  and 
down  between  the  bulb  of  the  thermometer  and  the  tube,  serves  to  stir 
the  urine.  The  thermometer  must  be  so  supported  by  the  rubber 
cork  that  the  bulb  is  in  the  axis  of  the  tube  and  a  centimetre  or  two  from 
the  bottom  of  it.  The  side-piece  E  on  the  tube  A  is  not  absolutely 
necessary,  but  it  is  convenient  for  '  inocidating  '  the  urine  with  a  crystal 
oi  ice  at  the  proper  time.  A  passes  through  a  rubber  cork  into  a  shorter 
and  wider  outer  glass  tube  B.  The  space  between  A  and  B  serves  as  a 
badly  conducting  mantle,  which  prevents  too  rapid  cooling  of  the 
contents  of  A.  B  passes  through  a  hole  in  the  metal  or  wooden  cover 
of  a  strong  glass  jar,  C,  w-hich  contains  the  freezing  mixture.  B  should 
fit  the  hole  so  tightly  that  it  does  not  bob  up  out  of  the  mixture  when 
A  is  removed.  In  C  is  a  stirreir,  G,  of  strong  copper  wire,  the  end  of 
which  passes  through  the  lid.  This  serves  to  stir  up  the  freezing 
mixture  from  time  to  time. 

Pulverize  some  ice  by  pounding  it  in  a  strong  wooden  box  with  a 
heavy  piece  of  wood.  Take  the  inner  tube  with  the  thermometer  out 
of  the  apparatus.     It  is  convenient  to  take  the  thermometer  out  of  the 

*  This  is  not  often  of  cUnical  value,  but  it  affords  an  opportunity  for  the 
student  to  practise  a  method  of  great  importance  in  physiology. 

34 


530  £XCRETI0>! 

tube,  and  to  hang  it  up  carefully  on  a  stand  by  means  of  a  fine  flexible 
copper  wire  passing  through  the  eye.  The  rubber  cork  can  be  taken 
out  with  the  thermometer,  and  the  platinum  wire  also,  the  bent  free 
end  of  the  latter  supporting  it  in  the  cork,  or  it  may  be  fiistened  tempor- 
arily to  the  thermometer  stem  by  a  small  rubber  band,  which  is  slid 
up  over  the  cork  when  the  thermometer  is  reinserted.  Tube  A  can  be 
set  temporarily  in  a  specially  heavy  test-tube  rack.  Remove  the  lid 
of  C,  and  with  it  tube  B.  Now  put  ice  and  salt  alternately  into  C  until 
it  is  nearly  full,  mixing  them  up  well.  Add  some  cold  water  from  the 
tap  till  the  stirrer  G  can  mo\  c  freely  up  and  down  in  the  mixture.  For 
very  exact  work  the  temperature  of  the  freezing  mixture  must  not  be 
more  than  a  few  degrees  below  the  freezing-point  of  the  liquid  which  is 
being  examined.  Put  on  the  lid.  and  immerse  tube  B.  Into  A.  which 
must  be  perfectly  clean,  put  enough  pure  distilled  water  to  fully  covet 
the  bulb  of  tlie  thermometer,  and  introduce  the  latter.  For  ordinary 
purposes  distilled  water  previously  boiled  to  expel  the  carbon  dioxide, 
and  then  cooled  in  a  stoppered  flask,  is  sufficiently  pure.  Immerse  A 
directly  in  the  freezing  mixture  through  the  hole  by  which  G  comes  out, 
or  through  a  separate  hole  (not  shown  in  the  figure)  till  some  ice  has 
formed  in  the  water.  Take  A  out  of  the  mixture,  wipe  it  with  a  cloth, 
and  hold  the  lower  part  of  it  in  the  hand  till  nearly  the  whole  of  the 
ice  has  melted.  If  there  is  a  cake  of  ice  at  the  bottom  see  that  it  is 
displaced  by  the  platinum  stirrer.  A  trace  of  ice  being  still  left  floating 
in  the  water,  place  A  in  B,  and  allow  the  temperature  to  fall  to  a  few 
tenths  of  a  degree  below  tiic  freezing-pcint  you  expect  to  get,  as  deter- 
mined bj-  a  previous  rough  experiment.  The  freezing  mixture  is 
stirred  up  occasionally .  The  meniscus  of  the  thermometer  is  to  be 
carefully  followed,  as  it  goes  on  falling,  bv  means  of  a  weak  hand  lens. 
Now  stir  the  water  in  A  briskly.  Suddenly  it  will  be  seen  that  the 
mercury'  begins  to  rise.  Keep  stirring  with  the  platinum  wire,  and 
read  off  the  maximum  height  of  the  mercury,  at  which  it  is  stationary 
for  some  time.  The  temperature  can  be  estimated  between  the  gradu- 
ations to  thousandths  of  a  degree.  Take  out  A,  and  obser\e  the  fine 
ice  crystals  in  the  water.  Heat  A  in  the  hand  as  before  till  nearly  all 
the  ice  has  disappeared ;  then  replace  A  in  B.  and  make  another  freezing- 
point  determination.  A  third  one  may  also  be  made,  and  the  mean 
of  the  three  readings  taken . 

Take  out  the  thermometer,  and  drj'  it  and  the  platinum  wire  with 
clean  filter-paper,  or  dip  them  in  some  of  the  urine,  which  is  then  thrown 
awav.  Dr\'  A  or  rinse  it  with  urine.  Then  make  a  determination  of 
the  freezing-point  of  the  urine  in  the  same  way  as  was  done  with  the 
water.     The  freezing-point  of  the  urine  will  lie  much  lower  on  the  scale. 

Instead  of  freezing  the  liquid  first  and  then  leaving  a  little  ice  in  it 
when  A  is  placed  in  B,  A  may  be  put  into  B  before  any  ice  has  formed. 
Cooling  is  then  allowed  to  go  on  with  gentle  stirring  to  a  few  tenths  of 
a  degree  below  the  anticipated  freezing-point.  A  small  crystal  of 
clean  dry  ice  is  then  introduced  through  the  side-piece  on  a  clean 
splinter  of  wood  or  the  loop  of  a  cooled  platinum  wire,  the  end  of  which 
passes  through  a  piece  of  cork,  by  which  it  is  held  to  prevent  conduction 
of  heat.  The  platinum  stirrer  can  be  raised  to  receive  the  crystal.  The 
liquid  is  now  vigorously  stirred ;  freezing  occurs,  and  the  observation  is 
made  as  before. 

Instead  of  the  above  method,  the  liquid  may  first  be  cooled  directly 
in  the  freezing  mixture,  but  not  so  much  that  ice  forms.  A  is  then  put 
in  B,  and  cooling  allowed  to  go  on  while  it  is  being  stirred.  Wlien  it 
has  been  undercooled  to  a  certain  extent — i.e.,  cooled  below  its  freezing- 
point — the  vigour  of  the  stirring  is  increased.  Ice  forms  suddenly,  as 
before,  and  the  temperature  rises  to  the  freezing-point.     With  urine 


PRACTICAL  EXERCISES 


531 


this  method  is  sufficiently  satisfactory,  but  it  is  not  usually  easy  to  get 
freezing  of  the  distilled  water  till  the  undercooling  is  considerable,  and 
it  has  been  sliown  that  this  introduces  some  error. 

Suppose  the  freezing-point  of  the  distilled  water  on  the  scale  of  the 
thermometer  was  5-245*  and  that  of  the  urine  3-625°,  the  value  of  A 
for  the  urine  is  1-620°.  Since  for  most  purposes  it  is  sufficient  to  fix 
the  second  decimal  point,  much  smaller  and  less  expensive  thermometers 
than  the  ordinary  Bcckmann  may  be  employed. 

In  the  same  way  the  freezing-point  of  blood-serum  (or  blood),  bile, 
and  other  physiological  liquids  can  be  determined. 

Systematic  Examination  of  Urine. — In  examining  urine,  it  is  con- 
venient to  adopt  a  regular  plan,  so  as  to  avoid  the  risk  of  overlooking 
anything  of  importance.  'I"he  following  simple  scheme  may  serve  as 
an  example;  but  no  routine  should  be  slavishly  followed,  the  object 
being  to  get  at  the  important  facts  with  the  minimum  of  labour.  More 
extensive  information  must  be  sought  in  the  treatises  on  examination 
of  the  urine  for  clinical  purposes. 

1 .  Anything  peculiar  in  colour  or  smell  ?  If  the  colour  suggests 
blood,  examine  with  spectroscope,  hsemin  test,  guaiacum  te^..  (pp.  76, 

2-2) ;  if  it  suggests  bile,  test  for  bile-pigments  by  Gmelin's  test  (p.  4O2), 
and  for  bile-salts  by  Pettenkofer's  test  (p.  462)  and  by  Hay's  test 
(pp.462.  528). 

2.  Reaction. 

3.  Sediment  or  not  ?  Sediment  may  be  procured  by  letting  the 
urine  stand  in  a  conical  glass,  or  in  a  few  minutes  by  the  centrifuge. 
If  the  appearance  of  the  sediment  suggests  anything  more  than  a  little 
mucus,  examine  with  the  microscope.  The  sediment  may  contain 
organized  or  unorganized  deposits. 

Organized  Sediments. — (a)  Red  blood-corpuscles  (considerably  altered 
if  they  have  come  from  the  upper  part  of  the  urinary  tract). 

{b)  Leucocytes.  A  few  are  present  in  health.  A  large  number 
indicates  pus.  When  pus  is  present  the  sediment  may  be  white  to  the 
naked  eye. 

(c)  Epithelium  from  the  bladder,  ureters,  pelvis  of  the  kidney  or  the 
renal  tubules.  A  few  squamous  epithelial  cells  from  the  urethra  are 
always  present  in  normal  urine. 

(d)  Tube  casts. 

(e)  Spermatozoa  (occasional). 
(/)  Bacteria. 

{g)  Parasites  (rare). 

{h)  Portions  of  tumours  (rare) . 

Unorganized  Sediments. 


IN    ACID    URINE. 

Uric  Acid. — Crystals  coloured 
brownish  -  yellow  with  urinary 
pigment.  Various  shapes,  espe- 
cially oval  '  whetstones,'  rhom- 
bic tables,  and  elongated  crystals, 
often  in  bundles  (Fig.  177). 

Urates. — Usually  amorphous,  in 
the  form  of  fine  granules,  often 
tinged  with  urinary  pigment, 
sometimes  brick-red.  Soluble  on 
heating.  On  addition  of  acids 
(including  acetic  acid)   they  dis- 


IN    ALK.\LINE    URINE. 

Triple  Phosphate. — Clear,  col- 
ourless, coffin  -  lid  or  knife  -  rest 
crystals.  Also  deposited  in  the 
form  of  feathery  stars  (Fig.  179). 

Calcium  Hydrogen  Phosphate 
('  stellar  '  phosphate),  CaHP04. — 
Crystals  often  wedge-shaped  and 
arranged  in  rosettes.  May  also 
occur  in  a  dumb-bell  form.  (A 
phosphate  of  calcium  is  also  occa- 
sionally seen  in  weakly  acid  urine.) 
(Fig.  181,  p.  479 .) 


53» 


EXCRETION 


Unorganized  Sediments  (continued)—' 


IN    ACID    URINE. 

solve  and  uric  acid  cystals  appear 
in  their  place.  Acid  urate  of 
sodium  and  of  ammonium  occa- 
sionally found  in  the  crystalline 
form  (rosettes  of  needles). 

Calcium  Oxalate. — Octahedral, 
'  envelope  '  crystals,  not  coloured. 
Insoluble  in  acetic  acid.  Soluble 
in    hydrochloric    acid    (Fig.    178, 

P-  478). 

Cystin.  —  Hexagonal  plates . 
Rare  (Fig.  180,  p.  470). 

Lencin  and  Ty rosin  (Figs.  186, 
187,  p.  488). — Rare.  Also  found 
in  alkaline  urine,  but  rarely. 

Triple  Phosphate.  —  Sometimes 
found  in  weakly  acid  urine. 


IN    ALK.M.IXE    URINE. 

Calcium  Phosphate,  Ca3(PO,)o. — 
Amorphous. 

Magnesium  Phosphate.  —  Long 
rliombic  tablets,  which  arc  dis- 
solved at  the  edges  by  ammonium 
carbonate  solution,  unlike  triple 
phosphate.  All  the  above  are 
soluble  in  acetic  acid  without 
effervescence. 

Calcium  Carbonate. — Small 
spherical  or  dumb  -  bell  -  shaped 
bodies  soluble  in  acetic  acid  with 
effervescence. 

Ammonium  Urate. — Dark  balls, 
often  covered  with  spines.  Soluble 
in  acetic  or  hydrochloric  acid, 
with  formation  of  uric  acid  crys- 
tals (Fig.  182,  p.  479). 

4.  Specific  gravity. 

5.  Quantity  of  urine  in  twenty-four  hours.  If  the  quantity  is 
abnormally  large  and  the  specific  gravity  high,  test  for  sugar. 

6.  Inorganic  constituents  not  generally  of  clinical  importance,  but 
in  special  diseases  they  should  be  examined — e.g.,  chlorides  in  pneu- 
monia. 

7.  Normal  organic  constituents.  Sometimes  quantitative  estima- 
tion of  urea  or  total  nitrogen  in  fever,  and  in  diabetes  and  Bright's 
disease. 

8.  Chemical  examination  for  abnormal  organic  constituents,  especi- 
ally albumin  and  sugar. 

Albumin.— (i)  Heat  to  boiling  some  of  the  urine  in  a  test-tube.  A 
precipitate  insoluble  on  addition  of  a  few  drops  of  acetic  acid  consists 
of  coagulable  protein.  A  precipitate  soluble  in  acetic  acid  consists  of 
earthy  phosphates. 

(2)  Heller's  test.  Put  some  strong  nitric  acid  in  a  test-tube  and 
run  on  to  it  some  urine.     A  white  ring  indicates  protein. 

A  very  rough  quantitative  estimation  may  be  made  by  the  method 
of  Ksbach  (p.  523). 

Sugar. — (i)  Trommer's  test.  (Fehling's  solution  may  be  used.)  1* 
the  result  is  indecisive^ 

(2)  Phenyl-hydrazine  test  (p.  525)- 

(3)  In  case  of  doubt  confirm  by  yeast  test. 

A  quantitative  estimation  may  be  made  with  Fehling's  solution  or 
the  polarimeter. 


CHAPTER  X 

METABOLISM,  NUTRITION  AND  DIETETICS 

We  return  now  to  the  products  of  digestion  as  they  are  absorbed 
from  the  ahmentary  canal,  and,  still  assuming  a  typical  diet  con- 
taining carbo-hydrates,  fats,  and  proteins,  we  have  to  ask,  What 
is  the  fate  of  each  of  these  classes  of  proximate  principles  in  the 
body  ?  what  does  each  contribute  to  the  ensemble  of  vital  activity  ? 
It  will  be  best,  first  of  all,  to  give  to  these  questions  what  roughly 
qualitative  answer  is  possible,  then  to  look  at  metabolism  in  its 
quantitative  relations,  and  lastly  to  focus  our  information  upon 
some  of  the  practical  problems  of  dietetics. 

Section  I. — Metabolism  of  Carbo-Hydrates — Glycogen. 

The  carbo-hydrates  of  the  food,  passing  into  the  blood  of  the 
portal  vein  in  the  form  of  dextrose,  are  in  part  arrested  in  the  liver, 
and  stored  up  as  glycogen  in  the  hepatic  cells,  to  be  gradually  given 
out  again  as  sugar  in  the  intervals  of  digestion.  The  proof  of  this 
statement  is  as  follows : 

Sugar  is  arrested  in  the  liver,  for  during  digestion,  especially  of  a 
meal  rich  in  carbo-hydrates,  the  blood  of  the  portal  contains  more 
sugar  than  that  of  the  hepatic  vein.  Popielski,  on  the  basis  of 
experiments  in  which  he  fed  with  known  quantities  of  sugar  dogs 
whose  inferior  vena  cava  and  portal  vein  had  been  united  by  an 
Eck's  fistula,  and  determined  the  amount  of  sugar  which  passed 
into  the  urine,  estimates  the  quantity  of  sugar  kept  back  by  the 
liver  at  from  12  to  20  per  cent,  of  the  whole.  In  the  liver  there 
exists  a  store  of  sugar-producing  material  from  which  sugar  is 
gradually  given  ofi  to  the  blood,  for  in  the  intervals  of  digestion  the 
blood  of  the  hepatic  veins  contains  more  dextrose  (2  parts  per  1,000) 
than  the  mixed  blood  of  the  body  or  than  that  of  the  portal  vein 
(about  I  part  per  1,000).  When  the  circulation  through  the  liver 
is  cut  off  in  the  goose,  the  blood  rapidly  becomes  free,  or  nearly  free, 
from  sugar  (Minkowski).  And  a  similar  result  follows  such  inter- 
ference with  the  hepatic  circulation  as  is  caused  by  the  ligation  of 
the  three  chief  arteries  of  the  intestine  in  the  dog,  even  when  the 
animal  has  been  previously  made  diabetic  by  excision  of  the  pancreas 

(p.  636). 


534  METABOLISM.   \CTRITIOX  AXD  DIETETICS 

The  nature  of  the  sugar- forming  substance  is  made  clear  by  the 
following  experiments:  (i)  A  rabbit  after  a  large  carbo-hydrate 
meal,  of  carrots  for  instance,  is  killed  and  its  liver  rapidly  excised, 
cut  into  small  pieces,  and  thrown  into  acidulated  boiling  water. 
After  being  boiled  for  a  few  minutt-s,  the  pieces  of  liver  are  rubbed 
up  in  a  mortar  and  again  boiled  in  the  same  water.  The  opalescent 
aqueous  extract  is  filtered  off  from  the  coagulated  proteins.  No 
sugar,  or  only  traces  of  it,  are  found  in  this  extract;  but  another 
carbo-hydrate,  glycogen,  a  polysaccharide  giving  a  port-wine 
colour  with  iodine  and  capable  of  ready  conversion  into  sugar  by 
amylolytic  ferments,  is  present  in  large  amount.  (See  Practical 
Exeicises,  p.  715.) 

{2)  The  liver  after  the  death  of  the  animal  is  left  for  a  time  in 
situ,  or,  if  excised,  is  kept  at  a  temperature  of  35°  to  40°  C,  or  for 
a  longer  period  at  a  lower  temperature;  it  is  then  treated  exactly 
as  before,  but  no  glycogen,  or  comparatively  little,  can  now  be 
obtained  from  it,  although  sugar  (dextrose)  is  abundant.  The 
inference  plainly  is  that  after  death  the  hepatic  glycogen  is  con- 
verted into  dextrose  by  some  influence  which  is  restrained  or  de- 
stroyed by  boiling.  This  transformation  might  theoretically  be 
due  to  an  unformed  ferment  or  to  the  direct  action  of  the  liver-cells, 
for  both  unformed  ferments  and  living  tissue  elements  are  destroyed 
at  the  temperature  of  boiling  water.  It  ha-  been  clearly  shown 
that  the  action  is  brought  about  by  a  diastatic  enzyme,  which  some 
wTiters  call  glycogenase,  for  it  readily  occurs  when  the  minced  liver 
is  mixed  with,  chloroform  water,  and  chloroform  kills  all  living 
tissues.  Although  blood  contains  a  diastase  in  small  amount,  the 
change  does  not  depend  essentially  upon  this,  since  the  glycogen 
also  undergoes  hydrolysis  (glycogenolysis)  to  dextrose  when  all  the 
blood  has  been  washed  out  of  the  organ.  Lymph  also  contains  a 
diastase,  but  there  is  evidence  that  the  post-mortem  glycogenolysis 
is  chiefly  due  to  an  enzyme  contained  in  the  hepatic  cells  (an  endo- 
enzyme)  (Macleod).  The  diastases  in  the  blood  and  lymph  seem 
to  be  '  discards  '  of  the  tissues  which  are  on  the  way  to  destruction 
or  ehmination  (Carlson).  The  post-mortem  change  is  to  be  regarded 
as  an  index  of  a  similar  action  which  goes  on  during  life:  sugar  in 
the  intact  body  is  changed  into  glycogen;  glycogen  is  constantly 
being  changed  into  sugar.  There  is  no  reason  to  doubt  that  here, 
too,  the  hydrolysis  is  effected  by  the  endo-enzyme.  It  might  be 
supposed,  indeed,  that  the  adjustment  of  the  two  processes  glyco- 
gi;nesis  and  glycogenolysis  is  simply  a  matter  of  the  alteration  of 
the  equilibrium  in  a  reversible  reaction  (p.  338),  according  to 
whether  the  dextrose  content  of  the  blood  tends  to  rise  or  fall.  If 
the  concentration  of  dextrose  in  the  blood  is  increased,  more  dex- 
trose might  be  expected  to  '  diffuse  '  into  the  hepatic  cells,  whose 
content  of  dextrose  in  proportion  to  glycogen  would  increase  till 
the  equilibrium  was  restored  by  the  conversion  of  the  excess  of 


METABOT.ISM  OF  CARBO-HYDRATES— GLYCOGEN         535 

sugar  into  glycogen.  Contrariwise,  a  diminution  in  the  dextrose 
content  of  the  bK)od  might  be  expeote<l  to  lead  to  diffusion  of 
ilextrose  out  of  the  liver-cells,  and  a  consetjuent  acceleration  of  the 
hydrolysis  of  the  glycogen.  We  have  already  learnt,  however,  that 
in  physiology — above  all,  perhaps,  in  the  physiology  of  the  glands 
— '  simple  '  explanations  are  usually  suspect.  And  when  we  come  to 
study  those  conditions  in  which,  as  a  consequence  of  the  derange- 
ment of  the  mechanisms  which  regulate  the  carbo-hydrate  metabo- 
lism, sugar  appears  in  the  urine,  it  will  be  seen  that  the  matter  is 
more  complicated.  For  one  thing,  the  nervous  system  seems  to 
take  a  hand  in  the  regulation,  and  where  the  nervous  system  takes 
a  hand  things  are  generally  doing  which  the  experienced  physiologist 
does  not  expect  to  be  simple.  We  may  be  certain,  as  in  the  case  of 
the  intracellular  proteolytic  ferments,  that  the  vital  action  of  the 
hepatic  cells  is  a  most  important  factor  in  controlling  the  rate  of 
production  of  the  ferment,  and  therefore  its  concentration  in  rela- 
tion to  that  of  the  substrate  and  the  rate  at  which  it  works. 

(3)  With  the  microscope,  glycogen,  or  at  least  a  substance  which 
is  very  nearly  akin  to  it,  which  very  readily  yields  it,  and  which 
gives  the  characteristic  port-wine  colour  with  iodine,  can  be  actually 
seen  in  the  liver-cells.  The  liver  of  a  rabbit  or  dog  which  has  been 
fed  on  a  diet  containing  much  carbo-hydrate  is  large,  soft,  and  very 
easily  torn.  Its  large  size  is  due  to  the  loading  of  the  cells  with  a 
hyahne  material,  which  gives  the  iodine  reaction  of  glycogen,  and 
is  dissolved  out  by  water,  leaving  empty  spaces  in  a  network  of  cell- 
substance.  If  the  animal,  after  a  period  of  starvation,  has  been 
fed  on  protein  alone,  less  glycogen  is  found  in  the  shrunken  liver- 
cells;  if  the  diet  has  been  wholly  fatty,  little  or  no  glycogen  at  all 
may  be  found.  Glycogen  can  even  be  formed  by  an  excised  liver 
when  blood  containing  dextrose  is  circulated  through  it. 

A  fact  of  great  interfst  recently  demonstrated  is  that  ir;  animals 
where  the  mobilization  of  the  hepatic  glycogen  is  accelerated  (as 
in  rabbits  after  puncture  of  the  medulla),  glycogen  in  the  form  of 
granules  and  small  masses  can  be  seen  in  the  blood  capillaries 
(or  rather  sinusoids)  between  the  liver  cells,  and  in  the  sublobular 
veins  (Huber  and  Macleod).  Chemical  evidence  has  also  i.icen 
obtained  of  the  presence  of  a  glycogen-like  polysaccharide  in  the 
blood  leaving  the  liver. 

Formation  of  Glycogen  from  Protein. — In  the  liver-cells  of  the 
frog  in  winter-time  a  great  deal  of  this  hyaline  material — this 
glycogen,  or  perhaps  loose  glycogen  compound — is  present;  in 
summer,  much  less.  The  difference  is  remarkable  if  we  con- 
sider that  in  winter  frogs  have  no  food  for  months,  while  summer 
is  their  feeding-time;  and  at  first  it  seems  inconsistent  with  the 
doctrine  that  the  hepatic  glycogen  is  a  store  laid  up  from  surplus 
sugar,  which  might  otherwise  be  swept  into  the  general  circulation 
and  excreted  by  the  kidneys.     It  has  been  found,  however,  that 


5.^6  METABOLISM.  NUTRITION  AND  DIETETICS 

the  quantity  of  glycogen  is  greatest  in  autumn  at  the  beginning  of 
the  winter-sleep,  and  slowly  diminishes  as  the  winter  passes  on, 
to  fall  abruptly  with  the  renewal  of  the  activity  of  the  animal  in 
the  spring.  The  glycogen  T)resent  at  any  moment  is,  therefore, 
believed  to  be  a  residue,  which  represents  the  excess  of  glycogen 
formed  over  gh'cogen  used  up;  and  the  amount  is  larger  in  winter, 
Rot  because  more  is  manufactured  than  in  summer,  but  because 
less  is  consumed.  It  is  possible,  indeed,  to  produce  the  '  summer  ' 
condition  of  the  hepatic  cells  merely  by  raising  the  temperature  of 
the  air  in  which  a  winter  frog  lives;  at  20°  or  25°  C.  glycogen  dis- 
appears from  its  liver.  Conversely,  if  a  summer  frog  is  artificially 
cooled,  a  certain  amount  of  gljxogen  accumulates  in  the  liver.  The 
meaning  of  this  seems  to  be  that  at  a  low  temperature,  when  the 
wheels  of  life  are  clogged  and  metabolism  is  slow,  some  substance, 
probably  dextrose,  is  produced  in  the  body  from  proteins  in  greater 
amount  than  can  be  used  up,  and  that  the  svirplus  is  stored  as 
glycogen;  just  as  in  plants  starch  is  put  by  as  a  reserve  which  can 
be  drawn  upon — which  can  be  converted  into  sugar — when  the 
need  arises.  That  carbo-hydrates  may  be  formed  from  proteins 
(or  their  constituent  amino-acids)  has  been  shown  in  various  ways — 
for  example,  by  feeding  dogs  with  almost  pure  protein  (casein)  after 
the  production  of  permanent  glycosuria  by  removal  of  the  pancreas 
(p.  636).  To  induce  the  animal  to  take  the  casein  it  had  to  be 
mixed  with  a  certain  amount  of  butter,  or  serum,  or  meat  extract. 
The  amount  of  sugar  excreted  was  much  more  than  could  possibly 
have  come  from  the  glycogen  originally  present  in  the  animal's  body, 
computing  it  on  the  most  generous  scale  (41  grammes  per  kilo- 
gramme of  body-weight,  according  to  Pfliiger),  or  from  free  carbo- 
hydrate present  in  traces  in  the  food,  or  as  prosthetic  groups  (p.  2) 
in  the  ingested  protein.  That  the  source  of  the  sugar  was  protein 
and  not  fat  was  indicated  by  the  fact  that  when  the  amount  of 
protein  food  was  increased,  the  dextrose  and  the  nitrogen  excreted 
increased  proportionally  (see  also  p.  538). 

Glycogen-Formers. — ^As  true  glycogen-formers  in  the  higher 
animals — that  is,  compounds  whose  elements  (particularly  the 
carbon)  actually  enter  into  the  composition  of  the  glycogen  mole- 
cule— may  be  mentioned  such  substances  as  proteins  (including 
gelatin),  the  fermentable  sugars,  and  glycerin.  In  the  case  of 
proteins  it  is,  of  course,  not  the  entire  molecule  which  is  transformed 
bodily  into  glycogen,  but  amino-acids  yielded  by  them,  or  dextrose 
derived  from  the  amino-acids.  The  Hver  is  of  itself  capable  of 
dealing  only  with  the  dextrose,  and  not  with  the  amino-acids.  At 
least,  when  the  isolated  liver  (of  the  tortoise)  is  perfused  with 
blood  containing  amino-acids  no  increase  in  the  glycogen  of  the 
liver  occurs.  When  glycerin  is  added  to  the  blood  the  glycogen 
content  of  the  liver  is  very  distinctly  increased.  Glycerin  is  a  tri- 
valent  alcohol  (CgHgOa)  whose  aldehyde,  obtained  from  it  by  gentle 


METABOLISM  OF  CARBO-HYDFATF.S-GLYCOGEN  537 

oxidation,  is  glyccrose  (CjHgOg),  a  substance  with  the  typical 
properties  of  a  sugar.  In  the  laboratory  it  has  been  shown  that 
two  niolc<mles  of  glyccrose  can  be  combined  to  form  one  molecule  of 
sugar  of  the  hexose  type  with  six  carbon  atoms  (CgHigOg).  A  similar 
transformation  is  accomplished  in  the  liver,  and  then  a  number  of 
the  monosaccharide  molecules  (CgHigOg)  are  condensed  with  loss  of 
water  to  form  glycogen.  Thus,  «(CgHi20g) -mH20  =  (CgHioOg)^. 
Since  glycerin  is  a  normal  product  of  the  hydrolysis  of  fats,  the 
possibility  that  the  fats  of  the  food  may  contribute  through  their 
glycerin  component  to  glycogen  formation  must  be  admitted.  The 
monosaccharides  dextrose,  levulose,  and  galactose  gave  a  similar 
result,  while  the  disaccharides  cane-sugar  and  lactose  caused  no 
increase  in  the  glycogen  of  the  perfused  liver,  since  the  liver  contains 
no  ferment  capable  of  splitting  them  into  monosaccharides.  And 
although  the  lirst  step  in  the  linking  of  the  monosaccharide  mole- 
cules would  seem  to  be  the  formr.tion  of  a  disaccharide  such  as 
maltose,  the  glycogen  molecule  must  apparently  be  built  up  from 
single  '  bricks,'  the  monosaccharides,  and  cannot  be  constructed 
from  bricks  which  are  already  coupled  in  pairs,  the  disaccharides. 
Of  course,  since  the  disaccharides  are  hydrolysed  in  the  digestive 
tube  to  simple  sugars,  they  are  to  be  reckoned  with  the  true  glycogen- 
formers,  for  in  the  intact  body  they  are  presented  to  the  hepatic 
cells  in  the  form  of  monosaccharides.  It  is  probable  that  levulose 
and  galactose  are  first  changed  into  dextrose. 

By  the  action  of  alkalies  such  structurally  related  sugars  can  easily 
be  transformed  into  each  other.  Thus  dextrose  is  an  aldehyde  of  an 
alcohol  with  six  carbon  atoms,  and  levulose  the  corresponding  keto- 
hexose . 

By  oxidizing  the  alcohol  we  get  an  aldehyde  or  a  ketone,  according 
to  whether  a  primary  alcohol  group  (CHg.OH)  or  a  secondary  group 
(CH.OH)  is  oxidized,  with  the  loss  of  two  atoms  of  hydrogen.     The 

aldehyde   is  characterized  by  the  presence  of  the  group  C^'jr,  the 

ketone  by  the  group  CO.  Both  the  aldehyde  and  the  ketone  are 
sugars,  and  since  each  contains  six  carbon  atoms,  they  are  both  sugars 
of  the  group  known  as  '  hexoses.'  Dextrose,  being  not  onlj-  a  hexose 
but  an  aldehyde,  may  be  called  an  '  aldohexose,'  and  levulose,  being 
not  only  a  hexose  but  a  ketone,  a  '  ketohexose.' 

CH.OH  C<0  CH,.0. 

CH.OH  CH.OH  CO 

I  I  I 

CH.OH  CH.OH  CH.OH 

I  J  i 

CH.OH  CH.OH  CH.OH 

I  I  I 

CH.OH  CH.OH  CH.OH 

J  I  I 

CH2.OH  CH2.OH  CH2.OH 

6-valent  alcohol.  Aldehyde,  Ketone. 


538  METABOLISM.   NUTRITION  AND  DIETETICS 

That  Icvulose  can  be  changed  into  dextrose  in  the  body  is  indi- 
cated by  the  observation  that  after  extirpation  of  the  pancreas  in 
dogs  the  administration  of  levulosc  is  followed  by  an  increase  in 
the  excretion  of  dextrose  nearly  equal  to  the  amount  of  levulose 
ingested.  It  is  also  stated  that,  when  the  sur\iving  liver  of  a 
normal  dog  is  perfused  with  a  suspension  of  washed  blood-corpuscles 
to  which  levulose  has  been  added,  dextrose  accumulates  in  the  blood 
and  levulose  disappears  from  it. 

It  has  not  hitherto  been  proved  that  the  fatty  acid  component  of 
the  food  fats  can  be  converted  into  glycogen.  But  a  fattv  acid, 
propionic  acid,  is  capable  of  complete  transformation  into  dextrose 
when  given  either  by  the  mouth  or  subcutaneously  to  dogs  under 
the  influence  of  phlorhizin  (Ringer).  Many  other  bodies  are  known 
to  influence  the  formation  of  glycogen  by  '  sparing  '  substances 
which  are  true  glycogen-producers,  but  their  carbon  does  not  actu- 
alty  take  its  place  in  the  glycogen  molecule.  It  has  been  shown  that 
proteins  can  directly  form  glycogen  or  sugar  apart  from  carbo- 
hydrate groups  contained  in  the  protein  molecule.  For  the  proteins 
of  meat,  gelatin,  and  casein  are  capable  of  forming  60  per  cent,  of 
their  own  weight  of  dextrose  in  diabetic  metabolism,  and  even  the 
end-products  of  pancreatic  digestion  of  meat  yield  so  much  sugar 
that  the  greater  part  of  it  must  have  come  from  the  amino-bodies, 
and  not  from  a  sugar-group  in  the  protein.  When  given  to  dogs 
with  total  phlorhizin  glycosuria  (p.  551),  glycin  and  alanin  are 
completely,  glutamic  and  aspartic  acids  in  great  part  (corresponding 
to  about  three  carbon  atoms  of  their  respective  molecules),  converted 
into  dextrose  (Lusk  and  Ringer),  and  there  is  no  reason  to  doubt 
that  when  such  substances  are  produced  by  hydrolysis  of  protein 
in  the  normal  body,  and  are  not  all  utilized  in  rebuilding  the  bio- 
plasm, a  portion  of  the  surplus,  after  deamidization,  can  be  trans- 
formed into  glycogen. 

Extra-Hepatic  Glycogen. — While  the  liver  in  the  adult  (con- 
taining as  it  does  from  2  to  10  per  cent,  of  glycogen,  or  even,  with 
a  diet  rich  in  sugar  or  starch,  more  than  18  per  cent.)  may  be  looked 
upon  as  the  main  storehouse  of  surplus  carbo-hydrate,  depots  of 
glycogen  are  formed,  both  in  adult  and  foetal  life,  in  other  situations 
where  the  strain  of  function  or  of  growth  is  exceptionally  heavy — 
in  the  muscles  of  the  adult  (03  to  0-5  per  cent,  of  the  moist  skeletal 
muscle,  or  on  a  carbo-hydrate  regimen  07  to  37  per  cent.),  in  the 
placenta,  in  many  developing  organs  in  the  embryo  (muscles,  lungs, 
epithelium  of  the  trachea,  oesophagus,  intestine,  ureter,  pelvis  of 
kidney,  and  renal  tubules).  The  fa'tus,  however,  is  not,  compared 
with  the  adult,  especially  rich  in  glycogen.  In  the  adult  under 
favourable  circumstances  the  absolute  amount  of  glycogen  in  the 
muscles  may  be  several  times  greater  than  that  in  the  Hver,  and 


MF.TAHOLISM  OF  CARBO-HY DRATES— GLYCOGEN  539 

usually  the  hepatic  glycogen  makes  up  considerably  less  than  half 
the  total  glycogen  of  the  body.  That  the  muscles  do  not  derive 
their  glycogen  by  the  migration  of  hepatic  glycogen,  but  can  them- 
selves form  it  from  dextrose,  has  been  shown  by  injecting  that  sugar 
subcutaneously  into  frogs  after  excision  of  the  liver.  The  muscle 
glycogen  was  found  to  be  increased. 

Function  and  Fate  of  the  Glycogen. — ^The  glycogen  store  of  the 
liver  fulfils  a  different  function  from  that  of  the  muscles.  This  is 
indicated  by  the  fact  that  when  dogs,  after  being  put  on  a  given  diet 
for  two  or  thr(>c  days,  are  starved  for  a  time,  and  then  put  again  on 
the  original  diet,  the  hepatic  and  the  muscular  glycogen  behave 
differently  at  first  during  the  period  of  re-alimentation.  While 
glycogen  accumulates  in  the  liver  in  greater  quantity  than  under 
normal  conditions  of  nutrition,  in  the  muscles  it  at  first  accumulates 
much  less  rapidly  than  normally.  This  is  entirely  in  accordance 
with  the  view  that  the  hepatic  glycogen  store  has  for  its  great  func- 
tion the  regulation  of  the  sugar  content  of  the  blood  in  the  interest 
of  all  the  tissues,  while  the  gljxogen  store  of  the  muscles  and  other 
tissues  is  mainly  in  the  interest  of  their  own  nutrition  and  a  source 
of  energy  for  their  own  work.  This  does  not  imply  that,  when  sugar 
is  being  absorbed  in  quantities  too  great  for  the  liver  to  deal  with 
after  the  current  needs  of  the  tissues  have  been  satisfied,  they  do 
not  add  to  their  glycogen  reserves.  There  is  every  reason  to  suppose 
that  they  do  so,  and  thus  act  as  a  subsidiary  regulating  mechanism, 
although  a  less  elastic  one  than  that  supplied  by  the  liver.  A  third 
way  in  which  a  portion  of  the  surplus  sugar  can  be  stored  is  in  the 
form  of  fat. 

When  a  fasting  dog  is  made  to  do  severe  muscular  work,  the 
greater  part  of  the  glycogen  soon  disappears  from  its  liver.  When 
a  dog  is  starved,  but  allowed  to  remain  at  rest,  the  glycogen  still 
markedly  diminishes,  although  it  takes  a  longer  time;  and  at  a 
period  when  there  is  stiU  plenty  of  fat  in  the  body,  there  may  be 
only  a  trace  of  hepatic  glycogen  left.  The  glycogen  which  is  usually 
contained  in  the  skeletal  muscles  also  diminishes  very  rapidly  in  the 
first  days  of  hunger,  but  the  heart  contains  the  normal  amount  of 
glycogen  at  a  time  when  the  proportion  in  the  skeletal  muscles  has 
sunk  to  ^  to  y\p  of  the  normal. 

Tliese  facts  have  been  taken  to  indicate  that  glycogen  and  the  sugar 
formed  from  it  are  the  readiest  resources  of  the  starving  and  working 
organism,  for  the  transformation  of  chemical  energy  into  heat  and 
mechanical  work.  To  borrow  a  financial  simile,  the  fat  of  the  body 
has  sometimes  been  compared  to  a  good,  but  rather  inactive  security, 
which  can  only  be  gradually  realized;  its  organ-proteins  to  long-date 
bills,  which  will  be  discounted  sparingly  and  almost  with  a  grudge; 
its  glycogen,  its  carbo-hydrate  reserves,  to  consols,  which  can  be  turned 
into  money  at  an  hour's  warning.     Glycogen,  on  this  view,  is  especiall} 


540  METABOLISM.  NUTRITION  AND  DIETETICS 

drawn  upon  for  a  sudden  demand,  fat  for  a  steady  drain,  tissue-protein 
lor  a  life-and-death  struggle.  While  there  may  be  some  such  diflercnce 
in  the  tenacity  with  which  the  different  kinds  of  reser\e  material  are 
held  back  from  consumption  when  the  floating  supplies  are  wearing 
low,  modern  investigation  tends  to  the  conclusion  that  the  interchange- 
ability  of  the  various  groups  of  nutritive  substances  is  greater  than 
had  been  supposed,  and  that  in  the  long-run  the  cells — in  normal  cir- 
cumstances at  least — never  work  without  dextrose,  even  after  the 
glycogen  store  has  been  practically  all  consumed,  but  secure  it  from 
other  sources. 

Pavy  has  put  forward  the  heterodox  view  that  the  glycogen  formed 
in  the  liver  from  the  sugar  of  the  portal  blood  is  never  reconverted 
into  sugar  under  normal  conditions,  but  is  changed  into  some  other 
substance  or  substances,  and  he  denies  that  the  post-mortem  formation 
of  sugar  in  the  hepatic  tissue  is  a  true  picture  of  what  takes  place 
during  life.  But  in  spite  of  the  brilliant  manner  in  which  he  has 
defended  this  thesis,  both  by  argument  and  by  experiment,  it  must  be 
said  that  the  older  doctrine  of  Bernard,  which  in  the  main  we  have 
followed  above,  is  attested  by  such  a  cloud  of  modem  witnesses  that  it 
seems  to  be  firmly  and  finally  established. 

Fate  of  the  Sugar — Glycolysis. — ^What,  now,  is  the  fate  of  the 
sugar  which  either  passes  right  through  the  portal  circulation  from 
the  intestine  without  undergoing  any  change  in  the  liver,  or  is 
gradually  produced  from  the  hepatic  glycogen  ?  When  the  pro- 
portion of  sugar  in  the  blood  rises  above  a  certain  low  limit  (about 
1-5  or  2  parts  per  1,000),  some  of  it  is  excreted  by  the  kidneys 
(Practical  Exercises,  p.  716). 

A  large  meal  of  carbo-hydrates  is  frequently  followed  by  a 
temporary  glycosuria,  but  much  depends  upon  the  form  in  which 
the  sugar-forming  material  is  taken.  We  have  seen  that  poly- 
saccharides are  quite  incapable  of  absorption  as  such,  and  that  they 
must  be  very  completely  hydrolysed  in  the  lumen  of  the  alimentary 
canal  before  their  constituent  sugars  have  any  chance  of  reaching  the 
blood.  It  is  therefore  not  to  be  expected  that  the  rapid  absorption 
of  such  considerable  quantities  of  sugar  as  would  lead  to  its  excretion 
should  easily  occur  when  the  carbo-hydrate  is  in  this  form.  Miura 
for  example,  after  an  enormous  meal  of  rice  (equivalent  to  64 
grammes  of  ash-  and  water-free  starch  per  kilo  of  body-weight), 
which,  as  he  mentions,  tasked  even  his  Japanese  powers  of  digestion 
for  such  food  to  dispose  of,  found  not  a  trace  of  sugar  in  the  urine. 
Dextrose,  cane-sugar  and  lactose,  on  the  other  hand,  when  taken  in 
large  amount,  were  in  part  excreted  by  the  kidneys,  as  was  also 
the  case  with  levulose  and  maltose  in  a  dog  (Practical  Exercises, 
p.  717).*     The  amount  of  any  carbo-hydrate  which  can  be  eaten 

*  Twenty-four  healthy  students,  whose  urine  had  previously  been  shown 
to  be  free  from  sugar,  ate  quantities  of  cane-sugar  varying  from  250  grammes 
to  750  grammes.  The  urine  was  collected  in  separate  portions  for  twelve 
to  twenty- four  hours  after  the  meal.  In  only  three  cases  was  reducing  sugar 
found  in  the  urine  (by  Fehling's  and  the  phenyl-hydrazine  test),  and  then 
merely  in  traces.  In  eight  cases  cane-sugar  was  found,  and  estimated  by  the 
polarimeter,  and,  after  boihng  with  hydrochloric  acid,  by  Fehling's  solutioa. 


METABOLISM  OF  CARBO-HYDRATES  54^ 

without  the  appearance  of  sugar  in  the  urine  is  sometimes  called  the 
assimilation  limit  for  that  carbohydrate.  The  attempt  has  been 
made  to  fix  the  limit  of  tolerance  of  dextrose  for  normal  persons 
and  persons  suffering  from  incipient  diabetes,  with  the  object  of 
aiding  in  early  diagnosis  of  that  condition.  But  the  limit  varies  with 
so  many  conditions,  only  some  of  which  can  be  controlled,  that  such 
observations  are  not  easily  interpreted. 

Except  as  an  occasional  phenomenon,  glycosuria  other  than  ali- 
mentary is  inconsistent  with  health;  and  therefore  in  the  normal 
body  the  sugar  of  the  blood  must  be  either  destroyed  or  transformed 
into  some  more  or  less  permanent  constituent  of  the  tissues.  The 
transformation  of  sugar  into  fat  we  have  alreadj^  mentioned,  and 
shall  have  again  to  discuss;  it  only  takes  place  under  certain  con- 
ditions of  diet,  and  no  more  than  a  small  proportion  of  the  sugar 
which  disappears  from  the  body  in  twenty-four  hours  can  ever,  in 
the  most  favourable  circumstances,  be  converted  into  fat.  The 
dextrose  which  is  taken  up  from  the  blood  by  the  tissues  and  there 
condensed  to  glycogen  suffers  sooner  or  later  the  converse  change, 
in  all  probability  under  the  influence  of  diastases  or  glycogenases 
produced  in  the  cells,  and  reappears  as  dextrose  to  take  its  place 
in  the  cellular  katabolism  and  begin  the  series  of  cleavages  and 
oxidations  by  which  its  chemical  energy  is  set  free.  Accordingly, 
it  is  the  destniction  of  sugar  which  concerns  us  here,  and  there  is 
every  reason  to  believe  that  this  takes  place,  not  in  any  particular 
organ,  but  in  all  active  tissues,  especially  in  the  muscles,  and  to  a 
less  extent  in  glands. 

It  has  been  asserted  that  the  blood  which  leaves  even  a  resting 
muscle,  or  an  inactive  salivary  gland,  is  poorer  in  sugar  than  that 
coming  to  it ;  and  the  conclusion  has  been  drawn  that  in  the  metabo- 
lism of  resting  muscle  and  gland  sugar  is  oxidized,  the  carbon 
passing  off  as  carbon  dioxide  in  the  venous  blood.  This  is  indeed 
extremely  likely,  for  we  know  that,  when  the  skeletal  muscles  of  a 
rabbit  or  guinea-pig  are  cut  off  from  the  central  nervous  system  by 
curara,  the  production  of  carbon  dioxide  falls  much  below  that  of 
an  intact  animal  at  rest ;  and  the  carbon  given  off  by  such  an  animal 
on  its  ordinary  vegetable  diet  can  be  shown,  by  a  comparison  of 
the  chemical  composition  of  the  food  and  the  excreta,  to  come 
largely  from  carbo-h\^drates.  But,  considering  the  relatively  feeble 
metabolism  of  muscles  and  glands  when  not  functionally  excited, 
the  large  volume  of  blood  which  passes  through  them,  the  difftculty 
of  determining  small  differences  in  the  proportion  of  sugar  in  such 
a  liquid,  the  possibilit}^  that  even  in  the  blood  itself  sugar  may  be 

The  greatest  quantity  of  cane-sugar  recovered  from  the  urine  was  8  grammes 
(7-92  grammes  by  FehUng's  method  and  8-29  grammes  by  the  polarimeter) ; 
the  highest  proportion  of  the  quantity  taken  which  appeared  in  the  urine  was 
2-5  per  cent.  When  dextrose  was  found,  cane-sugar  was  always  present  as 
well. 


54^  METABOLISM,  NUTRITION  AND  DIETETICS 

destroyed,  or  that  it  may  pass  from  the  blood,  without  being  oxi- 
dized, into  the  lymph,  too  much  weight  may  be  easily  given  to  the 
results  of  direct  analysis  of  the  in-coming  and  out-going  blood. 
And  although  the  results  of  Chauveau  and  Kaufmann,  obtained  in 
this  way,  lit  in  fairly  well  with  what  we  have  already  learnt  by  less 
direct,  but  more  trustworthy,  methods,  such  as  the  study  of  the 
respiratory  exchange,  they  cannot  be  accepted  as  yielding  exact 
quantitative  information.  They  found  that  in  one  of  the  muscles 
of  the  upper  lip  of  the  horse  the  quantity  of  dextrose  used  up  during 
activity  (feeding  movements)  was  35  times  as  much  as  in  the  same 
muscle  at  rest,  and  this  corresponded  with  the  deficit  of  oxygen  in 
the  blood  entering  the  muscle,  and  with  the  excess  of  carbon  dioxide 
in  the  blood  leaving  it.  More  dextrose  was  also  destroyed  in  the 
active  than  in  the  passive  parotid  gland  of  the  horse,  but  the  excess 
per  unit  of  weight  of  the  organ  was  far  less  than  in  muscle.  In  dogs 
whose  abdominal  viscera  have  been  removed,  so  that  they  constitute 
practically  preparations  composed  of  skeletal  muscles  it  has  been 
found  that  theamountof  dextrosewhichdisappearsfrom  100 grammes 
of  blood  per  minute  varies  from  047  to  18  milligrammes,  the  irregu- 
larities probably  depending  largely  upon  the  irregular  consumption 
by  the  muscles  of  the  glycogen  stored  in  them  (Macleod  and 
Pearce) . 

Intermediary  Metabolism  of  Carbo- Hydrates. — Concerning  the  pro- 
cesses and  the  stages  by  which  dextrose  is  destroyed  in  the  tissues, 
we  have  no  very  exact  information,  and  it  cannot  be  definitely  stated 
at  present  what  share  is  taken  by  cleavage  and  what  by  oxidation, 
or  rather  through  what  intermediate  products,  formed,  it  may  be, 
now  by  simple  cleavage,  now  by  oxidation,  again  by  a  combination 
of  cleavage  and  oxidation,  the  dextrose  molecule  is  finally  resolved 
into  carbon  dioxide  and  water.  It  must  be  remembered  that  the 
synthetic  powers  of  animal  cells  are  now  known  to  be  very  extensive. 
They  build  carbo-hydrates,  fats,  phosphatides,  and  proteins,  as 
well  as  destroy  them,  and  at  any  of  the  earlier  stages  at  any  rate 
the  degradation  products  of  dextrose,  or  some  of  them,  may  be 
utilized  in  the  construction  of  new  compounds — for  example,  of  fat — 
either  in  the  cells  where  they  arise  or  elsewhere  in  the  body.  In 
like  manner  the  decomposition  of  a  molecule  of  dextrose  begun  in 
one  cell  or  in  one  tissue  may  be  consummated  in  another  to  which 
intermediate  products  are  conveyed  in  the  blood.  In  such  ways 
it  is  obvious  that  the  katabolic  processes  may  be  finely  regulated 
both  qualitatively  and  quantitatively  in  accordance  with  the 
specific  wants  of  different  organs  and  the  intensity  of  their  func- 
tional activity  from  time  to  time.  It  must  be  said,  however,  that 
at  present  there  are  few  definitely  ascertained  facts  to  guide  us  in 
trying  to  form  a  scheme  of  the  actual  changes  which  occur  in  the 
intermediate  katabolism  of  carbo-hydrates,  and  the  sequence  which 


METABOLISM  Oh'  CARBO-HYDRATES  543 

they  normally  follow,  dlycuronic  acid  has  been  previously  men- 
tioned as  a  substance  occurring  even  in  normal  urine  in  small 
amount.  It  is  very  closely  related  to  dextrose,  as  a  comparison  of 
their  constitutional  formulae  shows: 

C(  )H  COOH  COH 

I  I  I 

H— C— OH       H— C— OH        H— CO— H 

I  I  I 

OH— C— H       OH— C— H         OH— C— H 

I  I  I 

H— C— OH       H— C— OH         H— C— OH 

I  I  I 

H— C— OH       H— C— OH         H— C— OH 

I  I  I 

CHgOH  CHaOH  COOH 

d-de.\trose.  <i-glyconic  acid.  <i-glycuronic  acid. 

Glycuronic  acid  agrees  with  dextrose  in  containing  the  character- 
istic aldehyde  group  C^yj.  but  differs  in  that  by  oxidation  two 

atoms  of  hydrogen  in  the  primary  alcohol  group  CHgOH  have  been 
replaced  by  one  atom  of  oxygen.  There  is  reason  to  believe  that 
in  the  tissues  glycuronic  acid  can  be  formed  from  dextrose  in  the 
same  way,  possibly  through  the  mediation  of  an  enzyme,  and  it 
may  therefore  represent  a  stage  in  the  katabolism  of  sugar.  But 
it  is  not  known  whether  this  is  a  normal  transformation  through 
which  the  whole  or  the  greater  part  of  the  dextrose  passes,  or  only 
a  transformation  involving  a  small  part  of  the  sugar  under  normal 
conditions.  The  appearance  in  the  urine  of  large  quantities  of 
glycuronic  acid,  paired  as  already  explained  with  various  com- 
pounds, in  certain  pathological  states  or  after  the  administration 
of  certain  drugs  (p.  48-.-'),  might  be  explained  either  as  the  result  of 
an  increased  production  of  that  substance  through  a  deflection  of  the 
normal  trend  of  carbo-hydrate  degradation,  or  as  the  result  of  a  failure 
on  the  part  of  the  cells  to  further  transform  the  glycuronic  acid  in 
the  quantities  normally  produced. 

Lactic  acid  is  the  one  intermediate  stage  in  the  decomposition  of 
dextrose  in  the  tissues  whose  importance  seems  to  be  definitely 
ascertained.  The  muscles  and  the  liver  have  been  proved  to  possess 
the  power  of  producing  lactic  acid  from  dextrose  obtained  directly 
from  the  blood  or  from  the  hydrolysis  of  their  own  store  of  glycogen, 
and  there  is  little  doubt  that  this  power  is  shared  by  many,  perhaps 
by  all,  of  the  other  organs.  There  is  also  good  evidence  that  the 
lactic  acid  thus  formed  can  be,  and  under  normal  conditions  is,  in 
large  part  oxidized  so  as  eventually  to  yield  carbon  dioxide  and 
water,  although  there  is  reason  to  believe  that  a  portion  of  it  may 
be  utilized  for  the  synthesis  of  more  complex  bodies. 

The  chemistry  of  the  change  or  series  of  changes  by  which  lactic 
acid  is  produced  from  dextrose  and  the  end-products,  carbon  dioxide 


544 


METABOLISM.  NUTRITION  AND  DIETETICS 


and  water,  from  lactic  acid  has  given  rise  to  much  discussion,  and  is 
not  yet  clearly  known.  The  following  scheme,  based  on  the  researches 
of  Embden  and  others,  and  quoted  from  Abderhalden,  illustrates  one 
suggestion  as  to  the  course  of  the  series  of  transformations,  although 
it  must  be  taken  only  as  a  diagram  of  the  sequence  of  some  of  the 
possible  stages.  A  molecule  of  dextrose  is  represented  as  giving  rise 
to  two  molecules  of  glyceric  aldehyde,  each  of  which  then  yields  a  mole- 
cule of  lactic  acid.  Each  molecule  of  lactic  acid,  losing  two  atoms  of 
hydrogen,  becomes  converted  into  a  molecule  of  pyruvic  acid,  which 
by  the  loss  of  the  elements  constituting  a  molecule  of  carbon  dioxide 
becomes  acetaldehyde  or  acetic  aldehyde,  and  this  by  oxidation  acetic 
acid,  which  is  then  oxidized  to  carbon  dioxide  and  water.     Thus — 


<g 


H— C— OH 

I 
HO— C— H 

I 
H— G— OH 

I 
H— C— OH 

I 
CH2OH 

(i-dextrose. 

COOH 

CO       -  CO2 

I 
CH3 

Pyruvic  acid. 


[\H 
H— C— OH 

I 
CHgOH 

p/O 
|\H 

H— C— OH 


CH2OH 

2  molecules 
glyceric  aldehyde. 

r^O 
^\H 


\ 


y" 


COOH 

I 
H— C— OH    -Ho 

I 
CH, 


<f-lactic  acid. 


COOH 


-> 


+  0 


+  4O 


CH3 

Acetaldehyde. 


CH3 

Acetic  acid. 


2CO3 

2H2O 

Carbon  dioxide 
and  w.iter. 


It  has  been  shown  that  acetaldehyde  and  carbon  dioxide  are  formed 
from  pyruvic  acid  by  the  action  of  a  ferment  contained  in  yeast,  and 
there  is  some  evidence  that  a  similar  transformation  may  occur  in  the 
liver. 

It  is  to  be  particularly  remarked  that  according  to  this  scheme 
the  whole  of  the  dextrose  molecule  is  still  represented  in  the  lactic 
acid  formed  from  it.  Up  to  this  stage  no  part  of  the  molecule  has 
been  burnt.  Nearly  the  whole  of  the  chemical  energy — ie.,  all  but 
about  3  per  cent,  of  it — is  still  available.  For  a  gramme  of  lactic 
acid  yields  3,661,  and  a  gramme  of  dextrose  3,762,  small  calories  on 
complete  combustion.  The  intermediate  products  of  the  decom- 
position may  therefore  be  transported  from  the  place  of  origin  and 
utilized  elsewhere  with  scarcely  any  loss  of  energy.  Further,  it  is 
indicated  in  the  scheme  that  the  degradation  process  is  not  merely 
a  series  of  cleavages  and  oxidations,  but  that  these  may  be  inter- 
spersed with  stages  of  reduction.  It  is  also  clearly  suggested  that 
at  certain  points  the  metabolism  may  become  recessive  and  syn- 


METABOr.fSM  OF  CARBO.HY DP ATES  545 

theses  be  started,  which  may  go  far  to  retrace  the  steps  of  the  pre- 
ceding katabohsm  in  respect  to  a  portion  of  the  dextrose. 

Thus,  lactic  acid  can  be  retransformed  into  dextrose  (Mandel  and 
Lusk).  and  this,  of  course,  into  glycogen.  Pyruvic  acid  can  be 
changed  into  lactic  acid  by  reduction,  and  dextrose  can  in  this  way 
be  again  produced.  There  is  evidence  also  that  under  certain 
conditions  pvrmic  acid  can  yield  dextrose  in  the  organism  by  a 
cUffert-nt  reaction,  being  changed  into  acetaldehyde,  which  can 
tlien  undergo  transformations  leading  back  to  dextrose  (Ringer). 
The  formation  of  fat  from  sugar  may  also  start  from  some  of  the 
stages  displayed  in  the  scheme,  for  it  is  only  a  short  step  to  obtain 
by  the  reduction  of  glyceric  aldehyde  its  alcohol  glycerin.  And 
from  acetaldehyde  fatty  acids  can  be  derived. 

Not  only  does  lactic  acid  afford  a  point  of  contact  between  the 
metabolism  of  carbo-hydrates  and  that  of  fats — a  junction,  so  to 
speak,  where  these  two  great  metabolic  currents  cross  each  other, 
and  where  material  originating  in  the  one  may  be  shunted  into  the 
other- — but  it  also  affords  a  point  of  junction  and  interchange  with 
the  current  of  protein  metabolism.  For  example,  the  amino-acid, 
alanin,  yields  as  a  decomposition  product  a  compound  called 
methylglyoxal  (CH3.CO.CHO),  a  ketonic  aldehyde,  which  by  the 
assumption  of  a  molecule  of  water  can  be  changed  into  lactic  acid. 
It  may  also  be  one  of  the  intermediate  stages  in  the  decomposition 
of  dextrose  as  a  precursor  of  lactic  acid,  and  one  of  the  ways  in 
which  the  conversion  of  amino-acids  into  dextrose  is  accomplished 
may  be  through  this  link.  The  presence  of  a  ferment  glyoxalase, 
or  probably  more  than  one  ferment  which  rapidly  changes  methyl- 
glyoxal into  lactic  acid,  has  been  demonstrated  in  tissue  extracts 
and  in  leucocytes.  The  same  change  is  effected  when  blood  con- 
taining methylglyoxal  is  perfused  through  an  excised  surviving 
liver.  The  reaction  can  be  reversed  for  methylglyoxal  like  lactic 
acid  when  given  to  an  animal  rendered  diabetic  by  phlorhizin  can  be 
shown  to  yield  dextrose,  possibly  being  first  converted  into  glyceric 
aldehyde.  The  conversion  of  methylglyoxal  into  lactic  acid  is  also 
a  reversible  reaction,  for  in  vitro,  at  any  rate,  lactic  acid  readily 
yields  methylglyoxal  (Dakin). 

Pyruvic  acid  is  another  possible  link.  As  has  just  been  mentioned, 
it  probably  forms  a  stage  in  the  decomposition  of  dextrose,  and  has,  in 
addition,  chemical  relations  on  the  one  hand  to  certain  of  the  amino- 
acids,  especially  to  alanin,  and  on  the  other  to  glycerin  and  even  to 
fatty  acids.     Thus — 


CH, 

1     ^ 

CH, 

1    ^ 

CH2.OH 

CH, 

1     ' 

CH.NHo  +  O 

1            " 

=  CO  4-NH3 

CH.OH+2O 

=  CO  +  2H 

1 

COOH 

Alanin  (a-amino-pro- 
pionic  acid. 

COOH 

Pyruvic  acid. 

CHg.OH 

Glycerin. 

COOH 

Pyruvic  acid. 

35 


5j6  METABOLfSM,   Nl'TRfTlOS  AXD  DIETETICS 

The  following  scheme,  doubtless  incomplete,  illustrates  a  probable 
chemical  sequence  through  which  the  interconversion  of  alanin,  lactic 
acid,  methylglyoxal  and  dextrose  may  be  brought  about  by  reactions 
only  involving  the  addition  or  removal  of  water  or  ammonia  (Dakin) : 

Dextrose 

i! 

Lactic  acid        ZH        Methylglyoxal  Z^  Alanin 

(CH3.CHOH.COOH)         (CHg.CO.CHO)  (CH3CH.NHj.COOH) 

Since  pyruvic  acid  can  be  reduced  to  lactic  acid,  any  reaction  in 
which  it  plays  a  part  in  the  intermediary  metabolism  of  carbohydrates 
or  proteins  can  also  be  fitted  into  the  scheme. 

The  more  completely  the  various  steps  in  the  metabolism  of  the 
three  great  groups  of  food  substances  are  unveiled,  the  more 
clearly  does  it  appear  that,  far  from  being  independent  circuits, 
the  three  currents  are  constantly  exchanging  materials  with  each 
other. 

It  is  to  be  supposed  that  in  many  of  these  transformations 
enzvmes  are  concerned,  although  comparatively  little  is  definitely 
known  as  to  this.  Normal  blood  itself  has  been  credited  \vith  a 
ferment  which  has  the  power  of  destroying  sugar  (glycolysis). 
But  with  rigid  aseptic  precautions  the  loss  of  sugar,  even  in  several 
hours,  is  small,  and  it  is  doubtful  whether  such  a  ferment  exists. 
Even  under  the  most  favourable  circumstances  the  quantity  of 
dextrose  which  blood  can  destroy  is  so  small  a  fraction  of  that  which 
disappears  in  the  same  time  in  the  body,  that  it  is  probably  of  no 
importance  in  carbo-hydrate  metabolism  (Macleod).  On  the 
other  hand,  Cohnheim  stated  that  while  no  glycolytic  ferment  can 
be  demonstrated  in  the  pancreas,  and  only  an  exceedingly'  weak 
glycolytic  action  in  muscular  tissue  (Brunton),  by  combining  ex- 
tracts of  pancreas  and  extracts  of  muscles,  distinct  glycolysis,  due 
to  a  ferment  action,  could  be  produced.  He  suggested  that  the 
glycolytic  ferment  is  activated  by  another  substance,  as  trypsinogen 
is  activated  by  enterokinase  (p.  372).  This  announcement  aroused 
great  interest,  since  it  is  known  that  the  pancreas  is  intimately 
concerned  in  the  metabolism  of  sugar.  That  sugar  disappears 
under  the  conditions  of  Cohnheim's  experiments  has  been  confirmed 
by  a  number  of  observers.  But  his  interpretation  of  his  results  lias 
not  been  generally  accepted.  According  to  Levene  and  Meyer, 
the  dextrose,  far  from  being  burnt,  seems  to  be  condensed  to  a  poly- 
saccharide, and  can  be  recovered  by  hydrolysing  this  compound 
when  the  mixture  is  acted  on  by  dilute  acid.  The  action  of  the 
pancreas- muscle  mixture  is,  therefore,  not  a  true  glycolysis.  In- 
deed, of  all  the  tissues  investigated  by  Levene,  leucoc^'tes  alone  can 
be  credited  with  a  real  glycolytic  action.  Excision  of  the  pancreas 
in  dogs  causes  permanent  glycosiuria  (pancreatic  diabetes)  (v.  Mering 
and  Minkowsla),  which  is  prevented  if  a  portion  of  the  pancreas  be 


METABOLISM  OF  CARBO-HYDRATES— GLYCOSl^RTAS        547 

loft  (p.  636).  Diabetes  in  man  is  known  to  be  frequently  associated 
with  pancreatic  lesions.  Although  much  still  remains  obscure,  the 
study  of  this  pathological  form  of  glycosuria  and  of  the  experimental 
glycosurias  has  thrown  light  upon  the  normal  metabolism  of  carbo- 
hydrates and  upon  those  regulative  mechanisms  whose  breakdown 
is  responsible  for  the  excretion  of  sugar.  It  will  be  best  to  discuss 
the  experimental  glycosurias  first,  and  to  begin  with  the  form  which 
probably  is  better  understood  than  any  other,  the  so-called  punc- 
ture glycosuria. 

Puncture  Glycosuria — Sugar-Regulating  Mechanism. — An  arti- 
ficial and  temporary  glycosuria,  in  which  the  sugar  in  the  urine  un- 
doubtedly arises  from  the  hepatic  glycogen,  can  be  caused  by  punc- 
turing the  medulla  oblongata  in  a  rabbit — for  example,  at  a  lev^el 
between  the  origins  of  the  auditory  nerves  and  the  vagi.  It  is  stated 
that  a  puncture  of  the  thalamencephalon,  or  'tween-brain  (p.  850), 
produces  the  same  effect.  If  the  animal  has  been  previously  fed  with 
a  diet  rich  in  carbo-hydrates — that  is,  if  it  has  been  put  under  con- 
ditions in  which  the  liver  contains  much  glycogen — the  quantity  of 
sugar  excreted  by  the  kidneys  mil  be  large.  The  immediate  cause 
of  the  glycosuria  is  an  increase  in  the  sugar  content  of  the  blood 
(hyperglycaemia),  an  increase  which  is  most  pronounced  in  the  blood 
of  the  hepatic  vein.  If,  on  the  other  hand,  the  animal  has  been 
starved  before  the  operation,  so  that  the  liver  is  free,  or  almost  free, 
from  glycogen,  the  puncture  will  cause  little  or  no  sugar  to  appear 
in  the  urine,  and  the  proportion  of  sugar  in  the  blood  will  remain 
normal.  That  nervous  influences  are  in  some  way  involved  in  the 
mobilization  of  the  glycogen  reserve  of  the  liver  is  shown  by  the 
absence  of  glycosuria  if  the  splanchnic  nerves,  or  the  spinal  cord 
above  the  third  or  fourth  dorsal  vertebra,  be  cut  before  the  puncture 
is  made.  But  sometimes  these  operations  are  themselves  followed 
by  temporary  glycosuria,  due,  it  is  believed,  to  irritation  of  the 
same  eferent  nervous  path  whose  elimination  when  the  splanchnics 
are  divided  prevents  the  glycosuria.  The  simplest  explanation  of 
the  phenomena  is  that  a  '  sugar  centre  ' — that  is  to  say,  a  centre 
which  has  the  important  ofhce  of  regulating  the  sugar  content  of  the 
blood  by  governing  the  rate  at  which  glycogen  is  built  up  and  de- 
composed in  the  liver,  as  the  salivary  centre  regulates  the  rate  at 
which  the  constituents  of  saliva  are  formed  and  discharged — has 
been  injured  or  irritated  by  the  puncture.  If  a  nervous  centre  does 
in  fact  preside  over  this  internal  secretion  of  the  liver,  it  will,  of 
course,  be  connected  with  efferent  and  afferent  nerves.  The  former, 
as  defined  by  the  experiments  alluded  to,  seem  to  be  confined  to 
the  splanchnic  nerves;  the  latter  are  believed  to  run  especially, 
though  not  exclusively,  in  the  vagus.  Section  of  the  vagi  has  no 
effect  either  in  causing  glycosuria  of  itself  or  in  preventing  the 
'  puncture  '  glycosuria,  but  stimulation  of  the  central  ends  of  these 


54'^  METABOLISM.   NUTRITION  AND  DIETETICS 

and  of  otluT  afferent  nerves  may  cause  sugar  to  appear  in  the 
urine,  altfiough  not,  it  is  said,  if  precautions  are  taken  to  prevent 
any  degree  of  asphyxia.  Asphyxia  produces  an  increase  in  the 
sugar  content  of  the  blood,  an  increase  in  the  flow  of  urine  and 
glycosuria. 

It  has  usually  been  assumed  that  this  action  of  asphyxia  is  due  to 
the  effect  upon  the  centre  of  blood  over-rich  in  carbon  dioxide  (and 
other  metabolic  products)  or  impoverished  as  regards  oxygen.  But 
there  is  some  evidence  that  the  altered  blood  may  also  affect  the 
liver-cells  directly,  or,  what  comes  to  the  same  thing  in  the  long-run, 
that  interference  with  the  internal  respiration  of  the  hepatic  tissue, 
operating,  it  may  be,  through  an  increase  in  the  concentration  of  the 
hydrogen  ions,  upsets  the  equilibrium  of  those  intracellular  reactions 
by  which  glycogen  is  formed  from  dextrose  and  dextrose  from 
glycogen.  In  like  manner  it  may  be  supposed  that  under  normal 
conditions  the  rate  of  transformation  of  the  hepatic  glycogen  into 
dextrose  is  adjusted  to  the  dextrose  content  of  the  blood,  not  only 
by  reflex  nervous  impulses  passing  through  the  sugar-regulating 
centre,  but  also  by  the  direct  influence  of  the  dextrose  itself  circu- 
lating in  the  blood,  upon  whose  concentration  the  reaction  of  the 
centre  on  the  one  hand  and  of  the  liver-cells  on  the  other  may  in 
part  depend.  So  that  when  the  proportion  of  sugar  in  the  blood 
tends  to  sink  we  may  perhaps  picture  the  centre  as  sending  impulses 
to  the  liver  which  increase  the  rate  at  which  the  glycogen  is  hydro- 
lysed;  and  when  the  proportion  tends  to  rise,  we  may  think  of  it  as 
sending  impulses  which  inhibit  the  hydrolysis,  both  effects  being 
accentuated  by  the  direct  influence  of  the  changes  of  concen- 
tration on  the  hepatic  cells.  Whatever  the  mechanism  may  be 
through  which  the  puncture  hastens  the  transformation  of  glycogen 
into  dextrose  in  the  liver,  there  is  no  evidence  that  the  amount  of  i  lie 
enzyme  which  hydrolyses  the  glj^cogen  is  increased.  Whether  the 
action  of  the  enzyme  is  favoured  in  some  other  way — e.g.,  by  the 
production  of  a  co-ferment  or  by  some  change  in  the  condition  of 
the  glycogen  which  renders  it  more  open  to  attack — is  unknown. 

Certain  facts  have  recently  been  brought  forward  which  go  to 
show  that  the  action  of  the  splanchnic  fibres  on  the  liver  is  not 
a  direct  action,  but  that  in  some  way  or  other  tlie  concomitant 
activity  of  the  adrenal  glands  is  essential.  For  if  the  adrenals  have 
been  previously  extirpated,  the  puncture  does  not  cause  glycosuria. 
It  was  at  first  thought  that  the  reason  for  this  was  that  the  removal 
of  the  adrenals  is  itself  followed  by  the  disappearance  of  glycogen 
from  the  liver,  and,  as  has  been  pointed  out,  the  presence  of  glycogen 
in  the  liver  is  essential  to  the  success  of  the  puncture  experiment. 
The  matter,  however,  is  not  so  simple.  For  although  in  certain 
animals — e.g.,  the  dog — the  liver  does  lose  all  its  glycogen  when  the 
adrenals  have  been  taken  away,  this  is  not  the  case  in  the  rabbit. 


METABOLISM    OF  CARBO-HYDRATES-GLYCOSURIAS       549 

and  yet  in  the  rabbit  also  the  urine  remains  free  from  sugar  after 
puncture  in  the  absence  of  the  adrenal  glands.     In  some  way  or 
other,  then,  the  adrenals  do  intervene  in  the  production  of  puncture 
glycosuria.     The  observation,  which  is  easily  confiimed,  that  the 
injection  of  adrenalin  (or  epinephrin)  (p.  550)  under  the  skin  or  into 
the  blood,  or  into  one  of  the  serous  sacs,  does  cause  a  pronounced 
increase  in  the  sugar  content  of  the  blood,  and  the  appearance  of 
dextrose  in  the  urine,  seemed  at  first  to  supply  the  missing  link   n 
the  chain  of  evidence.     What  could  be  simpler  than  the  assumpt:  n 
that  the  splanchnic  fibres  stimulated  in  the  puncture  experimi  nt 
were  fibres  going  not  to  the  liver,  but  to  the  adrenals,  which  ocra- 
sioned  an  outpouring  of  adrenalin  into  the  blood,  and  that  puncture 
glycosuria  was  therefore  merely  a  particular  case  of  adrenalin  glvco- 
suria  ?     It  is  known  that  excitation  of  the  splanchnic  nerves  cau  es 
the  passage  of  adrenalin  into  the  blood  of  the  adrenal  veins  (p  661). 
It  is  known  that  puncture  of  the  medulla  oblongata  diminishes  tlie 
epinephrin  content  of  the  adrenal  glands.     The  argument  seened 
straightforward,  and  the  adrenal  hypothesis  of  puncture  glycos^:ria 
triumphant.     As  soon,  however,  as  the  matter  was  put  to  the  test 
of  quantitative  experiments,  the  hypothesis  began  to  crumble.     It 
was  shown,  for  example,  that  during  a  stimulation  of  the  splanchnic 
nerves  sufficient  to  cause  a  decided  increase  in  the  dextrose  content 
of  the  blood,  a  quantity  of  adrenalin  was  given  off  to  the  adrenal 
veins,  which,  when  mingled  with  the  rest  of  the  blood  on  its  way 
to  the  liver,  could  not  possibly  amount  to  more  than  one  in  a  hundred 
million  parts  of  blood,  a  concentration  in  which  adrenalin,  when 
introduced  artificiall}'  into  the  blood-stream,  produces  no  glj-coiU-ia 
whate\'er.     Still  more  significant  is  the  fact  that,  after  destroying  the 
hepatic  plexus,  stimulation  of  the  splanchnic  nerves  causes  no  in- 
crease in  the  blood-sugar  in  spite  of  the  increased  output  of  adrenalin 
by  the  way  of  the  adrenal  veins.     On  the  other  hand,  excitation 
of  the  hepatic  plexus  causes  hyperglycaemia  (Macleod  and  Pearce). 
It  is  not,  then,  a  direct  action  on  the  liver  of  epinephrin  secreted  in 
response  to  stimulation  of  splanchnic  fibres  supplying  the  adrenal 
glands  which  is  responsible  for  the  increase  in  the  dextrose  content 
of  the  blood.     The  adrenals,  however,  pla}'  some  part.     For  in  their 
absence  stimulation  of  the  hepatic  plexus  is  not  followed  by  hyper- 
glycaemia.    But  whether  this  is  due  to  general  derangement  of  the 
normal  carbo-hydrate  metabolism  in  their  absence,  or  to  the  loss  of 
some  special  influence  on  the  liver,  without  which  stimulation  of  the 
hepatic  plexus  is  ineffective,  is  unknown. 

Although  several  of  the  operations  which  lead  to  temporary 
glycosuria  undoubtedly  bring  about  changes  in  the  hepatic  circula- 
tion, it  is  as  yet  impossible  to  say  whether  vaso-motor  effects  con- 
tribute essentially  to  the  result,  or  whether  it  is  due  entirely  to 
nervous  stimulation  of  the  liver-cells,  or  to  withdiawal  of  such 


550  METABOLISM,  NUTRITION  AND  DIETETICS 

stimulation  or  control  (sec  also  p.  509).  There  is  some  c\adence 
that  excitation  of  the  uncut  great  splanchnic  nerve  (on  the  left  side) 
in  dogs  may  cause  hyperglycaemia,  diuresis,  and  glycosuria,  even 
imder  conditions  in  which  as  far  as  possible  circulatory  effects  are 
eliminated.  Contrariwise,  when  in  the  puncture  experiment  on  an 
unnarcotized  animal  the  small  instrument  does  not  wound  the 
medulla  oblongata  in  the  right  place,  a  rise  of  blood-pressure  due 
to  excitation  of  the  vaso-motor  centre  may  occur  without  any 
glycosuria.  But  absolute  proof  of  the  existence  of  glycogenolytic 
nerve  fibres  going  to  the  liver — that  is,  fibres  whose  stimulation 
accelerates  the  hydrolysis  of  glycogen  into  dextrose  (Macleod) — has 
not  yet  been  brought  forward. 

Adrenalin  Glycosuria.— In  adrenalin  glycosuria  the  sugar-content 
of  the  blood  is  increased.  A  given  quantity  of  adrenalin  introduced 
subcutancously  produces  a  more  marked  hyperglycemia  and 
glycosuria  than  the  same  amount  injected  into  a  vein  or  into  muscle. 
The  best  evidence  is  that  the  glycosuria  is  produced  by  some  action 
on  the  liver,  possibly  through  the  excitation  of  sympathetic  fibres 
controlling  the  production  of  dextrose  from  glycogen  (Underbill  and 
Closson),  or  by  a  direct  effect  on  the  hepatic  cells,  which  hastens  the 
normal  transformation  of  glycogen  into  dextrose,  or  hinders  the 
normal  transformation  of  dextrose  into  glycogen.  It  has  been 
stated  that  in  the  isolated  surviving  liver  of  the  frog  adrenalin  causes 
the  glycogen  to  be  rapidly  converted  into  dextrose.  While  this 
confirms  the  view  that  experimental  adrenalin  glycosuria  is  due  to 
an  action  on  the  liver  which  increases  the  sugar-content  of  the  blood, 
it  docs  not  necessarily  show  that  the  action  is  exerted  directly  on 
the  hepatic  cells  without  the  intervention  of  nerve  fibres.  For  the 
sympathetic  nerve-endings  may  survive  a  considerable  time.  The 
theory  that  epinephrin  causes  glycosuria  by  inhibiting  the  internal 
secretion  of  the  pancreas,  and  that  the  condition  is  therefore  a  par- 
ticular variety  of  pancreatic  diabetes,  is  erroneous.  Adrenalin 
glycosuria  does  not  seem  to  be  in  any  way  related  to  true 
diabetes.  The  complete  metabolism  of  dextrose  is  not  interfered 
with.  Indeed,  a  much  larger  proportion  of  tlie  total  heat  produced 
comes  from  the  destruction  of  sugar  after  the  subcutaneous  injection 
of  epinephrin  into  dogs  than  in  the  normal  animals  (Lusk  and  Riche). 
If  in  spite  of  this  glycosuria  ensues,  it  is  only  because  the  carbo- 
hydrate reserve  of  the  body  is  mobilized  so  rapidly  that  it  cannot 
possibly  be  all  consumed.  Nor  does  epinephrin  cause  any  increased 
production  of  sugar  from  protein  or  from  fat.  For  in  dogs  rendered 
diabetic  by  phlorhizin  and  freed  from  glycogen  by  shivering,  injec- 
tion of  epinephrin  is  not  followed  by  an  increase  of  either  sugar  or 
nitrogen  in  the  urine  (Ringer).  After  repeated  injections  of  adren- 
alin, a  tolerance  for  it  is  established,  and  glycosuria  is  no  longer 
caused. 


MET.inOlJSM  OF  CARIiO-ini)jrt  IliS  -Cl.yCOSIJ^IAS       551 

Fhlorhizin  Glycosuria,  produced  by  subcutaneous  injection  of  the 
glucoside  phlorhizin,  agrees  vvitli  pancreatic,  but  differs  from  punc- 
ture diabetes  in  this,  that  it  can  be  produced  in  an  animal  free 
from  glycogen,  and  is  accompanied  by  extensive  destruction  of 
proteins.  It  differs  from  other  forms  of  diabetes  in  being  associated, 
not  with  an  increase,  but  with  a  diminution,  in  the  sugar  of  the  blood. 
This  is  best  explained  by  supposing  that  the  phlorhizin  acts  on  the 
kidney  in  such  a  way  as  to  increase  the  permeability  of  the  glomeru- 
lar epithelium  for  sugar,  or  (in  terms  of  the  secretion  theory  of  urine 
formation)  in  such  a  way  as  to  increase  its  sensitiveness  to  the 
stimulus  of  sugar  circulating  in  the  blood.  The  sugar  is  therefore 
rapidly  swept  out  of  the  circulation,  and  this  leads  secondarily  to 
an  increased  production  of  sugar  to  make  good  the  loss.  In  addi- 
tion, within  certain  limits  there  is  a  total  inability  on  the  part  of 
the  body  to  consume  dextrose. 

After  the  preliminary  sweeping  out  of  the  sugar  already  in  the 
bod}^  a  definite  ratio  is  established  between  the  dextrose  and  the 
nitrogen  eliminated  in  the  urine  (dextrose  :  nitrogen  :  :  3-6or  37  :  i). 
The  sugar  at  this  stage  is  produced  entirely  from  proteins,  and  not 
at  all  from  fat.  It  is  a  fact  of  considerable  interest  that,  if  small 
quantities  of  dextrose  are  now  given,  the  amount  of  protein  de- 
stroj'ed  is  reduced  to  some  extent,  although  all  of  the  dextrose  is 
excreted,  and  none  of  it  is  burnt  (Ringer).  This  supports  the 
hypothesis  of  Landergren  that  in  starvation  some  of  the  protein  is 
metabolized  for  the  formation  of  the  indispensable  dextrose,  and 
that  this  fraction  can  be  '  spared  '  by  carbohydrate,  though  not  by 
fat.  The  protein  metabolized  is  so  much  increased  under  the 
influence  of  phlorhizin  that  it  exceeds  the  starvation  requirement 
by  a  greater  amount  than  in  pancreatic  diabetes,  perhaps  because 
the  diminished  content  of  sugar  in  the  blood  constitutes  a  more 
insistent  call  upon  the  proteins  to  produce  sugar.  In  pancreatic 
diabetes,  where  hyperglycaemia  exists,  there  can  at  least  be  no 
reason  for  the  formation  of  sugar  from  protein  for  the  maintenance 
of  the  normal  sugar-content  of  the  blood,  and  it  is  interesting  that 
in  this  condition  the  giving  of  dextrose  does  not  seem  to  spare  any 
protein  (p.  606).  The  degree  of  intolerance  for  carbo-hydrates  in 
pathological  diabetes  may  be  arrived  at  by  putting  the  patient  on 
a  diet  of  protein  and  fat  (rich  cream,  meat,  butter,  and  eggs),  and 
determining  the  ratio  of  dextrose  to  nitrogen  excreted.  If  it  is 
3-6  or  37:  I,  intolerance  is  complete,  none  of  the  dextrose  produced 
from  protein  being  burned  (Lusk  and  Mandel). 

Glycosuria  can  be  caused  in  many  other  ways  than  those  already 
mentioned.  Sometimes  the  action  seems  to  be  a  direct  one  on  the 
sugar-regulating  centre — e.g.,  in  concussion  of  the  brain,  occlusion 
and  subsequent  release  of  the  arteries  supplying  the  brain  and 
cervical  cord,  and  acute  haemorrhage.     Carbon  monoxide  has  a 


552  MI^T.IBOLISM.   SLTh'lTIOX  AXl)  DIETETICS 

similar  action  owing  to  the  dcticicncy  of  oxygen  occasioned  by  it. 
Many  drugs  also  cause  glycosuria,  including  curara,  morphine, 
strychnine,  phosphorus,  chloroform,  ether,  and  other  substances, 
some  of  which  may  act  on  the  '  sugar  centre,'  although  others — e.g., 
phosphorus  and  chloroform — are  poisons  which  can  affect  the  liver 
directly.  It  is  probable  that  some  of  the  experimental  hypcr- 
glycccmias  are  due  to  an  associated  acidosis.  For  when  the  hydrogen- 
ion  concentration  of  the  blood  is  increased  the  transformation  of 
glycogen  into  dextrose  in  the  liver  is  accelerated.  The  adminis- 
tration of  alkali  is  said  to  have  a  beneficial  influence  upon  the 
oxidation  of  dextrose  in  dogs  after  total  or  partial  extirpation  of  the 
pancreas  (Murlin  and  Kramer).  Injection  of  water  or  physiological 
salt  solution  into  the  bile-ducts,  or  into  the  mesenteric  veins,  or  of 
salt  solution  in  considerable  amount  into  the  general  circulation, 
is  followed  by  glycosuria  (Fischer,  etc.).  It  is  a  mistake  to  apply 
the  term  diabetes  to  most  of  the  forms  of  artificial  hyperglycremia 
and  glvcosuria.  The  condition  produced  by  removal  of  the  pan- 
creas, which  will  be  returned  to  in  Chapter  XL,  is,  however,  a  true 
diabetes,  a  derangement  of  metabolism  of  the  sam**  general  nature 
as  that  which  underUes  human  diabetes. 

Diabetes  Mellitus. — In  the  natural  diabetes  of  man,  as  in  all 
the  forms  of  glycosuria  mentioned,  with  the  exception  of  that  pro- 
duced bv  phloriiizin,  the  immediate  cause  of  the  ghxosuria  is  the  in- 
crease of  sugar  in  the  blood.  Instead  of  the  i  part  per  1,000,  or  a 
little  more  or  less,  which  constitutes  the  normal  proportion  in  a 
healthy  man,  in  diabetes  3  or  4  parts,  and  in  exceptional  cases  even  7 
to  10  parts  per  i.ooo  may  be  present.  The  riddle  of  diabetes  is  the 
explanation  of  this  persistent  hyperglycsemia.  Innumerable  hypo- 
theses have  been  framed  to  account  for  this,  but  on  the  whole 
three  possibilities  have  been  emphasized:  (i)  That  the  power  of 
temporarily  storing  carbohydrates  is  deranged;  (2)  that  the  power 
of  the  tissues  to  utilize  carbo-hydrates  [i.e.,  eventually  dextrose) 
is  diminished  or  abolished;  (3)  that  too  much  sugar  is  produced  in 
the  body.  In  addition,  some  writers  have  postulated  a  fourth 
factor  to  explain  certain  cases  (of  so-called  '  renal  diabetes  ') — to  wit, 
an  increase  in  the  permeability  of  the  kidneys  for  sugar,  as  in 
phlorhizin  glycosuria.  Lest  the  student  should  be  bewildered 
amongst  all  these  theories,  he  should  take  note  that  while  the  second 
factor  is  now  recognized  as  the  essential  one,  there  is  some  reason 
to  believe  that  diabetes  mellitus  is  not  in  every  case  a  single  patho- 
logical condition,  but  may  comprise  a  group  of  such  conditions. 
Some  cases  mav  therefore  present  a  picture  conforming  closely  to 
one  or  to  another  of  the  experimental  glycosurias,  but  others  a 
picture  compounded  of  features  characteristic  of  two  or  of  several 
of  these  experimental  conditions. 


MI'TABOl.lSM  OF  CA  h'BO-HY  Dh'AI  l-S     CLYCOSU /^  I  A  S       553 

It  is  possible  that  in  some  cases  the  sugar  coming  from  the  aH- 
mentary  canal  passes  entirely  or  in  too  large  amount  through  tl:c 
liver,  owing  to  a  deficiency  in  its  power  of  forming  glycogen.  But 
although  in  certain  cases  of  diabetes  specimens  of  the  hepatic  cells, 
obtained  by  plunging  a  trocar  into  the  liver,  have  been  found  free 
from  glycogen,  in  others  gtycogen  has  been  present.  The  muscles 
also  are  usually  stated  to  be  much  poorer  in  glycogen  than  normal 
muscles,  but  this  might  just  as  well  be  the  case  because  glycogen 
was  being  transformed  into  sugar  with  abnormal  ease  as  because 
there  was  interference  with  glycogen  formation.  Indeed,  it  is  said 
that  in  the  heart  muscle  of  depancreatizcd  dogs  there  is  more  glycc- 
gcn  than  in  normal  heart  muscle.  It  must  be  carefully  remembered 
that  the  amount  of  glycogen  present  in  a  tissue  gives  no  information 
as  to  the  rate  at  which  it  is  being  formed  or  decomposed.  And  if 
the  cause  of  the  supposed  defect  in  glycogen-forming  power  be  the 
absence  of  a  glycogen-forming  ferment,  or  its  production  in  too  small 
an  amount,  the  same  circumstance  may  occasion  a  too  tardy 
transformation  into  sugar  of  whatever  glycogen  happens  to  be 
present.  In  this  case  the  sugar-regulating  function  of  the  glyco- 
gen store  would  be  equally  lost,  whether  the  storehouses  were 
permanently  filled  with  long-formed  glycogen  or  only  half-filled  or 
empty. 

In  addition  to  an  interference  with  the  due  and  regulated  storage 
of  the  surplus  sugar  as  glycogen,  it  has  usually  been  thought  neces- 
sary for  a  rational  explanation  of  the  facts  of  diabetes,  to  assume 
that  from  some  change  in  the  tissues  sugar  has  ceased  to  be  a  food 
for  them,  or  is  used  up  in  smaller  amount  than  in  the  healthy  body. 
More  and  more  the  evidence  points  to  this  as  the  fundamental 
change  both  in  the  human  disease  and  in  experimental  pancreatic 
diabetes. 

Why  the  tissues  cannot  decompose  and  utilize  dextrose  as  they 
normally  do,  if  it  be  really  the  case  that  they  fail  in  this  regard,  is  a 
question  of  great  interest,  but  as  yet  no  satisfactory  answer  can 
be  given.  It  appears  probable  that  the  failure  occurs  at  one  or  more 
of  the  earliest  stages  in  the  intermediate  metabohsm  of  carbo- 
hydrates (p.  542)  or  in  the  preliminary  processes,  whatever  they 
may  be,  which,  without  profoundly  altering  the  dextrose  molecule, 
prepare  it  for  the  series  of  decompositions,  in  the  course  of  which  it 
eventually  parts  with  all  its  chemical  energy.  For  it  has  been 
shown  that  many  of  the  products  of  the  cleavage  or  oxidation  of 
sugar,  even  those  in  which  the  decomposition  has  proceeded  but  a 
httle  way — e.g.,  glyconic  and  glycuronic  acids  (p.  543) — are  com- 
pletely utilized  by  the  tissues  of  diabetics  and  of  depancreatizcd 
dogs.  And  the  derangement  in  the  normal  sequence  of  events,  of 
whatever  nature  it  may  be,  is  not  so  deep-reaching  as  to  prevent 


554  METAIiOLIUM.   \UTRlTION  A\D   DIETETICS 

the  retracing  of  the  chcinical  steps  by  which  sugar  is  synthesized 
from  such  derivatives  of  the  proteins  as  amino-acids  or  tlieir  further 
degradation  prochicts.  As  to  the  actual  cause  of  the  alleged  in- 
capacity of  the  tissues  to  consume  dextrose,  the  change  has  by  some 
been  supposed  to  be  the  loss  or  diminution  of  a  glycolytic  ferment 
or  a  substance  necessary  for  the  activation  of  such  a  ferment.  And 
although  the  sugar-destroying  power  of  blood  from  diabetic  patients, 
or  from  animals  in  which  glycosuria  has  been  caused  by  phlorhizin, 
is  not  at  all  inferior  to  that  of  healthy  blood,  it  has  been  maintained 
that  the  intracellular  glycolytic  ferments,  if  such  really  exist,  are 
much  less  active,  especially  in  the  more  severe  forms  of  the  disease, 
which  conform  so  closely  in  their  clinical  manifestations  to  the  pic- 
ture presented  by  the  depancreatized  animal.  Nevertheless,  up  to 
the  present  all  attempts  to  satisfactorily  demonstrate  for  isolated 
tissues  a  loss  or  even  a  diminution  in  the  capacity  to  utilize  dextrose 
have  broken  down.  In  eviscerated  dogs,  for  example — that  is,  in 
preparations  consisting  mainly  of  skeletal  muscle — it  has  been  found 
impossible  to  make  out  any  deficiency  as  compared  with  normal 
animals  in  the  amount  of  dextrose  disappearing  in  a  given  time 
from  the  blood,  even  when  the  animals  have  been  deprived  of  the 
pancreas  as  long  as  a  week  before  the  experiment,  and  therefore 
exhibit  the  condition  of  pancreatic  diabetes  in  full  intensity 
{Macleod  and  Pearce).  This  conclusion  has  been  confirmed  for  the 
isolated  heart-lung  preparation. 

As  regards  the  hypothesis  that  an  increased  production  of  sugar 
from  proteins,  or  it  may  be  from  fat,  is  the  essential  proximate  cause 
of  the  hyperglycaemia  and  the  glycosuria,  there  is  no  good  evidence 
that  this  factor,  acting  by  itself  in  the  absence  of  a  derangement  of 
the  regulative  influence  of  the  glycogen  store,  and  in  the  absence  of 
a  derangement  of  the  normal  katabolism  of  dextrose,  is  ever  respon- 
sible for  pathological  diabetes.  But  a  secondary  overproduction 
of  sugar  unquestionably  occurs  in  many  cases.  The  tissues,  bathed 
as  they  are  in  liquids  rich  in  dextrose,  are  nevertheless  starving  for 
sugar,^if  they  cannot  use  what  is  offered  to  them,  and  the  body 
labours  to  avert  the  famine  by  increasing  its  production  of  sugar, 
the  sugar- forming  tissues  being  stimulated  to  their  task  either 
through  nervous  influences  or  by  chemical  messengers  circulating 
in  the  blood. 

In  depancreatized  dogs,  and  in  dogs  under  the  influence 
of  phlorhizin,  glycerin,  given  by  the  mouth,  causes  an  increase  in 
the  excretion  of  sugar  up  to  two  or  three  times  the  original  amount. 
The  giving  of  fat  does  not  increase  the  amount  of  sugar  excreted, 
which,  however,  is  increased  by  such  substances  as  egg-yolk,  which 
contain  lecithin.  These  should  accordingly  be  avoided  in  cases  in 
which  a  strictly  antidiabetic  diet  is  desired.  It  is  mm  h  more  ii  :- 
portant  to  exclude  carbo-hydrates  largely  or  entirely  from  the  food. 


METABOLISM  01-   CARbOllV URATES— GLYCOSVRl AS       555 

although  (latmeal  and  potatoes  arc  said  to  occupy  an  exceptional 
position,  and  have  even  been  recommended  as  beneficial.  Calcium 
chloride  has  been  stated  to  diminish  the  sugar  excretion  in  diabetes 
(Boigev).  and  it  has  a  similar  effect  in  certain  of  the  artificial  glyco- 
surias (Brown,  Fischer). 

In  manv  cases,  even  when  carbo-hydrates  are  completely,  or 
almost  completely,  omitted  from  the  food,  sugar,  derived  from  the 
breaking-down  of  proteins,  and  possibly  to  some  extent  from  fats, 
still  continues  to  be  excreted,  although  in  smaller  quantity.  Other 
products  formed  or  imperfectly  transformed  in  the  deranged  meta- 
bolism, cspeciallv  of  fats,  such  as  acetone,  aceto-acetic  acid,  and 
oxvbutyric  acid  (the  so-called  acetone  bodies),  may  also  appear  in  the 
urine  (ketonuria),  or,  accumulating  in  the  blood,  may,  by  uniting  with 
its  alkahes,  seriously  diminish  the  quantity  of  carbon  dioxide  which 
that  liquid  is  capable  of  carrying,  and  thus  lead  to  the  condition 
known  as  diabetic  coma.  The  small  amount  of  carbon  dioxide  in 
the  venous  blood  may  also  be  partly  due  to  the  hyperpnoea,  marked 
by  increased  depth  of  the  respirator}^  movements  produced  by 
stimulation  of  the  respiratory  centre  by  other  substances  than  carbon 
dioxide.  The  increased  ventilation  causes  a  fall  in  the  carbon 
dioxide  pressure  in  the  alveolar  air,  and  therefore  an  increased 
ehmination  of  that  gas  from  the  blood.  This  form  of  coma  appears 
to  be  really  in  part  an  acid-poisoning  comparable  to  the  condition 
produced  in  animals  by  doses  of  mineral  acids  too  large  to  be 
neutralized  by  the  ammonia  split  off  from  the  proteins.  The  ad- 
ministration of  very  large  doses  of  alkalies  (sodium  bicarbonate, 
for  instance,  to  the  amount  even  of  hundreds  of  grammes)  has 
been  recommended  for  the  treatment  of  this  serious  complication, 
and  in  some  cases  it  is  successful  in  staving  it  off  for  a  time.  Often, 
however,  in  spite  of  a  prolonged  course  of  treatment,  during  w-hich 
the  urine  has  continued  distinctly  alkaline,  fatal  coma  eventually 
occurs.  The  coma  then  is  not  merely  a  symptom  of  acidosis, 
but  is  also  due  to  the  specific  toxic  effects  of  the  acids  ev'en  when 
neutrahzed.  Other  toxic  products  may  also  be  formed  in  the 
deranged  metabolism.  The  appearance  of  the  acetone  bodies  in 
diabetes  presents  a  problem  which  cannot  be  said  to  have  been  as 
yet  completelv  solved.  Oxybutyric  acid,  from  which  aceto-acetic 
acid  and  acetone  are  easily  derived  (p.  567),  seems  to  be  one  of  the 
intermediate  steps  in  the  normal  metabohsm  of  fats.  But  whereas 
under  ordinary  circumstances  it  is  readily  oxidized  in  the  body,  in 
diabetes  the  power  of  the  tissues  to  burn  oxybutyric  acid  seems  to 
suffer  just  as  does  the  power  to  utihze  dextrose.  The  suggestion 
that  in  diabetes  the  abnormally  great  consumption  of  fat  entailed  by 
the  loss  of  availability  on  the  part  of  the  carbo-hydrates  causes  the 
intermediary  metabolism  of  fats  to  be  scamped,  as  it  were,  is  not 
satisfactory.     For  many  animals  and  some  races  of  men  dwelling 


356  METABOLISM.   NUTRITION  AND  DIETETICS 

in  cold  climates  consume  with  impunity  much  greater  quantities 
of  fat  than  any  diabetic  (*-ganism.* 

Section  II. — The  Metabolism  of  Fat. 
Chemistry  of  Fats. —  J'he  fats  are  compounds  (esters)  of  an  alcohol 
with  fatty  acids,  and  can  be  spUt,  with  assumption  of  water,  into  these 
constituents  by  the  action  of  acids  or  alkalies  or  of  enzymes  (lipases). 
In  the  majority  of  the  ordinary  fats,  and  in  all  those  wliich  are  of 
physiological  importance  (the  triglycerides),  the  alcohol  is  glycerin. 
The  fatty  acid  components  which  may  be  united  with  the  glycerin  are 
\cry  numerous,  and  the  physical  properties  of  the  different  fats — e.g., 
their  melting-points  and  solubilities — are  closely  n'latcd  to  the  physical 
jiropcrtics  of  the  corresponding  fatty  acids.  Thus  palmitic  and 
stearic  acids  are  solid  at  ordinary  temperatures,  and  so  are  palniitin 
and  stearin,  the  glycerin  esters  or  fats  formed  with  these  acids.  Oleic 
acid,  on  the  contrary,  is  fluid  at  the  ordinary  temperature,  and  the 
corresponding  fat,  olcin,  is  a  liquid  fat  or  oil.  On  the  chemical  side 
the  fatty  acids  can  be  distinguished  as  saturated  and  unsaturated. 
The  fatty  acids  of  the  series  CnHgre+i-COOH  are  saturated  acids. 
Where  n  is  o  we  have  formic  acid,  H.COOH;  where  n  is  i,  acetic  acid, 
CH3.COOH;  where  n  is  2,  propionic  acid,  CHg.CHj.COOH;  where 
n  is  3,  butyric  acid,  CH3.CH2CH2.COOH,  and  so  on,  each  acid  in  the 
series  differing  from  the  one  immediately  preceding  it  in  possessing  an 
additional  CHg  group.  In  the  case  of  the  higher  members  of  the  series 
these  carbon  chains  become  very  long.  In  palmitic  acid,  for  instance, 
CH3.(CH2)i4.COOH,  there  are  fourteen  CHj  groups,  and  in  stearic  acid, 

CH3.(CH,)ie.COOH,  sixteen.  Oleic  acid,  ^  ^Ji"/^  =  ^*\(CH  )  COOH, 
is  a  representative  of  a  series  of  unsaturated  fatty  acids  whose  general 
formula  is  C„H2n-iCOOH.  As  the  formula  of  oleic  acid  shows,  the 
unsaturated  fatty  acids  contain  in  their  molecule  two  carbon  atoms 
united  by  a  double  link,  and  one  of  these  valencies  can  be  occupied  by 
halogens  {e.g.,  chlorine)  or  by  oxygen.  Erucic  acid,  a  fatty  acid  occur- 
ring in  certain  vegetable  oils — for  example,  in  rape  oil — also  belongs  to 
this  series,  and  linolic  acid,  found  in  linseed  oil,  to  another  series  of 
unsaturated  fatty  acids.  Then  there  arc  the  so-called  oxyfatty  acids, 
which  in  their  turn  comprise  saturated  and  unsaturated  acids.  They 
differ  from  the  ordinary  fatty  acids  in  containing  one  or  more  OH 
groups.  Thus  a  dioxystearic  acid,  Ci7H33(OI-J)2.C"OOH,  in  which  two 
of  the  H  atoms  in  stearic  acid  are  replaced  by  OH.  is  found  in  castor-oil. 
It  is  clear,  from  the  great  variety  of  the  fatty  acids,  that  b}'  their  union 
with  glycerin  (with  loss  of  water)  a  very  large  number  of  different  fats 
can  be  formed.  Thus,  when  all  the  OH  groups  in  the  trivalcnt  alcohol  are 
replaced  by  palmitic  acid  we  have  tripalmitin ;  when  they  are  replaced 
by  stearic  acid,  tristearin ;  when  they  are  replaced  by  oleic  acid,  triolein  ; 
and  so  on .  As  a  group  such  fats  may  be  termed  homo-acid  fats,  since  all 
the  OH  groups  are  replaced  by  the  same  fatty  acid.     Thus — 

CH2.OH         Ci7H3,.COOH         CHa.O:OC.Ci7H3, 
CH.OH    +   C17H35.COOH    =    CH.O.OC.C17H35-1-3H2O 
CHjOH         Ci7H36.COOH         CHa.O.OC.Ci7H36 

Glycerin.  3  molecules  stearic  acid.  Tristearin.  Watet. 

*  The  importance  of  controlling  the  diet,  even  to  the  extent  of  introducing 
periods  of  fasting,  so  as  to  keep  the  diabetic  free  from  acidosis  and  glycosuria, 
has  been  receatly  emphasised  (Allen) . 


THE  METABOLISM  OF  l-AT  557 

But  it  is  not  necessary  that  each  OH  group  in  the  alcohol  should  be 
replaced  by  the  same  fatty  acid,  and  when  tnis  does  not  occur  wc  have 
hetcro-acid  fats.  For  instance,  one  can  be  replaced  by  stearic  acid, 
and  the  remaining  two  by  palmitic  acid,  yielding  a  fat  called  '  stearo- 
dipahnitin.'  Conversely,  one  OH  may  be  replaced  by  palmitic  and  two 
by  stearic  acid,  forming  palmito-distearin.  Similarly,  a  dioleo-stearin 
(glycerin  combined  with  two  molecules  of  oleic  and  one  of  stearic  acid), 
and  an  oleo-distearin  (glycerin  combined  with  two  molecules  of  stearic 
and  one  of  oleic  acid)  are  known.  Such  compounds  have  been  isolated 
from  the  fat  of  animals,  and  also  formed  synthetically.  Again,  each 
of  the  OH  groups  in  the  alcohol  can  be  re})laced  by  a  different  fatty  acid. 

It  is  obvious,  then — and  this  is  the  point  to  which  these  chemical 
details  arc  intended  to  lead  up — ^that  the  number  of  different  fats 
which  the  animal  organism  has  at  its  disposal  for  concocting  those 
varied  mixtures  designated  as  body  fat  is  very  great,  and  that  there 
is  room  for  a  considerable  degree  of  specificity  in  the  fat  stores  of 
different  animals,  and  it  may  be  in  the  fat  contained  in  different 
organs  of  the  same  animal,  even  if  this  specificity  is  not  as  marked 
as  in  the  case  of  the  proteins.  It  may  be  added,  in  connection  with 
the  composition  of  the  body  fat,  that  small  quantities  of  free  fatty 
acids  and  of  glycerin  may  be  present ;  but  there  is  reason  to  believe 
that  these  are  simply  the  surplus  of  raw  materials  which  is  about  to 
be  synthetized  to  neutral  fat,  or  the  surplus  of  decomposition 
products  of  the  neutral  fat  which  have  not  yet  left  the  fat  depots 
to  take  their  place  in  the  metabolism  of  the  tissues. 

The  discussion  of  the  metabolism  of  fat  involves  a  study — (i)  of 
the  transformations  and  migrations  of  the  food  fat  before  it  begins 
to  be  utilized ;  (2)  of  the  possible  production  of  fat  from  other  con- 
stituents of  the  food ;  (3)  of  the  processes  and  the  stages  by  which 
fat,  whatever  its  origin,  undergoes  katabolism  to  its  end  products. 
The  fat  of  the  food,  passing  along  the  thoracic  duct  into  the  blood- 
stream, is  soon  removed  from  the  circulation,  for  normal  blood 
contains  only  traces,  except  during  digestion.  Where  does  it  go  ? 
What  is  its  fate  ? 

Transformation  and  Migration  of  the  Food  Fat. — The  presence 
of  adipose  tissue  in  the  body  might  suggest  a  ready  answer 
to  these  questions.  The  fat-cells  of  adipose  tissue  are  ordinary 
fixed  connective-tissue  cells  which  have  become  filled  with  fat, 
the  protoplasm  being  reduced  to  a  narrow  ring,  in  which  the 
nucleus  is  set  like  a  stone.  It  would,  at  first  thought,  seem  natural 
to  suppose  that  the  fat  of  the  food  is  rapidly  separated  by  these 
cells  from  the  blood,  and  slowly  given  up  again  as  the  needs  of  the 
organism  require,  just  as  carbo-hydrate  is  stored  in  the  liver  for 
gradual  use.  And  it  has  been  found  that  a  lean  dog,  fed  with  a 
diet  containing  much  fat  and  little  protein,  puts  on  more  fat,  as 
estimated  by  direct  analysis,  or  keeps  back  more  carbon,  as  esti- 
mated by  measurements  of  the  respiratory  exchange,  than  can  be 
accounted  for  on  the  supposition  that  even  the  whole  of  the  carbon 
of  the  broken-down  protein  corresponding  to  the  excreted  nitrogen 


538  METABOLISM.  NUTRfTION  AND   DTF.TF.TICS 

has  been  laid  up  in  the  form  of  fat.  Even  with  a  diet  of  pure  fat— 
and  with  such  a  diet  digestion  and  absorption  are  carried  on  under 
unfavourable  conditions — more  carbon  is  retained  than  can  have 
come  from  the  metabolism  of  the  proteins  of  the  body,  as  measured 
by  the  nitrogen  given  off  in  the  urine  and  faces:  the  fat  passes 
rapidly  from  the  blood  into  the  organs,  and  especially  into  the  liver 
(Hofmann,  Pettenkofer  and  Voit).  It  is  thus  certain  that  some  of 
the  absorbed  fat  may  be  stored  up  as  fat  in  the  body. 

This  is  borne  out  by  the  careful  experiments  of  Munk  and  Lebe- 
deff,  who  found  that,  when  dogs  are  fed  with  excess  of  foreign  fat 
(Unseed  oil,  rape  oil,  mutton  fat),  a  fat  is  laid  down  which  is  quite 
different  from  dog's  fat,  and  has  the  greatest  resemblance  to  the  fat 
of  the  food.  Thus,  when  rape  oil,  which  contains  a  fatty  acid, 
erucic  acid,  not  found  in  animal  fat,  was  given,  erucic  acid  could  be 
detected  in  the  fat  laid  on.  When  the  dogs  were  fed  with  mutton 
fat,  whose  melting-point  is  much  higher  than  that  of  dog's  fat,  the 
fat  laid  on  did  not  melt  till  it  was  heated  to  40°  C  or  more.  When 
they  were  fed  with  linseed  oil,  the  body-fat  was  found  liquid  even 
at  0°  C.  We  have  already  referred  (p.  444)  to  the  fact  that  neutral 
fat  can  be  built  up  in  the  wall  of  the  intestine  from  fatty  acids  given 
in  the  food.  Munk  has  shown  that  fat  formed  in  this  way  can  also 
be  laid  down  as  body-fat.  But  besides  the  fat  and  fatty  acids  of 
the  food,  the  fat  of  the  body  has  other  sources,  and  some  of  it  is 
produced  by  more  complex  processes. 

The  fat  of  a  dog  consists  of  a  mixture  of  palmitin,  olein,  and 
stearin.  When  a  starved  dog  was  fed  on  lean  meat  and  a  fat  con- 
taining palmitin  and  olein,  but  no  stearin,  the  fat  put  on  contained 
all  three,  and  did  not  sensibly  differ  in  its  composition  from  the 
normal  fat  of  the  dog  (Subbotin).  Stearin  must,  therefore,  have 
been  formed  in  some  way  or  other  in  the  bod}'.  If  it  was  produced 
from  the  olein  and  palmitin  of  the  food,  the  portion  of  these  deposited 
in  the  cells  of  the  adipose  tissue  must  have  undergone  changes  before 
reaching  this  comparatively  fixed  position.  But  there  is  conclusive 
evidence  that  fat  may  be  derived  from  other  sources,  certainly 
from  carbo-hydrates,  and  probably  from  proteins;  and  the  stearin 
may  have  been  formed  from  the  carbo-hydrates  or  proteins  of  the 
food  or  tissues,  and  not  directly  from  fat.  And  if  the  stearin  was 
produced  from  proteins  or  carbo-hydrates,  it  is  evident  that  the 
olein  and  palmitin  might  have  been  formed  in  this  way  too,  the 
portion  of  the  carbo-hydrate  or  protein  devoted  to  this  purpose 
being  sheltered  from  oxidation  by  the  combustion  of  the  fats  of  the 
food.  It  is  well  known  that  not  only  neutral  fats,  but  also  fatty 
acids,  exert  such  a  '  protein-sparing  '  action.  It  is  possible  also  that 
the  fat  which  is  normally  excreted  into  the  intestine  (p.  443),  and 
which  is  perhaps  derived  from  broken-down  proteins,  may  be  re- 
absorbed, and  take  its  place  among  the  fat  '  put  on.' 


TIIF  MF.TABOIIS^T  OF  FAT  550 

At  this  point  in  the  discussion  it  is  necessary  to  remark  that  a 
distinction  ought  to  be  estabhshed  between  that  store  of  surplus  fat 
laid  down  in  the  connective  tissue  which,  in  order  to  avoid  com- 
plicating the  matter  unduly,  has  hitherto  been  referred  to  as  if  it 
constituted  the  whole  of  the  body-fat,  and  the  fat  which  is  contained 
in  greater  or  less  amount  in  all  the  tissue  cells.  The  fat  con- 
tained in  the  tissue  elements — e.g.,  in  the  liver  cells — in  the  visible 
form  of  droplets,  and  which  can  be  easily  extracted  from  them  by 
solvents  such  as  chloroform,  should  also  be  distinguished  from  the 
fat  which  is  so  intimately  incorporated  or  combined  with  the  cell 
substance  that  it  can  only  be  extracted  after  this  has  been  digested 
by  the  aid  of  proteolytic  ferments  or  acids.  The  latter  fraction  of 
the  body-fat  is  probably  an  integral  and  indispensable  constituent 
of  the  protoplasm.  Now,  it  is  in  the  great  fat  depots  of  the  sub- 
cutaneous tissue  and  the  mesentery  and  omentum  that  variations 
in  the  proportions  of  the  various  fatty  acids  corresponding  to  varia- 
tions in  the  nature  of  the  food-fat  are  most  easily  produced,  or,  at 
least,  most  easily  observed.  These  depots  are  laid  down,  not  in 
the  interest  of  the  fat  cells  themselves,  but  to  serve  the  purpose  of 
a  reserve  of  fat  which  may  be  drawn  upon  for  the  nutrition  of  the 
body  as  a  whole,  just  as  the  glycogen  store  of  the  liver  forms  a 
general  carbo-hydrate  reserve.  The  free  fat  in  the  cells  of  the  organs 
is  superficially  analogous  to  the  glycogen  reserves  of  such  tissues 
as  muscles  and  glands,  and  certain  facts  are  known  which  might 
be  interpreted  as  indicating  that  this  fraction  of  the  body-fat,  like 
the  fat  of  the  connective  tissue,  is  not  a  definite  and  specific  mixture 
of  fats  with  an  unvarying  composition  for  each  kind  of  animal,  but 
a  mixture  whose  composition  can  be  made  to  vary  by  altering  the 
nature  of  the  fats  in  the  food.  On  the  other  hand,  the  fat  combined 
in  the  tissues  appears  to  preserve  a  certain  specificity  which  is  inde- 
pendent of  the  fats  supplied  in  the  food.  Thus,  when  dogs  were 
fed  with  rape  oil,  and  had  accumulated  considerable  quantities  of 
this  fat  of  low  melting-point  in  the  subcutaneous  and  other  fat 
depots,  Ihe  fat  combined  in  the  organs  remained  in  all  respects  the 
same  as  normal  dog's  fat.  This  was  also  the  case  with  animals 
fed  on  fat  of  high  melting-point, such  as  sheep's  tallow  (Abderhalden). 
Although  the  liver  appears  to  have  a  special  relation  to  the  metabo- 
lism of  fat,  it  is  not  known  whether  any  particular  organ  is  more 
than  the  rest  responsible  for  the  manufacture  of  this  specific  mix- 
ture of  fats.  It  appears  more  probable  that  each  cell  has  the  power 
of  forming  for  itself  the  characteristic  fats  from  the  crude  materials 
represented  by  the  food-fat  directly  absorbed  from  the  tissue  lymph, 
or  the  fat  of  the  depots  after  it  has  been  mobilized  and  has  found 
its  way  again  into  the  blood,  or,  finally,  from  other  materials  than 
fats,  such  as  dextrose  or  some  of  its  decomposition  products. 

Even  in  the  case  of  the  subcutaneous  and  similar  collections  of 


56o  METABOLISM.  NUTRITION  AND  DIETETICS 

fat,  it  must  be  noted  that  upon  the  whole,  under  normal  conditions, 
it  is  their  specificity  of  composition  rather  than  their  dependence 
upon  the  composition  of  the  fat  mixture  in  tlie  food  which  is  the 
striking  fact,  and  undue  weight  can  easily  be  given  to  the  results 
of  feeding  experiments  where  great  quantities  of  quite  foreign  fats 
are  administered.  When  small  quantities  of  fats  very  far  removed 
in  their  properties  from  the  normal  fat  of  an  animal  are  given 
in  the  food,  they  are  either  completely  utilized  before  reaching 
the  fat  depots,  or  transformed  into  normal  body-fat,  since  no  change 
whatever  can  be  detected  in  the  latter.  If  they  have  been  utilized, 
then  it  may  be  that  a  corresponding  amount  of  fat,  formed,  say, 
from  dextrose,  has  been  laid  down  in  the  fat  stores.  If  this  fat  is 
formed  from  dextrose,  it  will,  of  course,  be  the  kind  of  fat  which 
the  particular  animal  is  accustomed  to  form  from  dextrose — ^that 
is,  the  fat  characteristic  of  the  animal.  If  the  foreign  fat  is  itself 
transformed  into  body-fat  when  given  in  small  amount,  this  same 
feat  can  without  doubt  be  gradually  accomplished  in  the  case  of 
the  surplus  of  foreign  fat  laid  down  in  the  depots  when  a  large 
quantity  of  it  is  given  in  the  food. 

Formation  of  Fat  from  Other  Sources  than  the  Fat  of  the  Food — 
(i)  From  Carbo-Hydrates. — It  has  been  found  that  the  addition  of 
protein  to  a  diet  of  fat,  and  especially  to  a  diet  of  carbo-hydrate, 
in  larger  amount  than  is  just  necessary  for  nitrogenous  equilibrium 
(p.  602),  leads  to  a  more  rapid  increase  in  the  carbon  deficit — that 
is,  in  the  fat  put  on — than  if  the  minimum  quantity  of  protein 
required  for  nitrogenous  equilibrium  had  been  given.  From  this  it  is 
inferred  that  the  carbonaceous  residue  of  the  broken-down  protein  is 
shielded  from  oxidation  by  the  fat,  and  to  a  still  greater  extent  by 
the  carbo-hydrates,  and  so  retained  in  the  body  as  fat.  And  there 
is  little  doubt  that  the  high  repute  of  carbo-hydrates  as  fattening 
agents  is  in  part  due  to  their  taking  the  place  of  proteins  and  fats 
in  ordinary  '  current  '  metabolism,  and  so  allowing  body- fat  to  be 
laid  down  from  these.  Voit,  indeed,  has  gone  so  far  as  to  assert 
that  this  is  the  only  sense  in  which  carbo-hydrates  can  be  said  to 
form  fat,  and  that,  in  carnivorous  animals  at  least,  a  direct  con- 
version never  occurs.  But  the  experiments  of  Rubner  have  shown 
that  in  a  dog  fed  with  a  diet  rich  in  carbo-hydrates,  and  containing 
but  little  fat  and  no  proteins  at  all,  the  carbon  deficit  was  greater 
than  could  be  accounted  for  by  the  proteins  being  broken  down  in 
the  body  and  the  fat  of  the  food.  In  the  pig  and  goose,  too,  the 
direct  formation  of  fat  from  carbo-hydrates  has  been  demonstrated. 

For  example,  in  an  experiment  by  Tscherwinsky  two  young  pigs 
of  the  same  litter  were  taken.  They  weighed  respectively  7,300  grammes 
aud  7,^90  grammes.  One  was  killed,  and  the  amount  of  fat  and  nitrogen 
in  its  body  directly  estimated.  From  the  nitrogen  the  maximum 
quantity  of  protein  which  could  be  present  was  calculated.  The  other 
pig  was  fed  for  four  months  with  barley,  which  was  analyzed.  The 
excreta  were  also  analyzed  to  determine  the  amount  of   unabsorbed 


THE  METABOLISM  OP  PAT  561 

fat  and  protein.  At  the  end  of  the  lour  months  the  pig  vveis  killed. 
It  now  wtighcd  24  kilogrammes,  and  contained  2-52  kilogrammes 
protein  and  9-25  kilogrammes  fat.  Subtracting  the  protein  (0-96  kilo- 
gramme) and  fat  (0*69  kilogramme)  originally  present,  1-56  kilogrammes 
of  protein  and  8-56  kilogrammes  of  fat  must  have  been  put  on.  The 
amount  of  protein  taken  in  the  food  was  7-49  kilogrammes,  and  of  fat 
O'bb  kilogramme.  Therefore,  5-93  kilogrammes  of  protein  must  have 
been  used  up,  and  7-90  kilogrammes  of  fat  laid  on.  At  least  5  kilo- 
grammes of  this  fat  must  have  come  from  the  carbo-hydrate  of  the 
food.  Only  a  small  amount  of  the  fat  put  on  could  possibly  have  come 
from  the  protein. 

The  production  of  wax  by  bees,  which  used  to  be  given  as  a  proof 
of  the  formation  of  fat  from  sugar,  is  not  decisive,  for  in  raw  honey 
proteins  are  present ;  and  even  when  bees  fed  on  pure  honey  or  sugar 
vnanufacture  wax,  it  may  be  derived  from  the  broken-down  proteins 
of  tlieir  own  bocUes. 

It  is  probable  that  in  the  formation  of  fats  the  carbo-hydrates 
are  first  spht  up  to  some  extent,  and  that  the  fats  are  then  con- 
structed from  their  decomposition  products,  oxygen  being  lost  in 
the  process,  since  fat  is  much  poorer  in  oxygen  than  carbo-hydrate. 
But  the  chemistry  of  the  transformation  as  it  takes  place  in  the  body 
is  still  imperfectly  known,  and  all  that  can  be  done  here  is  to  indicate 
one  or  two  of  the  ways  in  which  chemists  conceive  that  it  may  occur. 

The  formation  of  the  glycerin  component  of  the  neutral  fats  from 
carbo-hydrates  would  appear  to  present  little  difficulty.  In  dis- 
cussing the  formation  of  glycogen  from  glycerin  fp.  536),  it  was  stated 
that  two  molecules  of  glycerose  (glycerin  aldehyde),  a  triose  or  sugar 
with  three  carbon  atoms,  can  be  condensed  to  form  a  hexose  or  sugar 
with  six  carbon  atoms  like  dextrose,  from  the  condensation  or  union 
of  a  number  of  molecules  of  which,  with  abstraction  of  water,  glycogen 
is  built  up.  The  reaction  can  be  worked  equally  well  in  the  reverse 
direction — that  is,  from  the  hexose  dextrose  two  molecules  of  glycerin 
aldehyde  can  be  formed,  and  then  from  each  molecule  of  the  alde- 
hyde ,'by  reduction,  a  molecule  of  the  alcohol  glycerin.  As  a  matter  of 
fact,  it  has  been  demonstrated  that  glycerin  is  produced  when  the  cor- 
responding aldehyde  is  brought  into  contact  with  minced  liver. 

As  regards  the  fatty  acid  components  of  the  fats,  it  will  be  seen  from 
the  schematic  representation  of  the  katabolism  of  dextrose  on  p.  544 
that  acetic  acid,  a  fatty  acid,  is  represented  at  one  of  the  stages  as  being 
formed  by  the  oxidation  of  a  molecule  of  acetaldehyde.  Lactic  acid 
is  represented  in  the  same  scheme  as  a  previous  stage  in  the  decom- 
position of  dextrose,  and  lactic  acid  can  be  converted  into  acetaldehyde 
and  formic  acid,  the  lowest  of  the  same  series  of  fatty  acids  of  wdiich 
acetic  acid  is  the  next  highest  member.     Thus : 

^^sVh.COOH    =  CH3.C<^JJ  +   H.COOH 

Lactic  acid.  Acetaldehyde.  Formic  acid. 

Aldehydes  (as  well  as  ketones)  ha\e  a  great  capacity  for  entering  into 
reactions  with  other  substances,  and  their  molecules  show  also  a  marked 
tendency  to  combine  with  one  another,  forming  new  compounds  by 
their  condensation.      Thus,  from  two  molecules  of  acetaldehyde  one 

36 


362  METABOLISM.   SLTRITIOS  A\D  DILTLTICS 

molecule  ot  aldol  is  formed,  which  by  transposition  of  certain  groups, 
hecomcs  butyric  acid,  the  fourth  member  of  the  fatty  acid  scries  of 
which  acetic  acid  is  the  second  memljer,  and  palmitic  and  stearic  acids, 
which  form  such  important  constituents  of  the  ordinary  body -fats, 
the  sixteenth  and  eighteenth  members  respectively.  By  oxidation  aldol 
becomes  /3-oxybutyric  acid,  which  by  further  oxidation  yields  aceto- 
acetic  acid,  compounds  already  referred  to  in  connection  with  diabetes 
(p.  555).     The  following  equations  illustrate  these  reactions: 

CH3.C^g  +  CH3.C^g  =  CH3.CH(OH).CH,.c/g 

Aceuldehyde.        Acetaldebyde.  Aldol. 

CH3.CH(OH).CH2.CHO-CH3.CH2.CHa.COOH 

Aldol.  Butyric  acid. 

CH3.CH(OH).CH2.CHO  +  0=CH3.CH(OH).CH,.COOH 

Aldol.  /S-oxybutyric  acid. 

CH3.CH(OH)  .CH2.COOH  +  O  =  (CH3.CO).CH2.COOH  +  HjO 

/S-oxybutyric  acid.  Oxygen.  Aceto-acetic  acid.  Water. 

By  reduction  aceto-acetic  acid  is  reconverted  into  /3-oxybutyric  acid. 
Other  aldehydes  can  react  in  similar  ways,  and  thus  many  of  the  other 
fatty  acids  can  be  formed. 

It  may  be  added  that  acetone  (another  of  the  so-called  acetone 
bodies  which  appear  in  the  urine  in  diabetes  mellitus)  is  easily  obtained 
from  aceto-acetic  acid  by  the  splitting  off  of  carbon  dioxide.     Thus: 

(CH3.CO).CHj.COOH  =CH3.CO.CH3-i-  CO, 

Aceto-acetic  acid.  Acetone.  Carbon  dioxide. 

Formation  of  Fat — (2)  From  Protein. — Dry  protein  contains  on 
the  average  16  per  cent,  of  nitrogen  and  50  per  cent,  of  carbon,  and 
urea  contains  46  per  cent,  of  nitrogen  and  20  per  cent,  of  carbon. 
Urea  is  therefore  three  times  as  rich  in  nitrogen  as  the  protein  from 
which  it  is  derived,  but  two  and  a  half  times  poorer  in  carbon;  and 
less  than  one-seventh  of  the  carbon  of  protein  will  be  eliminated 
in  a  quantity  of  urea  sufficient  to  carry  off  all  the  nitrogen.  It 
is  probable  that  a  portion  of  the  remaining  carbon  may,  after  passing 
through  various  stages,  take  its  place  as  the  carbon  of  fat.  We 
have  seen  that  certain  amino-acids  derived  from  proteins  can  be 
converted  into  dextrose,  and  that  de.xtrose  can  be  converted  into 
fat.  So  that  the  mere  question  whether  carbon  atoms  or  carbon 
chains  originally  present  in  protein  molecules  are  ever  capable  of 
appearing  in  fat  molecules  can  be  straightway  answered  in  the 
affirmative.  But  it  is  still  in  doubt  whether  amino-acids  can  be 
transformed  into  glycerin  or  into  fatty  acids,  or  into  both,  by 
processes  which  do  not  involve  the  production  of  dextrose  from 
them.  And  in  any  case  proof  is  required  that  the  extent  of  the 
transformation,  let  the  steps  be  what  they  may,  is  great  enough 
to  be  satisfactorily  demonstrated.  In  regard  to  this  point  it  must 
be  said  that  absolutely  flawless  experiments  to  prove  the  direct 
production  of  fat  from  protein  seem  still  to  be  wanting. 


THE  METABOLISM  OF  FAT  5«3 

Phosphorus  Poisoning  and  Migration  of  Fat. — In  tiic  cxiCJ'iriicnts 
of  liaiKT,  the  HiiumnL  of  oxjgcn  consuinctl  and  of  carbon  dioxide 
and  nitrogen  excreted  was  dctennincd  in  starving  dogs.  Phosphorus, 
which,  as  is  well  known,  causes  extensive  fatty  changes  in  the 
organs,  was  then  administered  in  small  doses  for  se\cral  days. 
The  excretion  of  nitrogen  was  doubled,  the  excretion  of  carbon 
dioxide  and  the  consumption  of  oxygen  diminished  to  one-half.  When 
the  animals  died,  in  a  few  days,  the  organs  were  all  found  loaded  with 
fat.  In  one  case  42-4  per  cent,  of  the  solids  of  the  muscles  and  30  per 
cent,  of  the  solids  of  the  liver  consisted  of  fat.  This  is  much  more  than 
the  normal  amount.  It  was  iissumed  that  the  fat  could  not  have  been 
simply  transferred  from  the  adipose  tissue,  since  the  dog  had  been 
starved  for  twelve  days  before  the  phosphorus  was  given,  and  died  on 
the  twentieth  day  of  starvation.  Now^  after  such  a  period  of  hunger 
the  amount  of  fat  in  the  adipose  tissue  is  greatly  reduced.  It  was  there- 
fore concluded  that  the  source  of  the  fat  could  rnly  have  been  the 
broken-down  protein.  Since  the  nitrogen  excretion  was  increased,  while 
the  carbon  excretion  was  diminished,  it  was  supposed  that  a  residue 
rich  in  carbon  must  have  been  split  off  from  the  proteins,  and,  remaining 
unbumt  in  the  body,  must  have  been  converted  into  fat.  Experiments 
of  this  kind  are  open  to  criticism  on  several  grounds,  but  especially  on 
this :  that  unless  the  fat-content  of  the  whole  body  before  the  adminis- 
tration of  the  poison  is  known,  it  is  impossible  to  be  sure  that  the  fat 
in  a  particular  tissue  has  not  been  increased  simply  by  the  transportation 
of  fat  from  some  other  tissue.  It  has  been  conclusively  shown  that 
migration  of  preformed  fat  does  occur,  and  on  an  extensive  scale,  in 
phosphorus  poisoning.  For  example,  a  dog  was  fed  for  a  time  with 
sheep's  tallow,  and  fat  was  laid  down  in  its  adipose  tissue  with  the 
physical  and  chemical  characters,  not  of  dog's,  but  of  sheep's  fat.  The 
animal  was  then  poisoned  with  phosphorus,  and  the  fat  which  accumu- 
lated in  the  liver  examined.  It  also  resembled  sheep's  fat,  as  it  should 
have  done  had  it  migrated  from  the  adipose  tissue,  and  not  dog's  fat, 
as  it  might  have  been  expected  to  do  had  it  been  formed  in  the  hepatic 
cells  from  protein.  The  ease  with  which  connective-tissue  fat — i.e.,  food 
fat — migrates  to  the  liver  suggests,  with  other  facts,  that  the  liver  has  a 
special  relation  to  the  transformation  of  this  fat  into  the  fat  of  the  organs. 
This  '  organized  '  intracellular  fat  differs  in  various  ways  from  the  fats 
of  adipose  tissue.  Its  '  iodine  value  '  (p.  4)  is  higher  (Leathes),  and  a 
large  proportion  of  it  consists  of  phosphatide  lipoids  (p.  571.) 

The  most  convincing  evidence  that  fat  is  not  produced  in  increased 
amount  under  the  influence  of  phosphorus  has  been  obtained  by  deter- 
mining by  actual  analysis  the  total  fat  in  animals,  then  poisoning 
similar  animals  with  phosphorus  and  again  estimating  the  total  fat. 
Far  from  being  increased,  the  fat  may  even  be  decreased  in  the  poisoned 
animals  (Taylor,  etc.).  There  is  no  ground,  then,  for  the  assumption 
that  phosphorus  and  other  substances,  like  arsenic,  antimony,  etc.,  which 
bring  about  so-called  '  fatty  degeneration  '  of  the  organs,  act  by  causing 
or  accelerating  the  transformation  of  protein  into  fat.  Yet  there  is  good 
evidence  that  they  do  accelerate  the  decomposition  of  protein,  or  at 
least  interfere  with  its  normal  metabolism,  for  after  phosphorus  poison- 
ing amino-acids  (leucin,  ty rosin,  glycin)  appear  in  the  urine.  The 
observations  of  Lusk  and  his  pupils  indicate  that  phosphorus  does  not 
directly  increase  the  amount  of  protein  broken  down,  but  does  so 
indirectly,  by  favouring  the  conversion  of  the  carbohydrate -like  radicle 
of  the  protein  molecule  into  leucin,  tyrosin,  and  perhaps  fat,  and 
thereby  necessitating  an  increased  consumption  of  protein. 

A  celebrated  experiment,  performed  nearly  forty  years  ago,  was  long 


564  METABOLISM.   NUTRITION  AND  DIETETICS 

supposed  to  furnish  an  absolute  proof  of  the  formation  of  fat  from 
protein,  under  strictly  physiological  conditions,  although  in  a  humble 
form  of  animal  life.  Maggots  were  allowed  to  develop  from  the  egg  on 
blood  containing  a  known  amount  of  fat.  The  quantity  of  fat  in  the 
eggs  was  also  known.  After  the  maggots  had  grown,  ten  times  as 
much  fat  was  found  in  them  as  had  been  contained  in  the  blood  and 
eggs  together.  The  trifling  quantity  of  sugar  in  the  blood  was  utterly 
inadequate  to  account  for  the  fat,  which,  it  was  concluded,  must  there- 
fore have  come  from  the  proteins  of  the  blood  (Hofmann).  It  can  be 
objected  to  this  experiment  that  no  precautions  were  taken  to  prevent 
the  growth  of  micro-organisms  on  the  blood,  and  fat  might  have  been 
formed  by  them  from  the  proteins.  Further,  the  fat  estimations  would 
scarcely  pass  muster  according  to  the  present  standards. 

The  "experiments  of  Pettcnkofer  and  Voit,  which  were  supposed  to 
have  demonstrated  that  in  the  higher  animals  also  fat  is  formed  from 
proteins  imdcr  norini.l  conditions,  are  in  the  same  position.  According 
to  them,  a  dog  fed  for  a  time  on  a  liberal  diet  of  lean  meat  may  go  on 
excreting  a  quantity  of  nitrogen  equal  to  that  in  the  food,  while  there 
is  a  deficiency  in  the  carbon  given  ofif.  Or  if  the  dog  is  not  in  nitrog- 
enous equilibrium  (p  602),  but  putting  on  nitrogen  in  the  form  of 
'  flesh,'  the  deficiency  in  the  carbon  given  off  may  be  too  great  in  pro- 
portion to  the  nitrogen  deficit  to  warrant  the  assumption  that  all  the 
retained  carbon  has  been  put  on  in  the  form  of  protein.  In  either  case, 
carbon  in  large  amount  can  only  come  from  the  proteins  of  the  food, 
and  can  onlv  be  stored  up  in  the  body  in  the  form  of  fat.  For  lean  meat 
contains  but  a  trifling  quantity  of  carbon  in  any  other  proximate 
principle  than  protein,  and  the  non-protein  carbon  of  the  animal  body 
is  only  to  a  very  small  extent  contained  in  carbo-hydrates  or  other 
substances  than  fat. 

Pfliiger  has  criticized  these  experiments,  and  has  shown  that  lean 
meat  contains  more  fat  than  was  supposed,  and  this  is  now  generally 
admitted.  He  has  endeavoured  to  show  that  the  fat  and  ghcogen  in 
the  meat  given  to  the  animals  full)-  accounts  for  the  carbon  retained. 
Pfliiger,  indeed,  takes  up  the  position  that  the  fat  of  the  body  comes 
exclusively  from  the  carbo-hydrates  and  fats  of  the  food,  and  not  at  all 
from  the  proteins.  But  there  is  little  doubt  that  in  this  he  has  gone  too 
far,  although  his  criticism  has  rendered  it  impossible  any  longer  to  appeal 
to  Pettenkofer  and  Voit's  results  as  good  evidence  on  the  other  side. 

If  none  of  the  supposed  quantitative  proofs  of  the  conversion  of 
proteins  into  fat  which  have  hitherto  been  brought  forward  are 
free  from  flaw,  the  same  is  true  of  the  alleged  qualitative  indications 
of  its  possibility  and  of  its  actual  occurrence.  The  accumulation 
of  fat  between  the  hepatic  cells  caused  by  phlorhizin  is,  at  the  best, 
no  better  evidence  than  the  accumulation  within  the  cells  in  phos- 
phorus poisoning.  The  formation  of  adipocere  (a  cheesy  substance, 
rich  in  fatty  acids  united  with  calcium  or  ammonium),  sometimes 
seen  in  dead  bodies  which  have  remained  a  long  time  under  water 
or  in  moist  graveyards,  is  largely,  if  not  entirely,  due  to  the  fat 
already  present  in  the  parts  which  have  undergone  the  change, 
or  to  fat  removed  by  the  water  from  other  parts  of  the  body. 
If  any  portion  of  the  adipocere  represents  fat  formed  from  protein, 
this  transformation  may  well  be  credited  to  the  numerous  micro- 
organisms present,  and  throws  no  light  upon  the  question  of  fat 
formation  in  the  normal  organism.     The  fat  in  the  ceils  of  the 


THF  ^f^TA^lnTr^^r  of  fat  565 

sebaceous  glands,  and  of  the  mammary  glands,  may  be  produced 
from  protein  by  a  transformation  of  the  cell-substance.  But  abso- 
lutely convincing  proof  is  wanting.  The  old  idea  that  the  cells  of 
these  glands  underwent  a  physiological  process  of  transformation 
into  fat  analogous  to  the  fatty  degeneration  of  pathology,  and  then 
broke  down  bodily  into  the  secretion,  has  been  long  since  disproved 
for  milk  formation,  and  is  probably  erroneous  also  as  regards  the 
secretion  of  sebum.  The  rule  which  experience  has  taught,  that 
a  woman  during  lactation  requires  an  excess  of  proteins  in  her  food 
corresponding  not  only  to  the  proteins,  but  also  to  the  fat  given  off 
in  the  milk,  suggests  such  an  origin  for  the  milk-fat,  but  does  not 
prove  it.  Other  fat-containing  secretions  are  the  ear-wax  formed 
by  glands  in  the  wall  of  the  external  auditory  meatus,  and  the 
smegma  formed  by  the  glands  of  the  prepuce,  but  nothing  is  known 
of  the  sources  from  which  the  fatty  substances  are  derived. 

The  Intermediary  Metabolism  of  Fat. — The  mechanism  and  the 
stages  of  the  transformation,  including  the  migration,  of  fats  is 
not  well  understood — indeed,  not  as  well  as  that  of  the  carbo- 
hydrates. Many  of  the  tissues  contain  intracellular,  soluble, 
fat-splitting  ferments  called  lipases,  especially  the  liver,  the 
active  mammary  gland,  and  the  intestinal  mucosa.  We  have 
already  seen  that  there  is  evidence  that  these  lipases,  like  some 
other  enzymes,  have  a  reversible  action.  They  are  either  fat- 
splitting  or  fat-forming  ferments,  according  to  the  conditions 
(Kastle  and  Loevenhart).  It  is  stated  that  the  perfectly  aseptic 
blood  does  not  split  ordinary  neutral  fats,  although  it  contains  a 
ferment  which  splits  up  monobutyrin  (glycerin  but^Tate)  into 
glycerin  and  butyric  acid. 

The  question  how  the  fat,  after  absorption  from  the  intestine, 
passes  from  the  blood  into  the  cells,  and  how-  it  is  enabled  again  to 
pass  out  of  the  fat-cells  when  the  needs  of  the  tissues  call  for  its 
mobilization,  cannot  at  present  be  definitely  answered.  It  is 
possible  that  just  as  fat  is  split  in  the  lumen  of  the  intestine  before 
being  absorbed,  and  then  rebuilt  in  the  epithelium,  so  it  is  split  in 
the  blood  or  in  the  lymph  before  being  taken  up  by  the  fat-cells. 
The  lipase  in  these  cells  would  then  be  capable  of  synthetizing  the 
glycerin  and  fatty  acids  to  fat  in  their  interior.  \Vhen  the  fat  is 
about  to  pass  out  of  the  cells  in  response  to  the  call,  of  whatever 
nature  it  is,  of  the  tissues  for  fat,  it  may  again  be  split,  resynthetized 
in  the  blood,  and  again  hydrolysed  for  entrance  into  the  tissue 
cells.  Or  it  may  be  carried  to  the  cells  in  the  form  of  glj'cerin  and 
fatty  acids,  or  soaps,  in  such  small  concentration  as  to  be  harmless, 
and  there  built  up  again  into  the  original  fat,  or  transformed  into 
other  fats" characteristic  of  the  particular  tissues,  including  the  fatty 
acid  components  of  the  phosphatides,  or  utilized  without  synthesis 
into  fat.    An  alternative  hypothesis  avoids  this  series  of  decomposi- 


566  METABOLISM.   NUTRITION  AND  DIETETICS 

tions  and  syntheses  by  assuming  that  the  fat  passes  in  the  lorm  of 
very  fine  droplets  tlirougli  the  walls  of  the  cells  and  of  the  capil- 
laries. The  reader  will  observe  that  we  seem  to  be  discussing  again, 
and  almost  in  the  same  terms,  the  question  of  the  absorption  of  fat 
from  the  intestine.  It  is  indeed  at  bottom  the  same  question,  and 
it  might  be  argued  that  by  analogy  it  should  receive  the  same  solu- 
tion. Analogy,  however,  is  a  dangerous  guide  in  such  matters,  and 
it  is  even  more  difficult  to  secure  an  unambiguous  experimental  test 
of  the  manner  in  which  the  internal  migration  of  fat  is  accomplished 
than  to  secure  the  like  for  its  absorption  from  the  digestive  tube. 

As  to  the  ultimate  fate  of  the  fat,  from  whatever  source  it  may 
be  derived,  our  knowledge  may  be  compressed  into  very  few  sen- 
tences: Sooner  or  later  it  is  split  and  oxidized  to  carbon  dioxide  and 
water,  its  energy  being  converted  into  heat  or,  directly  or  indirectly,  into 
mechanical  or  other  fnnctional  work ;  some  of  the  fat  absorbed  from  the 
intestine  rapidly  undergoes  this  change  without  entering  the  fat-cells  of 
the  adipose  tissue.  A  portion  of  the  fat  may  be  changed  into  carbo- 
hydrt^^es.  This  has  been  proved  for  the  glycerin  component ;  its  possi- 
bility must  be  admitted  for  the  fatty  acids, but  proof  has  not  yet  been  given. 

Of  the  intermediate  stages  by  which  the  fatty  acids  are  degraded 
into  the  simple  end  products  but  little  is  surely  known.  Included 
among  these  stages  must  be  the  compounds  with  which  the  forma- 
tion of  the  acetone  bodies  (p.  563)  starts,  if  and  in  so  far  as  their 
formation  is  a  normal  event  which  is  merely  unveiled  by  the  dis- 
turbance of  the  ordinary  course  of  the  metabolism  in  diabetes. 
Among  these  intermediate  stages  must  also  be  included,  it  is  to  be 
supposed,  the  compounds,  whatever  they  may  be,  which  act  as 
connecting  links  between  the  currents  of  fatty  acid  and  of  carbo- 
hydrate metabolism,  and  with  which  the  transformation  of  fatty 
acids  into  carbo-hydrates  commences,  if  this  occurs  at  all. 

According  to  tlic  observations  of  Knoop,  the  saturated  as  well  as 
some  of  the  other  series  of  fatty  acids  when  oxidized  decompose  in  a  very 
characteristic  way.  As  already  remarked,  these  acids  are  made  up  of  a 
larger  or  smaller  number  of  CHj  groups  forming  a  chain  whicli  at  one 
end  terminates  with  a  carboxyl  (COOH)  group,  and  at  the  otlier  with  a 
CH3  group.  The  carbon  atoms  in  the  chain  are  designated  by  Greek 
letters,  a,  /3,  etc.,  the  a  position  being  that  next  the  carboxyl  group, 
the  ^  position  one  remove  from  the  carboxyl  group,  and  so  on .  Accord- 
ing to  Knoop,  the  oxidation  of  the  fatty  acid  chain  takes  place  in  such 
a  way  that  the  chain  is  shortened  by  the  cutting  off  from  the  carboxyl 
end  the  a  CH2  group  along  with  the  carboxyl  group,  wliile  in  place  of  the 
/3CH2  group  there  is  left  a  carboxyl  group,  an  operation  which  might 
be  fancifully  compared  to  the  naval  manoeuvre  of  breaking  the  enemy's 
,.  T,,         ,  . ,    CH3.CH2.CH2.CH2.  1  CHj.COOH.    ^^ 

line.      Thus   from   caproic   acid    c^yft\a 

get  by  oxidation   butyric  acid,  CH3.CH2.CHa.COOH,   ^^^rbon   dioxide 

and  water.  It  appears  that  the  oxidation  proceeds  in  two  stages,  the 
hydrogen  of  the  /3  group   being   first  oxidized  with  formation  of  an 


THE  METABOUSM  OF  FAT  ^r,j 

oxyacid  oxycaproic  ackl,  CiI3.CPJ2.Cil2.CllOH.CH2.COOH,  which  is 
then  by  further  oxidation  converted,  with  loss  of  two  carbon  atoms, 
into  butyric  acid.  The  oxidation  process  may  then  start  afresh  on 
the  /3  group  of  butyric  acid.  On  the  long  carbon  chains  of  the  higher 
fatty  acids  this  operation  may  be  repeated  again  and  again,  the  chain 
losing  two  atoms  of  carbon  at  each  attack.  If  this  represents  what 
occurs  in  the  normal  metabolism,  the  groups  cut  off  may  then  and  there 
undergo  the  fate  of  the  ships  isolated  by  a  successful  application  of[the 
manoeuvre  alluded  to,  complete  destruction — that  is  to  say,  oxidation 
to  the  end  products  carbon  dioxide  and  water,  a  portion  of  the  energy 
of  the  fatty  acid  being  thus  liberated  at  each  oxidation  of  the  /3  group. 
Eventually  a  fatty  acid  or  acids  with  very  few  carbon  atoms  will  be 
left.  There  is  some  reason  to  think  that  acetic  acid  (and  perhaps 
similar  simple  acids)  may  be  one  of  the  normal  stages  in  the  decom- 
position.    Thus,    butyric   acid   may   first   yield   by  oxidation   of  the 

a  .,  •,     /3         K  ^     •  -A      CHo.CHOH.CHo.COOH, 

/3    group    the     oxyacid    /3-oxy butyric     acid,  ^^  ^  ' 

which  by  further  oxidation  of  the  /3  group  and  the  cutting  off  of  the  a 
and  carboxyl  groups  would  give  CH3.COOH,  or  acetic  acid. 

If  this  is  the  general  course  of  the  oxidation  of  the  fatty  acids  in 
the  body,  it  is  to  be  assumed  that  numerous  intermediate  stages 
unrepresented  in  such  a  simple  scheme  may  exist.  Thus  it  is  known, 
as  has  been  mentioned  more  than  once  in  other  connections  (p.  562), 
that  ^-oxybutyric  acid  by  oxidation  yields  aceto-acetic  acid,  by 
losing  from  the  /3  group  two  atoms  of  hydrogen  which  unite  with 
oxygen  to  form  water.  A  molecule  of  aceto-acetic  acid  contains 
the  elements  of  two  molecules  of  acetic  acid  minus  the  elements  of 
one  molecule  of  water.  It  is  therefore  possible  that  aceto-acetic 
acid,  if  it  is  a  normal  stage  in  the  katabolism  of  fatty  acids,  yields 
by  its  hydrolysis  as  a  further  step  acetic  acid,  according  to  the 
equation 

CH3.CO.CH2.COOH  +  HaO  =2(CH3.COOH). 

Aceto-acetic  acid.  Acetic  acid. 

It  is  worth  while,  perhaps,  to  point  out  once  more  that  even  the 
relatively  simple  products  now  arrived  at  are  not  necessarily  at 
once  completely  oxidized  to  their  end  products.  That,  it  is  to  be 
assumed,  will  depend  upon  the  needs  of  the  organism.  Acetic  acid, 
for  example,  when  added  to  blood  and  perfused  through  the  sur- 
viving liver,  can  be  transformed  into  aceto-acetic  acid,  and  may 
thus  become  the  starting-point  of  new  syntheses. 

The  Liver  and  Fats. — The  liver  seems  to  play  an  important  part  in 
the  metabolism  of  fat,  as  it  does  in  the  metabolism  of  carbo-hydrates 
and  of  proteins.  It  contains  an  oxidizing  ferment,  /S-oxybutyrase 
(or  ,8-hydroxybut}Tase) ,  which  transforms  /3-oxybutyric  acid  into 
aceto-acetic  acid  (Dakin).  This  oxidation  appears  to  occur  in  the 
normal  as  well  as  in  the  diabetic  organism.  The  liver  seems  also  to 
possess  the  power  of  transforming  aceto-acetic  acid  into  acetone,  a 
reaction  which  does  not  involve  an  oxidation,  and  this  may  also  be 
accompHshed  by  means  of  an  enzyme.     But  it  is  not  at  all  likely 


3(*8  METABOLISM.  NUTRITIOX  AXD  DIETETICS 

that  acetone  forms  a  stage  in  the  normal  kataboHsm  of  the  fatty 
acids  or  of  the  /3-oxyacids  derived  from  them.  The  importance  of 
the  Hver  in  the  metabohsm  of  fats  is  further  indicated  by  the  extent 
of  the  migration  of  fat  to  that  organ  when  tlic  fat  stores  are  mobihzed 
in  unusual  amount  (p.  5bj).  The  reason  for  this  migration  seems 
to  be  that  the  fats  undergo  preparatory  changes  which  facilitate 
their  utilization  by  the  tissues.  For  example,  there  is  evidence 
that  saturated  fatty  acids  are  changed  in  the  liver  into  unsaturated 
acids,  which  are  then  carried  to  the  organs  to  be  metabolized. 
The  desaturation  may  serve  the  purpose  of  facilitating  the  rupture 
of  the  long  carbon  chains,  or  their  capacity  for  entering  into  reac- 
tions with  other  substances,  at  the  points  where  double  links  exist 
between  carbon  atoms  (p.  55b). 

Non -Nutritive  Functions  of  Fat. — In  connection  with  the  metabo- 
lism of  fat,  it  ought  to  be  noted  that,  in  addition  to  their  value  as 
reserve  material  for  the  nutrition  of  the  body,  the  deposits  of  fat 
under  the  skin  and  in  other  situations  perform  important  functions 
in  protecting  delicate  structures  from  mechanical  injury,  in  facili- 
tating their  movements  upon  each  other,  and  in  hindering  the  loss 
of  heat.  It  would  doubtless  be  a  gross  exaggeration  to  say  that  the 
mechanical  and  physical  properties  of  the  fat  depots  are  as  im- 
portant in  comparison  to  their  chemical  relations  as  is  the  case  for 
the  bones  and  ligaments,  but  it  would  be  an  error  not  less  gross  to 
consider  them  as  of  little  account.  It  will  even,  perhaps,  be 
\hought  not  unworthy  of  mention,  from  the  point  of  \new  of  the 
propagation  of  the  race,  that  in  the  human  species,  at  least,  the 
amount  and  distribution  of  the  cutaneous  fat  play  a  part  of  r-om? 
consequence  in  the  aggregate  of  qualities  which  determine  the 
physical  attractiveness  of  the  individual,  especially  of  the  female, 
although  the  standard  in  this  regard  varies  wdely  in  different 
communities. 

It  is  perhaps  partly  because  the  fat  depots  have  important 
mechanical  functions  that  the  fat  reserve  is  far  less  mobile  than  the 
glycogen  reserve.  The  semi-solid  panniculus  adiposus,  the  fatty 
tissue  around  the  great  nerve  trunks,  between  the  muscles,  around 
the  eyeball,  on  the  soles  of  the  feet,  etc.,  possesses  as  a  protective 
packing  the  good  qualities  of  a  water  cushion  with  none  of  its  dis- 
advantages. But  if  the  fat-cells  were  subject  to  sudden  depletion,  as 
the  hepatic  cells  are — nay,  in  still  greater  degree,  since  they  contain 
hardly  any  protoplasm — ^they  would  never  serve  for  such  a  function. 
Of  course,  in  the  emergency  of  starvation,  when  even  the  glands 
and  the  muscles  themselves  are  wasting,  the  fat  reserves  are  neces- 
sarily mobilized,  let  their  mechanical  functions  suffer  as  they  may. 

Obesity. — The  proportion  of  tlie  total  mass  of  the  body  wliicli  is  made 
Tip  of  fat  varies  greatly  in  different  individuals,  and  often  in  the  same 
individual  at  different  stages  in  hfe.     When  the  accumulation  of  fat 


THE  MF.T.WOLJSM  OF  FAT  369 

passes  beyond  a  certain  point  it  causes  obvious  changes  in  the  contours 
of  the  body,  and  often  some  embarrassment  in  its  movements.     Thia 
condition  is  termed  obesity.     It  is  extremely  difficult  to  say  when  the 
condition  oversteps  the  physiological  bounilary  and  becomes  actually 
pathological.     Some  individuals  who  are  notoriously  stout  are  noted 
also  for  tlicir  intellectual  activity,  and  may  not  fall  below  the  average 
even  in  the  ordinary  kinds  of  physical  ettort.     It  would  be  an  exaggera- 
tion to  speak  of  such  persons  as  suffering  from  a  disease .     In  other  cases 
the  pathological  stamp  is  clearly  imprinted  upon  the  metabolic  anomaly 
which  leads  to  the  overfilling  of  the  fat  depots.     This  is  perhaps  best 
illustrated  in  those  cases  of  extreme  obesity  in  children  where,  in  spite 
of  the  intense  metabolism  associated  with  growth,  with  the  restless 
muscular  acti\ity  characteristic  of  that  age,  and  with  the  relatively 
great  surface  through  which  heat  is  lost,  great  quantities  of  fat  continue 
to  be  put  on.     Muscular  activity  by  itself  is  no  certain  antidote  to  or 
prophylactic  against  obesity,  and  it  is  a  mistake  to  suppose  that  the 
condition  is  cxceedinglj'  rare  among  manual  workers  sufficiently  well 
paid  to  be  able  to  gratify  their  tastes  in  the  quality  and  quantity  of 
their  food.     Statistics  or  rough  estimates  covering  the  whole  of  the 
hand-workers  of  a  country-  throw  no  light  on  such  a  question,  for  few 
indeed  are  the  lands  where  the  masses  of  the  people  have  such  well-filled 
purses  that  they  are  able  to  nourish  themselves  according  to  their  wishes. 
While  it  is  true  that  the  great  majority  of  normal  individuals  (although 
not  all,  since  even  in  the  fattening  of  stock  for  market  some  animals  are 
rejected  as  bad  feeders)  can  be  compelled  to  lay  on  fat  when  overfed 
with  fat  and  especially  with  carbo-hydrates,  and  prevented  from  takmg 
much  exercise  or  from  losing  heat  freely,  the  most  important  factor  in 
the  excessive  storing  of  fat  b}-  human  beings  leading  a  free  life  seems  to 
be  an  anomaly  in  the  metabolism  which  permits  the  machine  to  be  run  on 
less  than  the  usual  amount  of  fuel.     From  the  point  of  view  of  thenno- 
djTiamics  the  fat  man,  in  verj-  many  instances  at  least,  grows  fat  and 
fatter  because  his  body  is  a  machine  whose  '  efficiency  '  is  greater  than 
the  normal — that  is  to  say,  a  machine  which  is  capable  of  doing  a  given 
amount  of  work  and  of  keeping  itself  in  repair  with  a  food  intake  of 
smaller  heat  value  than  is  usually  needed.     Whether  this  anomaly  is  to 
be  considered  a  metabolic  fault  or  a  metabolic  virtue  depends  largely 
upon  the  ease  with  which  the  intake  is  adjusted  to  the  actual  require- 
ment of  the  body.     If  the  adjustment  is  rendered  accurate,  the  man 
with  the  anomalous  tendency  to  put  on  fat,  the  adiposophil .  ashe  might 
be  called,  is  in  all  probability  j ust  as  well  off  in  every  physiolog  ical  sense 
on  a  smaller  diet  than  a  so-called  normal  individual  of  the  same  age, 
weight,  and  daily  routine,  on  a  larger  quantity  of  food,  and   on  this 
smaller  diet  he  does  not  become  fat.     In  this  connection  it  may  be 
recalled  that,  in  speaking  of  the  blood-flow  in  the  hands  and  feet  (p.  127), 
which  are  in  this  relation  to  be  regarded  as  essentially  an  '  outcrop  ' 
of  the  cutaneous  circulation,  it  was  pointed  out  that  some  healthy 
persons  have  habitually  small  flows  and  a  habitually  cool  skin  which 
perspires  little,  in  comparison  witYi  others  living  practically  the  sam  e  life. 
It  was  suggested  that  this  difference  in  the  blood-flow  through  the  skin, 
.vhich  of  course  would  correspond  with  a  difference  in  the  rate  of  heat 
loss,  and  therefore  in  the  rate  of  heat  production,  may  be  correlated  with 
a  difference  in  the  intensity  of  the  metabolism  and  the  intake  of  food. 

The  difficulty-  of  adjusting  the  appetite  to  the  actual  physiological 
requirement  is  perhaps  the  real  anomaly  in  adiposophilia.  Several 
factors  seem  to  be  involved  in  the  group  of  sensations  comprised  under 
appetite  and  hunger  (Chapter  XVIII),  and  the  onset  and  intensity  of 
these   sensations  are   imquestionably  influenced   by   habit.     The  real 


570  METABOLISM.  XUTRITJON  AND  DIETETICS 

question  in  many  cases  of  obesity  may  be  not  why  the  metabolism  is 
managed  so  parsimoniously — that  is,  in  the  physiological  sense,  so 
thriftily — but  why  the  fat  man  or  the  man  tending  to  Income  fat  still 
experiences  so  strong  a  desire  for  food  after  he  has  eaten  what  in  pro- 
portion to  his  metabolic  wants  is  enough,  whereas  the  man  with  no 
tendency  to  obesity  is  no  longer  hungrj-  after  he  has  eaten  an  amount 
of  food  sufficient  for  the  requirements  of  his  tissues.  Is  there  here 
perhaps  an  anomaly  in  the  nervous  mechanism  in  virtue  of  which,  for 
instance,  the  gastric  himgcr  contractions  are  more  readily  initiated 
and  less  easily  stilled  than  in  the  normal  person  ?  It  is  recognized 
that  in  the  usually  much  more  serious  anomaly  of  the  carbo-hydrate 
metabolism,  diabetes  mcllitus,  the  nervous  element  may  be  important. 
The  influence  of  the  loss  of  certain  of  the  internal  secretions  on  the 
deposit  of  fat  will  be  alluded  to  in  the  next  chapter. 

In  the  treatment  of  obesity  the  factor  of  appetite  and  hunger  control 
has  to  be  specially  kept  in  mind.  Bulky  but  comparatively  innu- 
tritious  food,  such  as  green  vegetables,  e.g.,  in  the  form  of  salads,  should 
form  an  important  constituent  of  the  dietary-,  since  the  mere  distension 
of  the  stomach  staves  off  hunger.  The  total  heat  value  of  the  food 
must  be  reduced  gradually.  Carbo-hydrates  must  be  largely  excluded, 
and  also  fats,  although  a  certain  amount  of  fat,  say  in  the  form  of 
butter,  is  permissible  and  even  beneficial  as  aiding  in  the  passage  of 
the  food  along  the  digestive  tube.  Alcoholic  beverages  are  in  general 
contra-indicated,  because  alcohol,  as  an  easily  oxidizable  substance, 
protects  the  carbo-hydrates  and  fats  from  oxidation,  and  perhaps  also 
because  the  normal  oxidative  power  of  the  tissues  nxa.y  be  depressed  by 
its  habitual  use.  On  the  other  hand,  tobacco  smoking,  which  has  some 
power  of  inhibiting  the  gastric  hunger  contractions,  may  be  permitted. 
Muscular  exercise,  cold  baths,  light  clothing  both  during  the  day  and 
at  night,  and  a  cool  environment,  are  favourable  to  the  reduction  of 
fat  by  increasing  the  consumption  of  material  and  the  loss  of  heat, 
just  as  a  sedentary  life  in  an  o\erheated  house  in  a  person  predisposed 
to  obesity,  and  eating  too  much  for  his  requirements,  favours  the 
putting  on  of  fat.  But  if  the  appetite  of  the  patient  is  allowed  to 
govern  the  intake  of  food,  the  increased  decomposition  brought  about 
by  exercise,  etc.,  is  ver\-  likeh-  to  be  balanced  by  an  increased  ingestion, 
and  no  progress  will  be  made. 

Metabolism  of  Sterins  or  Sterols. — It  has  been  previously  stated 
that  cholesterin  appears  to  be  the  only  representative  of  the  sterins 
in  the  higher  animals.  Its  source  and  function  have  been  much 
discussed  of  late  years.  As  to  its  source,  there  seems  to  be  no 
reason  to  believe  that  any  part  of  the  cholesterin  of  the  tissues  is 
formed  from  decomposition  products  of  ordinary  fats,  carbo- 
hydrates, or  proteins.  It  is  probably  entirely  derived  from  the 
cholesterins  of  animal,  and  the  phytosterins  of  vegetable  food.  On 
this  assumption,  its  metabolism,  imlike  that  of  the  great  groups  of 
food  substances,  is  carried  on  in  a  closed  circuit.  E\ndence  that 
it  can  be  s\Tithesized  from  other  substances  in  the  body  is  lacking. 
No  increase  in  the  cholesterin  lias  been  observed  during  the  develop- 
ment of  eggs,  and  the  cholesterin  content  of  gro\nng  chickens 
appears  to  correspond  to  the  sterins  taken  in  the  food  (Gardner). 
The  portion  of  the  cholesterin  which  is  ingested  in  the  form  of  esters 


THE  METABOLISM   Of  tAT  571 

is  probably  split,  with  liberation  of  the  fatty  acid,  in  the  course  of 
digestion.  But  if  this  be  so,  cholesterin  esters  are  again  formed 
in  the  tissues,  for  the  cells  and  the  blood  contain  both  cholesterin 
esters  and  free  cholesterin.  While  some  cholesterin  is  excreted  in 
the  faeces  (p.  423),  there  is  evidence  that  a  portion  of  the  cholesterin 
of  the  bile  may  be  reabsorbed,  a  '  circulation  '  of  cholesterin  taking 
place  analogous  to  the  circulation  of  bile-salts.  The  appearance  of 
cholesterin  in  the  bile  has  been  connected  by  some  writers  with  the 
destruction  of  erythrocytes  in  the  liver,  or  the  conveyance  of  the 
products  of  their  decomposition  to  that  organ  (p.  21),  but  there 
are  no  means  of  distinguishing  between  the  cholesterin  set  free  from 
blood-corpuscles  and  that  liberated  from  other  cells.  Since  it  is 
contained  in  all  cells,  every  cell  may  be  supposed  to  contribute 
something  from  time  to  time  to  the  cholesterin  excretion. 

As  to  the  office  of  the  tissue-cholesterin,  it  can  only  be  suggested 
that  a  substance  so  ubiquitous  must  be  important.  There  is  some 
evidence  that  cholesterin,  free  or  combined,  plays  a  part  in  con- 
ferring on  the  cells  those  peculiarities  in  their  permeability  upon 
which  their  functions,  and  indeed  their  integrity,  depend.  Free 
cholesterin,  for  instance,  hinders  the  haemolytic  action  of  the 
saponins  (p.  28),  apparently  by  forming  compounds  with  them 
Whether  it  or  its  esters  are  actually  concentrated  at  the  surface  of 
the  cell,  and  contribute  to  the  formation  there  of  the  so-called 
'  lipoid  '  envelope,  is  not  definitely  known,  although  there  are  facts 
in  favour  of  this  idea. 

Metabolism  of  Phosphatides. — The  lecithins,  which  are  the  best- 
known  members  of  this  class  of  compounds,  have  been  already 
described  (p.  366).  They  are  built  up  of  gl3^cerin,  fatty  acids, 
phosphoric  acid  in  the  form  of  glyceryl-phosphoric  acid,  and  a 
nitrogenous  base  cholin.  There  is  some  reason  to  think  that  the 
lecithins  of  the  tissues  are,  in  part  at  least,  not  free,  but  combined 
with  proteins  or  with  carbo-hydrates.  Other  bodies  belonging  to 
the  phosphatide  group  are  kephalin,  a  constituent  of  nervous  tissue 
and  of  yolk  of  egg,  cuorin  found  in  heart  muscle,  etc. 

It  is  probable,  as  stated  in  the  chapter  on  Digestion,  that  the 
phosphatides  of  the  food  are  hydrolysed  in  the  alimentary  canal 
with  liberation  of  the  glycerin,  fatty  acids,  and  the  other  com- 
ponents. It  is  not  known  whether  they  are  resynthesized  in  the 
intestinal  wall,  but  it  is  more  probable  that  they  pass  directly  to 
the  tissues,  where  they  can  be  utilized  for  building  up  the  phos- 
phatides of  the  cells.  Chohn  is  found  in  small  quantities  free  in  the 
tissues,  and  also,  it  is  said,  in  the  blood-plasma.  Glyceryl-phos- 
phoric acid  has  also  been  obtained  in  small  amount  from  various 
tissues.  The  other  components  of  lecithin  are,  of  course,  never 
wanting,  and  there  can  be  no  doubt  that  the  cells  possess  the  power 
of  reconstructing  phosphatides  from  such  materials.     They  can  do 


572  METABOLISM,   NUTRITION  AND  DIETETICS 

more  than  this:  they  can  prepare  the  'building-stones 'themselves. 
For  even  when  the  ingestion  of  phosphatides  in  the  food  is  excluded, 
or  the  intake  is  so  small  as  to  be  negligible,  the  formation  of  phos- 
phatides in  the  body  goes  on  apparently  without  chock.  An  instance 
of  this  will  be  given  on  a  future  page  in  discussing  experiments  on 
the  relative  value  of  different  proteins  for  nutrition  and  growth. 
A  very  striking  observation  has  been  recorded  by  McCollom,  who 
fed  three  hens  on  a  diet  almost  free  from  fat.  In  about  three  and  a 
lialf  months  they  laid  fifty-seven  eggs,  containing  over  9  per  cent,  of 
phosphatides.  Calculation  showed  that  here,  first  of  all,  fats  or  their 
components  must  have  been  constructed  from  carbo-hydrates. 
Then  the  nitrogenous  component  of  the  phosphatides  (cholin  in  the 
case  of  lecithin,  at  least)  must  have  been  obtained  from  some  source, 
possibly  from  an  amino-acid  by  the  addition  of  methyl  groups 

/CH3 

(CH3),  of  which  cholin,  OH-H^CHgC  -NC^fJs  (trimethyl-oxyethyl- 

OH 
ammonium  hydroxide)  contains  three. 

Section  III. — Metabolism  of  Proteins. 

Blood-Proteins. — The  two  chief  proteins  of  the  plasma,  serum- 
globulin  and  serum-albumin,*  must,  as  has  been  already  pointed  out, 
be  recruited  from  proteins  absorbed  from  the  intestine  and  for  the  most 
part,  at  any  rate,  profoundly  altered  in  its  lumen  and  in  their  passage 
through  the  epithelium  which  lines  it.  Even  when  proteins  are  being 
actively  absorbed,  the  plasma,  after  the  blood-proteins  have  been 
separated,  contains  no  substances  which  give  the  biuret  reaction 
(p.  449).  So  that  the  peptones,  which  can  be  demonstrated  in  the 
intestinal  contents,  suffer  great  changes  before  or  during  their 
absorption.  The  physiological  reasons  for  this  alteration  are  in  a 
measure  known,  and  have  already  been  alluded  to  in  connection 
with  the  digestion  of  proteins.  No  doubt  the  far-reaching  decom- 
position of  the  protein  molecule  may  to  some  extent  facilitate  the 
absorption  of  protein  food.  No  doubt  also  it  is  imperative  that 
such  comparatively  slightly  hydrolysed  products  as  peptone,  and 
particularly  proteose,  should  not  appear  in  quantity  in  the  blood, 
for  when  injected  they  cause  profound  changes  in  that  liquid,  one 
expression  of  which  is  the  loss  of  its  power  of  coagulation,  and  are 
rapidly  excreted  by  the  kidneys,  or  separated  out  into  the  Ij-mph. 
But  the  passage  of  the  food  from  the  stomach  is  so  gradual  an  affair, 
the  quantity  of  digesting  protein  present  at  one  time  in  any  loop 
of  intestine  is  so  small,  and  the  rush  of  blood  which  irrigates  the 

*  It  is  probable  that  plasma  contains  a  mixture  of  different  albumins  anc* 

globulins. 


METABOLISM  OF  PROTEINS  573 

active  mucosa  is  so  large,  that  the  concentration  of  peptone  or 
proteose  necessary  to  procUice  injurious  eltects  could  hardly  in  any 
case  be  realized.  Again,  there  is  no  evidence  tluU:  the  simpler 
decomposition  products  of  further  hydrolysis  are  not  in  equal  con- 
centration as  poisonous  as  proteose  and  peptone. 

Apart  from  any  influence  which  it  may  have  in  favouring  absorp- 
tion, the  complete  shattering  of  the  protein  molecule  has  a  double 
significance.  In  the  first  place,  as  already  pointed  out,  the  food- 
proteins  cannot  be  used  directly  in  the  upbuilding  and  repair  of  the 
protoplasm  (p.  448),  since  the  tissue-proteins  differ  from  them  and 
from  each  other  in  the  amount  and  nature  of  the  amino-acids  and 
other  groups  in  their  molecule  (p.  2).  Secondly,  under  ordinary 
dietetic  conditions  a  surplus  of  nitrogen  in  the  protein  food  has  to 
be  got  rid  of  by  being  converted  into  urea  without  being  built  up 
into  the  tissue  substance.  Here  we  come  upon  the  fundamental 
fact  that  the  protein  katabolism  is  not  a  single  uniform  process. 
Two  forms  may  be  distinguished  which  are  essentially  independent 
in  course  and  character.  One  kind  varies  extremely  in  its  quantita- 
tive relations,  according  to  the  amount  of  protein  in  the  food.  Its 
chief  end-products  are  urea,  representing  the  nitrogen,  and  inorganic 
sulphates,  representing  the  sulphur  of  the  proteins.  Since  this  form 
of  katabolism,  as  we  shall  see  directly,  is  not  essentially  connected 
with  the  life  and  nutrition  of  the  living  substance,  it  is  termed 
exogenous.  The  other  variety  is  practically  constant  in  amount 
for  one  and  the  same  individual,  and  independent  of  the  quantity 
of  protein  in  the  food.  Its  characteristic  end-products  are  creatinin 
and  neutral  sulphur.  This  form  of  protein  katabolism  is  essentially 
an  expression  of  the  waste  of  the  living  substance  itself,  and  is 
therefore  spoken  of  as  endogenous. 

Some  have  supposed  that  the  intestinal  mucosa  has  as  one  of  its 
special  functions  the  resynthesis  of  a  great  part  of  the  digestive 
decomposition  products  into  the  proteins  of  the  blood-plasma.  If 
this  is  the  case,  these  proteins  must  be  again  decomposed  in  the 
cells  of  the  various  tissues  in  order  that  the  '  building-stones  '  may 
be  recombined  to  form  the  tissue-proteins.  For  the  proteins  of  the 
organs  are  not  the  same  as  those  of  the  blood,  and  the  proteins  of 
different  organs  differ  characteristically  from  each  other.  The 
significance  of  the  synthetic  function  of  the  intestinal  wall  would 
then  lie  in  this:  that  from  the  varjdng  mixture  of  amino-acids,  etc., 
derived  from  the  food-proteins  an  always  uniform  and  suitable 
protein  mixture  (the  blood-proteins)  is  fabricated  for  the  feeding 
of  the  tissues.  Experiments  intended  to  test  this  hypothesis  have 
hitherto  yielded  a  negative  result.  No  accumulation  of  protein  in 
the  wall  either  of  the  intestine  in  situ  or  of  the  isolated  surviving 
intestine  has  been  detected  during  absorption  of  the  decomposition 
products  of  protein.  An  alternative  assumption,  and  superficially 
at  least  a  simpler  one,  is  that  no  more  extensive  synthesis  of  proteins 


574  METABOLISM.   NUTRITION  AND  DIETETICS 

occurs  in  the  wall  of  the  ahmentary  canal  than  is  necessary  for  the 
needs  of  the  tissues  composing  it,  and,  perhaps  in  addition,  for  the 
maintenance  of  the  normal  composition  of  the  ])lasma,  and  that  the 
decomposition  products  of  the  proteins  are  mainly  absorbed  as  such, 
and  pass  in  the  blood  to  the  tissues  for  which  they  are  destined.  If 
this  is  the  case,  the  blood-proteins  can  no  longer  be  looked  upon  as 
representing  the  main  current  of  protein  supply  for  the  organs,  but 
rather  the  store  of  protein  material  proper  to  the  circulating  tissue 
blood  itself,  and  which  confers  on  it  certain  chemical  and  physio- 
chemical  properties  {e.g.,  the  due  degree  of  viscosity)  necessary  for 
its  function.  Slowly  accumulated,  under  ordinary  conditions,  and 
slowly  consumed,  this  protein  store  may,  of  course,  be  at  the  dis- 
posal of  the  organs  in  an  emergency — for  instance,  in  starvation — 
or  may  be  rapidly  recruited  from  the  organ-proteins,  as  after 
haemorrhage,  just  as  in  prolonged  hunger  the  proteins  of  skeletal 
muscle  may  be  utiUzed  to  feed  the  heart.  That  the  blood-proteins 
can  serve  as  nutritive  material  for  the  cells  without  undergoing 
digestion  in  the  alimentary  canal  is  well  shown  by  the  observations 
of  Carrell  and  Burrows  on  the  growth  of  isolated  tissues  in  a  medium 
composed  of  clotted  blood-plasma.  But,  as  previously  pointed  out 
in  another  connection  (p.  449),  a  portion,  and  probably  a  large 
portion,  of  the  digested  protein  is  absorbed  from  the  intestine  by 
the  blood  in  the  form  of  amino-acids.  Considerable  quantities  of 
these  compounds  can  be  separated  by  dialysis  from  blood  drawn 
off  during  the  absorption  of  proteins  or  by  the  process  of  vivi- 
diffusion  (p.  48)  (Abel).  Among  these  amino-acids,  glycocoU, 
alanin,  glutaminic  acid,  and  leucin,  have  been  identified.  While 
the  quantity  of  amino-acids  in  the  blood,  which  is  very  small  in  the 
fasting  animal,  is  decidedly  increased  during  protein  digestion,  it 
is  probable  that  even  in  starvation  amino-acids  derived  from  the 
decomposition  of  the  body-proteins  are  not  entirely  lacking.  The 
normal  concentration  of  amino-acids  in  the  general  blood  of  man  and 
of  the  dog  is  about  01  per  cent. — i.e.,  about  the  same  as  that  of 
dextrose,  and  it  may  be  nearly  twice  as  great  in  the  portal  blood 
of  dogs  after  a  heavy  protein  meal.  The  amino-acids  are  very 
rapidly  absorbed  by  the  tissues  from  the  blood,  and  can  be  demon- 
strated in  muscles  and  other  organs  as  free  amino-acids.  They 
accumulate  there  in  much  greater  concentration  than  that  in  which 
they  exist  in  the  blood.  Accordingly,  the  tissues  take  them  up  from 
the  blood  by  some  other  process  than  simple  diffusion  (Van  Slyke). 
It  has  been  surmised  that  amino-acids  constitute  the  form  in  which 
proteins  are  transported  from  tissue  to  tissue,  as  well  as  the  form  in 
which  proteins  are  normally  utilized  by  the  cells.*  Although  this 
cannot  be  regarded  as  yet  established,  there  is  reason  to  believe  that 

•  Recent  experiments  of  Abel  tend  to  rehabilitate  the  old  view  that  some 
protein  is  absorbed  as  proteoses,  which  can  also  be  isolated  from  the  tissues 


METABOLISM  OF  PROTEINS 


573 


the  amino-acids  play  a  great  part  in  protein  metabolism,  perhaps  as 
great  a  part  as  the  dextrose  docs  in  the  metabohsm  of  the  carbo- 
hydrates. There  is  some  evidence  that  serum-albumin  is  more 
directly  related  to  thf  proteins  of  the  food  than  scrum-globulin. 
And  it  is  said  that  during  starvation  the  albumin  is  relativelv 
diminished,  and  the  globulin  relatively  increased.  It  is,  of  course, 
not  at  all  improbable  that  the  plasma-proteins  have  a  double  source 
— organ-proteins  on  the  one  hand,  food-proteins  on  the  other.  In 
any  case,  it  is  certain  that  serum-albumin  and  serum-globulin 
c  annot  be  intercliangeable  without  far-reaching  decomposition,  for 
their  composition  is  very  different.  The  globulin,  e.g.,  yic^lds  glyco- 
coll,  but  the  albumin  does  not.  That  the  plasma-protein  mixture 
maintains  a  very  constant  composition  in  the  face  of  wide  variations 
in  the  composition  of  the  food-protein  is  indicated  b}'  the  following 
experiment: 

A  horse  fed  mainly  on  hay  and  oats  was  bled  to  the  amount  of 
6  litres,  and  in  the  total  protein  of  the  serum  the  content  of  tyrosin  and 
glutaminic  acid  was  detennined.  In  order  to  eliminate  the  influence 
of  remains  of  the  food  in  the  digestive  canal,  nothing  was  given  to  the 
animal  for  a  week.  'Ihen  6  litres  of  blood  were  again  removed,  and  the 
tyrosin  and  glutaminic  acid  in  the  serum-protein  again  estimated. 
The  horse  was  now  fed  with  gliadin  (one  of  the  prolamins  or  alcohol- 
soluble  proteins  obtained  from  flour),  a  substance  which  contains  36'5  per 
cent,  glutaminic  acid  and  2-37  per  cent,  tyrosin — that  is,  about  the 
same  amount  of  tyrosin  as  the  serum-protein,  but  about  four  times  as 
much  glutaminic  acid.  The  serum-protein  was  again  analyzed  for  the 
two  amino-acids  after  this  diet.  The  results  of  one  experiment  are 
shown  in  the  table  : 


Normal. 

After  8  Days' 
Hunger. 

After  Feeding 

with  1,500 

Grammes 

Gliadin. 

After  Feeding 

again  with  1,500 
Grammes 
Gliadin. 

Tyrosin   -         -         - 
Glutaminic  acid 

2-43 
8-85 

2 -60 
8-20 

2-24 

7-88 

2-52 

8-25 

No  increase  in  the  glutaminic  acid  content  of  the  serum-protein 
occurred,  although,  owing  to  the  loss  of  blood,  much  new  scrum-protein 
must  have  been  formed.  If  the  amino-acids  of  the  gliadin  were  used 
without  change  to  build  up  the  new  serum-protein,  three-quarters  of 
the  glutaminic  acid  must  have  been  superfluous,  and  the  nitrogen  of 
this  portion  may  have  been  straightway  changed  into  urea  and  excreted. 
But  the  possibility  that  the  glutaminic  acid,  or  a  portion  of  it,  may 
have  been  changed  into  other  amino-acids  in  the  body  cannot  be 
excluded.  In  the  case  of  some  of  the  amino-acids  it  has  been  shown 
that  such  a  transformation  occurs  (p.  613)  (Abderhalden). 

The  high  degree  of  independence  of  the  food  and  body  proteins  is 
still  more  clearly  exhibited  in  the  table  from  Abderhalden  on  p.  57b, 
in  which  the  proteins  of  milk  are  compared  with  some  of  the  proteins 
which  must  be  formed  from  them  in  the  body  of  the  suckling.  The 
numbers  represent  percentages  of  the  weight  of  each  protein. 


576 


METABOLISM.  NUTRlTlOX  AND  DIETETICS 


Living  and  Dead  Proteins. — Carried  to  the  tissues,  the  decomposition 
produLls  of  the  food -proteins,  or  the  regenerated  proteins  of  the  plasma, 
which  in  ordinary  language  are  still  to  be  regarded  as  dead  material, 
arc  built  up  into  the  living  protoplasm,  at  any  rate  to  the  extent  neces-, 
sary  to  make  good  its  waste.  In  this  form  they  sojourn  for  a  time 
within  the  cells,  and  then  they  become  dead  material  again.  The 
nature  of  this  tremendous  transformation  has,  of  course,  been  the 
subject  of  speculation,  but  the  truth  is  that  we  do  not  understand 
wherein  the  difference  between  a  living  and  a  dead  cell,  between  a  living 
and  a  dead  particle  in  one  and  the  same  cell,  really  consists.  All  we 
know  is  that  now  and  again  a  protein  molecule  or  an  aggregate  of  such 
molecules  incorporated  in  the  colloid  mass  which  constitutes  the  proto- 
plasm of  a  muscle-fibre,  or  a  gland-cell,  or  a  nerve-cell,  must  fall  to 
pieces.  Now  and  again  a  molecule  of  protein ,  hitherto  dead  (or  perhaps, 
to  speak  more  correctly,  hitherto  not  a  constituent  of  living  protoplasm, 
since  protoplasm  is  certainly  more  than  protein),  or  a  molecule  of  a 
particular  amino-acid,  or  perhaps  a  polypeptide  group  intermediate  in 
complexity  between  amino-acid  and  protein,  coming  within  the  grasp 
of  the  molecular  forces  or  chemical  affinities  of  the  living  substance,  is 
caught  up  by  it,  takes  on  its  peculiar  motions,  acquires  its  special  powers, 
and  is,  as  we  phrase  it,  made  alive.  Each  cell  has  tlic  power  of  selecting 
and,  if  necessary,  further  decomposing  or  further  synthesizing  the 
protein  materials  offered  to  it ;  so  that  a  particle  of  sx-rum-albumin  or  a 
mixture  of  amino-acids  may  chance  to  take  its  place  in  a  liver-cell  and 
help  to  form  bile,  while  an  exactly  similar  particle  or  mixture  may 
furnish  constituents  to  an  endothelial  scale  of  a  capillary  and  assist  in 
forming  lymph,  or  to  a  muscular  fibre  of  the  heart  and  help  to  drive  on 
the  blood,  or  to  a  spermatozoon  and  aid  in  transferring  the  peculiarities 
of  the  father  to  the  offspring.  And  just  as  a  tomb  and  a  lighthouse,  a 
palace  and  a  church,  may  be,  and  have  been,  built  with  the  same  kind 
of  material,  or  even  in  succession  with  the  verj^  same  stones,  so  every 
organ  builds  up  its  own  characteristic  structure  from  the  common 
quarry  of  the  blood. 


1 

6 

il 
4 

3 

O 

5 

ft 

=;5 

c 
•3 

5 

2 

Glycocoll  - 

o 

O 

o 

3 -.5 

o 

3-0 

0-5 

26-0 

47 

1  Alanin 

0-9 

2-5 

2-7 

2-2 

4-2 

3-6 

3-5 

6-6 

1-5 

:  Valin 

I-O 

0-9 

some 



some 

I-O 

i-o 

0-9 

{  Leucin 

10-5 

I9-.5 

20*0 

18-7 

29-0 

I5-0 

II-8 

21-4 

7-1  ! 

1  Serin 

0-2 

0-6 

0-6 

some 

— 

_   i 

1  Cystin 

o-oy 

— 

2-3 

0-7 

0-3 

— 

— 

— 

0-6 

Asparaginic  acid 

1-2 

I'O 

3-1 

2-5 

4*4 

2-0 

— 

— 

lO-O 

Glutaminic  acid 

II-O 

lO'O 

77 

8-=i 

17 

8-0 

0'3 

0-8 

37 

Lysin 

.V« 

— 

4-3 

— 

6-q 

— 

Arginin 

4-8 

— 

— 

— 

5'4 



I5'5 

o-^ 



Phenylalanin      - 

3-2 

2-4 

3-1 

3-8 

4-2 

2-0 

2-2 

3-9 

— 

Tyrosin     - 

4*5 

I-O 

2-1 

2-5 

1-5 

3-3 

.5-2 

0-34 

3-2 

Prolm 

3-1 

4-0 

i-o 

2-8 

2-3 

2-5 

1-5 

1-7 

3  "4 

Histidin    - 

2-6 



— 

II-O 

1-5 

M ETA  HOLISM  OF  PROTEINS  577 

It  is  not  any  difference  in  tlic  kind  of  protein  oflcrcd  tliem  which 
determines  the  difference  in  structure  and  action  between  one  organ 
and  another.  In  tliis  quarry  alongside  of  the  plasma  proteins  the  tissue 
cells  find  what  is  probably  more  important  for  their  individual  nutrition, 
the  building-stones  of  the  shattered  food-protein  molecules.  They  are 
only  under  exceptional  circumstances  confronted  with  intact  molecules 
of  food-proteins.  '  The  body  cells  do  not  know  what  the  kind  of  food 
was  '  (Abderhalden).  In  the  case  of  the  more  highly  developed  tissues, 
at  least,  no  mere  change  of  food  will  radically  alter  the  structure  of  the 
cells,  nor  even,  as  we  have  seen,  the  composition  of  the  tissue  proteins. 
A  cell  may  be  fed  with  different  kinds  of  food,  it  may  be  overfed,  it  may 
be  ill-fed,  it  may  be  starved;  but  its  essential  peculiarities  remain  as 
long  as  it  continues  to  live.  What  may  be  called  its  organization,  per- 
haps at  bottom  a  more  or  less  metaphorical  expression  for  its  tssential 
physico-chemical  make-up,  dominates  its  nutrition  and  function. 

'  We  must  assume  that  many  of  the  enigmatical  properties  of  living 
matter  depend  upon  the  activity  of  intact  protein  molecules.  We  can 
obtain  some  idea  of  the  possible  variety  in  the  combinations  of  the 
''  building-stones  "  of  the  proteins  by  recalling  the  fact  that  they  are  as 
numerous  as  the  letters  of  the  alphabet,  which  are  capable  of  expressing 
an  infinite  number  of  thoughts.  Every  peculiarity  of  species  and  every 
occurrence  affecting  the  individual  may  be  indicated  by  special  com- 
binations of  the  "building-stones  " — that  is  to  say,  by  specific  proteins. 
Consequently  we  may  readily  understand  how  peculiarity  of  species 
may  find  expression  in  the  chemical  nature  of  the  proteins  constituting 
living  matter,  and  how  they  may  be  transmitted  through  the  material 
contained  in  the  generative  cells  '  (Kossel).  Add  to  the  great  variety 
of  compounds  rendered  possible  by  the  enormous  number  of  permuta- 
tions and  combinations  of  the  protein  '  building-stones,'*  the  still  greater 
variety  rendered  possible  by  the  fact  that  the  quantitative  relations  of 
given  amino-acids  may  vary  greatly  in  different  proteins,  and  it  will  be 
seen  what  a  practically  infinite  power  of  functional  adjustment  and 
reaction,  correlated  with  a  practically  infinite  variety  of  chemical 
changes  in  the  midst  of  which  the  cell  still  preserves  its  specificity 
through  and  through,  may  be  conferred  upon  the  living  substance  by 
its  content  of  protein. 

Some  have  supposed  that  the  protein  of  the  living  substance  is  es- 
sentially different  from  dead  protein,  especially  in  possessing  a  character- 
istic instability,  a  prodigious  power  of  dissociation  and  reconstruction. 
All  the  older  theories  which  attempted  to  explain  this  alleged  difference 
require  revision  in  accordance  with  the  newer  chemistr^^  of  proteins, 
and  speculations  on  the  subject  are  probably  in  any  case  premature 
till  the  constitution  of  the  proteins  is  thoroughly  understood.  In  the 
meantime  it  is  enough  to  say  that  the  velocity  of  the  reactions  into 
which  the  proteins  of  living  protoplasm  or  their  constituent  amino- 
acids  may  enter  must  depend  upon  intracellular  conditions,  which  may 
vary  rapidly  and  within  wide  limits.  For  example,  enz^-mes  may  be 
present  ia  greater  or  smaller  concentration,  or  be  activated  and  aided 
more  or  less  powerfully  by  other  substances,  or  by  a  more  or  less  favour- 
able chemical  reaction  of  the  medium.  The  protein  itself,  too,  or  such 
part  of  it  as  is  ready  for  decomposition,  may  exist  in  a  physical  con- 
dition now  more  and  again  less  favourable  to  the  attack  of  the  enzymes. 

*  Twenty  different  amino-acids,  each  used  only  once,  but  in  a  different  order, 
would  be  capable  of  forming  about  2,000,000,000,000,000,000  (two  thousand 
million  times  a  thousand  millions)  of  different  poI\-peptides,  all  contaimng  the 
various  amino-acids  in  the  same  proportions  (Abderhalden). 

37 


578  M  ETA  HOLISM.  NUTRITION  AND  DIETETICS 

It  may  not  be  superfluous  at  tliis  point  to  again  warn  the  reader  that 
protoplaspi  and  tissuc-profeins  are  by  no  means  synonymous.  The 
physical,  physico-chemical,  and  chemical  changes  involved  in  the 
katabolism  of  the  colloid  aggregates,  including  water,  salts,  phosphatides, 
sterins,  and  probably  fats  and  dextrose  as  well  as  proteins,  to  which 
the  term  protoplasm  is  applied,  may  be  many  and  complex  before  the 
individual  proteins  known  to  the  chemist  come  face  to  face  in  the 
interior  of  the  cells  with  the  ferments  which  decompose  them.  On  the 
other  hand,  it  has  not  been  proved  that  in  the  katabolic  processes  of  the 
living  substance  isolated  proteins  ever  form  a  stage.  It  may  well  be 
that  without  the  complete  decomposition  of  the  protein  molecules,  or 
even  without  their  complete  detachment  from  the  protoplasm,  indi- 
vidual amino-acids  or  mixtures  cf  amino-acids,  or  polypeptide  groups, 
are  cut  out  of  the  protoplasmic  mass. 

It  is  now  necessary  to  follow,  as  far  as  is  possible*,  the  steps 
in  the  degradation  of  the  body-proteins.  Since  there  is  reason  to 
believe  that  these,  like  the  food-proteins,  are  first  split  up  into  the 
amino-acids  from  which  they  were  originally  synthesized  before 
undergoing  further  decomposition,  a  study  of  protein  metabolism 
is  to  a  great  extent  r  study  of  the  metabolism  of  amino-acids.  In 
this  study  it  is  for  most  purposes  impracticable,  even  if  it  were 
desirable,  to  distinguish  between  amino-acids  directly  derived  from 
the  food,  and  which  have  not  yet  been,  and  may  never  be,  built  up 
into  tissue-proteins,  and  those  derived  from  the  tissue  proteins. 
There  is  nothing  to  indicate  that  the  fate  of  a  given  amino-acid, 
once  it  has  reached  the  blood,  depends  in  the  least  upon  its  source. 
It  may  be  said  at  once  that  the  katabolism  of  the  amino-acids  is  not 
a  single  and  uniform  process,  one  step  in  which  inevitably  follows 
another  till  the  final  end-products  are  reached.  On  the  contrary, 
certain  of  the  stages  may  become  the  starting-points  of  syntheses, 
which  may  lead  back  to  the  original  or  to  another  protein,  or  it 
may  be  to  sugar  or  to  fat.  The  extent  of  such  synthesis,  and 
even  in  some  degree  the  stage  from  which  it  starts,  may  be  assumed 
to  depend  upon  the  needs  of  the  tissues  and  the  relative  abundance 
of  protein  and  of  other  foods. 

Formation  of  Amino-Acids  from  Tissue-Proteins. — That  amino- 
acids  are  formed  in  the  metabolism  of  the  cells  and  by  the  action  of 
intracellular  enzymes  is  indicated  by  the  fact  that  proteolytic  en- 
zymes (proteases)  are  invariably  present  in  the  tissues,  and  can 
be  obtained  from  them  by  appropriate  methods — e.g.,  by  subjecting 
the  organ  in  a  finely  divided  state  to  a  high  pressure  and  collecting 
the  expressed  juice.  Not  only  do  imicellular  organisms,  like  leuco- 
cytes, yeast  cells,  and  bacteria,  which  must  naturally  depend  upon 
themselves  alone  for  all  enzymatic  reactions,  yield  ferments  which 
have  the  power  of  splitting  proteins,  peptones,  and  polypeptides 
into  amino-acids,  but  their  existence  has  been  demonstrated  in 
practically  all  the  organs  of  the  higher  animals  and  man.  When  a 
piece  of  liver,  e.g.,  is  removed  with  aseptic  precautions  and  kept  at 


METABOLISM  OI-    PROTniNS  57O 

body-temperature,  extensive  auto-digestion  occurs,  and  ammonia 
and  otlu-r  basic  substances,  glycin,  and  tryptophane,  appear  among 
the  prochicts.  Tyrosin  appears  so  early  that  it  is  scarcely  possible 
to  doubt  that  it  must  be  a  product  of  protein  decomposition  in  the 
liver-cells  under  normal  conditions — a  decomposition  which  could 
be  observed  also  in  the  organ  in  situ  were  the  circumstances  as 
favourable.  The  circumstances  are  less  favourable  in  an  organ 
whose  circulation  is  going  on,  becaiise  the  amino-acids  are  removed 
by  the  blood  as  they  are  formed.  Further,  it  is  to  be  assumed  that 
the  regulation  of  the  ferment  action,  which  is  a  characteristic 
property  of  the  normal  cell,  becomes  feebler  the  longer  it  is  with- 
drawn from  normal  conditions.  Similar  autolytic  processes  have 
been  observed  in  the  spleen,  muscle,  lymph-glands,  kidneys,  lungs, 
stomach  wall  (independently  of  pepsin),  thymus,  and  placenta; 
also  in  pathological  new  growths  like  carcinoma,  in  the  breaking 
down  of  which  anti  in  the  removal  of  such  exudations  as  occur  in 
the  alveoli  in  pneumonia,  these  proteolytic  ferments  seem  to  play 
a  part.  It  is  to  be  assumed  that  the  syntheses  of  the  proteins  or 
their  products,  which  are  scarcely  less  characteristic  of  the  tissue 
cells  than  the  decompositions  effected  by  them,  are  also  due  to 
the  action  of  separate  intracellular  ferments  or  upon  the  reversed 
activity  of  the  proteolytic  ferments. 

More  direct  proofs  of  the  production  of  amino-acids  in  the  tissues 
are  not  lacking.  A  rare  condition  known  as  cystinuria  has  been 
alluded  to  on  a  previous  page  (p.  488).  Here  there  is  a  continuous 
excretion  of  the  sulphur-containing  amino-acid  cystin  in  the  urine. 
Sometimes  the  cystin  is  accompanied  by  other  amino-acids,  as 
leucin  and  tyrosin,  a  condition  which  might  be  called  amino- 
aciduria. Cystinuria,  while  of  course  resulting  from  a.gross  anomaly 
in  metabolism,  is  of  little  clinical  importance  unless  the  sparingly 
soluble  cystin  should  form  calculi  somewhere  in  the  urinary  tract. 
The  most  plausible  explanation  of  the  condition  is  that  in  the 
normal  course  of  the  metabolism  each  of  the  '  building-stones '  of 
the  proteins  is  sooner  or  later  further  decomposed  by  special  fer- 
ments, and  that  for  some  reason  the  ferment  which  acts  on  cystin 
is  absent,  or  if  it  is  still  produced,  the  conditions  are  more  or  less 
unfavourable  to  its  action.  Unable  to  take  its  place  in  the  meta- 
bolic current,  except  in  so  far  as  it  can  be  utilized  to  form  taurin, 
and  therefore  taurocholic  acid — for  this  property  it  has  not  lost — 
cystin  becomes  a  chemical  outcast  in  the  body  of  the  cystinuric 
individual,  and  is  got  rid  of  by  the  kidneys  as  an  '  unemployable.' 
By  comparing  the  amount  of  cystin  excreted  with  the  amount 
ingested  in  the  food-proteins  and  with  the  (undiminished)  amount 
contained  in  the  tissues  (especially  the  hair  and  the  nails,  since 
keratin  is  exceptionally  rich  in  cystin),  it  has  been  shown  that  a 
portion  of  the  cystin  in  the  urine  must  have  come  from  the  tissues 


5?^!  METABOLISM.  NUTRITION  AND  DIETETICS 

(Abdcrlialilcn).  Observations  on  animals  in  prolonged  starvation 
afford  additional  evidence.  The  hair  and  nails  continue  to  grow 
and  to  maintain  the  high  cystin  content,  and  taurocholic  acid  con- 
tinues to  be  excreted.  In  like  manner  glj'cin  continues  to  be  pro- 
duced and  to  unite  with  cholic  acid  to  form  the  glycocholic  acid  of 
the  bile. 

There  are  other  and  more  striking  proofs  that  glycin  can  be 
formed  in  the  body  in  large  amount.  For  example,  as  already 
stated  (p.  481),  when  benzoic  acid  is  ingested  it  is  not  excreted  as 
such  in  the  urine,  but  coupled  with  glycocoll  as  hippuric  acid. 
Thus— 

CjHb.COOH  +  CH2(NH2).COOH  -  HgO  =CaH6.CO.NH.CH2.COOH 

Ben7oic  acid.  Glycocoll.  Hippuric  acid. 

Benzoic  acid,  therefore,  meets  glycin  in  the  body,  and  combines 
with  it,  as  fatty  acids  meet  glycerin  and  combine  with  it.  Even 
starving  animals  fed  with  benzoic  acid  excrete  large  quantities  of 
hippuric  acid.  Yet  their  tissues,  as  shown  by  analysis  after  death, 
yield  as  much  glycocoll  as  starving  animals  which  have  received  no 
benzoic  acid,  and  excreted  little  or  no  hippuric  acid.  Many  other 
acids  which  are  totally  foreign  to  the  body  are,  when  ingested, 
paired  in  the  same  way  with  glycocoll  and  excreted  in  the  urine. 
Even  substances  whose  chemical  nature  does  not  permit  of  a  direct 
union  with  the  glycin  are  often  altered  by  oxidation  or  reduction 
till  they  can  unite  with  it,  and  then  the  coupling  takes  place,  and 
the  conjugated  acid  is  eliminated  by  the  kidneys.  The  paired  or 
aromatic  sulphuric  acid  which  we  have  already  recognized  as  a 
normal  constituent  of  the  urine  affords  another  instance  of  this 
coupling.  Cystein  among  the  derivatives  of  proteins,  and  glycu- 
ronic  acid  (p.  482)  among  the  derivatives  of  carbo-hydrates,  can 
also  unite  in  the  same  way  with  numerous  compounds.  There  is 
some  evidence  that  the  physiological  significance  of  this  process  is 
that  the  toxicity  of  the  foreign  substances,  or,  as  in  the  case  of  the 
aromatic  sulphuric  acid  of  the  urine,  of  substances  formed  by 
bacteria  in  the  intestine,  or  even  produced  in  the  metabolism  of  the 
tissues,  is  diminislied  by  the  pairing. 

The  place  and  manner  of  formation  of  hippuric  acid  have  been 
investigated  with  the  following  result:  If  an  excised  kidney  is  per- 
fused with  blood  containing  benzoic  acid,  or,  better,  benzoic  acid 
and  glycin,  hippuric  acid  is  formed.  Oxygen  is  required,  for  if  the 
blood  is  saturated  with  carbon  monoxide,  or  if  serum  is  employed 
for  perfusion,  the  synthesis  does  not  take  place.  The  kidney  cells 
must  be  intact,  for  if  a  mixture  of  blood,  glycin,  and  benzoic  acid 
be  added  to  a  minced  kidney  immediately  after  its  removal  from 
the  body,  hippuric  acid  is  produced,  but  not  if  the  kidney  has  been 
crushed  in  a  mortar.     Nevertheless,  there  is  some  evidence  that  a 


METABOLISM  OF  PROTEINS  581 

ferment  is  concerned,  and  the  known  mechanism  of  similar  reactions 
in  the  body  scarcely  permits  the  physioloi^ist  to  acquiesce  in  any 
other  explanation.  It  must  not  be  forg(jtten  that  the  urinary 
constituents  which  must  come  into  contact  with  the  ferment  when 
the  kidney  is  crushed  may  injure  or  inhil^it  the  enzyme.  In 
herbivora  hippuric  acid  cannot  normally  be  detected  in  the  blood; 
it  is  present  in  large  quantities  in  the  urine;  it  must  therefore  be 
manufactured  in  the  kidney,  not  merely  separated  by  it.  In  certain 
animals,  as  the  dog,  the  kidney  is  the  sole  seat  of  the  production 
01  hippunc  acid.  But  in  the  rabbit  and  the  frog  some  of  it  must 
also  be  formed  in  other  tissues,  for  after  extirpation  of  the  kidneys 
the  administration  of  benzoic  acid  causes  hippuric  acid  to  appear 
in  the  blood.  It  has,  indeed,  been  recently  shown  that  when  the 
rabbit's  liver  is  perfused  with  blood  containing  benzoic  acid,  hip- 
puric acid  is  produced.  The  benzoic  acid  required  for  the  normal 
excretion  of  hippuric  acid  comes  mainly  from  substances  of  the 
aromatic  group  contained  in  vegetable  food,  but  a  small  amount  is 
produced  in  the  body,  since  hippuric  acid  does  not  entirely  dis- 
appear from  the  urine  in  starvation. 

The  differences  which  may  exist  in  the  metabohsm  of  different 
groups  of  animals  is  well  illustrated  by  the  fact  that  in  birds,  when 
benzoic  acid  is  given  in  the  food,  it  unites  not  with  glycin,  but  with 
ornithin,  a  derivative  of  arginin,  forming  not  hippuric  acid,  but 
ornithuric  acid  (dibenzoyl-ornithin).  A  much  more  important 
instance  of  such  a  difference  will  be  seen  when  we  come  to  consider 
the  formation  of  urea  and  uric  acid. 

The  method  by  which  the  presence  and  the  production  of  glyco- 
coll  in  the  body  are  demonstrated  by  coupling  it  with  benzoic  acid, 
and  so  sa\ang  it  from  decomposition  and  bringing  it  to  excretion, 
can  also  be  applied  to  other  amino-acids.  If  instead  of  fishing 
with  the  bait  benzoic  acid  we  fish  with  a  bait  called  brom-benzol  or 
bromo-benzene  (CgHg.Br),  a  substance  derived  from  benzol  by 
the  substitution  of  an  atom  of  bromine  for  an  atom  of  hydrogen, 
we  capture  the  amino-acid  cj-stein  in  the  form  of  a  compound 
called  mercapturic  acid,  produced  by  the  union  of  brom-benzol  with 
cystein  and  acetic  acid,  with  oxidation  and  loss  of  water.  In  other 
words,  when  this  substance  is  administered,  mercapturic  acid  is 
excreted  in  the  urine,  the  cystein,  which  is  very  unstable  and  readily 
changes  into  cystin  (p.  360),  being  thus  preserved  from  decom- 
position. Another  instance  in  which  amino-acids  (tyrosin  and 
phenylalanin),  which  would  normally  be  decomposed  and  so  escape 
detection,  come  to  the  surface  by  being  excreted  in  the  urine,  has 
a'ready  been  alluded  to  in  connection  with  alkaptonuria  (p.  483). 
In  this  condition,  which  seems  to  have  no  serious  significance  so 
far  as  the  well-being  of  the  patient  is  concerned,  not  only  does  the 
taking  of  food  containing  the  aforesaid  amino-acids  lead  to  an 


582  RIETABOLISM.  NVTIilTlOK  AND  DIETETICS 

increased  cx(  vction  of  homogentisinic  acid,  but  even  in  starvation 
this  substance  still  continues  to  appear  in  tlie  urine.  Since  liomo- 
gcntisinic  acid  is  undoubtedly  formed  from  tyrosin  and  from  phenyl- 
alanin,  this  observation  constitutes  a  convincing  proof  that  these 
amino-acids  are  produced  from  tissue-proteins.  A  striking  illus- 
tration of  the  fact  that  the  amino-acids  of  the  tissues  are  not  simply 
a  store  of  reserve  material  derived  directly  from  the  alimentary  canal 
is  the  failure  of  a  period  of  starvation  to  make  any  impression  upon 
their  amount.  They  normally  constitute  2  to  4  per  cent,  of  the  dry 
weight  of  the  tissues,  and  if  anything,  tend  somewhat  to  increase 
in  the  tissues  of  a  starving  animal. 

Fate  of  Amino- Acids  in  the  Body. — The  problem  of  the  kata- 
bolism  of  proteins  is  thus  reduced  to  the  question,  What  becomes  of 
the  amino-acids  ?  Where,  how,  by  what  stages,  and  to  what  end- 
products  are  they  decomposed  ?  Some  possible  or  probable  steps 
in  their  metabolic  history  have  been  already  suggested  in  dealing 
with  the  intermediary  metabohsm  of  carbohydrates  (p.  54-)- 
Something  more  will  have  to  be  said  of  the  where  and  the  how  of 
their  chemical  degradation  in  treating  of  the  place  and  manner  of 
urea  formation.  As  to  the  end-products  by  which  they  are  repre- 
sented in  the  final  balance-sheet  of  the  bodily  economy,  the  answer 
is  easy.  The  amino-acids,  whatever  intermediate  stages  they  may 
pass  through,  whatever  cleavages,  oxidations,  or  reductions  they  may 
undergo,  yield  eventually  carbon  dioxide,  water,  and  comparatively 
simple  nitrogen-containing  substances,  which  after  further  changes 
appear  in  the  urine  principally  as  urea,  and  in  birds  and  reptiles  as 
uric  acid.  When  amino-acids  are  fed  to  mammals  or  introduced 
parenterally,  a  very  large  proportion  of  the  nitrogen  appears  in  the 
urine  as  urea.  The  same  is  true  when,  instead  of  simple  amino- 
acids,  polypeptides,  hke  glycyl-glycin,  alanyl-alanin,  or  leucyl-leucin, 
are  given.  When  amino-acids  are  administered  to  birds,  the  great 
bulk  of  the  nitrogen  is  excreted  in  the  form  of  uric  acid.  Whether 
in  mammals,  and  if  so  to  what  extent,  uric  acid  is  also  one  of  the 
nitrogenous  end-products  of  the  decomposition  of  ordinary  proteins 
or  of  the  amino-acids  which  they  yield,  are  moot  questions.  In 
any  case,  the  most  important  and  characteristic  source  of  the  uric 
and  in  mammals  and  the  other  groups  of  animals  whose  chief 
nitrogenous  end-product  is  urea,  is  not  the  ordinary  proteins,  but 
the  nucleins  which  form  constituents  of  the  nucleo-proteins. 

We  have  no  definite  information  as  to  the  production  of  water  from 
the  hydrogen  of  the  tissues,  except  what  can  be  theoretically  deduced 
from  the  statistics  of  nutrition  (p.  620).  A  few  words  will  be  said 
a  little  farther  on  about  the  production  of  carbon  dioxide  from 
proteins;  we  have  now  to  consider  the  seat  and  manner  of  formation 
of  the  nitrogenous  metabolites.  And  since  in  man  and  the  other 
mammals  urea  contains,  under  ordinary  conditions,  by  far  the 


METABOLISM  OF  PROTEINS  583 

greater  part  of  the  excreted  nitrogen,  it  will   be  well  to  take  it 

first. 

Formation  of  Urea. — The  starting-point  of  all  inquiries  as  to  the 
place  of  formation  of  urea  is  the  fact  that  it  occurs  in  the  blood  in 
small  amount  (4  to  6  parts  per  10,000  in  man;  3  to  15  parts  per 
10,000  in  the  dog),  the  largest  quantity  being  found  when  the  food 
contains  most  protein  and  at  the  height  of  digestion,  the  smallest 
quantity  in  hunger  (Schondorff).  Evidently,  then,  some,  at  least, 
of  the  urea  excreted  in  the  urine  may  be  simply  separated  by  the 
kidney  from  the  blood;  and  analysis  shows  that  this  is  actually 
the  case,  for  the  blood  of  the  renal  vein  is  poorer  in  urea  than  that 
of  the  renal  artery,  containing  only  one-third  to  one-half  as  much. 
If  we  knew  the  exact  quantity  of  blood  passing  through  the  kidneys 
of  an  animal  in  twenty-four  hours,  and  the  average  difference  in 
the  percentage  of  urea  in  the  blood  coming  to  and  leaving  them, 
we  should  at  once  be  able  to  decide  whether  the  whole  of  the  urea  in 
the  urine  reaches  the  kidneys  ready  made,  or  whether  a  portion  of 
it  is  formed  by  the  renal  tissue.  Although  data  of  this  kind  are  as 
yet  inexact  and  incomplete,  it  is  not  difficult  to  see  that  all,  or  most 
of,  the  urea  may  be  simply  separated  by  the  kidney. 

If  we  take  the  weight  of  the  kidneys  of  a  dog  of  35  kilos  at  x6o  grammes 
(olyth  of  the  body-weight  is  the  mean  result  of  a  great  number  of 
observations  in  man),  and  the  average  quantity  of  blood  in  them  at 
rather  less  than  one-fourth  of  their  weight,  or  35  grammes,  and  con- 
sider that  this  quantity  of  blood  passes  through  them  in  the  average 
time  required  to  complete  the  circulation  from  renal  artery  to  renal 
vein,  or,  say,  ten  seconds,  we  get  about  300  kilos  of  blood  as  the  flow 
through  the  kidneys  in  twenty-four  hours.  Even  at  0*3  per  1,000,  the 
urea  in  300  kilos  of  blood  would  amount  to  90  grammes.  Now,  Voit 
found  that  a  dog  of  35  kilos  body-weight,  on  the  minimum  protein  diet 
(450  to  500  grammes  of  lean  meat  per  day)  which  sufficed  to  maintain 
its  weight,  excreted  35  to  40  grammes  of  urea  in  the  twenty-four  hours. 
If,  then,  tlae  renal  epithelium  separated  somewhat  less  than  half  of  the 
90  grammes  urea  offered  to  it  in  the  circulating  blood,  the  whole  excre- 
tion in  the  urine  could  be  accounted  for,  and  the  blood  of  the  renal  vein 
would  still  contain  more  than  half  as  much  urea  as  that  of  the  renal 
artery.  So  that  the  whole  of  the  urea  in  the  urine  may  be  simply 
separated  by  the  kidney  from  the  ready-made  urea  of  the  blood. 

Another  line  of  evidence  leads  to  the  same  conclusion :  that  the 
kidney  is,  at  all  events,  not  an  important  seat  of  urea-formation. 
When  both  renal  arteries  are  tied,  or  both  kidneys  extirpated,  in  a 
dog,  urea  accumulates  in  the  blood  and  tissues;  and,  upon  the  whole, 
as  much  urea  is  formed  during  the  first  twenty-four  hours  of  the 
short  period  of  Ufe  which  remains  to  the  animal  as  would  under 
normal  circumstances  have  been  excreted  in  the  urine. 

Where,  then,  is  urea  chiefly  formed  ?  The  answer  to  this  question 
is  that,  while  some  urea  is  probably  produced  from  amino-acids  in 
all  the  tissues,  one  organ  is  particularly  associated  with  this  function 
— namely,  the  liver. 


5S4  Min'ABOLISM.   NUTRITION  AND  DIETETICS 

Tlieic  is  no  reason  to  suppose  that  the  hepatic  cells,  so  far  as  the 
repair  of  their  own  protoplasm  or  the  supply  of  energy  for  their  own 
special  work  is  concerned,  require  to  metabolize  particularly  large 
quantities  of  amino-acids  as  compared,  for  instance,  with  the 
muscles.  Glycin,  however,  they  must  have  for  the  manufacture  of 
glycocholic,  and  cystin  for  the  manufacture  of  the  taurin  of  taurocholic 
acid.  In  addition,  the  liver  is  known  to  possess  the  power  of  utilizing 
amino-acids  for  the  formation  of  dextrose  and  eventually  of  glyco- 
gen, and  a  portion  of  the  surplus  amino-acids  of  the  food  may  be 
withdrawn  from  the  blood  of  the  portal  vein  for  this  purpose,  just 
aj  the  surplus  of  dextrose  is  withdrawn. 

The  liver  contains  a  relatively  large  amount  of  urea,  and  there  is 
strong  evidence  that  it  is  the  manufactory  in  which  a  great  part  of 
the  nitrogenous  relics  of  broken-down  proteins,  including  amino- 
acids,  reach  the  final  stage  of  urea.  This  evidence  may  be  summed 
up  as  follows: 

(i)  An  excised  '  surviving  '  liver  forms  urea  from  ammonium 
carbonate  mixed  with  the  blood  passed  through  its  vessels,  while 
no  urea  is  formed  when  blood  containing  ammonium  carbonate  is 
sent  through  the  kidney  or  through  muscles.  Other  salts  of  am- 
monium, such  as  the  lactate,  the  formate,  and  the  carbonate,  under- 
go a  like  transformation  in  the  liver.  It  is  difficult,  in  the  hght  of 
this  experiment,  to  resist  the  conclusion  that  the  increase  in  the 
excretion  of  urea  in  man,  when  salts  of  ammonia  are  taken  by  the 
mouth,  is  due  to  a  similar  action  of  the  hepatic  cells. 

(2)  If  blood  from  a  dog  killed  during  digestion  is  perfused  through 
an  excised  liver,  some  urea  is  formed,  which  cannot  be  simply 
washed  out  of  the  liver-cells,  because  when  the  blood  of  a  fasting 
animal  is  treated  in  the  same  way  there  is  no  apparent  formation 
of  urea  (v.  Schroeder).  This  suggests  that  during  digestion  certain 
substances  which  the  liver  is  capable  of  changing  into  urea  enter  the 
blood  in  such  amount  that  a  surplus  remains  for  a  time  unaltered. 
These  substances  may  come  directly  from  the  intestine;  or  they 
may  be  products  of  general  metabolism,  which  is  increased  while 
digestion  is  going  on;  or  they  may  arise  both  in  the  intestine  and  in 
the  tissues.  Leucin — which,  as  we  have  seen,  is  constantly,  or,  at 
least,  very  frequently,  present  in  the  intestine  during  digestion — 
can  certainly  be  changed  into  urea  in  the  body.  So  can  other 
amino-acids  of  the  fatty  series,  like  glycocoll  or  glycin.  and  aspartic 
acid,  and  it  has  been  shown  by  perfusion  experiments  that  this 
change  can  take  place  in  the  liver.  I'-urther,  the  blood  of  the  portal 
vein  during  digestion  contains  several  times  as  much  ammonia  as 
the  arterial  blood,  and  the  e.xcess  disappears  in  the  li\cr. 

(3)  During  digestion  the  blood  loses  a  greater  proportion  of  its 
amino-nitrogen  (amino-acids)  in  passing  through  the  liver  than  in 
passing  through  other  organs,  as  shown  by  the  fact  that  the  excess 


METABOLISM  01-   PROTEINS  585 

in  the  portal  blood,  as  compared  with  the  blood  of  the  hepatic  vein, 
is  greater  than  the  difference  between  the  arterial  and  the  vena 
cava  blood.  Now  it  has  been  proved  that  the  liver  does  not  store 
amino-acids  to  an  appreciable  extent  as  such,  and  therefore  it  must 
either  have  destroyed  or  condensed  them  into  proteins.  There  is  no 
evidence  that  the  liver  forms  a  store  of  reserve  protein  from  amino- 
acids  as  it  does  of  glycogen  from  carbohydrates,  although  this  is 
possible.  But  there  is  good  reason  to  believe  that  a  portion  at  least 
of  the  amino-acids  taken  up  by  the  liver  is  quickly  broken  down, 
and  that  urea  is  formed  from  them.  For  when  amino-acids  were 
injected  into  a  vein  in  such  amount  that  the  content  of  amino-acids 
in  all  the  tissues  was  considerably  increased,  they  disappeared  far 
more  rapidly  from  the  liver  than  from  muscle  or  kidney,  and  their 
disappearance  from  the  liver  was  accompanied  by  an  increase  in  the 
urea  content  of  the  blood  (Van  Slyke) . 

(4)  Uric  acid — which  in  birds  is  the  chief  end-product  of  protein 
metabolism,  as  urea  is  in  mammals — is  formed  in  the  goose  largely, 
and  almost  exclusively,  in  the  liver.  This  has  been  most  clearly 
shown  by  the  experiments  of  Minkowski,  who  took  advantage  of 
the  communication  between  the  portal  and  renal-portal  veins 
(P-  385)  to  extirpate  the  liver  in  geese.  When  the  portal  is  ligated 
the  blood  from  the  alimentary  canal  can  still  pass  by  the  round- 
about road  of  the  kidney  to  the  inferior  cava,  and  the  animals 
survive  for  six  to  twenty  hours.  While  in  the  normal  goose  50  to 
60  per  cent,  of  the  total  nitrogen  is  eliminated  as  uric  acid  in  the 
urine,  and  only  9  to  18  per  cent,  as  ammonia,  in  the  operated  goose 
uric  acid  represents  only  3  to  6  per  cent,  of  the  total  nitrogen,  and 
ammonia  50  to  60  per  cent.  A  quantity  of  lactic  acid  equivalent 
to  the  ammonia  appears  in  the  urine  of  the  operated  animal,  none 
at  all  in  the  urine  of  the  normal  bird.  The  small  amount  of  urea  in 
the  normal  urine  of  the  goose  is  not  affected  by  extirpation  of  the 
liver.  And  while  urea,  when  injected  into  the  blood,  is  in  the 
normal  goose  excreted  as  uric  acid,  it  is  in  the  animal  that  has  lost 
its  liver  eliminated  in  the  urine  unchanged. 

(5)  After  removal  of  the  liver  in  frogs,  or  in  dogs  which  have 
survived  the  previous  connection  of  the  portal  vein  with  the  inferior 
vena  cava  by  an  Eck's  fistula  (p.  385),  the  quantity  of  urea  excreted 
is  markedly  diminished,  and  the  ammonium  salts  in  the  urine  are 
increased.  When  the  Eck's  fistula  is  estabhshed  and  the  portal 
vein  tied,  without  any  further  interference  with  the  hepatic  circula- 
tion, the  amount  of  urea  in  the  urine  is  not  lessened  to  nearly  the 
same  extent,  evidently  because  the  substances  from  which  urea  is 
formed  still,  for  the  most  part,  gain  access  to  the  liver  through  the 
hepatic  artery  and  by  means  of  the  back-flow  which  is  known  to 
take  place  through  the  hepatic  vein.  Yet  while  in  normal  dogs  the 
proportion  of  ammonia  to  urea  in  the  urine  is  only   i  :22  to  i :  73, 


586  METABOLISM.  XVTRITIOS  ASD  DIETETICS 

in  dogs  with  Erk's  fistula  it  rises  to  1 :  8  to  i:  ^^.  If  the  animals 
are  ktpt  on  a  diet  poor  in  proteins,  no  symptoms  may  develop  for 
a  considerable  time.  But  if  much  protein  is  given,  characteristic 
symptoms,  including  convulsions,  always  appear.  These  may  be 
produced  by  the  saturation  of  the  organism  with  ammonia  com- 
pounds, which  are  formed  from  the  proteins  as  in  the  normal  animal, 
but  which  the  liver,  with  its  circulation  crippled,  is  unable  to  cope 
with,  and  to  completely  change  into  urea,  although  the  statement 
has  been  made  that  when  ammonia  or  ammonium  salts  are  injected 
into  the  blood  larger  quantities  must  be  present  to  produce  these 
symptoms  than  are  found  in  animals  with  the  Eck's  fistula. 
Although  the  portal  vein  <?arries  to  the  liver  a  greater  supply  of 
blood  than  the  hepatic  artery  (about  twice  as  much,  according  to 
Opitz  and  Macleod  and  Pearce),  ligation  of  the  latter  causes  a 
greater  diminution  in  the  ratio  of  the  amount  of  urea  to  the  total 
nitrogen  in  the  urine  than  ligation  of  the  former.  WTiile  the  blood 
of  the  hepatic  artery  is,  of  course,  nearly  saturated  with  oxygen, 
that  of  the  portal  vein  is  not  half  saturated,  so  th^t  the  total  quan- 
tity of  oxygen  transported  to  the  liver  by  the  hepatic  artery  is 
actually  greater  than  the  quantity  transported  by  the  portal  vein. 
This  indicates  that  a  good  supply  of  oxygen  is  an  important  factor 
in  the  formation  of  urea  in  the  liver  (Doyen  and  Dufourt).  But 
this  is  no  proof  that  the  process  by  which  it  is  formed  is  an  oxidation. 
The  work  of  the  liver,  like  that  of  other  tissues,  is  no  doubt  deranged 
by  lack  of  oxygen. 

(6)  In  acute  yellow  atrophy,  and  in  extensive  fatty  degeneration 
of  the  liver,  urea  may  almost  disappear  from  the  urine,  and  leucin, 
tvrosin,  and  other  amino-acids  may  appear  in  it  along  with  a  much 
larger  amount  of  ammonia  than  normal.  Here  it  may  be  supposed 
that  the  amino-acids  and  ammonia  formed  in  the  intestine  in 
the  digestion  and  absorption  of  proteins,  perhaps  also  ami  no-groups 
formed  in  the  tissues  which  would  normally  be  culled  from  the  blood 
bv  the  hepatic  cells  for  the  manufacture  of  uiea,  pass  unchanged 
through  the  degenerated  liver,  and  are  excreted  by  the  kidney. 

It  would,  however,  be  very  easy  to  overdo  this  argument ;  for  it 
is  sometimes  observed  that  in  pathological  and  experimental  condi- 
tions in  which  the  liver  has  suffered  severely  considerable  quantities 
of  urea  continue  to  be  excreted.  Urea  does  not  entirely  cease  to 
be  produced  ev-en  when  the  liver  is  removed;  and  it  must  again 
be  pointed  out  that  there  is  reason  to  believe  that  the  formation 
of  urea  is  not  a  function  peculiar  to  the  liver,  but  one  shared  prob- 
ably with  all  tissues.  The  liver  certainly  does  not  arrest  the  whole 
of  the  amino-acids  coming  from  the  alimentary  canal ;  for  the  non- 
protein nitrogen  in  the  muscles  is  distinctly  increased  during  the 
absorption  of  amino-acids,  and  the  muscular  tissue,  even  when  freed 
from  blood,  contains  some  urea,  which  in  all  probability  is  formed 


METABOLISM  OF  PROTEINS  SSI 

tliere  in  the  decomposition  of  aniino-acids.  Some  writers,  indeed, 
take  the  view  that  the  muscles,  containing  as  tlicy  do  three-fourths 
of  the  proteins  of  the  body,  and  utilizing  as  they  appear  to  do  a 
large  proportion  of  the  amino-acids  of  the  food-protein,  are  more 
important  seats  of  urea  formation  than  the  liver.  Yet  the  fact  that 
it  is  far  easier  to  demonstrate  this  power — e.g.,  by  perfusion  experi- 
ments— for  the  liver  than  for  such  tissues  as  the  muscles,  renders  it 
difficult  to  avoid  the  conclusion  that  in  the  preparation  of  an  end- 
product  so  important  as  that  in  which  the  great  bulk  of  the  nitrogen 
leaves  the  body, a  certain  degree  of  specialization  has  been  developed, 
and  that  this  preparation  has  been  largely  entrusted  to  a  special 
organ.  And,  while  it  may  be  true  that  larger  amounts  of  amino-acids 
are  taken  up  and  utilized  by  the  muscles  than  by  the  liver  under 
certain  conditions,  this  does  not  show  that  amino-groups  removed 
from  the  amino-acids  in  the  muscles  may  not  be  largely  transferred 
to  the  liver  before  being  changed  into  urea.  Further,  the  transforma- 
tion of  amino-acids  into  dextrose  (and  glycogen)  may  be  assumed  to 
entail  a  considerable  absorption  of  amino-acids  by  the  hepatic  cells. 

Processes  by  which  Urea  is  formed. — In  the  case  of  only  one  of  the 
amino-acids  derived  from  proteins  can  urea  be  obtained  by  a  simple 
process  of  hydrolytic  cleavage.  This  is  arginin  (a-amino-5-guanidin- 
«-valerianic  acid) — that  is  to  say,  normal  valerianic  acid, 

CH3.CH2.CHa.CH2.COOH, 

i         y        13        a 

in  which  an  amino  group  is  attached  to  the  a  carbon  atom,  while 
guanidin  tTir^^CNH  is  attached  to  the  S  carbon  atom  (p.  566)- 

When  arginin  is  hydrolysed  by  barium  hydroxide  it  yields  urea  and 
ornithin  (diamino-valerianic  acid),  half  of  the  nitrogen  of  the  arginin 
appearing  in  each.     Thus, 

NH2 

JJJJaXc.NH.CHg.CHaCHa.CH.COOH  +  HgO  = 

Arginin. 

NHj 
^^aXc^o  +  NHg.CHa.CHaCHaCH.COOH 

Urea.  Ornithin. 

The  amount  of  arginin,  and  therefore  the  amount  of  urea  which  can  be 
artificially  obtained  in  this  way,  varies  extremely  with  the  different 
proteins.  Thus,  salmin,  a  protamin  (p.  2),  prepared  from  the  milt 
of  salmon,  yields  84-3  per  cent,  of  its  weight  of  arginin,  while  the 
casein  of  cow's  milk  yields  only  4-8  per  cent.,  and  gluten-fibrin,  one  of 
the  proteins  of  wheat,  only  3  per  cent.  In  the  body  the  hydrolysis  of 
a'"ginin  to  urea  and  ornithin  is  accomplished  by  the  ferment  arginase 
(Kossel  and  Dakin).  This  ferment  is  found  in  the  liver,  and  also  in 
many  other  organs.  The  urea  formed  in  this  way  appears  very 
rapidly  in  the  urine .  The  ornithin  itself  is  then  more  slowly  transformed 
into  urea.     Since  the  ordinary  food-proteins  are  poor  in  arginin,  the 


583  METABOLISM,  NUTRITION  AND  DIETETICS 

amount  of  urea  which  can  possibly  be  formed  in  mammalian  metabolism 
by  this  process  cannot  be  large,  even  if  most  of  the  arginin,  as  is  the 
case  when  it  is  fed  to  an  animal,  is  transformed  into  urea. 

There  is  no  reason  to  suppose  that  urea  can  be  directly  split  off  from 
the  other  amino-acids  with  which  we  are  concerned.  A  comparison 
of  their  constitutional  formula^  with  that  of  urea  (or  with  that  of  uric 
acid)  shows  that  a  more  far-reaching  decomposition  must  take  place 
before  products  are  obtained  from  which  urea  (or  uric  acid)  can  be 
formed.  Urea  has  been  artificially  obtained  from  protein  by  oxidation 
with  an  ammoniacal  solution  of  permanganate  at  body-tcmperaturc. 
When  the  protein  is  first  split  into  its  cleavage  products,  and  these  are 
then  oxidized,  a  very  large  amount  of  urea  is  produced — e.g.,  as  much 
as  3  grammes  of  urea  from  lo  grammes  of  glycm. 

While  these  facts  suggest  possible  ways  of  formation  of  urea  in  the 
body,  we  cannot  assume  that  what  happens  in  the  test-tube  must 
happen  in  the  tissues.  The  best  evidence  is  to  the  effect  that  in  the 
body  the  removal  of  the  amino-group  (NHj)  in  the  form  of  ammonia 
from  the  amino-acids  is  the  essential  step  in  the  formation  of  at  least 
a  great  part  of  the  urea,  which  is  then  synthesized  from  ammonia  and 
carbonic  acid.  The  possibility  exists  that  this  deaminization  (or  deamidi- 
zation)  of  the  amino-bodies  is  the  result  of  hydrolysis,  or  of  oxidation,  or 
of  reduction,  or  of  a  combination  of  these  processes.  Evidence  has  been 
found  that  in  the  case  of  some  of  the  amino-acids  the  deaminization  is 
associated  not  with  hydrolysis  in  which  hydroxyl  is  substituted  for 
the  NHj  gioup,  but  with  oxidation  (Neubauer).  But  this  has  not  been 
shown  to  hold  good  for  all  amino-acids.  In  either  case,  however, 
whether  the  deaminization  process  is  oxidative  or  hydrolytic  tlie  nitrogen 
is  split  off  as  ammonia,  and  it  is  to  such  ammonium  compounds  as  have 
been  already  mentioned  as  being  transformed  into  urea  when  circulated 
through  an  excised  liver  (p.  584)  that  w^e  have  to  look  for  the  source  of, 
at  any  rate,  a  large  portion,  of  the  urea.  Ammonia  in  the  form  of 
carbonate  or  carbamate  is  constantly  found  in  the  blood  (p.  583).  The 
excess  of  ammonia  in  the  portal  blood,  which,  however,  is  not  admitted 
by  all  observers  to  be  very  large  or  very  constant,  has  been  interpreted 
as  indicating  that  a  considerable  decomposition  of  iamino-acids  with 
liberation  of  the  amino-groups  occurs  in  the  intestinal  lumen  or  the 
intestinal  wall.  It  is  not  established  beyond  doubt  that  ammonia  is 
itself  present  in  the  protein  molecule,  or  that  its  liberation  in  the 
hydrolysis  of  proteins  can  take  place  except  at  the  expense  of  further 
decomposition  of  amino-bodies.  It  has  been  shown,  however,  that  a 
great  part  of  the  ammonia  in  the  blood  is  produced  in  the  decomposition 
of  protein  in  the  digestive  tube  by  putrefactive  bacteria  (Folin  and 
Denis).  This  is  a  necessary  part  of  the  reaction  by  which  phenol  and 
indol  are  formed  in  tlie  intestine. 

It  has  been  generally  taught  that  the  deaminization  of  the  surplus  of 
amino-bodies  takes  place  chiefly  in  the  liver,  the  extra  nitrogen  being 
thus  '  shunted  '  out  of  the  blood-stream  before  it  has  had  a  chance  to 
reach  the  tissues.  It  would  seem  more  advantageous  in  tlie  light  of 
our  present  knowledge  that  a  large  and,  so  to  say,  a  miscellaneous 
assortment  of  amino-bodies  should  be  placed  at  the  disposal  of  the 
tissues  to  facilitate  the  selection  of  those  which  are  indispensable. 
We  have  seen  that  tissues  such  as  muscle  can  and  do  take  up  amino- 
acids  when  protein  is  digested  in  the  intestine,  and  it  is  very  probable 
that  they  take  up  not  merely  the  relatively  small  amount  necessary  to 
replace  their  wear  and  tear,  but  also  a  portion  of  the  surplus,  which 
after  deaminization  in  the  cells  takes  its  place  as  a  source  of  energy 
to  drive  the  machine.    The  nitrogen  in  the  form  of  ammonia  may  pass 


METABOLISM  OF  PROTEINS  589 

back  into  the  blood,  and  may  thus  be  carried  to  the  liver  for  conversion 
into  urea.  It  is  not  necessary,  however,  to  suppose  that  all  of  the 
nitrogen  must  perforce  make  this  journey  before  being  changed  into 
urea.  There  i.s  evidence  that  all  the  tissues  share  to  some  extent  with 
the  liver  the  power  of  forming  urea  just  as  they  share  with  the  liver  the 
power  of  splitting  off  NHg  from  the  amino-bodies.  It  may  be  that 
the  liver  surpasses  other  tissues  in  its  deamidizing  power  just  as  it  seems 
to  surpass  other  tissues  in  its  power  of  transforming  ammonium  com- 
pounds into  urea.  But  this  does  not  prevent  at  least  a  considerable 
proportion  of  the  amino-substances  absorbed  from  the  intestine  from 
passing  into  the  general  circulation.  It  is  of  importance  to  remark 
that  such  hydrolytic  cleavages  as  are  associated  with  the  splitting  of 
protein  into  amino-acids,  etc.,  only  slightly  reduce  the  available  energy 
of  the  compounds.  In  so  far  as  the  liberation  of  the  nitrogen  from 
the  amino-acids  is  also  accomplished  by  hydrolytic  cleavage  (sup- 
posedly by  a  ferment  dcsaminase),  the  residue,  relatively  rich  in  carbon, 
will  still  be  available  for  yielding  to  the  bodv  by  its  oxidation  an  amount 
of  energy  not  much  less  than  could  be  obtained  from  the  original  protein. 
The  combination  of  ammonia  with  carbon  dioxide  and  the  conversion 
of  the  carbonate  into  urea,  perhaps  through  the  intermediate  stage  of 
ammonium  carbamate,  does  not  require  any  oxidation.     Thus, 

/OH  /O.NH4  /O.NH4  /NHo 

C^O     -f2NH,=C=0  ;    -HaO=C<-0  ;    -H20=Cf^0 

\OH  \0.NH4  \NH2  \nH2 

Carbonic  acid.  Ammonium  Ammonium  Urea. 

carbonate.  carbamate. 

Another  way  in  which  some  of  the  urea  may  be  produced  is  by  the 
direct  formation  of  ammonium  carbamate  in  the  katabolism  of  amino- 
acids  without  the  preliminary  liberation  of  ammonia.  By  the  loss  of  a 
molecule  of  water  the  carbamate  would  then  become  urea.  But  if,  as 
there  is  every  reason  to  believe,  a  part  of  the  carbonaceous  residue  is 
converted  into  carbo-hydrate,  a  certain  amount  of  oxidation  must 
occur  in  the  transformation. 

Such  compounds  as  guanin,  sarkin  or  hypoxanthin,  xanthin,  uric 
acid,  and  creatin,  used  to  be  cited  as  among  the  possible  intermediate 
substances  between  protein  and  urea.  But  while  there  is  now  complete 
evidence  that  the  first  three  bodies  can  be  and  are  converted  into  uric 
acid,  there  is  nothing  at  all  to  indicate  that  they  are  stages  on  the 
way  to  urea.  Uric  acid  is,  indeed,  very  closely  related  to  urea,  and 
can  be  made  to  yield  it  by  oxidation  outside  the  body.  Not  only  so, 
but  it  is,  in  part  at  least,  excreted  as  urea  when  given  to  a  mammal 
by  the  mouth  and  it  replaces  urea  as  the  great  end-product  of  nitro- 
genous metabolism  almost  wholly  in  the  urine  of  birds  and  reptiles. 
But  none  of  these  things  can  be  admitted  as  evidence  that  in  the 
normal  metabolism  of  mammals  uric  acid  lies  on  the  direct  line  from 
protein  to  urea.  Creatin  exists  in  the  body  in  greater  amount  than 
any  of  these,  muscle  containing  from  0-2  to  0-4  per  cent,  of  it;  and  the 
total  quantity  of  nitrogen  present  at  any  given  time  as  creatin  is  not 
only  greater  than  that  of  the  nitrogen  present  in  urea,  but  greater 
than  the  whole  excretion  of  nitrogen  in  twenty-four  hours.  But 
although  there  are  facts  which  indicate  that  creatin  is  an  important 
derivative  of  the  decomposed  tissue  proteins  (p.  597)  there  is  no 
evidence  that  it  is  related  to  urea  formation. 

b'ummary  :  Here  may  be  summed  itp  the  most  probable  view  of  the 
normal  decomposition  in  the  body  of  the  amino-acids,  whether  they  undergo 
decomposition  without  being  incorporated  into  the  tissue  proteins  or  prater- 


590  METABOLISM.   NUTRITION  . I  S'D   DIETETICS 

plasm,  or  are  liberated  as  the  protof>lasm  breaks  down.  The  first  step  may 
be  conceived  of  as  the  splitting  off  of  the  NHo  group,  which  yields  ammonia. 
The  ammonia  is  transformed  into  urea.  The  non-nitrogenous  residue 
after  removal  of  the  amino-group  differs  according  to  the  amino-acid. 
Some  of  the  amino-acids,  such  as  alanin,  glycin,  prolin  and  aspartic  acid, 
yield  substances  which  can  be  changed  into  dextrose  in  the  body,  as  shown 
by  the  increased  amount  of  dextrose  excreted  by  phlorhizinized  animals 
when  the  amino-acids  are  fed  to  them.*  Other  amino-acids — e.g.,  lysin, 
histidin  and  tyrosin,  phenylalanin,  etc.,  have  such  a  chemical  structure 
that  the  non-nitrogenous  compounds  derived  from  them  cannot  form  dextrose. 
From  certain  amino-acids,  such  as  histidin,  phenylalanin,  tyrosin  and 
leucin,  it  has  been  shown  that  acetone  bodies  can  be  derived.  These  facts 
explain  how  sugar  can  be  formed  and  the  acidosis  associated  ivith  the 
acetone  bodies  developed  in  diabetes,  even  wheti  the  diet  consists  of  protein 
only  or  when  the  patient  is  living  on  his  own  tissues. 

Formation  of  Uric  Acid. — Uric  acid,  like  urea,  is  separated  from 
tlie  blood  by  the  kidne\'S,  not  to  any  appreciable  extent  formed  in 
them.  In  birds,  and  often  in  man,  it  can  be  detected  in  normal 
blood.  It  is  present  in  increased  amount  in  the  blood  and  transuda- 
tions of  gouty  patients,  in  whose  joints  and  ear-cartilages  it  often 
forms  concretions.  '  Chalk-stones  '  may  contain  more  than  half 
their  weight  of  sodium  urate. 

As  to  the  place  and.  manner  of  formation  of  uric  acid,  it  has  already 
been  stated  that  in  birds,  after  extirpation  of  the  liver,  the  uric  acid 
excretion  is  greatly  diminished,  and  that  ammonium  lactate  appears 
instead  in  the  urine.  The  simplest  interpretation  of  this  result  is, 
that  ammonia  and  lactic  acid  pass  into  the  urine  because  they  can 
no  longer  be  utilized  for  the  synthesis  of  uric  acid.  Chemical 
schemata  can  indeed  be  constructed,  which  show  more  or  less 
plausibly  how  lactic  acid,  pyruvic  acid  (p.  545)  and  other  substances 
reacting  with  ammonia  or  with  the  urea  derived  from  it  (and  birds 
form  some  urea)  might  yield  uric  acid.  It  has  been  further  stated 
that  when  blood  containing  ammonium  lactate  is  circulated  through 
the  surviving  liver  of  the  goose,  an  increase  in  the  uric  acid  content 
of  the  blood  occurs.  As  demonstrated  by  control  experiments,  this 
increase  is  too  great  to  be  due  merely  to  the  sweeping  out  of  pre- 
viously formed  uric  acid  from  the  hepatic  cells ;  also  the  feeding  of 
lactic  acid,  pyruvic  acid,  and  other  organic  acids  leads  to  an  increased 
output  of  uric  acid.  The  story  seems  fairly  complete,  although 
criticisms  have  not  been  lacking.  It  has  been  suggested,  for  instance, 
that  for  some  reason  the  loss  of  the  liver  leads  to  acidosis,  an  in- 
creased production  of  acids,  especially  lactic  acid,  in  the  organism ; 
that  ammonia,  which  would  otherwise  be  employed  in  the  formation 
of  uric  acid,  is  needed  to  neutralize  these  acids,  and  that  the  appear- 
ance of  this  ammonia  in  the  urine  is  only  a  secondary  consequence 
of  the  elimination  of  the  liver.     The  deficiency  in  the  uric  acid 

•  In  animals  under  the  influence  of  phlorhizin  sugar  is  formed  from  all 
substances  capable  of  producing  it  in  the  organism. 


METABOLISM  OF  PROTEINS  591 

excreted,  it  is  said,  is  therefore  due,  not  to  inability  on  the  part  of 
the  remannng  tissues  to  form  uric  acid,  but  to  the  absence  of  the 
ammonia  which  they  require  for  its  formation.  This  criticism,  if 
it  were  admitted  as  apjainst  the  current  interpretation  of  such  ob- 
servations on  the  bird's  hver,  coidd  scarcely  be  denied  some  vahdity 
as  against  the  current  interpretation  of  similar  observations  on  the 
results  of  interference  with  the  mammalian  liver.  It  is  therefore 
important  to  point  out  that  there  is  still  the  same  deficiency  of  uric 
acid  when  alkali  is  administered  to  neutralize  the  acids,  although 
ammonia  ought  now  to  be  available.  There  can  be  no  question, 
then,  that  the  liver  in  birds  is  the  seat  of  an  extensive  synthesis  of 
uric  acid,  and  there  is  little  doubt  that  ammonia  compounds  are 
essentially  concerned  in  the  process,  whatever  the  role  of  the  lactic 
or  other  acids  may  be.  A  similar  synthetic  formation  of  uric  acid 
from  ammonia  and  a  derivative  of  lactic  acid  may  take  place  in 
mammals,  and  probably  exclusively  in  the  liver,  but  it  is  of  much 
less  importance.  Another  way  in  which  uric  acid  arises  both  in 
mammals  and  in  birds  is  by  the  splitting  and  oxidation  of  nucleins. 
This  is  by  far  the  most  important  mode  of  formation  in  mammals, 
as  synthesis  is  the  chief  mode  of  formation  in  birds.  In  both  groups 
of  animals  the  oxidative  production  of  uric  acid  takes  place,  not  in 
any  particular  organ,  but  in  the  tissues  in  general,  including  the  liver. 
It  has  been  shown  that  when  air  is  blown  through  a  mixture  of 
splenic  pulp  and  blood,  uric  acid  is  formed  from  purin  bodies  already 
present  in  the  spleen.  When  the  quantity  of  these  is  increased  by 
the  decomposition  of  nucleins  induced  by  slight  putrefaction,  the 
yield  of  uric  acid  is  also  increased.  Uric  acid  is  also  formed  by  the 
perfectly  fresh  surviving  spleen,  liver,  and  thymus  in  the  presence 
of  oxygen,  and  the  quantity  is  increased  when  purin  bodies  are 
artificially  added. 

Sources  of  the  Uric  Acid. — It  is  well  established  that  in  the  bird 
it  arises  both  from  amino-acids  derived  from  the  hydrolysis  of 
protein  and  from  nuclein  compounds  and  their  derivatives  in  the 
food  and  tissues.  The  amino-acids  constitute  by  far  the  greatest 
source  of  uric  acid  in  these  animals  and  in  the  reptiles,  and  it  is 
practically  certain  that  the  course  of  the  decomposition  of  the 
amino-acids  and  the  form  in  which  nitrogen  is  liberated  from  them 
in  its  transformation  into  this  end-product  are  not  essentially  differ- 
ent from  what  obtains  in  the  formation  of  urea  in  the  mammal  and 
the  amphibian.  This  is  sufficiently  illustrated  by  the  role  played  by 
ammonia  and  ammonia  compounds  in  the  production  of  uric  acid 
in  the  birds  and  their  congeners.  In  the  mammal,  the  taking  of 
food  rich  in  nucleated  cells,  and  therefore  in  nucleo-proteins  and 
nucleins,  the  characteristic  conjugated  proteins  of  nuclei  (thymus 
gland,  pig's  pancreas,  and  herring  roe),  or  of  food  rich  in  purin 
bases  (Liebig's  meat  extract),  increases  the  quantity  of  uric  acid  in 


592  METABOLISM.   NUTRITIOX  .1\D  DIETETICS 

the  urine.  The  increase  is  mainly  due  to  the  produt  tion  of  uric 
add  from  the  nuclein  substances  of  the  food.  But  this  is  not  the 
only  source  of  the  uric  acid,  since  extracts  of  the  thymus  glanrl 
containing  only  traces  of  nucleins  or  nucleic  acid  cause,  when  in- 
jected, a  characteristic  increase  in  the  uric  acid  excretion,  just  as 
the  entire  gland  does  when  taken  by  the  mouth.  And  during  the 
period  of  increased  nitrogen  excretion  occasioned  by  a  meal  contain- 
ing protein,  the  increase  in  the  uric  acid  occurs  particularly  in  the 
hours  immediately  following  the  ingestion  of  the  food,  and  does  not 
last  so  long  as  the  increa.se  in  the  urea.  Now,  the  nucleins  of  the 
food  are  comparatively  little  affected  during  the  earlier  stages  of 
digestion  (Hopkins  and  Hope).  Whether  in  mammals  any  portion 
of  the  uric  acid  comes  from  amino-acids  is  still  in  doubt,  but  there 
are  facts  which  indicate  that  a  fraction  of  it  may  do  so.  We  may 
conclude,  therefore,  that  in  the  mammal,  as  well  as  in  the  bird,  a 
portion  of  the  uric  acid,  although  certainly  a  far  smaller  portion  in 
the  mammal,  is  derived  from  bodies  other  than  the  nuclein  substances 
of  the  food — that  is  Lo  say,  from  the  nuclein  substances  of  the  tissues 
contained  particularly  in  the  cell-nuclei  and  probably  from  the 
ordinary  proteins  of  both  food  and  tissues.  The  portion  derived 
irom  tne  protems  may  be  assumed  to  be  that  small  fraction  which 
has  already  been  spoken  of  as  sjmtheticallv  formed. 

Metabolism  of  the  Nucleic  Acids  and  Purin  Bases. — Our  know- 
ledge of  the  metabolism  of  the  nucleo- proteins  and  nucleins  has 
been  greatly  augmented  in  recent  years.  When  nucleo- protein  is 
digested  by  gastric  juice,  a  certain  amount  of  protein  is  easily  split 
off  and  hydrolysed  to  peptone  and  the  other  ordinary  products 
of  proteolysis.  An  insoluble  residue  of  nuclein  remains.  This  is 
acted  upon  with  difficulty  by  gastric  juice,  although  eventually  an 
active  juice  will  split  it  up  also.  By  the  action  of  pancreatic  juice, 
or  b}'  heating  with  dilute  acids,  it  is  more  easily  hydrolysed,  yielding 
a  further  quantity  of  protein  along  with  nucleic  acid.  This  second 
fraction  of  protein,  which  is  split  off  with  so  much  more  difficulty 
than  the  first,  undergoes  proteolysis  in  the  usual  way.  The  result- 
ing amino-acids  no  doubt  take  their  place  in  the  general  metabolism 
precisely  like  the  amino-acids  derived  from  ordinary  proteins,  and 
yield  the  same  end-products.  As  regards  the  nucleic  acid  (or  rather 
acids,  since  different  nucleo- proteins  contain  different  nucleic  acids), 
pancreatic  juice  is  practically  inert,  although  succus  entericus  can 
effect  a  partial  hydrolysis.  For  their  complete  decomposition  more 
drastic  treatment  is  required — namely,  heating  with  hydrochloric 
acid  in  a  sealed  tube.  Thus  treated,  nucleic  acids  yield  a  number 
of  components,  out  of  which  they  may  be  assumed  to  be  built  up, 
as  the  proteins  are  built  up  out  of  amino-acids,  etc.  The  charac- 
teristic components  are  purin  bases  (adenin,  C5H3N4.NH2;  guanin, 
C5HJN4O.NH2;  hypoxanthin,  C6H4N4O;  and  xanthin,  C5H4N4O2); 


METABOLISM  OF  PROTEINS 


593 


pvrimidin  bases  (uratil.  C.H.N.Pj;  oytosin,  C4H.,X2^.NH2;  thymin 

QHgNjOj.CHg);  phosphoric  acid  and  a  carbo-hydrate  group. 

Some  of  the  nucleic  acids  contain  all  these  components;  they  are 
sometimes  spoken  of  as  the  true  nucleic  acids.  In  others  certain  of  the 
components  arc  absent,  and  to  these  nucleic  acids  the  name  nucleotids 
has  been  applied.  The  purin  bases  are  always  present.  The  carbo- 
hydrate group  varies  in  different  nucleic  acids,  being  in  some  a  hexose 
(p.  537),  in  others  a  pentose  (p.  487).  The  pentose  d-ribosc  is  especially 
often  met  with.  It  is  probable  that  the  nucleotids  are  merely  simpler 
decomposition  products  of  the  true  nucleic  acids.  Thus,  inosinic  acid, 
a  nucleotid  first  isolated  from  meat  extract,  yields  phosphoric  acid, 
rf-ribose,  and  the  purin  base  hypoxanthin.  The  nucleotid  guanylic  acid 
found  in  the  pancreas  yields  phosphoric  acid,  rf-ribose,  and  the  purin 
base  guanin.  There  is  evidence  that  nucleic  acids  may  be  built  up  out 
of  a  number  of  nucleotid  groups,  and  for  this  reason  they  have  been 
termed  polynucleotids  (Levene).  The  purin  bases  have  a  very  close 
chemical  relationship  to  uric  acid,  which,  like  them,  is  characterized  by 
the  possession  of  a  group  called  the  purin  nucleus.  For  convenience 
of  reference  the  atoms  composing  the  purin  nucleus  are  numbered, 
and  the  purin  bodies  are  named  with  reference  to  the  position  of  the 
carbon  atom  or  atoms  at  which  oxygen  or  the  amino-group  (NH^)  is 
introduced.  Purin  consists  of  the  nucleus  with  H  atoms  introduced  at 
the  pomts  shown  in  the  constitutional  formula.  Adenin  is  a  6-;imino- 
purin- — i.e.,  purin  in  which  NH2  replaces  the  H  attached  to  C(«).  Guanin 
is  2-amino-6-oxypurin,  NHg  bemg  united  with  C(2)  and  oxygen  with  C(9) 
in  purin.  Uric  acid  is  2,  6,  8-trioxypurin — i.e.,  purin  in  which  oxygen 
is  united  to  the  carbon  atoms  2,6,  and  8.  Hypoxanthin  is  6-oxypurin, 
ox^'gen  being  introduced  at  the  position  of  C(6)  in  purin.  By  removal 
of  the  amino-group  from  adenin  hypoxanthin  is  formed.  Xanthin  is 
2,  6,  dioxy purin,  oxygen  being  introduced  at  C(2)  and  C(6)  in  the  purin 
molecule.  Xanthin  can  be  derived  from  guanin  in  the  same  way  as 
hypoxanthin  from  adenin. 


N(i)— C(8) 

C(2)       C{5) N(7) 


N=CH 

I       I 
HC     C— NH 


/C(8) 


N(3)      _C(4, N(9) 

Purin  nucleus. 

NH— CO 


/ 


CH 


N— C— N 


NHgC        C— NH 


Purin. 

NH— CO 

1  i 

CO     C— NH 


N  =C.NHj 

I       I 
HC     C— NH 

il     '!     \cH 

N— C— N 

Adenin. 


;CH 


N  —  C— N 

Guanin. 


NH— C— NH 

Uric  acid. 


CO 


N  =C.OH  NH— CO 

I     L  II 

HC      C— NH        CO     C— NH 

II    II    >«  I     II    >« 

N— C— N  NH— C— N 

Hypoxanthin.  Xanthin. 


Besides  the  purin  bases  combined  in  the  nuclein  substances,  purin  bases 
and  uric  acid  are  widely  spread  in  the  tissues  in  the  free  state,  although 
in  very  small  amounts. 

A  portion  of  the  intake  of  purin  bodies  is  therefore  ready  formed, 
especially  in  the  animal  constituents  of  the  food,  and  does  not  require 
the  decomposition  of  nucleic  acid  for  its  liberation.  The  nuclei  of 
vegetable  cells  contain  nucleo-proteins,  and  accordingly  can  contribute 
to  the  purin  intake.     The  most  interesting  contribution  of  vegetable 

38 


594  METABOLISM,  SVTRITIOS  ASD  DlJiTLTlCS 

origin  has  been  previously  alluded  to  (p.  481) — namely,  the  methyl 
purins  forming  tlio  active  principles  of  lea,  coffee,  and  cocoa,  caffcin, 
or  I,  3,  7-trimclhylxanthin  (^81110X402),  thcobromin,  or  3,  7-dinK-thyl- 
xanthin     (C7HgN402).     and     theophyllin,     or     i,     3-dimethylxanthin 

CHj.N— CO  NH— CO  CH3.N— CO 


:0  C— N.CH,  CO      C— N.CH3  CO  C— NH 


:h 


I  I   >"       I    \^^-        I      / 

CH3.N— C— N  CH3.N  —  C-^  CH3.N— C— N 

CafTein.  Theobromin.  Theophyllin. 

Nucleic  acid,  as  stated,  can  be  partially  decomposed  by  the 
succus  entericus,  by  means  of  a  ferment  called  nuclease  or,  more 
accurately,  nucleic-acidase.  The  groups  into  which  it  is  split 
are  nucleotids  (see  above).  By  another  ferment,  nucleotidase,  a 
portion,  at  any  rate,  of  the  nucleotids  is  further  decomposed  to 
yield  nucleosides,  bodies  of  the  glucoside  class  containing  a  com- 
pound of  a  purin  base  with  the  carbo-hydrate  group  of  the  nucleic 
acid,  to  which  phosphoric  acid  is  also  coupled.  Beyond  this  stage 
the  liydrolysis  of  nucleic  acid  does  not  proceed  in  the  intestine. 
The  resultant  products,  probably  along  with  unchanged  nucleic 
acid,  are  absorbed,  mainly  at  least,  by  way  of  the  bloodvessels. 

It  will  be  well,  however,  to  remember  that  our  knowledge  of 
the  digestion  of  the  nuclein  bodies  is  still  incomplete,  and  the 
natural  tendency  of  the  mind  to  think  in  diagrams  is  apt  to  give  it 
greater  precision  than  is  justified  by  the  facts;  for  example,  it  is 
known  that  even  gastric  juice  is  capable  of  liberating  some  of  the 
phosphoric  acid  from  nucleo-proteins. 

In  the  tissues  the  absorbed  products  of  the  digestion  of  nucleic 
acids  may  be  partially  utilized  without  further  decomposition  for 
the  synthesis  of  nucleo-proteins,  to  take  the  place  of  those  which  are 
destroyed  in  the  metabolism  of  the  cells;  or  they  may  be  split  com- 
pletely into  their  components,  and  these  resynthesized.  Finally, 
and  this  fate  is  probably  not  long  delayed  in  the  case  of  the  surplus 
of  purin  compounds  contained  in  ordinary  dietaries,  both  the  purins 
of  the  food  and  the  purins  arising  from  the  waste  of  the  tissues  are 
for  the  most  part  converted  into  uric  acid  and  excreted  in  the  urine. 
Small  quantities  of  purins  leave  the  body  in  the  faeces  (p.  425). 
The  phosphoric  acid  can  be  utilized  not  only  for  the  building  of 
nucleu-])roleins,  but  for  the  synthesis  of  phosphatides.  Eventually 
it  is  eliminated  as  phosphates  in  the  urine.  The  carbo-hydrate 
groups,  so  far  as  they  are  not  utilized  in  the  synthesis  of  nucleic 
acids,  may  be  supposed  to  undergo  metabolism  like  other  carbo- 
hydrates. The  metabolic  history  of  the  pyrimidin  bases  has  not 
been  made  clear. 

Steps  in  Formation  of  Uric  Acid. — As  to  the  manner  in  which 


METABOLISM  OF  PROTEINS  593 

liri';  acid  arises  from  the  nuclcin  substances,  we  may  picture  the 
process  as  taking  place  by  the  following  steps  :  Certain  organs  have 
been  shown  to  contain  ferments  which  split  up  nucleo-proteins  into 
protein  and  nucleic  acid.  This  nucleic  acid,  or  nucleic  acid  arising 
in  other  ways  in  the  metabohsm  of  nuclein,  and  also  any  nucleic 
acid  absorbed  as  such  from  the  alimentary  canal  in  the  digestion  of 
nuclein-containing  substances,  are  then  decomposed  by  another 
ferment,  similar  to  or  identical  with  the  nuclease  or  nuclcic-acidase 
previously  encountered  in  the  intestine.  The  resulting  nucleotids  are 
split  up  by  a  special  ferment  (nucleotidase)  so  as  to  yield  nucleosides. 
These  are  in  turn  decomposed  by  appropriate  enzymes  (nucleo- 
sidases), so  that  we  finally  arrive  at  the  individual  '  building-stones,' 
the  nucleic  acid  molecule,  phosphoric  acid,  the  carbo-hydrate  group, 
pyrimidin  and  purin  bases,  especially  adenin  and  guanin.  Then 
follows  the  action  of  ferments  (adenase  and  guanase),  which  remove 
the  amino-group  from  these  purin  bases,  transforming  adenin  into 
hypoxanthin,  and  guanin  into  xanthin  (Jones).  The  deaminiza- 
tion  is  associated  with  hydrolysis.     Thus : 

CsHsNs  +  HjO  -C5H4N40-fNH3;  C5H6N6O  + HgO  =C6H4N40j+ NH3. 

Adenin.  Hypox.-inthin.  Guanin,  Xanthin. 

By  oxidation  hypoxanthin  is  changed  into  xanthin  and  xanthin 
into  uric  acid,  and  the  oxidation  seems  to  be  accomplished  by  a 
separate  oxidizing  ferment,  xanthin  oxidase,  whose  action  may  be 
thus  represented : 

C5H4N4O  +  O  =C5H6N402 ;  C6H6N4O3+  O  =C6H4N40,. 

Hypoxanthin.  Xanthin.  Xanthin.  Uric  Acid. 

Evidence  of  the  existence  of  these  ferments,  and  of  their  wide  dis- 
tribution, has  been  obtained  by  making  experiments  on  the  various 
substances  mentioned  with  extracts  of  different  tissues. 

The  portion  of  the  uric  acid  which  comes  from  the  food  (mainly 
from  the  purin  bodies  in  it)  is  sometimes  denominated  the  exogenous 
portion,  while  that  which  arises  from  the  tissues  is  called  the  endog- 
enous portion.  The  latter  moiety,  which  generally  amounts  to 
about  0-6  gramme  in  the  twenty-four  hours,  can  be  estimated  by 
restricting  the  diet  to  articles  of  food  free  from  purin  bodies,  such  as 
bread,  milk,  cheese,  eggs,  and  butter.  It  is  stated  that  the  endog- 
enous uric  acid  remains  practically  constant  in  the  same  individual 
under  constant  conditions,  and  is  unaffected  by  changes  in  the  diet. 

The  total  excretion  of  uric  acid  (and  the  other  purin  bodies)  is 
by  no  means  identical  with  the  sum  of  the  uric  acid  taken  in  as 
purin  bases  in  the  food  and  that  produced  in  the  body.  A  con- 
siderable destruction  of  uric  acid  (and  other  purin  bodies)  goes  on 
in  the  body,  and  mainly  in  the  Uver.  The  quantity  of  endogenous 
uric  acid  excreted  by  the  kidneys  bears  a  certain  ratio  to  the  total 
amount  which  has  entered  the  circulation.  This  ratio  varies  much 
in  different  mammalian  species.     In  man  a  full  half  is  said  to  be 


396  METABOLISM,  NUTRITION  AND  DIETETICS 

excreted  and  about  a  half  destroyed,  being  mainly  changed  into  urerx. 
Some  of  the  exogenous  moiety  is  also  broken  down.  When  uric  acid 
is  heated  in  a  sealed  tube  with  strong  hydrochloric  acid,  it  is  broken 
up  into  glycin,  carbon  dioxide,  and  ammonia.  There  are  grounds 
for  believing  that  a  similar  decomposition  takes  place  in  the  body, 
and  that  the  products  are  then  transformed  to  urea  in  the  liver. 

The  process  of  uricolysis,  or  destruction  of  uric  acid,  is  usually 
attributed  to  a  ferment  called  the  uricolytic  ferment,  and  it  has  been 
supposed  that  one  of  the  factors  in  the  production  of  gout  may  be 
a  diminution  in  the  amount  or  activity  of  this  ferment.  In  some 
cases  it  is  said  to  be  entirely  absent.  It  is  doubtful,  however, 
whether  in  man  and  the  anthropoid  apes  the  oxidizing  enzyme, 
uricase  or  uricoxydase,  which  oxidizes  uric  acid  to  allantoin 
{C^H6N403),  exists.  In  all  other  mammals  hitherto  investigated  it 
has  been  found  in  some  of  the  tissues.  In  accordance  with  this, 
only  a  trace  of  allantoin  is  present  in  human  urine  and  in  the  urine 
of  the  higher  apes,  while  in  the  other  mammals — for  example,  in 
the  dog — a  large  proportion  of  the  purin  excretion  assumes  this 
form.  It  is  probable  that  there  is  more  than  one  way  in  which 
uric  acid  may  be  decomposed  in  the  body,  and,  if  so,  that  there  is 
more  than  one  ferment  concerned  in  its  transformation.  It  would 
be  well,  therefore,  not  to  speak  of  uricolysis  as  if  it  were  synonymous 
with  the  well-ascertained  process  by  which  allantoin  is  formed 
from  uric  acid,  and  not  to  identify  all  enzymes  which  may  take 
part  in  uricolysis  with  uricoxydase. 

It  is  worthy  of  remark  in  this  connection,  as  a  further  illustration 
of  the  differences  which  may  exist  in  the  purin  metabolism  in 
different  kinds  of  animals,  that  in  man  and  the  anthropoid  apes  the 
quantity  of  purin  bases  in  the  urine  is  small  in  proportion  to  the 
quantity  of  uric  acid.  In  the  pig,  which  is  included  among  the 
animals  that  form  allantoin  from  uric  acid,  the  purin  bases  exceed 
the  uric  acid  in  amount,  whereas  in  the  dog,  which  likewise  excretes 
allantoin,  the  purin  bases  exist  in  very  small  amount  compared 
with  the  uric  acid. 

In  concluding  our  consideration  of  the  metabolism  of  the  nucleic 
acids,  the  question  may  be  raised  whether  it  is  related  to  the  metabo- 
lism of  the  other  substances — carbo-hydrates,  fats,  and  proteins — 
in  such  a  way  that  derivatives  of  nucleic  acid  can  contribute  to  the 
formation  of  any  of  these,  or  derivatives  of  carbo-hydrares,  fats,  or 
proteins  contribute  to  the  formation  of  any  of  the  components  of 
nucleic  acid.  It  has  been  already  mentioned  that  the  phospiioric 
acid  can  aid  in  the  synthesis  of  phosphatides,  and  that  the  carbo- 
hydrate groups  probably  take  their  place  in  the  ordinary  carbo- 
hydrate metabolism.  There  is  no  evidence  that  the  purin  bases  can 
take  part  or  can  yield  products  capable  of  taking  part  in  the  forma- 
tion of  any  of  the  other  substances.     The  piirin  metabolism,  so  far 


METABOLISM  OF  PROTEINS  597 

as  is  known,  moves  in  a  closed  circuit.  Of  (lie  fate  of  the  pyrimidin 
bases  nothing  is  surely  known.  Without  doubt  nucleic  acid  can  be 
formed  in  the  body  when  none  is  contained  in  the  food.  More  than 
one  source  of  the  phosphoric  acid  and  the  carbo-hydrate  are  known 
and  ha\e  been  already  pointed  out,  but  how  and  from  what 
materials  the  purin  and  pyrimidin  bases  are  formed  cannot  yet 
be  stated. 

It  has  been  suggested  that  arginin  and  histidin  constitute  the 
raw  material  for  the  synthesis  of  the  purin  ring.  Rats  will  grow 
when  fed  with  an  amino-acid  mixture  prepared  by  hydrolyzing 
caseinogen  and  lactalbumin,  but  they  rapidly  lose  weight  if  arginin 
and  histidin  have  been  removed  from  the  mixture,  and  the  allantoin 
in  the  urine  decreases.  Restoration  of  the  missing  amino-acids 
causes  growth  to  be  resumed  and  a  rise  in  the  allantoin  excretion  to 
normal.  This  is  true,  although  in  lesser  degree,  even  when  one  of 
these  amino-acids  is  restored  to  the  mixture,  as  they  seem  to  be  inter- 
convertible (Ackroyd  and  Hopkins).  Recently  the  synthesis  of 
nucleosides  has  been  accomplished  in  the  laboratory  (Fischer). 
It  only  needs  the  introduction  of  phosphoric  acid  in  the  appropriate 
way  into  the  molecule  to  give  nucleic  acid. 

The  Significance  of  Creatin  and  Creatinin  in  Protein  Metabolism. 
— A  glance  at  the  tables  of  composition  of  the  urine  (p.  477)  will  show  _ 
that  creatinin,  as  regards  the  quantity  excreted,  is  a  much  more 
important  product  of  nitrogenous  m.etabolism  than  uric  acid,  stand- 
ing, indeed,  with  the  ammonia  compounds,  next  in  order  to  urea; 
but  our  information  as  to  its  source  and  significance  is  very 
scanty. 

Creatin  is  a-methylguanidin-acetic  acid,  and  creatinin  is  derived 
from  it  by  loss  of  the  elements  of  water : 

/XH,      /NH,  /NHo  /NH— CO 

C4XH    C^NH  CH3.COOH  C^XH  C^XH 

\nH2      \XH.CH3a  \X(CH3).CH.2.C00H\N(CH3).CH2 

Guanidin.        Methylguanidin.     Acetic  acid.  Creatin.  Creatinin. 

On  heating  with  baryta-water  creatin  is  decomposed,  yielding  urea, 
methylglycocoll  or  sarcosin,  and  other  substances.  It  can  be  prepared 
synthetically  from  sarcosin  and  cyanamid.     Thus: 

^NH^     H.X(CH3)  /XHa 

C^N     +1  =      C^XH 

CHa-COOH  \x(CH3).CH2.COOH 

Cyanamid.  Methylglycocoll.  Creatin. 

Creatin  is  found  in  considerable  amount  in  muscular  tissue 
(much  less  in  children  than  in  adults),  and  in  traces  in  other 
tissues  and  in  blood,  which  also  contains  small  amounts  of 
creatinin. 

Creatinin  can  be  so  readily  obtained  from  creatin  outside  the 
body  that  it  is  tempting  to  suppose  that  the  portion  of  the  creatinin 


598  METABOUFM.   NUTRITION  AND  DIETETICS 

of  the  urine  which  is  not  formed  from  the  creatin  in  the  f(jO(l  is 
derived  from  tlie  creatin  of  the  muscles  and  other  tissues,  and  many 
theories  have  been  evolved  to  connect  the  creatinin  of  urine  with 
the  creatin  of  the  muscles.  But  it  is  doubtful  whether  there  is  any 
direct  connection.  The  fact  that  persons  who  have  been  long  ill 
and  are  feeble  and  wasted  have  a  low  creatin  content  in  their 
muscles,  and  a  low  creatinin  content  in  their  urine  relatively  to  the 
total  nitrogen  (Shaffer)  is,  so  far  as  it  goes,  in  favour  of  some  re- 
lationship between  the  two.  The  alleged  absence  of  creatinin  from 
muscle  seemed  to  be  opposed  to  the  idea  that  the  creatin  store  of  the 
muscular  tissue  was  an  important  source  of  urinary  creatinin;  for 
if  a  constant  transformation  of  this  kind  was  going  on,  traces  of 
creatinin  not  yet  absorbed  by  the  blood  might  have  been  expected 
to  be  present  in  the  muscles.  Recently,  however,  it  has  been 
reported  that  small  quantities  of  creatinin  do  exist  in  fresh  muscle 
(4  to  8  milligrarrmes  in  100  grammes  of  tissue),  and  that  when  the 
muscle  is  allowed  to  undergo  autolysis  the  creatinin  increases  at  a 
very  uniform  rate  at  the  expense  of  the  creatin.  Added  creatin 
experiences  the  same  fate  as  the  creatin  originally  present,  while 
added  creatinin  inhibits  the  reaction,  or  even  reverses  it  (Myers  and 
Fine).  A  parallelism  with  the  conversion  of  glycogen  into  dextrose 
in  the  liver  easily  suggests  itself,  and  it  is  possible  that  we  are  here 
in  the  presence  of  a  normal  reaction  which  may  account  for  at 
least  a  portion  of  the  creatinin  excretion.  It  is  probable  that  both 
creatin  and  creatinin  can  undergo  changes  in  the  body,  especially 
in  the  liver,  and  it  is  possible  that  the  products  may  be  further 
utilized  in  metabolism.  If  this  were  so,  the  creatin  store  of  the 
muscles  would  acquire  new  significance  as  a  reserve  of  useful  material 
with  perhaps  a  long  and  varied  metabolic  career  before  it,  and  would 
not  constitute  merely  a  temporary  depot  of  waste  material  whose 
metabolic  history  was  ended,  and  which  was  waiting  to  be  excreted. 
The  novel  view  has  recently  been  advanced  that  the  living  muscles 
contain  little  or  no  creatin,  but  that  the  creatin  found  on  analysis 
is  a  post-mortem  product  original^  constituting  a  part  of  the 
living  protoplasm  (I'olin  and  Denis). 

However  this  may  be,  the  constancy  of  the  creatinin  elimination 
on  a  meat-free  diet  (p.  4S2),  and  its  complete  independence  of  the 
changes  in  the  total  nitrogen  excretion,  show  that  it  has  a  diflfcrent 
significance  in  protein  metaboHsm  from  the  urea.  Evidence  is  accumu- 
lating that  it  is  especially  in  the  metabolism  of  the  organized  or  tissue 
protein  that  the  product  eventually  excreted  as  creatinin  arises ;  in  other 
words,  that  it  represents  especially  the  nitrogenous  waste  connected 
with  the  wear  and  tear  of  the  bodily  machinery,  while  urea  represents 
also,  and  under  ordinary  conditions  of  diet  chiefly,  the  nitrogen  of  the 
surplus  amino-acids  which  are  not  utilized  in  the  building  of  new  or  the 
repair  of  old  tissue  elements.  The  fact  that  the  amount  of  creatinin 
excreted  by  different  persons  seems  to  be  related  to  the  weight  of  active 
tissue  in  the  body,  excluding  fat,  is  in  favour  of  tliis  suggestion,  and 


METABOLISM  OF  PROTEINS  599 

there  is  other  evidence  pointing  in  the  same  direction;  for  example 
in  ordinary  circumstances  crcatin  is  either  absent  from  the  nrine  or 
present  in  very  small  amovint,  except  in  yonng  children.  When,  how- 
ever, the  decomposition  of  tissue-protein  is  abnormally  increased,  as  in 
starvation,  in  fevers,  in  women  after  delivery,  while  involution  of  the 
uterus  and  the  associated  destruction  of  a  considerable  mass  of  smooth 
muscle  is  taking  place,  crcatin  appears  in  larger  cpiantities  in  the  urine, 
perhaps  because  it  can  no  longer  be  all  converted  into  creatinin.  Now, 
the  increased  excretion  of  creatin  in  starvation  can  be  prevented  by 
giving  carbo-hydrate  food,  which  is  known  (p.  606)  to  lead  to  sparing 
of  tissue-protein  (Mendel  and  Rose).  That  the  depletion  of  the  body 
of  carboliydrate  is  in  some  way  related  to  the  elimination  of  creatin 
is  further  shown  by  the  fact  that  creatinuria  is  associated  with  diabetes 
and  with  the  action  of  substances  like  phlorhizin,  hydrazin,  phosphorus, 
etc.,  all  of  which  cause  carbo-hydrate  deficiency.  Something  more  is 
involved,  however,  for  under  conditions  of  diet  which  produce  acidosis 
(an  increase  in  the  hydrogen-ion  concentration  of  the  blood),  creatin 
appears  in  the  urine  no  matter  how  rich  the  food  may  be  in  carbo-hy- 
drate. For  example,  a  diet  of  oats  and  maize,  which  are  typical  acid- 
producing  foods,  causes  creatinuria  in  rabbits,  which  promptly  disappears 
when  carrots,  a  base-prodvicing  food,  are  added  (Underbill). 

The  statement  that  the  content  of  the  urine. in  creatinin  is  increased 
by  muscular  work  may  indicate  that  the  muscular  machine  wears  out 
faster  during  activity  than  during  rest,  or  perhaps  only  that  already- 
formed  creatin  leaves  the  muscles  in  greater  amount  when  the  blood-flow 
in  increased ;  but  recent  observations  tend  to  show  that  this  statement 
may  require  revision. 

As  to  the  manner  in  which  creatin  is  changed  into  creatinin  in  the 
body,  a  highly  suggestive  fact  is  the  presence  of  ferments  in  various 
organs  which  possess  this  power.  Ferments  also  exist  which  can 
decompose  both  creatin  and  creatinin.  The  existence  of  such  enzymes 
is  presumptive  evidence  that  the  changes  which  they  are  capable  of 
producing  actually  occur  in  the  organism ;  but  the  seat  of  the  changes 
if  they  do  take  place,  and  their  metabolic  significance,  are  unknown. 
Creatin  when  given  by  the  mouth  or  injected  into  the  blood  does  not 
cause  any  increase  in  the  virinary  creatinin,  nor  when  administered  in 
moderate  quantities  does  it  seem  to  be  excreted  as  creatin.  Like  urea, 
creatinin,  and  amino-acids,  it  is  taken  up  very  rapidly  by  the  muscles. 
Creatinin,  on  the  other  hand,  when  added  to  the  food,  causes  an  increase 
in  the  creatinin  of  the  urine. 

Intracellular  Ferments — Autolysis. — As  to  the  agencies  by  which 
the  decomposition  of  the  proteins  is  carried  out  in  the  cells,  we  have 
already  spoken  of  the  oxidizing  cell  ferments,  or  oxydases  (p.  272). 
Reducing  ferments,  or  reductases,  are  also  known,  and  can  be  ex- 
tracted from  most  organs,  if  not  all.  Like  oxydases,  they  act  in  a 
weakly  alkaline  medium,  causing  in  the  presence  of  hydrogen  such 
reductions  as  the  formation  of  nitrites  from  nitrates.  There  is  some 
evidence  that  one  and  the  same  ferment  may  act  as  an  oxydase  or 
a  reductase  according  to  the  conditions.  Recent  researches  have 
brought  to  light  in  addition  hydrolytic  intracellular  ferments,  which 
split  up  proteins  very  much  in  the  same  way  as  the  proteoh'tic 
ferments  of  the  digestive  juices. 

The  significance  of  these  autolytic  enzymes  in  the  normal  metabo- 


6oo  METABOLISM.  NUTRITION  AND  DIETETICS 

lism  of  prott'ins  lias  been  already  discussed  (p.  578) ;  indeed,  so  many 
of  the  chemical  reactions  of  the  body  have  been  found  to  depend 
upon  enzymes  that  modern  physiology  may  at  first  thought  seem 
almost  to  have  reverted  to  the  position  of  Van  Helmont  and  his 
school  in  the  seventeenth  century,  who  resolved  all  difficulties  by 
murmuring  the  magic  word  '  ferment.'  No  fewer  than  eleven  fer- 
ments lune  been  stated  to  be  present  and  active  in  the  liver  alone 
— viz.,  a  proteolytic  and  a  nuclein-splitting  ferment,  a  ferment 
which  splits  off  ammonia  from  amino-acids,  a  milk-curdling  ferment, 
a  fibrin  ferment,  a  bactericidal  ferment,  an  oxydase,  a  lipase,  a 
maltase,  a  ferment  called  glycogenase,  which  changes  glycogen  into 
dextrose,  and  an  autolytic  ferment.  In  the  presence  of  such  an 
array  of  enzymes  the  organs  might  seem  to  be  little  more  than 
incubators  in  which  the  ferments  do  their  work.  It  must  not  be 
supposed,  however,  that  the  intracellular  ferments,  whether  they 
cause  decomposition  or  synthesis,  oxidation  or  reduction,  work  in- 
dependently of  what,  for  want  of  a  better  name,  we  must  call  the 
organization  of  the  cell.  We  may  be  sure  they  are  the  servants 
and  not  tlie  masters  of  the  protoplasm,  and  that  a  drop  of  an  extract 
containing  intracellular  ferments  has  very  different  powers  from  a 
living  cell.  '  It  is  not  in  the  existence  of  the  ferments,  but  in  their 
combined  action  at  the  proper  time  and  in  the  proper  intensity,  that 
the  riddle  of  metabolism  lies  '  (Hober) . 

Summary.~At  this  point  let  us  sum  up  wliat  we  have  learnt  as 
to  the  relation  between  the  approximate  principles  of  the  tissues  and 
the  proximate  principles  of  the  food.  Inside  the  body  we  recognize 
representatives  of  the  three  groups  of  organic  food-substances  in  a 
typical  diet — proteins,  carbo-hydrates,  and  fats.  But  we  should 
greatly  err  if  we  were  to  imagine  that  the  three  streams  of  food- 
materials  have  flowed  from  the  intestines  into  the  tissues  each  in  its 
separate  channel,  neither  giving  to  nor  taking  from  the  others. 
The  fats  of  the  body  may,  indeed,  in  part  be  composed  of  molecules 
which  xvere  present  as  fat  in  the  food  ;  but  they  may  also  be  formed 
from  carbo-hydrates,  and  probably  from  proteins.  The  carbo-hydrates 
of  the  body — the  glycogen  of  the  liver  and  muscles,  the  sugar  of  the  blood 
— may  undoubtedly  be  derived  from  carbo-hydrates  in  the  food,  but  they 
may  also  be  derived  from  proteins  and  from  fats  {certainly  from  their 
glycerin  constituent,  perhaps  from  the  fatty  acids  as  well).  The  pro- 
teins of  the  body  come  mainly,  if  not  solely,  from  the  proteins  of  the  food. 
Although,  of  course,  neither  fats  nor  carbo-hydrates  can  by  themselves 
form  protein,  being  devoid  of  nitrogen,  it  is  possible  that  products 
arising  in  the  intermediary  metabolism  of  either  may,  by  combining 
li'ith  nitrogenous  groups,  be  tranfsormed  into  amino-bodies,  -which  can 
then  take  part  in  the  synthesis  of  proteins.  In  any  case  there  is  no 
doubt  that  both  carbo-hydrates  and  fats  can  economize  proteins  and 
shield  them  from  an  overhasiy  metabolism. 


STATISTICS  OF  NUTRITION 


60 1 


Section  IV.— Statistics  of  Nutrition — The  Income  and 
Expenditure  of  the  Body  in  Terms  of  Matter  * 

Preliminary  Data. — The  office  of  the  food  is  to  maintain  the  con- 
stituents of  the  body  upon  the  whole  in  their  normal  proportions.  A 
knowledge  of  the  chemical  composition  of  the  body  is,  therefore,  an 
important  datum  in  the  consideration  of  the  statistics  of  its  metabolism. 
The  body  of  a  man  analyzed  by  Volkmann  had  the  following  composition  : 

,  .        ,.  (Water     -         -         -         -  65-9  per  cent. 

Inorganic  substances  I ^.j^^j.^^^^^^^ J.        .         .    ^.^^     ^^ 

rCarbon       18-4  per  cent."\ 

Organic  substances     ^Nrtrogfr    2-6        ','.        [^97        -. 
(.Oxygen        6'0         ,,        J 
The  muscles,  the  adipose  tissue,  and  the  skeleton  form  nearly  four- 
fifths  of  the  total  body-weight  in  the  adult.     The  following  table  shows 
the  percentage  amount  of  each  of  these  tissues  in  a  man,  a  woman,  and 
a  child  (Bischoff) : 


Man. 

Woman. 

New-born 
Child. 

Voluntary  muscles 
Adipose  tissue     - 
Skeleton      - 
Rest  of  body 

41.8 
l8-2 

15-9 
24-1 

35-8 

2  8-2 

15-1 

20*9 

23-5 

13-5 
157 
47-3 

The  nitrogen  is  contained  chiefly  in  the  muscles,  glands,  and  nervous 
system,  and  in  the  constituents  of  the  connective  tissues,  which  yield 
gelatin,  various  mucoids,  and  elastin.  The  ordinary  proteins  make  up 
about  9  per  cent,  of  the  weight  of  the  body,  or  22  per  cent,  of  its  solids; 
the  albuminoids  or  sclero-proteins  (gelatin-yielding  material,  etc.)  (p.  2) 
about  6  per  cent,  of  the  body-weight.  Nitrogen  exists  in  proteins  to 
the  extent  of  16  per  cent.,  so  that  the  6-5  kilos  of  protein  of  a  70-kilo 
body  contain  about  i  kilo  of  nitrogen. 

The  carbon  is  contained  chiefly  in  the  fat,  which  forms  a  very  large 
proportion  of  the  water-free  substance  of  the  body,  and  in  the  proteins. 
A  small  amount  is  present  as  calcium  carbonate  in  the  bones.  In  the 
body  of  a  strong  young  man  weighing  68-6  kilos,  Voit  found  the  following 
quantities  of  dry  fat  in  the  various  tissues : 

-     8809*4  grammes. 


Adipose  tissue 

Skeleton 

Muscles 

Brain  and  spinal  cord 

Other  organs 

Total    - 


26I7-2 

636-8 

226-9 

73-2 

12363-5 


equivalent  to  18  per  cent,  of  the  whole  body-weight,  or  44  per  cent,  of 
the  solids.  In  dry  fat  rather  more  than  75  per  cent,  of  carbon  is  present, 
and  in  protein  about  50  to  55  per  cent. ;  so  that  while  the  fat  of  the  body 
analyzed  by  Voit  contained  more  than  9  kilos  of  carbon,  only  about  a 
third  of  this  amount  would  be  found  in  the  proteins. 

*  The  income  and  expenditure  of  the  body  in  terms  of  energy  are  considered 
in  Chapter  XII. 


6o2  METABOLISM.  NUTRITION  AND  DIETETICS 

In  the  fat  there  is,  roughly  speaking,  12  per  cent,  of  hydrogen,  in 
proteins  only  7  per  cent. ;  so  that  from  three  to  four  times  as  much 
hydrogen  is  contained  in  the  fat  of  the  body  as  in  its  proteins. 

Oxygen  forms  about  12  per  cent,  of  fat,  and  20  to  24  per  cent,  of 
proteins;  the  protein  constituents  of  the  body,  therefore,  contain  about 
as  much  of  its  oxygen  as  the  fat. 

Of  the  inorganic  salts,  calcium  phosphate,  Ca3(P04)2,  is  much  the 
most  abundant,  owing  to  tlie  large  amount  of  it  in  bone,  in  the  ash  of 
which  it  is  found  to  the  extent  of  83  per  cent.,  along  with  13  per  cent, 
of  calcium  carbonate. 


Income  and  Expenditure  of  Nitrogen — The  Nitrogen 
Balance-Sheet. 

Nitrogenous  Equilibrium. — It  is  a  matter  of  cornmon  experi- 
ence that  the  weight  of  the  body  of  an  adult  may  remain  approxi- 
mately constant  for  many  months  or  years,  even  when  the  diet  varies 
greatly  in  nature  and  amount.  And  not  only  may  the  weight  remain 
constant,  but  the  relative  proportions  of  the  various  tissues  of  the 
body,  so  far  as  can  be  judged,  may  remain  constant  too.  Here  it 
is  evident  that  the  expenditure  of  the  body  must  precisely  balance 
its  income :  it  must  lose  as  much  nitrogen  as  it  takes  in,  otherwise 
it  would  put  on  flesh;  it  must  lose  as  much  carbon  as  it  takes  in, 
otherwise  it  would  put  on  fat.  Or,  again,  the  body  may  be  losing 
or  gaining  fat,  giving  off  more  or  less  carbon  than  it  receives,  while 
its  '  flesh  '  (its  protein  constituents)  remains  constant  in  amount, 
the  expenditure  of  nitrogen  being  exactly  equal  to  the  income.* 
In  both  cases  we  say  that  the  body  is  in  nitrogenous  equilibrium. 

A  starving  animal  or  a  fever  patient,  on  the  other  hand,  is  living 
upon  capital,  the  former  entirely,  the  latter  in  part;  the  expenditure 
of  nitrogen  is  greater  than  the  income.  A  growing  child  is  living 
below  its  income,  is  increasing  its  capital  of  flesh.  In  neither  case 
is  nitrogenous  equilibrium  present. 

The  starving  animal,  as  long  as  life  lasts,  excretes  urea,  kreatinin, 
and  other  nitrogenous  substances,  and  gives  off  carbon  dioxide; 
but  its  expenditure,  and  especially  its  expenditure  of  nitrogen,  is 
pitched  upon  the  lowest  scale.  It  lives  penuriously,  it  spins  out 
its  resources;  its  glycogen  goes,  its  fat  goes,  a  certain  part  of  its 
protein  goes,  and  when  its  weight  has  fallen  from  25  to  50  per  cent, 
it  dies.  At  death  the  heart  and  central  nervous  system  are  found 
to  have  scarcely  lost  in  weight ;  the  other  organs  have  been  sacrificed 
to  feed  them.  Fig.  199  shows  the  percentage  loss  of  weight  and 
the  proportion  of  tlie  total  loss  which  falls  upon  each  of  the  organs 
of  a  cat  in  starvation  (Voit). 

♦  For  long  experiments  extending  over  many  days  the  nitrogen  balance 
may  be  considered  as  practically  the  same  as  the  protein  balance,  but  this 
is  not  necessarily  true  of  short  periods  of  time,  since  the  stock  of  nitrogen 
present  in  the  body  in  other  forms  than  proteins,  although  relatively  small, 
is  subject  to  variations. 


STATISTICS  OF  NUTRITION 


603 


For  the  first  day  of  starvation  the  excretion  of  urea  in  a  dog  or 
cat  is  not  diminished;  it  takes  about  twenty-four  hours  for  all  the 
nitrogen  corresponding  to  the  proteins  of  the  last  meal  to  be  elimin- 
ated. On  the  second  day  the  quantity  of  urea  sinks  abruptly; 
then  begins  the  true  starvation  period,  during  which  the  daily  output 
of  urea  remains  constant  or  diminishes  very  slowly  until  a  short  time 
before  death,  when  it  rapidly  falls,  and  soon  ceases  altogether.  An 
increase  in  the  excretion  may  precede  the  final  abrupt  decline  (pre- 
mortal increase).  This  seems  to  indicate  the  time  at  which  all  the 
available  fat  has  been  used  up,  and  after  which  protein  is  no  longer 
'  spared  '  by  the  fat.*  If  the  animal  has  little  fat  in  its  body  to 
begin  with,  the  rise  in  the  urea  excretion  takes  place  even  after  the 
first  few  days.      So  long  as  the  fat  lasts  the  rate  at  which  it  is 


/ 

n 

«•/    Muscle 

W-r: 

.^.ijlIl.C  ,.,..;-.^__  J!.i_, 

^itfitf 

-Hc-Tlf-I 

r- 

Bra'-n            i 

262   Fat 
a-7     Sk'in 

J 

'!^!||ji!liiliilii;iliiiiiliiilil 

Heart  J 
Bones          '"■ 

J -5    Bones 

Pancreas    i7 

■^■U    Liver 
2-6    Blood 

r- 

Intestines  '8 
L  ungs           10 

ZO  Intestine:. 
0-6   Kidney i 
i^O-5   Spleen 

_.„q^rrrr 
— ii — 

Skin              il 

Kidnevs  2S 
Blood          27 

0-3   Lungs 

i  ' 

Vusdes       31 

O'l    Pancreas 

Teste  <        40 

■  Oil    Testes 

|7 



Liver          S4 

jO-l  Brain  i  Cora 

' 

Spleen       67 

(0-1  Heart 

, 

,:  ,-, 

\ 

Fof^              97 

Fig.  igs- — Diagram  showing  Loss  of  Weight  of  the  Organs  in  Starvation.  The 
numbers  under  I.  are  the  percentages  of  the  total  loss  of  body -weight  borne  by 
the  various  organs  and  tissues.  The  numbers  under  II.  give  the  percentage  loss 
of  weight  of  each  organ  calculated  on  its  original  weight  as  indicated  by  com- 
parison with  the  organs  of  a  similar  animal  killed  in  good  condition. 

destroyed — as  estimated  from  the  amount  of  carbon  given  off  minus 
the  carbon  corresponding  to  the  broken-down  proteins — remains 
very  nearly  constant  after  the  first  day.  The  fat  to  a  certain  extent 
economizes  the  proteins  of  the  starving  body,  but  however  much 
fat  may  be  present,  a  steady  waste  of  the  tissue-proteins  goes  on. 
If  non-nitrogenous  food  in  the  form  of  sugar  is  supplied  to  an  other- 
wise starNang  animal,  the  premortal  rise  in  the  nitrogen  excretion 
does  not  occur.  By  giving  a  sufficient  quantity  of  sugar,  or  of 
sugar  and  fat,  but  practically  no  protein  (so-called  nitrogen  starva- 
tion), the  excretion  of  nitrogen  may  be  reduced  to  one-third  of  its 
amount  when  no  food  at  all  is  given.     This  is  true  both  in  animals 

*  If  the  animal  has  been  for  some  time  on  a  diet  containing  an  abundance 
of  proteins,  several  days  may  elapse  before  the  constant  excretion  of  urea 
is  reached;  if  the  previous  diet  has  been  poor  in  protein,  the  constant  star- 
vation output  may  be  at  once  established. 


6o4 


METABOLISM.  NUTRITION  AND  DIETETICS 


and  man  In  this  way  the  daily  excretion  of  nitrogen  in  a  man  has 
been  reduced  to  4  grammes.  It  is  a  remarkable  fact  that  while  a 
mixture  of  carbo-hj'drate  and  fat  will  act  just  as  well  as  carbo- 
hydrate alone  in  bringing  about  this  reduction  in  the  nitrogen 
output,  fat  without  carbo-hydrate  is  much  less  effective.  The 
hypothesis  suggested  by  Landergren  to  explain  this  is  alluded  to 
on  another  page  (p.  551). 

The  results  obtained  on  fasting  men  differ  in  some  respects  from 
those  obtained  on  starving  animals.  In  ten  days  of  hunger,  Cetti, 
a  professional  '  fasting  man  '  of  meagre  habit,  excreted  112  grammes 
nitrogen,  or  an  average  of  11  grammes  a  day.  The  excretion  was 
least  on  the  eighth,  ninth,  and  tenth  days — namely,  about  9  grammes 
a  day.  On  the  third  day  it  was  higher  than  on  the  second,  and 
almost  as  high  on  iS^ra/vs 
the  fourth  as  on  the 
third.  A  similar  rise 
in  the  nitrogen 
excretion  on  the 
second  day  has  been 
observed  in  other 
fasting  men,  but  is 
either  rare  or  absent 
in  fasting  dogs.  The 
explanation  appar- 
ently is  that  in  the  ^ig. 
ordinary  food  of 
man  there  is  a 
greater  abundance 
of  carbo  -  hydrates 
and  fats,  the  pro- 
tein -  sparing  action 
of    which    is    most 


!0 


Cjrarr,^ 


6  grary?s 


A  60 


^2U 


•99.' 


Excretion  of  Urea  in  Starvation.  .\  is  a  curv« 
representing  the  quantity  of  urea  e.\creted  daily  by  a 
fat  dog  in  a  starvation  period  of  si::ty  days.  B  is  the 
curve  of  urea  excretion  in  a  lean  young  dog  in  a 
starvation  period  of  twenty-four  days.  Both  are  con- 
structed from  Falck's  numbers,  but  in  A  only  every 
third  day  is  put  in,  in  order  to  save  space.  The  num- 
bers along  the  vertical  axis  represent  grammes  of  urea; 
those  along  the  horizontal  axis  days  from  the  beginning 
of  star\'ation. 


pronounced  at  the  very  beginning  of  the  starvation  period.  The 
quantity  of  chlorine  and  alkalies  in  the  urine  was  also  diminished, 
while  the  phenol  was  increased.  The  respiratory  quotient  sank  to 
0-66  to  0-69 — even  less  than  the  quotient  corresponding  to  oxida- 
tion of  fats  alone.  The  meaning  of  this,  in  all  probability,  is  that 
some  of  the  carbon  of  the  broken-down  proteins  was  laid  up  in  the 
body  as  glycogen  (Zuntz).  In  another  professional  fasting  man 
(Succi)  with  a  considerable  amount  of  body-fat,  the  excretion  of 
nitrogen  was  found  to  diminish  continuously  during  a  fast  of  thirty 
days,  being  less  than  7  grammes  on  the  tenth  day.  In  another  fast 
of  twenty-one  days  by  the  same  person  it  was  a  little  less  than 
3  grammes  on  the  last  day.  The  surprisingly  small  nitrogenous 
waste  in  this  case  is  perhaps  to  be  accounted  for  by  the  protein- 
sparing  action  of  the  abundant  body-fat.     The  nitrogenous  metabo- 


STATI:iTICS  OF  NUTRITION 


605 


lism  has  also  been  investigated  during  long-continued  liypnotic  sleep 
(Hoover  and  Solhnann).  The  results  were  very  much  the  same  as 
in  an  ordinary  starvation  experiment 

It  might  be  supposed  that  if  an  animal  was  given  as  much  nitrogen 
in  the  food  in  the  form  of  proteins  as  corresponded  to  its  daily  loss 
of  nitrogen  diu-ing  starvation,  this  loss  would  be  entirely  prevented 
and  nitrogenous  equilibrium  restored.  The  supposition  would  be 
very  far  from  the  reality.  If  a  dog  of  30  kilos  weight,  which  on 
the  tenth  day  of  starvation  excreted  11-4  grammes  urea,  had  then 
received  a  daily  quantity  of  protein  equivalent  to  this  amount — 
that  is  to  say,  about  34  grammes  of  dry  protein,  or  175  grammes  of 
lean  meat — the  excretion  of  nitrogen  would  at  once  have  leaped 
up  to  nearly  double  its  starvation  value.  If  the  quantit}^  of  protein 
in  the  diet  was  progressively  increased,  the  output  of  urea  would 
increase  along  with  it,  but  at  an  ever-slackening  rate;  and  at  length 
a  condition  would  be  reached  in  which  the  income  of  nitrogen 
exactly  balanced  the  expenditure,  and  the  animal  neither  lost  nor 
gained  flesh. 

In  an  experiment  of  Volt's,  for  instance,  the  calculated  loss  of  flesh 
in  a  dog  with  no  food  at  all  was  190  grammes  a  day.  The  animal  was 
now  fed  on  a  gradually  increasing  diet  of  lean  meat,  with  the  following 
result : 


Flesh  in  the 

Flesh  used  up  in 

Net  Loss  oJ 

Food. 

the  Body. 

Body-flesh. 

0 

190 

190 

250 

341 

91 

350 

411 

61 

400 

454 

54 

450 

471 

21 

480 

492 

12 

The  loss  of  nitrogen  in  the  urine  and  faeces  is  what  was  measured. 
Knowing  the  average  composition  of  '  body-flesh  '  (muscles,  glands, 
etc.),  it  is  possible  to  translate  results  stated  in  terms  of  nitrogen  into 
results  stated  in  terms  of  '  flesh.'  Muscle  contains  approximately 
3'4  per  cent,  of  nitrogen.  Here,  with  a  diet  of  480  grammes  of  meat,  the 
dog  was  still  losing  a  little  flesh ;  it  would  probably  have  required  from 
500  to  600  grammes  for  equilibrium.  The  results  are  graphically 
represented  in  Fig.  200,  p.  007. 

The  quantity  of  protein  food  necessary  for  nitrogenous  equili- 
brium varies  with  the  condition  of  the  organism ;  an  emaciated  body 
requires  less  than  a  muscular  and  well-nourished  body.  The  least 
quantity  which  would  suffice  to  maintain  in  nitrogenous  equilibrium 
the  famous  35  kilo  dog  of  Voit,  even  in  very  meagre  condition,  was 
480  grammes  of  lean  meat,  corresponding  to  16  grammes  of  nitrogen, 
or  35  grammes  of  urea — that  is,  about  three  times  the  daily  loss 


6o6  METABOLISM.  NUTRITION  AND  DIETETICS 

during  starvation.  From  this  lower  limit  up  to  2,500  grammes  of 
meat  a  day  nitrogenous  equilibrium  could  always  be  attained,  the 
animal  putting  on  some  flesh  at  each  increase  of  diet,  until  at  length 
the  whole  2,500  grammes  was  regularly  used  up  in  the  twenty-four 
hours.  A  further  increase  was  only  checked  by  digestive  troubles. 
A  man,  or  at  least  a  civilized  man,  can  consume  a  much  smaller 
amount  both  absolutely  and  in  proportion '  to  the  body- weight. 
Rubner,  with  a  body-weight  of  72  kilos,  was  able  to  digest  and  absorb 
over  1,400  grammes  of  lean  meat;  Ranke,  with  about  the  same 
body-weight,  could  only  use  up  1,300  grammes  on  the  first  day  of 
his  experiment,  and  less  than  1,000  grammes  on  the  third.  But 
whether  the  surplus  of  protein  food  above  the  necessary  minimum 
is  great  or  small,  nitrogen  equilibrium  is  eventually  attained,  and 
thereafter  all  the  nitrogen  of  the  food  regularly  appears  in  the 
excreta;  the  explanation  of  this  fact  will  be  considered  a  little 
later  (p  O09). 

So  much  for  a  purely  protein  diet.  When  fat  is  given  in  addition 
to  protein,  nitrogenous  equilibrium  is  attained  with  a  smaller  quantity 
of  the  latter.  A  dog  which,  with  protein  food  alone,  is  putting  on 
flesh,  will  put  on  more  of  it  before  nitrogenous  equihbrium  is  reached 
if  a  considerable  quantity  of  fat  be  added  to  its  diet.  Fat,  therefore, 
economizes  protein  to  a  certain  extent,  as  we  have  already  recog- 
nized in  the  case  of  the  starving  animal.  On  the  other  hand,  when 
protein  is  given  in  large  quantities  to  a  fat  animal,  the  consumption 
of  fat  is  increased;  and  if  the  food  contains  little  or  none,  the  body- 
fat  will  diminish,  while  at  the  same  time  '  flesh  '  may  be  put  on. 
The  Banting  cure  for  corpulence  consists  in  putting  the  patient 
upon  a  diet  containing  nuicli  protein,  but  little  fat  or  carbo-hydrate; 
and  the  fact  just  mentioned  throws  light  upon  its  action. 

All  that  we  have  here  said  of  fat  is  true  of  carbo-hydrates.  To  a 
great  extent  these  two  kinds  of  food  substances  are  complementary. 
Carbo-hydrates  economize  proteins  as  fat  does,  but  to  a  greater 
extent,  so  that  with  an  abundant  supply  of  carbo-hydrate  in  the 
food  the  minimum  protein  requirement  can  be  forced  down  much 
below  what  is  possible  on  a  diet  of  protein  and  fat  alone.  Carbo- 
hydrates also  economize  fat,  so  that  when  a  sufficient  quantity  of 
starch  or  sugar  is  given  to  an  otherwise  starving  animal,  all  loss  of 
carbon  from  the  body,  except  that  which  goes  off  in  the  urea,  krea- 
tinin,  etc.,  still  excreted,  can  be  prevented.  Of  course,  the  animal 
ultimately  dies,  because  the  continuous,  though  diminished,  loss  of 
protein  cannot  be  made  good.  The  fact  that  carbo-hydrates  econo- 
mize proteins  so  much  more  efficiently  than  fat  indicates  that  sugar 
is  essential  in  the  bodily  metabolism,  so  that  when  carbo-hydrates 
are  absent  from  the  food  some  of  the  protein  must  be  broken  down 
so  as  to  yield  eventually  the  compounds  necessary  for  the  formation 
of  carbo-hydrate.     It  is  probable,  indeed,  that  purified  proteins, 


STATISTICS  OF  NUTRITION 


607 


Grarr}5 
joo 

300 
200 
100 


WO    ip 


absolutely  free  from  admixture  with  carbo-hydrates,  which,  of 
course,  is  not  the  case  with  the  natural  protein  foods,  will  not  per- 
manently suffice  for  nutrition,  but  that  the  protein  must  be  supple- 
mented by  a  certain  amount  of  carbo- 
hydrate in  some  form  available  for  the 
tissues.  It  would  appear,  indeed,  that 
fats  are  not  absolutely  indispensable 
either  for  maintenance  or  for  growth. 
White  rats  have  been  seen  to  grow  nor- 
mally over  long  periods  with  dietaries 
devoid  of  fat ;  for  example,  mixtures  of  the 
purified  protein  edestin  (from  hemp  seed) 
or  casein  with  starch,  sugar,  and  '  protein- 
free  milk  '  freed  from  fat  by  extraction 
with  ether  (Osborne  and  Mendel).  While 
in  these  experiments  the  food  might  not 
have  been  free  from  the  so-called  '  lipoids,' 
it  has  been  demonstrated  that  an  impor- 
tant group  of  substances  of  this  class,  the 
phosphatides,  can  be  S5mthesized  in  the 
body,  the  necessary  phosphorus  being  ob- 
tainable even  from  inorganic  phosphates 
(McCollom). 

Relation  between  Nitrogen  excreted  and 
the  Quantity  of  Protein  Food. — At  this 
point  we  may  consider  a  little  more 
closely  a  phenomenon  already  alluded  to, 
and  to  which  much  discussion  used  to  be 
devoted  by  writers  on  metabolism.  It 
has  been  stated  that  within  the  limits  of 
nitrogenous  equilibrium,  which  is  the  nor- 
mal state  of  the  healthy  adult,  the  body 
lives  up  to  its  income  of  nitrogen ;  it  lays 
by  nothing  for  the  future.  In  the  actual 
pinch  of  starvation  the  organism,  when 
its  behaviour  is  tested  by  a  comparison 
of  the  intake  and  excretion  of  nitrogen, 
appears  to  have  become  suddenly  econo- 
mical. When  a  plentiful  supply  of  protein 
is  presented  to  the  starving  body,  it  seems, 
judged  by  the  same  criterion,  to  pass  at 
once  from  extreme  frugality  to  luxury. 
Some  flesh  may  be  put  on  for  a  short  time,  some  nitrogen  may  be 
stored  up;  but  the  excretion  of  nitrogen  is  soon  adjusted  to  the  new 
scale  of  supply,  and  the  protein  income  is  apparently  spent  as  freely 
as  it  is  received.     These  facts  were  usually  summed  up  in  the 


Fig.  200. — Curves  constructed 
to  illustrate  Nitrogenous 
Equilibrium  (from  an  Ex- 
periment of  Voit's).  The 
loss  of  flesh  in  grammes  is 
laid  off  along  the  horizontal 
axis.  The  income  and 
expenditure  corresponding 
to  a  given  loss  are  laid  ofl' 
(in  grammes  of  '  flesh ') 
along  the  vertical  axis.  The 
continuous  curve  is  the 
curve  of  income;  the  dotted 
curve,  of  expenditure.  With 
no  income  at  all  the  expen- 
diture is  190  grammes; 
with  an  income  of  480 
grammes  the  expenditure 
is  492  and  the  loss  12 
grammes.  Nitrogenous 
equilibrium  is  represented 
as  being  reached  with  an 
income  of  about  530 
grammes;  here  the  two 
curves  cut  one  another. 


6o8  METABOLISM.  NUTRITION  AND  DIETETICS 

dictum,  often  dignified  as  a  '  law  '  of  nitrogenous  metabolism  that*. 
Consxnnption  of  protein  is  largely  determined  by  supply  (Practical 
Exercises,  p.  720). 

To  explain  this  many  hypotheses  were  invented.  The  famous  theory 
of  Voit  assumed  that  the  food-protein  after  absorption  (the  so-called 
'  circulating-protein  ')  is  carried  to  the  tissues  and  taken  up  by  the 
cells,  where  the  greater  part  of  it,  without  being  incorporated  with  the 
protoplasm,  is  nevertheless  acted  upon,  rendered  unstable,  shaken  to 
pieces,  as  it  were,  by  the  whirl  of  life  (by  the  intracellular  enzymes  we 
might  now  say  less  dramatically)  in  the  organized  framework,  the 
interstices  of  which  it  fills. 

Pfliiger,  on  the  other  hand,  maintained  that  we  have  no  right  to 
draw  a  distinction  between  the  consumption  of  organ-  and  circulating- 
protein;  that  the  whole  of  the  latter  ultimately  rises  to  the  height  of 
organ-  or  tissue-protein,  and  passes  on  to  the  downward  stage  of 
metabolism  only  through  the  topmost  step  of  organization .  An  increase 
in  the  supply  of  nitrogenous  material  in  the  blood  must,  on  this  view, 
be  accompanied  with  an  increased  tendency  to  the  break-up,  the  dis- 
sociation, as  Pfliiger  put  it,  of  the  living  substance.  The  actual  organ- 
ized elements,  however,  the  existing  cells,  were  not  supposed  to  be 
destroyed;  the  building  remained,  for  although  stones  were  constantly 
crumbling  in  its  walls,  others  were  being  constantly  built  in. 

A  much  less  plausible  view  was  that  the  tissue  elements  themselves  are 
short-li\-ed ;  that  the  old  cells  disappear  bodily  and  are  replaced  by  new 
cells ;  and  that  the  whole  of  the  proteins  of  the  food  take  part  in  this 
process  of  total  ruin  and  reconstruction.  Histological  evidence,  as  soon 
as  the  methods  of  examining  tissues  with  the  microscope  became 
sufficiently  refined,  told  strongly  against  this  idea.  Although  the  cells 
of  certain' glands,  such  as  the  mammary,  perhaps  the  mucous  glands, 
and  especially  the  sebaceous  glands  (p.  565),  exhibit  changes  which, 
hastily  interpreted,  might  seem  to  indicate  that  they  break  dovra 
bodily,  as  an  incident  of  functional  activity,  no  proof  could  be  obtained 
of  the  production  of  new  cells  on  the  immense  scale  which  this  theory 
would  require.  The  relatively  small  and  constant  amount  of  the 
endogenous  metabolism  indicates  that  the  actual  protoplasmic  sub- 
stance, the  living  framework  of  the  cell,  is  comparatively  stable; 
that  it  does  not  break  down  rapidly;  and  that  only  a  small  and 
fairly  constant  amount  of  food-  or  circulating-protein,  or  of  the 
decomposition  products  of  protein,  is  required  to  supply  the  waste 
of  the  organ -protein. 

We  have  referred  to  these  theories  because  there  could  scarcely  be  a 
more  instructive  instance  of  the  way  in  which  theories  become  obsolete 
with  the  adv^ance  of  knowledge  and  of  the  way  in  which,  with  the 
advance  of  knowledge,  a  phenomenon  which  appears  an  absolute  riddle 
to  one  generation  may  become  fairly  intelligible  to  the  next,  perhaps 
childishly  simple  to  a  third.  The  student  will  not  derive  much  benefit 
from  the  perusal  of  this  page  should  he  fail  to  recognize  that  the 
hypotheses  of  the  twentieth  century  are  mortal  too,  and  bound  for  the 
same  bourne  as  those  of  the  nineteenth. 

It  is  apparent  in  the  first  place  from  our  study  of  the  metabolism 
of  the  proteins  that  the  conclusion,  '  consumption  of  protein  is  pro- 
portional to  supply,'  cannot  be  drawn  from  the  equality  of  nitrogen 
intake  and  nitrogen  output.  The  amino-acids  derived  from  proteins, 
except  that  relatively  small  fraction  employed  in  repairing  the 


STATISTICS  OF  NUTRITION  609 

waste  of  the  tissues,  which  in  nitrogen  equilibrium  is  exactly  com- 
pensated for  by  a  corresponding  release  of  amino-acids  or  their 
equivalent  from  the  cell-proteins,  are  indeed  speedily  deaminated 
and  the  nitrogen  of  the  amino-groups  excreted  as  urea  (with 
ammonia  compounds  and  creatinin).  But,  as  we  have  seen,  only  a 
small  proportion  of  the  chemical  energy  of  the  amino-acids  and  only 
a  small  fraction  of  their  carbon  are  liberated  in  this  process.  The 
carbon-containing  residues  are  katabolized  only  to  the  extent  re- 
quired by  the  momentary  needs  of  the  tissues,  any  balance  being 
stored  as  part  of  the  reserve  of  carbo-hydrate  or  of  fat.  The  body 
does  not  possess  the  means  of  storing  surplus  amino-acids  as  such 
or  even  in  the  form  of  proteins,  except  to  the  small  extent  corre- 
sponding to  any  increase  which  may  occur  in  the  body-protein 
when  the  food-protein  is  increased  beyond  the  minimum  required 
for  nitrogen  equilibrium.  Why  the  organism  has  not  developed 
the  capacity  to  store  large  quantities  of  protein  is,  of  course,  an 
interesting  question,  but  it  need  scarcely  be  discussed  here.  One 
obvious  reason  is  that  protein  is  not  a  suitable  source,  nor  are  amino- 
acids  apparently  a  suitable  source  of  energy  for  the  tissues  until 
they  have  been  deaminated  and  have  probably  undergone  further 
decomposition  and  transformation.  Therefore  they  are  decomposed 
at  once  and  their  available  residue  stored,  if  it  is  in  any  case  to  be 
stored,  in  the  more  available  form  of  carbo-hydrate  (or  fat). 
Where  the  food-proteins  differ  greatly  from  the  body-proteins  in 
the  proportions  of  the  various  amino-acids,  there  would  be  no  object 
in  storing  a  great  surplus  of  those  which  are  most  plentiful  in  the 
food,  if  they  were  at  the  same  time  the  scarcest  in  the  tissues,  or, 
in  the  case  of  gland-cells,  the  scarcest  in  the  proteins  which  they 
manufacture  for  their  secretions. 

At  any  moment  the  magnitude  of  this  non-utilizable  surplus  will 
depend  upon  the  quantity  of  that  one  of  the  indispensable  amino- 
acids  which  is  present  in  the  smallest  amount.  For  the  proper 
proportion  must  be  preserved  between  the  different  '  stones  '  out  of 
which  the  molecule  is  built.  \M"ien  a  single  amino-acid  is  intro- 
duced into  the  body,  it  is  at  once  changed  into  urea  and  excreted, 
since  it  cannot  be  utihzed  by  itself  for  building  up  protein. 

When  the  cells  have  once  culled  from  the  mixture  circulating  in 
the  blood  the  amino-acids,  a  full  supply  of  which  they  have  most 
difficulty  in  obtaining,  a  residue,  large  or  small,  according  to  the 
quantity  and  quality  of  the  protein  intake,  will  be  left,  and  this  can 
only  be  utilized  to  supply  energy  or  to  add  to  the  fat  and  carbo- 
hydrate stores.  For  these  uses  removal  of  the  amino-group  is  an 
essential  preliminary.  The  question  whether  the  deamination  of  a 
large  part  of  the  amino-acids  coming  from  the  intestine  takes  place 
in  the  liver,  so  that  the  surplus  nitrogen  is  shunted  out  of  the  main 
metabolic  current  at  its  verv  source,  has  been  already  touched  upon 

39 


6io  METABOLISM.  NUTRITION  AND  DIETETICS 

(p.  5&S).  Some  writers  conceive  that  in  such  a  short-cut  from  pro- 
tein to  urea  we  have  a  kind  of  physiological  safety-valve  to  protect 
the  tissues  from  the  burden  of  an  excessive  metabolism.  And  if 
by  this  is  meant  that  it  is  advantageous  to  the  tissues  that  a  special 
mechanism  should  exist  to  eliminate  a  surplus  of  nitrogen  which  they 
do  not  require,  and  which  they  cannot  store,  and  to  present  them 
with  a  residue  which  they  can  utilize,  the  conception  is  certainly 
correct.  But  there  is  no  good  evideuce  that  in  the  presence  of  an 
over-abundant  supply  of  amino-acids  the  endogenous  protein  meta- 
bolism would  be  essentially  modified. 

Relation  of  Nitrogenous  Metabolism  to  Muscular  Work. — This  is 
another  of  those  classical  physiological  problems  which  it  is  difficult 
to  present  properly  apart  from  its  historical  setting.  The  general 
result  of  much  experimental  work  and  long-continued  discussion  is 
that  when  the  work  does  not  transgress  what  may  be  called  '  normal 
limits,'  the  excretion  of  nitrogen  is  nearly  independent  of  mus- 
cular work — ^that  is  to  say,  the  quantity  of  nitrogen  excreted  by  a 
man  on  a  given  diet  is  practically  the  same  whether  he  rests  or  works. 
Before  this  was  known  it  was  maintained  by  Liebig  that  proteins 
alone  could  suppl}^  the  energy  of  muscular  contraction — that,  in 
fact,  proteins  were  solely  used  up  in  the  nutrition  and  functional 
activity  of  the  nitrogenous  tissues,  while  the  non-protein  food 
yielded  heat  by  its  oxidation.  As  exact  experiments  multiplied,  it 
was  found  that  muscular  work,  the  production  of  which  is  the 
function  of  by  far  the  greatest  mass  of  protein-containing  tissue, 
had  little  or  no  effect  upon  the  excretion  of  urea  in  the  urine.  More 
than  this,  it  was  shown  that  a  certain  amount  of  work  accomplished 
(by  Fick  and  Wislicenus  in  climbing  a  mountain)  on  a  non-nitrog- 
enous diet  had  double  the  heat  equivalent  of  the  whole  of  the  pro- 
tein consumed  in  the  body,  as  estimated  by  the  urea  excreted  during, 
and  for  a  given  time  after,  the  work.  On  the  assumption  that  all 
the  urea  corresponding  to  the  protein  broken  down  was  eliminated 
during  the  time  of  this  experiment,  a  part  at  least  of  the  work  must 
have  been  derived  from  the  energy  of  non-nitrogenous  material. 
And  other  experiments  in  which  account  was  taken  of  the  increase 
in  the  carbon  dioxide  given  off  (as  conspicuous  an  accompaniment 
of  muscular  work  as  the  constancy  of  the  urea  excretion),  showed 
that  during  muscular  exertion  carbonaceous  substances  other  than 
proteins — that  is  to  say,  fats  and  carbo-hydrates — are  oxidized  in 
gi  eater  amount  than  during  rest. 

So  the  pendulum  of  physiological  orthodoxy  came  full-swing  to  the 
other  side.  Liebig  and  his  school  had  taught  that  proteins  alone  were 
consumed  in  functional  activit}-;  the  majority  of  later  physiologists 
following  Voit  denied  to  the  proteins  any  share  whatever  in  the  energy 
which  appears  as  muscular  contraction.  The  proteins,  they  said, 
'  repair  the  slow  waste  of  the  framework  of  the  muscular  machine, 
replace  a  loose  rivet,  a  worn-out  belt,  as  occasion  may  require :  the 


STATISTICS  OF  NUTRITION  6ii 

carbo-hydrates  and  fats  are  the  fuel  which  feeds  the  furnaces  of  life, 
the  materal  which,  dead  itself,  is  oxidized  in  the  interstices  of  the 
living  substance,  and  yields  the  energy  for  its  work.' 

Now,  it  is  a  singular  circumstance,  and  full  of  instruction  for  the 
ingenuous  student  of  science,  that  the  facts  which  were  supposed 
absolutely  to  disprove  the  older  theory,  and  absolutely  to  establish  its 
more  modem  rival,  are  now  seen  to  do  neither  the  one  thing  rtor  the 
other.  The  fact — and  it  is  a  fact — that  the  excretion  of  nitrogen  is 
but  little  affected  by  muscular  contraction,  docs  not  prove  that  none 
of  the  energy  of  muscular  work  comes  from  proteins;  the  fact  that, 
under  certain  conditions,  some  of  the  muscular  energy  must  apparently 
come  from  non-nitrogenous  materials,  does  not  prove  that  these  are  the 
normal  source  of  it  all.  The  distinction  had  again  been  made  too 
absolute.  The  pendulum  must  again  swing  back  a  little;  and  the 
experiments  of  Pfli'igcr  and  his  pupils  were  soon  to  set  it  moving. 

In  the  first  place,  it  is  not  perfectly  correct  to  say  that  work 
causes  no  increase  in  the  excretion  of  nitrogen;  excessive  work  in 
man,  and  work,  severe  but  not  excessive,  in  a  flesh-fed  dog  (Pfliiger), 
do  cause  somewhat  more  nitrogen  to  be  given  off.  On  the  first  day 
of  work  the  increase  is  always  much  less  than  on  the  second  and  third ; 
and  on  the  first  and  second  rest  days,  following  work,  the  elimina- 
tion of  nitrogen  is  still  increased.  After  excessive  exercise  in  man 
not  only  is  the  urea  increased,  but  also  the  ammonia,  kreatinin,  and 
if  the  subject  is  in  poor  training,  the  uric  acid  and  purin  bases  (Pat on. 
Stockman,  etc.).  Moderate  exercise  causes  no  increase  on  the  first 
day,  but  a  slight  increase  on  the  second.  The  meaning  of  these 
facts  seems  to  be  that  during  muscular  work  the  intensity  of  which 
does  not  exceed  certain  limits,  the  protein  waste  of  the  muscular 
substance  itself  is  no  greater  than  during  rest.  When,  however,  the 
machine  is  '  speeded  up  '  beyond  a  certain  point  the  wear  and  tear 
is  sensibly  increased  and  an  excess  of  tissue-protein  is  katabolized. 
There  is  no  reason  to  suppose  that  the  tissue-protein  thus  broken 
down  will  not  yield  energy  for  the  muscular  work  by  the  oxidation 
of  its  non-nitrogenous  residue,  just  as  well  as  the  surplus  amino- 
bodies  derived  from  food-protein.  The  muscular  machine  has  the 
peculiarity  that  it  is  constructed  of  combustible  material;  even  the 
dust  and  the  splinters,  if  we  may  so  express  it,  which  represent  the 
wear  and  tear  of  the  machine  can  be  burnt  in  the  furnace  which  keeps 
it  going. 

In  the  second  place,  even  if  the  excretion  of  nitrogen  were  entirely 
unaffected  by  work,  this  would  not  prove  that  none  of  the 
energy  of  the  work  comes  from  proteins.  For,  as  we  have  seen, 
it  is  after  the  nitrogen  has  been  split  off  and  converted  into  urea 
that  the  energy  of  a  great  part  of  the  food-protein  is  developed  by 
oxidation.  Further,  since  the  animal  body  is  a  beautifully-balanced 
mechanism  which  constantly  adapts  itself  to  its  conditions,  it  is 
conceivable  that  it  may,  when  called  upon  to  labour,  save  proteins 
from  lower  uses  to  devote  them  to  muscular  contraction.     In  this 


6i2  METABOLISM.  NUTRITION  AND  DIETETICS 

case  the  excretion  of  nitrogen  would  not  necessarily  be  altered;  the 
proteins  which,  in  the  absence  of  work,  would  have  been  oxidized 
within  the  muscular  substance  or  elsewhere,  their  energy  appearing 
entirely  as  heat,  may,  wlien  the  call  for  protein  to  take  the  place  of 
that  broken  down  in  muscular  contraction  arises,  be  diverted  to  this 
purpose. 

In  any  case,  there  is  no  doubt  that  a  dog  fed  on  lean  meat  may 
go  on  for  a  long  time  performing  far  more  work  than  can  be  yielded 
by  the  energy  of  fat  and  carbo-hydrates  occurring  in  traces  in  the 
food,  or  taken  from  the  stock  in  the  animal's  body  at  the  beginning 
of  the  period  at  work.  A  large  portion,  and  perhaps  the  whole,  of 
the  work,  must  in  this  case  be  derived  from  the  energy  of  the  pro- 
teins (Pfiiiger).  On  the  other  hand,  it  is  well  established  that  when 
fats  and  carbo-hydrates  are  present  in  sufficient  quantity  in  the 
tissues  or  the  food,  they  constitute  the  main  source  of  the  energy 
of  muscular  contraction  (p.  772),  and  there  is  some  evidence  that  of 
the  two  classes  of  food  materials  carbo-hydrates  in  the  form  of 
dextrose  (or  glycogen)  is  the  material  of  election. 

The  outcome,  then,  of  this  famous  controversy  is  essentially  a 
compromise.  Everybody  now  admits  that  the  muscular  machine 
can  and  does  utilize  predominantly  any  one  of  the  great  groups 
of  food  substances,  be  it  carbo-hydrate,  fat,  or  protein,  when  the 
dietetic  conditions  are  such  that  only  one  of  these  is  offered  to  it 
in  large  amount,  the  others  being  either  absent  or  offered  in  small 
amount.  To  be  sure,  amino-acids  are  not  the  first  choice,  but  if 
it  must  do  so  the  muscle  can  make  shift  with  them,  and  can  indeed 
make  them  serve  excellently  well.  When  all  the  food  substances 
are  present  in  abundance,  carbo-hydrate  is  favoured  above  fat,  and 
fat  above  protein. 

Experience  has  shown  that  the  mininmm  quantity  of  nitrogen 
required  in  the  food  of  a  man  whose  daily  work  involves  hard 
physical  toil  is  higher  than  the  minimum  required  by  a  person  lead- 
ing an  easy,  sedentary  life.  This  is  evidently  in  accordance  with 
the  view  that  protein  is  actually  used  up  in  muscular  contraction ; 
but  it  is  not  inconsistent  with  the  opposite  view.  For  the  body  of  a 
man  fit  for  continuous  hard  labour  has  a  greater  mass  of  muscle 
to  feed  than  the  body  of  a  man  who  is  only  fit  to  handle  a  composing- 
stick,  or  drive  a  quill,  or  ply  a  needle ;  and  the  greater  the  muscular 
mass,  the  greater  the  muscular  waste.  But  if  an  animal  just  in 
nitrogenous  equilibrium  on  a  diet  of  lean  meat  when  doing  no  work 
is  made  to  labour  day  after  day,  it  will  lose  flesh  unless  the  diet 
be  increased.  This  must  mean  that  some  of  the  protein  is  being 
diverted  to  muscular  work,  and  that  the  balance  is  not  sufficient 
to  keep  up  the  original  mass  of  '  flesh  '  (see  p.  628). 

Relative  Value  of  Different  Proteins  in  Nutrition — Synthesis  of 
Amino-Acids. — The  fact  that  the  various  proteins  differ  quantita- 


STATISTICS  OF  NUTRITION  6i-{ 

ti  vely  and  qualitatively  in  respect  to  their  amino-acids  raises  the  ques- 
tion of  the  relative  value  of  different  proteins  in  nutrition.  In  this  is 
involved  the  further  question,  whether  the  body  can  itself  synthesize 
from  other  materials  any  of  the  amino-acids  which  may  be  deficient, 
or  change  one  amino-acid  into  another.  That  the  '  peptones  '  derived 
from  a  protein  which  is  itself  capable  of  permanently  supplying 
the  whole  nitrogenous  intake  of  the  organism  can  be  substituted 
for  the  protein  scarcely  needs  demonstration,  since  it  is  known  that 
the  protein  is  converted  into  peptones  in  digestion.  Nevertheless, 
this  has  been  proved  conclusively  by  feeding  experiments  with 
peptones.  It  was  to  be  expected,  too,  leaving  out  of  account  all 
consideration  of  the  means  of  overcoming  the  repugnance  of  animals 
to  accepting  such  unnatural  food  substances,  that  the  further 
products  of  protein  hydrolysis,  the  amino-acids,  etc.,  could  be 
substituted  for  the  original  proteins  when  these  were  themselves 
adequate.  For  it  is  in  the  form  of  amino-acids  or  at  most  of  such 
relatively  simple  polypeptide  groups  as  may  still  hang  together 
after  complete  digestion  and  absorption,  that  the  nitrogenous  food 
substances  are  normally  offered  to  the  tissues.  Experimental 
demonstration  of  the  feasibility  of  this  substitution  has  also  been 
obtained.  The  split  products  of  meat,  for  example,  will  keep  an 
animal  in  nitrogen  equilibrium  as  well  as  the  meat  from  which  they 
are  derived.  But  what  happens  when  one  or  more  of  the  amino- 
acids  found  in  the  proteins  of  the  body  are  missing  from  the  protein 
of  the  food  ?  That  the  components  of  an  amino-acid  like  ^rginin 
(ornithin  and  urea),  into  which  it  can  be  split  not  only  by  the 
possibly  crude  and  violent  methods  of  the  chemical  laboratory,  but 
also  by  the  delicate  and  precisely-adapted  '  biological  '  action  of  a 
special  enzyme  (arginase),  should  be  able  to  replace  the  original 
amino-acid  is  a  fact  which  does  not  greatly  help  towards  an  answer. 
For  when  these  components,  or  ornithin  alone,  since  urea  is  al\Vays 
present  in  the  body,  are  given  instead  of  arginin,  the  reversal  of  the 
enzyme  reaction  by  which  arginin  is  decomposed  is  all  that  is  neces- 
sary for  its  synthesis,  and  the  reversal  of  such  a  reaction  is  doubtless 
a  very  commonplace  affair  in  tissue  metabolism.  The  formation 
of  one  amino-acid  from  another,  or  from  materials  which  do  not 
originate  exclusively  from  protein,  is  a  different  thing,  and  the 
answer  to  the  question  raised,  so  far  as  it  can  yet  be  given,  is  that 
the  way  in  which  the  body  deals  with  a  deficiency  in  the  protein 
'  building  stones  '  depends  upon  the  nature  of  the  missing  amino- 
acids.  Thus,  the  phospho-protein  casein  does  not  yield  glycin  on 
hydrolysis;  yet  it  has  been  shown  that  casein  is  a  perfectly  adequate 
or  complete  protein  food  capable  of  covering  the  whole  nitrogen 
requirement  of  the  body  over  long  periods.  The  same  is  true  of  the 
cleavage  products  of  casein  which  has  been  subjected  to  pancreatic 
digestion.     In  an  animal  fed  on  no  other  protein  than  casein,  with 


6i4  METABOLISM.  NUTRITION  AND  DIETETICS 

suitable  quantities  of  carbo-hydrate  and  fat  in  addition,  the  G:lycin 
contained  in  certain  of  the  body  proteins  must  therefore  have  been 
produced  in  the  body  itself.  We  have  already  seen  (p.  580)  that 
for  the  synthesis  of  hippuric  acid  after  the  administration  of  benzoic 
acid,  glycin  is  necessary,  and  the  quantity  of  hippuric  acid  which 
can  be  thus  produced  is  so  great  that  it  is  impossible  to  suppose 
that  it  all  comes  from  glycin  preformed  in  the  body  or  from  glycin 
in  the  food  substances.  It  may  accordingly  be  taken  as  pro\ed 
that  the  tissues  have  the  power  of  synthesizing  at  least  this  one  of 
the  amino-acids  (amino-acetic  acid),  reckoned  among  the  protein 
'  building  stones. '  It  is  said  that  if  the  casein  has  been  hydrolysed 
by  acid,  the  products  will  not  preserve  nitrogen  equilibrium,  per- 
haps because  the  acid  has  broken  up  all  the  polypeptides  (p.  2), 
some  of  which  the  cells  may  need  as  the  starting-point  of  protein 
s}Tithesis.     This,  however,  is  uncertain. 

Lysin  also  appears  to  be  capable  of  being  s\iithesized  in  the  body, 
and  protein  foods  free  from  lysin,  or  containing  only  a  trace  of  it, 
may  yet  be  adequate  for  nutrition  and  growth.  Prohn,  too,  is  not 
indispensable,  and  this  is  of  special  interest,  for  the  amino-acids 
hitherto  mentioned  as  capable  of  being  built  up  in  the  tissues  are 
all  more  or  less  directly  related  to  each  other,  being  derivatives  of 
the  series  of  saturated  fatty  acids.  The  task  of  changing  one  of 
these  into  another  in  which  the  food  is  deficient  may,  therefore,  be 
considered  a  comparatively  easy  one.  But  prolin  has  no  obvious 
relation  to  most  of  the  other  amino-acids. 

It  is  a-pyrrolidin  carboxylic  acid, 

CH2— CH^  CH2— CH, 

CH.     CH.COOH—i.e..  pyrrolidin,    CH,     CHg 

NH  NH 

in  which  H  in  one  of  the  CH2  groups  is  replaced  by  carboxyi  (COOH). 
It  lias  been  suggested  Dial  prolin  may  be  formed  in  the  body  from 
glutaminic  (amino-glutaric)  acid,  which  by  loss  of  a  molecule  of  water 
can  be  made  to  jdeld  a-pyrrolidon  carboxylic  acid.     Thus, 

CHa.CH«.CH.COOH  CHj— CH, 

COOH      XHo  -HoO      =     CO       CH.COOH 

\     / 
NH 

Glutaminic  acid.  a-pyrrolidoB  carboxylic  acid. 

By  reduction  the  latter  compound  might  be  changed  into  prolin. 

With  proteins  deficient  in  certain  other  amino-acids  a  totally 
different  result  has  been  obtained.  Gelatin,  for  example,  contains 
most  of  the  amino-acids  and  other  groups  which  compose  the  body 
proteins,  but  tyrosin,  cystin,  and  tryptophane  are  lacking  in  the 


STATISTICS  Of  NUTRITION  615 

gelatin  molecule.  Zein,  an  alcohol-soluble  protein  or  prolamin* 
derived  from  maize,  yields  no  tryptophane,  glycin,  or  lysin.  Now, 
it  is  found  that  neither  gelatin  nor  zein  can  replace  tlic  whole  of 
the  ordinary  proteins  in  the  food.  When  only  enough  protein  is 
taken  to  prevent  loss  of  nitrogen  from  the  body,  one-fifth  of  the 
necessary  nitrogen  can  be  supplied  in  the  form  of  gelatin.  When 
the  food  is  much  richer  than  this  in  ordinary  protein,  a  correspond- 
ingly greater  proportion  of  the  protein  can  be  replaced  by  gelatin. 
The  surplus  is  not  used  in  the  endogenous  metabolism  of  the  cells 
(p.  573),  but  supplies  energy  to  the  body  after  the  elimination  of 
its  nitrogen  as  urea,  just  as  the  surplus  protein  would  do.  Thus 
gelatin  economizes  protein  in  the  same  way  that  fat  and  carbo- 
hydrates do,  but  also  to  some  extent  in  a  different  way  by  supplying 
'  building  stones  '  for  the  protoplasm.  It  is  therefore  an  interesting 
question  whether  gelatin  can  fully  replace  protein  when  the  missing 
substances  are  given  in  addition.  Kauffmann  has  stated  that  his 
own  nitrogen  requirement  (15  2  grammes)  was  almost  completely 
covered  by  a  mixture  containing  93  per  cent,  of  the  nitrogen  in  the 
form  of  gelatin,  4  per  cent,  as  tyrosin,  2  per  cent,  as  cystin,  and 
I  per  cent,  as  tryptophane,  in  addition  to  the  same  amounts  of 
carbo-hydrate  and  fatty  food  as  in  the  comparison  diet,  in  which 
the  nitrogen  was  supphed  in  the  form  of  plasmon,  a  commercial 
preparation  of  casein. 

Similar  results  have  been  reported  in  experiments  on  animals  in 
which  attempts  have  been  made  to  '  complete  '  such  inadequate 
proteins  by  addition  of  the  missing  amino-bodies,  with  fair  but, 
according  to  Osborne  and  Mendel,  not  entirely  satisfactory  results. 
The  converse  experiment,  in  which  an  amino-acid  such  as  trypto- 
phane has  been  purposely  eliminated  from  the  food  mixture,  has 
also  been  tried,  with  the  result  that  rapid  deterioration  in  the 
condition  of  the  animal  ensued.  It  would  seem,  indeed,  that 
whatever  capacity  the  animal  body  may  have  for  synthesizing 
certain  of  the  amino-acids,  this  power  does  not  extend  to  the  cyclic 
compounds  tr5^tophane,  tyrosin,  phenylalanin,  and  histidin,  which 
must  be  supplied  in  the  food.  It  has  been  suggested  by  Osborne 
that  in  this  regard  an  essential  difference  exists  between  the  animal 
and  the  plant,  the  latter  alone  being  endowed  with  the  function  of 
'  cyclopoiesis,'  or  formation  of  substances  of  the  cychc  type.  It 
is  not  clearly  understood  as  yet  on  what  this  difference  really  hinges, 
whether,  as  some  have  supposed,  on  the  inability  of  the  animal 
organism  to  form  the  appropriate  fatty  acid  radicals,  or  on  some 

*  The  prolamins  are  so  called  because  on  hydrolysis  they  yield  exceptionally 
large  amounts  of  prolin  (p.  360)  and  ammonia.  They  are  insoluble  in  water 
and  absolute  alcohol,  but  soluble  in  70  to  80  per  cent,  alcohol  and  in  dilute 
acids  and  alkalies.  Besides  zein  they  include  gliadin  (from  wheat  and  rye), 
hordein  (from  barley),  and  bynin  (from  malt).  They  are  extraordinarily  rich 
in  glutaminic  acid,  hordein  yielding  more  than  any  protein  hitherto  investi- 
gated (over  41  per  cent). 


6i6  METABOLISM,  NUTRITIOX  AKD  DIETETICS 

other  limitation  of  its  chemical  powers.  While  the  cyclic  (and  hetero- 
cyclic) compounds  cannot  be  replaced  by  other  '  Bausteinc  '  of  the 
proteins,  they  may  to  some  extent  replace  each  other.  Thus  it  would 
seem  that  t\Tosin  can  be  replaced  by  phenylalanin  (Abderhalden). 
While  some  of  the  food  proteins  like  casein  are  sufficient  by 
themsehes  to  supply  all  the  amino-bodies  necessary  not  only  for 
the  maintenance,  but  also  for  the  growth  of  the  body,  and  can 
accordingly  be  termed  adequate  or  complete  protein  food  sub- 
stances, others,  like  gelatin,  are  insufficient  by  themselves  to  supply 
the  protein  required  for  mere  maintenance,  still  less  for  growth. 


Fig.  201 . — Two  Female  Rats  of  the  Same  Age  (140  days).  The  upper  one  was  fed  on 
an  ordinary  diet,  and  is  of  the  normal  weight  for  its  age.  The  lower  one  was 
fed  on  a  diet  composed  of  a  mixture  of  isolated  food-stuffs.  Its  weight  is  only 
equal  to  that  of  a  normal  rat  thirty-six  days  old  (Osborne  and  Mendel). 

and  may  be  spoken  of  as  inadequate  or  incomplete  proteins.  There 
is  a  third  intermediate  group,  comprising  proteins  which  suffice 
when  given  as  the  sole  protein  food  to  maintain  the  body  for  an 
indefinitelv  long  period,  and  to  repair  the  tissue  waste  without  per- 
mitting growth  of  the  animal  to  take  place.  Gliadin  and  hordein 
(see  footnote,  p.  615)  are  representatives  of  this  group.  The  ex- 
periments of  Osborne  and  Mendel  with  gliadin  are  of  special  interest, 
since  this  substance  is  very  differently  constituted  from  the  ordinary 
food  proteins,  as  well  as  from  the  tissue  proteins  of  the  animal 
body.  While,  as  already  stated,  it  yields  very  large  quantities  of 
glutaminic  acid,  prolin,  and  ammonia,  it  either  contains  no  lysin 


STATISTICS  Of  XUTI^ri  ION  G17 

and  no  glycin,  or  yields  too  little  to  be  detected  with  certainty. 
It  also  yields  comparatively  little  histidin  and  arginin.  Now,  it 
has  been  found  that  a  dietary  containing  carbo-hydrate  in  the  form 
of  starch,  fats  in  the  form  of  lard,  and  inorganic  salts,  but  no  pro- 
tein except  gliadin*  suffices  to  maintain  adult  rats  in  good  condition 
for  very  long  periods  (up  to  290  days),  and  also  to  maintain  young 
rats  in  a  stationary  condition  as  regards  growth,  but  in  perfect 
health.  The  youthful  appearance  of  the  rats  whose  growth  was 
thus  inhibited  was  very  striking,  and  corresponded  with  their  size 
rather  than  with  their  age.  The  capacity  for  growth  on  a  normal 
diet  was  apparently  not  in  the  least  diminished;  the  growth  pro- 
cesses simply  remained  in  abeyance. 

'  In  one  rat,  after  a  continuous  suppression  of  growth  lasting  277  days, 
when  the  animal  was  314  davs  old — an  age  at  which  normally  little  or 
no  growth  takes  place — satisfactory  growth  was  resumed  on  a  suitable 
diet.'  A  still  more  remarkable  experiment  was  the  following:  '  A  male 
rat,  kept  for  154  days  with  gliadin  as  the  sole  protein  in  the  food,  was 
paired  with  a  female  also  on  the  gliadin  diet.  At  the  end  of  178  days 
on  the  gliadin  diet  she  gave  birth  to  four  young,  which  were  satisfactorily 
nourished  by  the  mother,  still  on  gliadin,  during  the  first  month  of 
their  existence.  After  a  month  three  of  the  young  rats  were  removed 
from  the  mother  and  put  on  diets  of  casein  food  [i.e.,  casein  plus  suitable 
proportions  of  carbo-hydrate,  fat,  and  inorganic  materials),  edestin 
food  and  milk  food  respectively.  The  fourth  was  left  with  the  mother. 
The  fourth  rat  began  to  evince  a  failure  to  grow  at  about  the  period 
(thirty  days)  when  young  rats  are  wont  to  depend  upon  extraneous 
food. 

The  meaning  of  this  last  observation  can  only  be  that  the  young 
animal,  when  obliged  to  depend  upon  its  share  of  the  ghadin  food 
left  with  the  mother  in  place  of  the  milk  formed  by  the  mother 
from  this  same  gliadin  food  mixture,  showed  the  topical  failure  to 
grow  on  a  diet  inadequate  as  regards  the  power  of  producing  growth 
in  respect  to  the  protein  contained  in  it.  On  the  other  hand,  in  the 
body  of  the  mother  this  inadequate  diet  had  been  so  transformed 
that  not  only  had  she  maintained  her  body-weight  and  repaired 

*  Certain  accessory  substances  of  unknown  nature,  contained  in  some  of 
the  natural  foods  must  also  be  supplied  (p.  <>;i-L).  Osborne  and  Mendel,  for 
instance,  gave  their  animals  a  certain  amount  of  '  protein-free  milk,'  contain- 
ing the  salts  of  milk,  but  only  traces  of  milk  proteins.  The  important  thing 
in  the  '  protein-free  milk  '  is  neither  the  slight  residue  of  protein  nor  the  salt, 
but  an  unknown  substance,  a  so-called  'water-soluble  vitamine.'  When  this 
was  supplied  in  the  '  protein-free  milk  '  the  animals  were  maintained  on  the 
artificial  diet  for  very  long  periods,  although  they  did  not  grow.  It  has  since 
been  rendered  probable  that  in  addition  to  the  water-soluble  vitamine,  fat- 
soluble  vitamine  (McCollom)  is  necessary'  for  full  growth  of  rats  and  the  main- 
tenance in  health  of  the  adults,  upon  otherwise  complete  artificial  diets,  for 
a  great  part  of  their  natural  life-span.  Such  fat-soluble  vitamines  may  be 
supplied  by  replacing  a  part  of  the  lard  by  butter-fat.  egg-yolk  fat,  beef  fat, 
or  codliver  oil. 


6i8  METABOLISM.  NUTRITION  AND  DIETETICS 

her  tissue  waste  completely,  but  she  had  produced  from  it  every- 
thing necessary  for  the  development  of  the  embryo  rats  up  to  full 
term,  and  after  that  everything  necessary  (in  the  form  of  milk) 
for  their  normal  growth  during  the  period  of  suckling.  On  the 
whole,  a  very  large  amount  of  body  tissue  in  proportion  to  the 
original  weight  of  the  mother  must  have  been  formed  or  renewed 
in  the  200  days  or  more  during  which  the  experiment  continued, 
and  during  which  gliadin  was  being  steadily  transmuted  into  tissue 
protein,  and  latterly  into  the  proteins  of  milk  as  well,  by  what 
might  almost  be  called  a  feat  of  chemical  legerdemain.  There  must 
have  occurred  a  synthesis  '  not  only  of  the  Bausteine  (the  "  building- 
stones  ")  deficient  in  the  protein  intake,  but  likewise  of  tissue  and 
milk  components  like  the  nucleic  acids  (with  their  content  of  purins, 
pyrimidins,  and  organically  combined  phosphorus)  and  phospho- 
proteins  like  casein,  etc.,  which  were  completely  missing  '  in  the  food. 

It  has  been  suggested  that  the  bacteria  of  the  alimentary  canal, 
which,  of  course,  are  plant  cells,  may  have  and  may  exercise  on  a  large 
scale  the  power  of  building  up  new  amino-acids  from  a  variety  of 
materials  in  the  intestinal  contents,  and  that  they  may  thus  be  synthe- 
sizing agents,  thanks  to  which  inadequate  proteins  may  be  reshaped  to 
proteins  adequate  to  the  needs  of  the  body.  It  is  precisely,  however, 
in  the  case  of  incomplete  proteins  like  gelatin  deficient  in  cyclical 
compounds,  that  the  body  fails  to  effect  the  necessary  transformation 
in  spite  of  the  fact  that  plant  cells  are  supposed  to  be  specially  capable 
of  forming  these  compounds.  In  any  case  bacterial  action  would  not 
explain  wliy  proteins  like  gliadin  and  hordein  are  only  adequate  for  the 
renewal  of  tissue,  and  not  for  its  growth.  This  points  rather  to  the 
possibility  that  the  processes  by  which  the  nitrogenous  compounds 
degraded  in  cellular  metabolism  are  replaced  are  not  of  the  same  char- 
acter as  the  processes  by  which  new  nitrogenous  complexes  are  built 
up  into  growing  protoplasm.  If,  for  instance,  the  protein  molecule  is 
not  completely  disrupted  in  ordinary  metabolism,  it  will  not  need  to  be 
completely  reconstructed,  while  in  the  formation  of  new  tissue  complete 
protein  molecules  will  have  to  be  synthesized.  Incomplete  proteins 
like  gliadin  may  furnish  building-stones  adequate  for  repairing  the 
house,  but  inadequate  for  building  it  from  the  foundations. 

Income  and  Expenditure  of  Carbon — The  Carbon  Balance-Sheet. — 
This  division  of  the  subject  has  been  necessarily  referred  to  in 
treating  of  the  nitrogen  balance-sheet,  and  may  now  be  formally 
completed. 

Carbon  Equilibrium. — A  body  in  nitrogenous  equiUbrium  may  or 
may  not  be  in  carbon  equihbrium.  It  has  been  repeatedly  pointed 
out  that  the  continued  loss  or  gain  of  carbon  by  an  organism  in 
nitrogenous  equilibrium  means  the  loss  or  gain  of  fat ;  and,  since 
the  quantity  of  fat  in  the  body  may  vary  within  wide  limits  without 
harm,  carbon  equilibrium  is  less  important  than  nitrogen  equili- 
brium. It  is  also  less  easily  attained  when  the  carbon  of  the  food 
is  increased,  for  the  consumption  of  fat  is  not  necessarily  increased 


STATISTICS  OF  NUTRITION  619 

with  the  supply  of  fat  or  fat-producing  food,  and  there  is  by  no 
means  the  same  prompt  adjustment  of  expenditure  to  income  in 
the  case  of  carbon  as  in  the  case  of  nitrogen. 

Carbon  equiHbrium  can  be  obtained  in  a  flesh-eating  animal,  like 
a  dog,  with  an  exckisively  protein  diet;  but  a  far  higher  minimum 
is  required  than  for  nitrogenous  equilibrium  alone.  Voit's  dog 
required  at  least  1,500  grammes  of  meat  in  the  twenty- four  hours 
to  prevent  his  body  from  losing  carbon.  For  a  man  weighing 
70  kilos,  the  daily  excretion  of  carbon  on  an  ordinary  diet  is  250  to 
300  grammes.  About  2,000  grammes  of  lean  meat  would  be  re- 
quired to  yield  this  quantity  of  carbon;  and,  even  if  such  a  mass 
could  be  digested  and  absorbed,  more  than  three  times  the  necessary 
nitrogen  would  have  to  undergo  preliminary  cleavage  and  excretion 
as  urea  or  be  thrown  upon  the  tissues. 

Not  only  may  carbon  equilibrium  be  maintained  for  a  short  time 
in  a  dog  on  a  diet  containing  fat  only,  or  fat  and  carbo-hydrates,  but 
the  expenditure  of  carbon  may  be  less  than  the  income,  and  fat  may 
be  stored  up.  But,  of  course,  if  this  diet  is  continued,  the  animal 
ultimately  dies  of  nitrogen  starvation. 

So  far  we  have  spoken  only  of  the  income  and  expenditure  of 
carbon  and  nitrogen;  and  from  these  data  alone  it  is  possible  to 
deduce  many  important  facts  in  metabolism,  since,  knowing  the 
elementary  composition  of  proteins,  fats,  and  carbo-hydrates,  we 
can,  on  certain  assumptions,  translate  into  terms  of  proteins  or  fat 
the  gain  or  loss  of  an  organism  in  nitrogen  and  carbon,  or  in  carbon 
alone.  But  the  hydrogen  and  oxygen  contained  in  the  sohds  and 
water  of  the  food,  and  the  oxygen  taken  in  by  the  lungs,  are  just  as 
important  as  the  carbon  and  nitrogen;  it  is  just  as  necessary  to  take 
account  of  them  in  drawing  up  a  complete  and  accurate  balance- 
sheet  of  nutrition.  Fortunately,  however,  it  is  permissible  to 
devote  much  less  time  to  them  here,  for  when  we  have  determined 
the  quantitative  relations  of  the  absorption  and  excretion  of  the 
carbon  and  nitrogen,  we  have  also  to  a  large  extent  determined 
those  of  the  oxygen  and  hydrogen. 

Income  and  Expenditure  of  Oxygen  and  Hydrogen. — The  oxygen 
absorbed  as  gas  and  in  the  solids  of  the  food  is  given  off  chiefly  as 
carbon  dioxide  by  the  lungs;  to  a  small  extent  as  water  by  the  lungs, 
kidneys,  and  skin;  and  as  urea  and  other  substances  in  the  urine 
and  faeces.  The  hydrogen  of  the  solids  of  the  food  is  excreted  in 
part  as  urea,  but  in  far  larger  amount  as  water.  The  hydrogen  and 
oxygen  of  the  ingested  water  pass  off  as  water,  without,  so  far  as 
we  know,  undergoing  any  chemical  change,  or  existing  in  any  other 
form  within  the  body.  But  it  is  important  to  recognize  that 
although  none  of  the  water  taken  in  as  such  is  broken  up,  some 
water  is  manufactured  in  the  tissues  by  the  oxidation  of  hydrogen. 


6iO  METABOLISM.  NUTRITION  AND  DILIETICS 

We  have  already  considered  (p.  241)  the  gaseous  exchange  in  the 
lungs,  and  we  have  seen  that  all  the  oxygen  taken  in  does  not 
reappear  as  carbon  dioxide.  It  was  stated  there  that  the  missing 
oxygen  goes  to  oxidize  other  elements  than  carbon,  and  especially 
to  oxidize  hydrogen.  We  have  now  to  explain  more  fully  the  cause 
of  this  oxygen  deficit 

The  Oxygen  Deficit. — The  carbo-hydrates  contain  in  themselves 
enough  oxygen  to  form  water  with  all  their  hydrogen ;  they  account  for 
a  part  of  the  water-formation  in  the  body,  but  for  none  of  the  oxygen 
deficit. 

The  fats  are  very  different ;  their  hydrogen  can  be  nothing  like  com- 
pletely oxidized  by  their  oxygen.  A  gramme  of  hydrogen  is  contained 
in  8-5  grammes  of  dry  fat,  and  needs  8  grammes  of  oxygen  for  its  com- 
plete combustion.  Only  i  gramme  of  oxygen  is  yielded  by  the  fat 
itself;  so  that  if  a  man  uses  100  grammes  of  fat  in  twenty-four  hours, 
rather  more  than  80  grammes  of  the  oxygen  taken  in  must  go  to 
oxidize  the  hydrogen  of  the  fat. 

The  proteins  also  contribute  to  the  deficit.  In  100  grammes  of 
dry  proteins  there  are  15  grammes  of  nitrogen,  7  grammes  of  hydrogen, 
and  21  grammes  of  oxygen.  The  carbon  docs  not  concern  us  at  present. 
The  33  grammes  of  iirea,  corresponding  to  100  grammes  of  protein, 
contains  15  grammes  of  nitrogen,  a  little  more  than  2  grammes  of 
hydrogen,  and  a  little  less  than  9  grammes  of  oxygen.  There  remain 
5  grammes  of  hydrogen  and  12  grammes  of  oxygen.  But  5  grammes  of 
hydrogen  needs  for  complete  combustion  40  grammes  of  oxygen ;  there- 
fore 28  grammes  of  the  oxj^gen  taken  in  must  go  to  oxidize  the  hydrogen 
of  100  grammes  of  protein.  Taking  140  grammes  of  protein  as  the 
amount  in  a  liberal  diet  for  a  man,  we  get  39  granmies  as  the  required 
quantity  of  oxygen.  This,  added  to  tlie  80  grammes  needed  for  the 
hydrogen  of  the  fat,  makes  a  total  of,  say,  120  grammes,  equivalent  to 
about  85  litres  of  ox\-gen.  A  small  amount  of  oxygen  also  goes  to 
oxidize  the  sulphur  of  proteins. 

With  a  diet  containing  less  fat  and  protein  and  more  carbo-hydrate, 
the  oxygen  deficit  would  of  course  be  less. 

The  Production  of  Water  in  the  Body. — One  gramme  of  hydrogen 
corresponds  to  9  grammes  of  water.  In  140  grammes  of  proteins  and 
100  grammes  of  fat  there  are,  in  round  numbers,  22  grammes  of  hydro- 
gen;  in  350  grammes  of  starch,  21 -5  grammes.  With  this  diet, 
43'5  grammes  of  hydrogen  is  oxidized  to  water  within  the  body  in 
twenty-four  hours,  corresponding  to  a  water  production  of  391  grammes, 
or  15  to  20  per  cent,  of  the  whole  excretion  of  water.  It  has  been 
observed  that  during  starvation  the  tissues  sometimes  become  richer 
in  water,  even  when  none  is  drunk.  The  only  explanation  is  that  the 
elimination  of  water  does  not  keep  pace  with  the  rate  at  which  it  is 
produced  from  the  liydrogen  of  the  broken-down  tissue-substances,  or 
set  free  from  the  solids  with  which  it  is  (physically  ?)  united. 

Inorganic  Salts. — The  inorganic  salts  of  the  excreta,  like  the 
water,  are  for  the  most  part  derived  from  the  salts  of  the  food, 
which  do  not  in  general  undergo  decomposition  in  the  body.  A 
portion  of  the  chlorides,  however,  is  broken  up  to  yield  the  hydro- 
chloric acid  of  the  gastric  juice.    Within  the  body  some  of  the  salts 


STATISTICS  01-  NUTRTTION  621 

are  more  or  less  intimately  united  to  the  proteins  ot  the  tissues  and 
juices,  some  simply  dissolved  in  the  latter.  The  chlorides,  phos- 
phates and  carbonates  are  the  most  important;  the  potassium  salts 
belong  especially  to  the  organized  tissue  elements,  the  sodium  salts 
to  the  liquids  of  the  body;  calcium  phosphate  and  carbonate  pre- 
dominate in  the  bones.  The  amount  and  composition  of  the  ash 
of  each  organ  only  change  within  narrow  limits.  In  hunger  the 
organism  clings  to  its  inorganic  materials,  as  it  clings  to  its  tissue- 
proteins;  the  former  are  just  as  essential  to  life  as  the  latter.  In  a 
starving  animal  chlorine  almost  disappears  from  the  urine  at  a  time 
when  there  is  still  much  chlorine  in  the  body;  only  the  inorganic 
salts  which  have  been  united  to  the  used-up  proteins  are  excreted, 
so  that  a  starving  animal  never  dies  for  want  of  salts. 

When  sodium  chloride  is  omitted  as  an  addition  to  the  food  of 
man,  the  decomposition  of  protein  seems  to  be  shghtly  accelerated, 
but  for  a  time,  at  least,  there  are  no  serious  symptoms  (Belli). 

It  is  a  general  rule  that  purely  carnivorous  animals  do  not  desire 
salt,  and  the  same  is  true  of  human  beings  living  on  a  purely  animal 
diet,  while  vegetable  feeders  eagerly  seek  it.  On  the  other  hand, 
when  an  animal,  even  a  carnivore,  is  fed  with  a  diet  as  far  as  possible 
artificially  freed  from  salts,  but  otherwise  sufficient,  it  dies  of  salt- 
hunger.  The  blood  first  loses  inorganic  material,  then  the  organs. 
The  total  loss  is  very  small  in  proportion  to  the  quantity  still 
retained  in  the  body;  but  it  is  sufficient  to  cause  the  death  of  a 
pigeon  in  three  weeks,  and  of  a  dog  in  six,  with  marked  symptoms 
of  muscular  and  nervous  weakness.  A  deficiency  of  lime  salts 
causes  changes  particularly  in  the  skeleton,  although  the  nutrition 
of  the  rest  of  the  body  is  also  interfered  with.  These  changes  are 
of  course  most  marked  in  young  animals,  in  which  the  bones  are 
growing  rapidly.  In  pigeons  on  a  diet  containing  very  little  calcium 
the  bones  of  the  skull  and  sternum  become  extremely  thin  and 
riddled  with  holes,  while  the  bones  concerned  in  movement  scarcely 
suffer  at  all  (E.  Voit). 

It  is  not  indifferent  in  what  form  the  calcium  is  taken,  nor  can  it  be 
replaced  to  any  great  extent  by  other  earthy  bases,  as  magnesium  or 
strontium.  Weiske  fed  five  young  rabbits  of  the  same  litter  on  oats, 
a  food  relatively  poor  iu  calcium.  One  of  the  rabbits  received  in 
addition  calcium  carbonate,  another  calcium  sulphate,  a  third  mag- 
nesium carbonate,  and  a  fourth  strontium  carbonate.  At  the  end  of  a 
certain  time  it  was  found  that  the  skeleton  of  the  rabbit  fed  with  calcium 
carbonate  was  the  heaviest  and  strongest  of  all,  and  contained  the 
greatest  proportion  of  mineral  matter.  Then  came  the  rabbit  fed  with 
calcium  sulphate.  The  animal  which  received  only  oats  had  the  worst- 
developed  skeleton;  the  condition  of  the  animals  fed  with  magnesium 
and  strontium  carbonates  was  but  little  better. 

Milk  as  a  Food. — Milk  is  a  food  rich  in  calcium  and  also  in  phos- 
phorus, a  circumstance  evidently  related  to  the  rapid  development 


622  METABOLISM.  NUTRITION  ASD  DIETETICS 

of  the  skeleton  in  the  young  child.  As  in  the  other  natural  foods, 
the  calcium  and  phosphorus  are  partly  in  the  form  of  organic  com- 
pounds, united  with  the  proteins,  the  calcium  especially  with 
caseinogen,  and  partly  in  the  form  of  inorganic  salts.  Both  of  these 
elements  are  more  easily  assimilated  by  the  body  in  the  organic 
than  in  the  inorganic  form.  The  same  is  true  of  iron,  which  exists 
in  organic  combination  in  the  bran  of  wheat,  in  the  haemoglobin  of 
the  blood  and  of  muscular  fibres,  in  the  nuclei  of  most  cells,  vegetable 
and  animal,  and  conspicuously  in  the  nuclein  compounds  of  the  yolk 
of  the  egg.  Attempts  have  been  made  to  increase  the  amount  of 
iron  in  hen's  eggs  by  giving  them  food  mixed  with  preparations  of 
iron — e.g.,  iron  citrate.  An  increase  takes  place,  but  only  after  a 
long  time.  Thus  in  one  experiment  loo  grammes  of  egg-substance 
contained  44  milligrammes  of  FeaOj  before  the  administration  of 
the  iron  was  begun;  after  feeding  with  iron  for  three  and  a  half 
weeks  the  amount  was  45  milligrammes,  after  more  than  two 
months  74  miHigrammes;  and  after  a  year  only  73  milligrammes. 
Although,  as  we  have  seen,  inorganic  iron  can  be  absorbed,  it  is 
certainly  the  case  that  under  ordinary  conditions  all  the  iron  that 
the  body  receives  or  needs  is  taken  in  the  form  of  organic  com- 
pounds, since  there  is  no  inorganic  iron  in  the  natural  food  sub- 
stances. Stockman,  from  careful  estimations  of  the  quantity  of  iron 
in  a  number  of  actual  dietaries,  finds  that  it  only  amounts  to  about 
8  to  10  milligrammes  a  day.  He  concludes  that  the  greater  part  of 
it  must  be  retained  in  the  body  and  used  over  and  over  again. 

Milk  is  poor  in  iron,  but  this  does  not  hinder  the  development  of 
the  young  child,  except  when  it  is  weaned  too  late,  when  it  is  apt  to 
become  anaemic  unless  the  milk  is  supplemented  with  a  food  rich 
in  iron,  such  as  yolk  of  egg.  The  explanation  rs  that  the  foetus, 
especially  in  the  last  three  months  of  intra-uterine  life,  accumulates 
a  store  of  iron  in  the  liver  and  other  organs;  so  that,  in  proportion 
to  its  body-weight,  it  is  at  birth  several  times  richer  in  iron  than  the 
adult.  This  iron,  of  course,  all  comes  from  the  mother,  and  the 
loss  is  not  exactly  balanced  by  the  excess  of  iron  in  her  food ;  certain 
of  her  organs,  the  spleen,  for  instance,  though  not  apparently  the 
liver,  are  impoverished  as  regards  their  content  of  iron. 

Section  V. — Dietetics. 

There  are  two  ways  in  which  we  can  arrive  at  a  knowledge  of  the 
amount  of  the  various  food  substances  necessary  for  an  average 
man:  (a)  By  considering  the  diet  of  large  numbers  of  people  doing 
fairly  definite  work,  and  sufficiently,  but  not  extravagantly,  fed — 
e.g.,  soldiers,  gangs  of  navvies,  or  plantation  labourers;  (6)  by  making 
special  experiments  on  one  or  more  individuals. 

Voit,  bringing  together  a  large  number  of  observations,  concluded 


nrr.TFTTCS  621 

that  an  '  average  workman,'  weighing  70  to  75  kilos,  and  working 
ten  hours  a  day,  required  in  the  twenty-four  liours  118  grammes 
protein,  56  grammes  fat,  and  500  grammes  carbo-hydrate,  corre- 
sponding to  about  18 -8  grammes*  nitrogen,  and  at  least  328  grammes 
carbon. 

Ranke  found  the  following  a  sufficient  diei  for  himself,  with  a 
body- weight  of  74  kilos : 

Proteins  ------     100  grammes. 

Fat 100 

Carbo-hydrates  -         -         •         -     240 

This  corresponds  to  only  16  grammes  nitrogen  and,  say,  230  grammes 
carbon. 

A  German  soldier  in  the  field  receives  on  the  average: 

Proteins  -         -         -         -         -         -151  grammes. 

Fat 46         ,, 

Carbo-hydrates  -         -         -         -     522  ,, 

representing  about  24  grammes  nitrogen  and  340  grammes  carbon. 
The  average  ration  for  four  British  regiments  in  peace-time  con- 
tained 133  grammes  protein,  115  grammes  fat,  and  424  grammes 
carbo-hydrate  (  =  3,400  calories).  But  in  addition  the  soldiers 
constantly  obtained  at  their  own  expense  a  supper,  generally  com- 
prising meat  (Pembrey).  The  Russian  army  war  ration  in  the 
Manchurian  campaign  is  said  to  have  comprised  187  grammes 
protein  and  775  grammes  carbo-hydrate,  but  only  27  grammes  fat 
(  =  4,900  calories).  The  diet  of  certain  miners  (Steinheil)  and  lum- 
berers (Liebig)  contained  respectively  133  and  112  grammes  protein, 
113  and  309  grammes  fat,  and  634  and  691  grammes  carbo-hydrates. 
The  diet  of  a  Japanese  jinricksha  man  with  a  body-weight  of 
62  kilos  contained  158  grammes  protein,  and  its  total  heat  value 
was  5,050  calories.  The  work  of  these  men  in  running  long  dis- 
tances with  passengers  is  very  laborious.  They  consume  large 
amounts  of  fish,  eggs,  beef,  and  pork  during  their  periods  of  rest, 
and  large  quantities  of  rice  during  their  working  periods  (McCay). 
The  diet  of  prize-fighters  and  of  athletes  in  training  is  richer  in 
protein  than  any  of  these.  The  members  of  two  college  football 
teams  are  stated  to  have  consumed  on  the  average  225  grammes 
protein,  334  grammes  fat,  and  633  grammes  carbo-hydrates 
(  =  6,800  calories).  Caspari,  from  a  study  of  the  phenomena  of 
training,  concluded  that  continuous  bodily  work  at  a  rate  above 
the  ordinary  requires  a  large  amount  of  protein  (2  to  3  grammes  a 
day  per  kilo  of  body- weight).  But  there  seems  to  be  a  considerable 
difference  between  different  individuals.  So  that  a  definite  and 
typical  diet  for  severe  labour  does  not  exist.  And  although  perhaps 
the  hardest  physical  work  ever  done  in  the  world  is  to  break  athletic 

*  Taking  the  percentage  of  nitrogen  in  protein  at  16. 


6*4  METABOLISM,  NUTRITION  AND  DIETETICS 

records,  to  cut  and  handle  timber,  to  mineTcoal,  and  to  make  war, 
the  diet  on  which  these  things  are  accomphshed  is  very  variable. 

Recent  observations  tend  to  reduce  the  amount  of  protein  con- 
sidered necessary  for  a  person  under  ordinary  conditions.  Siven 
remained  in  nitrogen  equilibrium,  for  a  time  at  least,  with  an  intake 
of  only  007  to  008  gramme  of  nitrogen  (04  to  05  gramme  of 
protein)  per  kilo  of  body-weight,  or  not  much  more  than  one-third 
of  the  amount  in  Kanke's  diet.  It  is  obvious  that  the  endogenous 
protein  katabolism  sets  the  limit  below  which  it  must  be  impossible 
permanently  to  reduce  the  allowance  of  protein.  But  it  would  be 
very  hazardous  to  assume  that  this  theoretical  minimum  limit 
corresponds  with  the  permissible  physiological  limit.  From  ex- 
periments on  men  of  various  callings  extending  over  many  months, 
Chittenden  has  concluded  that  the  average  man  eats  at  least  twice 
as  much  protein  as  he  really  requires.  We  have  already  seen  that 
the  amount  of  nitrogen  required  to  repair  the  actual  waste  of  the 
tissues  is  comparatively  small,  and  that  with  the  ordinary  amount 
of  protein  in  the  food  a  very  large  fraction  of  the  total  nitrogen  is 
rapidly  excreted  as  urea.  There  is  no  doubt,  also,  that  many 
persons  consume  too  much  protein,  at  any  rate  in  the  form  of 
animal  food,  and  would  feel  better,  work  better,  and  probably  live 
longer,  if  they  restricted  themselves  in  this  regard.  But  there  is 
no  evidence  that  the  digestion  of  such  quantities  of  protein  as  the 
average  healthy  man  eats,  or  the  elaboration  and  excretion  of  the 
corresponding  amounts  of  urea,  '  strain  '  in  the  least  the  digestive 
apparatus,  the  liver,  or  the  kidneys.  And  it  may  just  as  well  be 
argued  that  it  is  advantageous  that  much  more  than  the  minimum 
protein  requirement  should  be  offered  to  the  tissues,  so  that  the 
appropriate  amino-acids,  even  the  scarcest  of  them,  may  be  sure 
to  be  present  in  sufficient  amount,  rather  than  that  the  organs 
should  be  subjected  to  the  unnecessary  '  strain  '  of  reconstructing 
some  of  the  amino-acids  themselves,  supposing  that  they  possess 
this  power.  In  a  question  of  this  sort  tlie  immemorial  experience 
and  instinct  of  mankind  cannot  be  hghtly  waved  aside. 

McCay  points  out  that  while  Bengalis  in  Lower  Bengal  subsist  on 
food  containing  only  about  one-third  the  amount  of  protein  in  such 
a  '  standard  '  diet  as  Voit's  (6  to  7  grammes  of  nitrogen  a  day),  and 
may  therefore  be  supposed  to  be  immune  from  the  dangers  of  an 
excessive  protein  metabolism,  the  large  intake  of  carbo-hydrate 
rendered  necessary  by  the  poverty  of  the  food  in  protein  is  associated 
with  perhaps  greater  evils,  among  them  a  marked  predisposition  to 
diabetes  and  renal  troubles.  Their  weight,  chest  measurement,  and 
muscular  development  are  inferior  to  those  of  other  Asiatics  living 
in  the  same  climate,  but  with  dietetic  habits  or  economic  conditions 
which  ensure  them  a  larger  supply  of  protein.  Thus  the  natives  of 
Behar,  with  a  larger  intake  of  nitrogen,  derived  from  wheat,  and  the 
natives  of  Eastern  Bengal  with  a  larger  intake  of  nitrogen,  derived 


DIETETICS  625 

from  wheat  and  fish,  arc  pliysically  much  superior  to  the  rice-eating 
Bengahs  of  Lower  Bengal,  although  all  belong  to  the  same  race. 

If  we  decide  the  matter  merely  on  physiological  grounds,  we  may 
say  that  for  a  man  of  70  kilos,  doing  fairly  hard,  but  not  excessive, 
work,  15  grammes  nitrogen  and  250  grammes  carbon  are  a  sufficient 
allowance.  The  15  grammes  nitrogen  will  be  contained  in  95 
grammes  dry  protein,  which  will  also  yield  50  grammes  of  the 
required  carbon.  The  balance  of  200  grammes  carbon  could 
theoretically  be  supplied  either  in  450  grammes  starch  or  in 
260  grammes  fat.  But  it  has  been  found  by  experiment  and  by 
experience  (which  is  indeed  a  very  complex  and  proverbially  expen- 
sive form  of  experiment)  that  for  civilized  man  a  mixture  of  these 
is  necessary  for  health,  although  the  nomads  of  the  Asian  steppes, 
and  the  herdsmen  of  the  Pampas,  are  said  to  subsist  for  long  periods 
on  flesh  alone,  and  a  dog  can  live  very  well  on  proteins*  and  fat. 
The  proportion  of  fat  and  carbo-hydrates  in  a  diet  may,  however, 
be  varied  within  wide  limits.  Probably  no  '  work  '  diet  should 
contain  much  less  than  40  grammes  of  fat,  but  twice  this  amount 
would  be  better;  80  grammes  fat  give  about  60  grammes  carbon, 
so  that  from  proteins  and  fat  we  have  now  got  no  grammes  of  the 
necessary  250,  leaving  140  grammes  carbon  to  be  taken  in  about 
310  grammes  starch,  or  an  equivalent  amount  of  cane-sugar  or 
dextrose.  Adding  30  grammes  inorganic  salts,  we  can  put  down  as 
the  solid  portion  of  a  normal  diet  sufficient  from  the  physiological 
point  of  view  for  a  man  of  70  kilos: 

95  grammes  proteins    -        -  =y^o  of  body-weight. 

80         ,,        fat  -         -         -  =9^  ,, 

310         ,,        carbo-hydrates  =225  >> 

30         ,,        salts. 

5 15  „        solid  food  -    =1^5 

Now,  knowing  tlie  composition  of  the  various  food-stuffs,  we  can 
easily  construct  a  diet  containing  the  proper  quantities  of  nitrogen 
and  carbon,  by  using  a  table  such  as  appears  on  p.  626. 

Economic  and  social  influences — prices  and  habits — and  not 
purely  physiological  rules,  fix  the  diet  of  populations.  The  Chinese 
labourer  in  a  rice  district,  for  example,  is  apt  to  live  on  a  diet  which 
no  physiologist  would  commend.  In  order  to  obtain  15  grammes 
nitrogen  or  95  grammes  protein,  he  must  consume  more  than 
1,500  grammes  rice,  which  will  yield  700  grammes  carbon,  or  twice 
as  much  as  is  required.  But  if  many  of  the  Chinese  labourers  could 
not  live  on  rice,  or  often  on  grains  cheaper  than  rice,  they  could  not 
live  at  all.  The  Irish  peasant,  in  the  days  when  the  potato  was  his 
staple,  was  even  in  worse  case;  he  would  have  been  obhged  to 
consume  nearly  4  kilos  of  potatoes  to  obtain  his  15  grammes  nitrogen,- 
while  little  more  than  half  this  amount  would  have  furnished  the 

*  A  little  glycogen  is.  of  course,  supplied  in  the  meat. 

40 


626 


METABOLISM,  NUTRITION  AND  DIETETICS 


necessary  250  grammes  carbon.  Of  course  a  diet  consisting,  week 
in  week  out,  entirely  of  potatoes  or  rice,  would  represent  an  extreme 
case,  and  no  doubt  the  total  nitrogen  ingested  would  be  considerably 
below  the  usual  proportion.  A  certain  amount  of  the  necessary 
nitrogen  is  obtained  even  by  the  poorest  populations,  in  the  form 
of  fish,  milk,  eggs,  or  bacon.  A  man  attempting  to  live  on  flesh  alone 
would  be  well  fed  as  regards  nitrogen  with  500  grammes  of  meat, 
but  nearly  four  times  as  much  would  be  required  to  yield  250 
grammes  of  carbon.  Oatmeal  and  wheat-flour  contain  nitrogen  and 
carbon  in  nearly  the  right  proportions  (i  N:  15  C),  oatmeal  being 
rather  the  better  of  the  two  in  this  respect ;  and  the  best-fed  labour- 
ing populations  of  Europe  still  live  largely  on  wheaten  bread,  while, 
one  hundred  years  ago,  the  Scotch  peasant  still  cultivated  the  soil, 
as  the  Scotch  Reviewer  the  Muses,  '  on  a  little  oatmeal.'  But 
although  bread  may,  and  does,  as  a  rule,  form  the  great  staple  of 
diet,  it  is  not  of  itself  sufficient. 


Quantity 

Quantity 

Carbo- 

I 

required 

required 

Nin 

Gin 

Proteir. 

Fat  in 

hydrate 

Water 

I 

:o  yield 

to  yield 

100 

100 

in  100 

100 

in  100 

IS  Grms. 

N. 

250  Grms. 

c. 

Grms. 

Grms. 

Grms. 

Grins. 

in  zoo 
Grms. 

Grms. 

Chfese» 

• 

(Gruyere)  - 

300 

040 

5 

39 

31 

31 

— 

34 

Peas  (dried) 

430 

700 

3-5 

35-7 

22 

2 

55 

15 

Lean  meat  - 

440 

i860 

3-4 

13-5 

21 

3-5 

— 

74 

Wheat- flour 

650 

625 

2-3 

39-8 

12 

2 

70 

15 

Oatmeal-     - 

580 

620 

2-6 

40-3 

13 

5-5 

65 

15 

Eggs  -     -     - 

790 

1700 

1-9 

14-7 

11-5 

12 

— 

75 

Maize 

810 

610 

1-85 

40-9 

IO-5 

7 

65 

15 

Wheat- 

bread    -     - 

1200 

U20 

1-25 

22-4 

8 

1-5 

49 

40 

Rice  -     -     - 

1530 

685 

0-9 

36-6 

5 

I 

83 

10 

Milk  -     -     - 

2380 

3540 

0-6 

7 

4 

4 

5 

85 

Potatoes 

3750 

2380 

0.4 

IO-5 

2 

0-15 

21 

75 

Good  butter 

1 0000 

360 

0-I5 

69 

I 

90 

8 

It  is  necessary  to  recognize  that  habit  has  much  to  do  with  the 
quantity  as  well  as  the  quality  of  the  food  used  by  an  individual 
or  a  community.  Some  concession  may  be  made  to  custom  in 
what  is  after  all,  not  a  purely  physiological  question,  and  in  this 
country  it  is  probable  that  20  grammes  of  nitrogen  and  300  grammes 
of  carbon,  while  a  liberal  is  not  an  excessive  allowance,  although 
it  is  certain  that  a  man  can  maintain  a  normal  body-weight  and 
perform  a  normal  amount  of  work  on  considerably  less,  in  some 
cases  even  with  advantage  to  his  health. 

We  may  take  500  grammes  of  bread  and  250  grammes  of  lean 
meat  as  a  fair  quantity  for  a  man    fit    for  hard  work.     Adding 

*  A  cheese  manufactured  from  whole  milk,  curdled  before  the  cream  has 
had  time  to  rise,  and  therefore  rich  in  fat. 


DIETETICS 


617 


500  graninies  milk,  75  grammes  oatmeal  (as  porridge),  30  grammes 
butter,  30  grammes  fat  (with  the  meat,  or  in  other  ways),  and 
450  grammes  potatoes,  we  get  approximately  20  grammes  nitrogen 
and  300  grammes  carbon  contained  in  135  grammes  protein,  rather 
less  than  100  grammes  fat,  and  somewhat  over  400  grammes  carbo- 
hydrates.    Thus — 


N. 

C. 

Proteins. 

Fat. 

Carbo- 
hydrates. 

Salts. 

(9  oz.)  250  grms.  lean  meat  - 
(18  oz.)  500  grms.  bread 
(i  pint)  500  grms.  milk 
fi  oz.)  30  grms.  butter 
(I  oz.)  30  grms.  fat 
(16  oz.)  450  grms.  potatoes  - 
(3  oz)  75  grnas.  oatmeal 

8 
6 
3 

1-5 

1-7 

33 
112 

35 
20 
22 
47 
30 

55 

40 
20 

10 
10 

8-5 
7-5 
20 

27 
30 

4 

245 
25 

95 

48 

4 

6-5 
3-5 
0-5 

4-5 
2 

20-2 

299 

135 

97 

413 

21 

This  would  be  a  fair  '  hard  work  '  diet  for  a  well-nourished  labourer. 
But  the  great  elasticity  of  dietetic  formulae  is  shown  in  the  following 
tables,  which  give  the  ration  of  the  German  soldier  in  peace  and  war 
and  the  minimum  allowance  per  '  statute  adult  '  prescribed  in  the 
British  regulations  concerning  passenger- ships  from  Great  Britain 
to  America. 

Ration  of  the  German  Soldier. 


Peace. 

War. 

Bread 

750  grammes. 

Bread  -         -         - 

750  grammes 

Meat 

150 

Biscuit 

500 

Rice    - 

50 

Meat    - 

375 

or  barley  groats 

120         ,, 

Smoked  meat 

250 

Legumes     - 

230 

or  fat 

170          ». 

Potatoes     -        -  I 

■  500 

Rice     -         -         - 

125 

or  barley  groats 

125 

Legumes 

250          „ 

Minimum  Ration  fo^ 

'  Passenger  Ships. 

Bread  or  biscuit  - 

227  grammes. 

Sugar  -         -         - 

65  grammes 

Wheaten  flour 

65 

or  treacle  - 

97 

or  bread  - 

81 

Tea      - 

8 

Oatmeal 

97 

or  coffee  or  cocoa 

14 

Rice     -         -         - 

97 

Salt     - 

8 

Peas    -         -         - 

97 

Mustard 

2         ,, 

Potatoes 

130 

Pepper 

I         •> 

Beef    - 

81 

Vinegar  or  pickles 

20  c.c. 

Pork  or  preserved 

meat 

65         .. 

In  prisons  the  object  is  to  give  the  minimum  amount  of  the  plamest 
food  which  will  suf&cc  to  maintain  the  prisoners  in  health.  A  '  hard 
work  '  prison  diet  in  Munich  was  found  to  contain  104  grammes  proteins, 
38  grammes  fat,  and  521  grammes  carbo-hydrates;  a  'no-work'  diet, 
only  87  grammes  proteins,  22  grammes  fat,  and  305  grammes  carbo- 
hydrates. Here  we  recognize  the  influence  of  price;  carbon  can  be 
much   more   cheaply  obtained   in   vegetable    carbo-hydrates  than  in 


628  METABOLISM.  NUTRITION  AND  DIETETICS 

animal  fats;  the  cheapest  possible  diet  contains  a  minimum  of  animal 
fat  and  proteins. 

Many  poor  persons  live  on  a  diet  which  would  not  maintain  a  strong 
man,  for  an  emaciated  bodv  has  a  smaller  mass  of  ficsh  to  keep  up,  and 
therefore  needs  less  protein ;  it  can  do  little  work,  and  therefore  needs 
less  food  of  all  kinds.  A  London  needlewoman,  according  to  Play- 
fair,  subsists,  or  did  subsist  forty  years  ago,  on  54  grammes  protein, 
29  grammes  fat,  and  zqz  grammes  carbo-hydrates.  But  this  is  the 
irreducible  minimum  of  the  deep>est  poverty,  not  so  much  in  the  protein 
content,  perhaps,  £is  in  the  very  low  heat  equivalent  (1,600  calories); 
and  a  woman,  with  a  smaller  mass  of  flesh  and  leading  a  less  active  life 
than  a  man,  requires  less  food  of  all  sorts.  Even  the  Trappist  monk, 
who  has  reduced  asceticism  to  a  science,  and,  instead  of  eating  in  order 
to  live,  lives  in  order  not  to  cat,  consumes,  according  to  Voit,  68  grammes 
protein,  11  grammes  fat,  and  469  grammes  carbo-hydrates;  but  manual 
labour  is  a  part  of  liie  discipline  of  the  brotherhood,  and  this  must  be 
still  above  the  lowest  subsistence  diet. 

The  question  whether  it  is  best  to  derive  the  proteins  (and  fats)  of 
the  food  mainly  from  plants  or  mainly  from  annnals  is  one  which  is 
never  left  to  physiology  alone  to  decide.  But  it  has  been  definitely 
proved  that  vegetable  proteins  and  vegetable  fats  are  (when  properly 
prepared)  digested  and  absorbed  as  completely  as  those  of  animal  origin, 
and  plav  the  same  part  in  the  metabolism  of  the  body.  Nor  is  there 
any  difference  in  the  basal  metabohsm  (p.  686)  of  vegetarians  and 
persons  living  on  an  ordinary  diet. 

A  growng  child  needs  far  more  food  than  its  weight  alone  would 
indicate;  the  expenditure  of  organisms  of  different  size  in  the  same 
physiological  condition  is  proportional  not  to  the  mass,  but  more 
nearly  to  the  surface  area.  Now,  speaking  roughly,  the  cube  of  the 
surface  of  an  animal  varies  as  the  square  of  the  mass;  when  the 
weight  is  doubled,  the  surface  only  becomes  ^^4,  or  one  and  a  half 
times  as  great.  The  surface  of  a  boy  of  six  to  nine  years,  with  a 
body-weight  of  18  to  24  kilos,  is  two-fifths  to  one-half  that  of  a  man 
of  70  kilos ;  and  this  would  indicate  that  he  should  have  about  half 
as  much  food  as  the  man.  This  is  not  all,  the  child  is  not  in  the  same 
physiological  condition  as  the  adult.  It  is  growing.  Its  income 
must  exceed  its  expenditure,  and  by  a  far  greater  amount  than  the 
actual  gain  in  weight,  for  growth  is  a  ph\'siologically  expensive 
process.  It  needs  many  pounds  of  food  to  put  on  one  pound  of 
flesh.  And  in  accordance  \nth  this  it  has  been  found  that  the  basal 
metabolism  of  a  child  per  unit  of  surface  is  decidedly  greater  than 
that  of  an  adult  (p.  (^gj). 

An  infant  for  the  first  seven  months  should  have  nothing  except 
milk.  Up  to  this  age  vegetable  food  is  unsuitcd  to  it ;  it  is  a  purely 
carnivorous  animal.  By  careful  observations  on  the  ainount  of 
carbon  dioxide  and  nitrogen  excreted  by  a  child  nine  weeks  old,  fed 
exclusively  on  its  mother's  milk,  it  has  been  shown  that  the  ab- 
sorption and  assimilation  of  milk  in  the  infant  is  very  complete, 
over  91  per  cent,  of  the  total  energ}'  being  utilized;  while  an  adult, 
taking  as  much  milk  as  is  necessary  for  the  maintenance  of  nitrog- 


DIETETICS  629 

rnous  equilibrium,  does  not  utilize  at  most  more  than  84  per  cent. 
Human  milk  contains  about  2  per  cent,  of  protein  (mainly  caseino- 
gi-n),  J  \K'\-  cent,  of  fat,  5  or  6  per  cent,  of  carbo-hydrate  (lactose  or 
milk-sugar),  and  from  0*2  to  0*3  per  cent,  of  salts.  Cow's  milk 
contains  about  4  per  cent,  of  protein,  4  to  6  per  cent,  of  fat,  4  per 
cent,  of  lactose,  and  0*7  per  cent,  of  salts.  When  given  to  infants  it 
should,  as  a  geiieral  rule,  be  diluted  with  water,  and  some  sugar 
should  be  added  to  it.  Ass's  milk  has  about  the  same  amount  of 
protein,  lactose,  and  salts  as  human  milk,  but  less  than  half  as  much 
fat.     It  is  very  well  borne  and  very  completely  absorbed. 

As  to  the  place  of  water  and  inorganic  salts  in  diet,  it  is  neither 
necessary  nor  practicable  to  lay  down  precise  rules.  In  most  well- 
settled  countries  they  cost  little  or  nothing;  very  different  quantities 
can  be  taken  and  excreted  without  harm ;  and  both  economics  and 
physiolog}^  may  well  leave  every  man  to  his  taste  in  the  matter. 
Salt  is  indeed  for  the  most  part  used,  not  as  a  special  article  of  diet, 
but  as  a  condiment  to  give  a  rehsh  to  the  food,  just  as  a  great  deal 
more  water  than  is  actually  needed  is  often  drunk  in  the  form  of 
beverages.  It  is  certain  that  the  quantity  of  salt  required,  in 
addition  to  the  salts  of  the  food,  to  keep  the  inorganic  constituents 
of  the  body  at  their  normal  amount,  is  very  small.  When  the  food 
is  entirely  animal,  no  additional  salt  is  necessary.  A  30-kilo  dog 
obtains  in  his  diet  of  500  grammes  of  lean  meat  only  o  -6  gramme 
sodium  chloride,  and  needs  no  more.  An  infant  in  a  litre  of  its 
mother's  milk,  which  is  a  sufficient  diet  for  it  at  six  to  nine  months, 
gets  only  0-8  gramme  sodium  cliloride.  The  Hererosin  Damaraland, 
who  are  physically  one  of  the  finest  races  in  Africa,  do  not  use  salt 
(Reclus).  In  this  they  resemble  other  tribes  in  different  parts  of 
the  world  who  eat  no  vegetable  food,  for  example  the  Kirghiz,  who 
live  on  meat  and  milk,  and  the  Todas,  a  pastoral  tribe  in  Southern 
India,  who  are  ignorant  of  the  use  of  vegetable  foods  and  know 
nothing  of  salt  (IMcCay).  Bunge  has  explained  the  difference 
between  the  flesh  and  the  vegetable  feeder  by  showing  that  the 
proportion  of  potassium  and  sodium  salts  in  the  food  is  a  factor  in 
determining  the  quantity  of  sodium  chloride  required.  A  double 
decomposition  takes  place  in  the  body  between  potassium  phosphate 
and  sodium  chloride,  potassium  chloride  and  sodium  phosphate 
being  formed  and  excreted;  and  the  loss  of  sodium  and  chlorine  in 
this  way  depends  on  the  relative  proportions  of  potassium  and 
sodium  in  the  food.  In  most  vegetables  the  proportion  of  potassium 
to  sodium  is  much  greater  than  in  animal  food,  so  that  vegetable- 
feeding  animals  and  men  as  a  rule  desire  and  need  relatively  great 
quantities  of  sodium  chloride.  But  it  is  stated  that  the  inhabitants 
of  a  portion  of  the  Soudan  use  potassium  chloride  instead  of  sodium 
chloride,  obtaining  the  potassium  salt  by  burning  certain  plants 
which  leave  an  ash  poor  in  carbonates,  and  then  extracting  the 
residue  with  water  and  evaporating  (Dybowski).     A  beef-eating 


630  METABOLISM.  NUTRITION  AND  DIETETICS 

English  soldier   in    India   consumes  about    7  grammes   (J  oz.),   a 
v^egetarian  Sepoy  about  18  grammes  ()-;  oz.),  of  common  salt  per  day. 

Stimulants.  Wine,  beer,  tea,  coffee,  cocoa,  etc.,  belong  to  the 
important  class  of  stimulants.  Some  of  them  contain  small  quanti- 
ties of  food  substances,  but  these  are  of  secondary  interest.  In 
beer,  for  example,  tliere  are  not  inconsiderable  amounts  of  proteins, 
dextrin,  and  sugar.  But  14  litres  of  beer  would  be  required  to  yield 
15  grammes  nitrogen,  and  10  litres  to  give  250  grammes  carbon; 
and  nobody,  except  a  German  corps  student,  could  consume  such 
quantities.  The  minimum  nitrogen  requirement,  however,  as  well 
as  the  necessary  heat  value,  could  theoretically  be  covered  by  6  or 
7  litres  of  good  German  beer. 

In  some  cocoas  there  is  as  much  as  50  per  cent,  of  fat,  4  per  cent, 
of  starch,  and  13  per  cent,  of  proteins;  and  in  the  cheaper  cocoas 
much  starch  is  added.  Still,  a  large  quantity  of  the  ordinary 
infusion  would  be  needed  for  a  satisfying  meal.  Frederick  the 
Great,  indeed,  in  some  of  his  famous  marches  dined  off  a  cup  of 
chocolate,  and  beat  combined  Europe  on  it;  but  his  ordinary  menu 
was  much  more  varied  and  substantial. 

Alcohol. — The  great  social  and  hygienic  evils  connected  with  the 
abuse  of  alcohol,  as  well  as  its  applications  in  therapeutics,  render 
it  necessary,  or  at  least  permissible,  to  state  a  little  more  fully, 
though  only  in  the  form  of  summary,  some  of  the  chief  conclusions 
that  may  be  drawn  as  to  its  action  and  uses. 

(i)  In  small  quantities  alcohol  is  oxidized  in  the  body,  a  little  of  it, 
however,  being  excreted  unchanged  in  the  breath  and  urine.  A  certain 
amount  of  protein  is  saved  from  decomposition  when  alcohol  is  taken, 
just  as  when  fat  or  sugar  is  taken.  For  example,  the  addition  of 
130  grammes  of  sugar  to  the  daily  food  of  an  individual  caused  a 
'  sparing  '  of  0-3  gramme  nitrogen.  The  substitution  of  72  grammes 
alcohol  for  the  sugar  caused  0-2  gramme  nitrogen  to  be  spared  (Atwater 
and  Benedict).  Alcohol  is  therefore  to  some  extent  a  food  substance, 
although  it  is  not,  under  ordinary  circumstances,  taken  for  the. sake  of 
the  energy  its  oxidation  can  supply,  but  as  a  stimulant. 

(2)  There  is  no  reason  to  suppose  that  this  energy  cannot  be  utilized 
as  a  source  of  work  in  the  body.  Indeed,  a  certain  amount  of  alcohol 
may  be  normally  formed  in  the  tissues  as  one  of  the  intermediate 
products  in  the  oxidation  of  sugar.  Heat  can  certainly  be  produced 
from  it,  but  this  is  far  more  than  counterbalanced  by  the  increase  in 
the  heat  loss  which  the  dilatation  of  the  cutaneous  vessels  caused  by 
alcohol  brings  about. 

(3)  It  is  a  valuable  drug,  when  judiciously  employed,  in  certain 
diseases — e.g.,  pneumonia  and  puerperal  insanity  (Clouston). 

(4)  Alcohol  is  occasionally  of  use  in  disorders  not  amounting  to 
serious  disease — e.g.,  in  some  cases  of  slow  and  difficult  digestion.  In 
these  cases  it  may  act  by  increasing  the  flow  of  certain  of  the  digestive 
secretions,  as  saliva  and  gastric  juice.  This  effect  seems  to  more  tlian 
counterbalance  the  retarding  influence  which,  except  when  well  diluted, 
it  exerts  on  the  chemical  processes  of  digestion. 

The  action  of  alcohol  on  the  secretion  of  gastric  juice  has  been  studied 
in  a  dog  with  a  double  gastric  and  oesophageal  fistula.  Before  or 
during  a  sham  meal  of  meat,  alcohol  diluted  with  water  was  given  as 


DIETETICS  631 

an  enema.  After  the  enema  the  quantity  of  hydrochloric  acid  secreted 
increased  in  about  the  same  proportion  as  the  quantity  of  juice,  but  the 
pepsin  was  diininishccl,  reaching  a  minimum  after  three-quarters  to 
one  and  a  quarter  hours.  The  increase  in  the  total  quantity  of  the 
juice  and  in  the  acid  over-compensated  the  moderate  diminution  in  the 
digestive  power,  so  that  the  net  result  was  beneficial  (Pekelharing). 
But  it  must  be  remembered  that  strong  alcoholic  beverages,  when  mixed 
with  the  gastric  juice,  and  therefore  when  taken  by  the  mouth,  retard 
the  proteolytic  action,  so  that  any  favourable  effect  on  the  secretion  of 
the  juice  may  easily  be  lost  in  the  subsequent  digestion,  unless  the 
alcohol  is  dilute  (Chittenden  and  Mendel).  The  action  of  alcohol  intro- 
duced into  the  rectum  on  the  gastric  secretion  is  both  reflex  and  direct. 

(5)  Alcohol  is  of  no  use  for  healthy  men. 

(6)  Alcohol  in  strictly  moderate  doses,*  properly  diluted  and  especi- 
ally when  taken  with  the  food,  is  not  harmful  to  healthy  men,  living 
and  working  under  ordinary  conditions. 

(7)  Modern  experience  goes  to  show  that  in  severe  and  continuous 
exertion,  coupled  with  exposure  to  all  weathers,  as  in  exploring  expedi- 
tions, alcohol  is  injurious,  and  it  is  well  known  that  it  must  be  avoided 
in  mountain  climbing. 

The  drastic  restrictions  placed  upon  the  use  of  alcoholic  beverages  in 
most  of  the  belligerent  countries  during  the  present  war,  although 
adopted  for  economic  as  well  as  for  physiological  reasons,  do  not  favour 
the  view  that  the  efficiency  of  the  fighting  man,  or  of  the  man  who  works 
at  high  pressure  to  equip  and  supply  him,  is  increased  by  alcohol.  But 
it  would  be  quite  erroneous  to  conclude  that  because  alcohol,  as  such, 
may  not  at  all  improve  the  working  or  staying  power  of  men  accustomed 
to  use  it  moderately,  it  can  be  suddenly  and  completely  prohibited 
without  detriment  to  their  work.  The  factor  of  habit  and  its  influence 
on  efficiency  has  been  far  too  little  considered  in  connection  with  this 
question.  The  man  who  craves  his  wonted  glass  of  beer,  even  if  he 
does  not  resent  its  withdrawal,  will  almost  certainly  suffer  in  efficiency 
for  a  while,  although  the  beer  in  itself  may  not  have  aided  him  in  his 
work. 

Alcohol  in  small  doses,  when  given  by  the  stomach  or  (in  animals) 
injected  into  the  blood,  causes  stimulation  of  the  respiratory  centre  and 
increase  in  the  pulmonary  ventilation.  In  man,  this  increase  usually 
amounts  to  8  to  15  per  cent.,  but  is  occasionally  much  greater.  But  the 
limit  which  separates  the  favourable  action  of  the  small  dose  from  the 
hurtful  action  of  the  large,  is  easily  overstepped.  When  this  is  done, 
and  the  dose  is  continually  increased,  the  activity  of  the  respiratory 
centre  is  first  diminished  and  finally  abolished.  In  dogs,  for  instance, 
after  the  injection  of  considerable  quantities  of  alcohol  into  the  stomach, 
death  takes  place  from  respiratory  failure,  and  the  breathing  stops 
while  the  heart  is  still  unweakened  (Fig.  85,  p.  191).  This  is  the  final 
outcome  of  a  progressive  impairment  in  the  activity  of  the  centre,  of 
which  the  slow  and  heavy  breathing  of  the  drunken  man  represents  an 
earlier  stage. 

Tea,  coffee,  and  cocoa  are  more  suitable  stimulants  for  healthy 
persons,  because  they  are  less  dangerous  than  alcohol,  and  they 
leave  no  unpleasant  effects  behind  them.     But  it  should  be  remem- 

*  Not  more  than  i^  oz.  of  absolute  alcohol,  corresponding  to  about  4  oz.  of 
whisky,  or  2  to  3  wineglasses  of  sherry  or  port,  or  a  pint  of  claret,  or  a  couple 
of  pints  of  light  beer  in  24  hours. 


63*  METABOLISM.  S'UTRITION  AND  DIETETICS 

bered  that  there  is  no  stimulant  which  is  not  liable  to  be  abused. 
It  has  been  shown  by  ergographic  experiments  (p.  750)  that,  lik: 
alcohol,  tea,  coffee,  mate,  and  cola-nut,  which  all  contain  the  alka- 
loid theine  or  caffeins,  restore  the  power  of  performing  muscular 
work  after  exhaustion,  but  only  if  food  has  been  recently  or  is 
simultaneously  taken. 

Vitamines. — Certain  substances,  although  neither  in  the  ordinary 
sense  foods  nor  condiments,  seem  to  be  necessary  for  the  main- 
tenence  of  health,  for  in  circumstances  in  which  these  cannot  be 
obtained  for  long  periods  so-called  '  deficiency  diseases,'  such  as 
scurvy,  are  liable  to  occur.  Scurvy  used  to  be  the  scourge  of  the 
sailing-ship  in  the  days  when  fresh  meat,  and  particularly  fresh 
vegetables  and  fruits,  were  unobtainable  on  long  voyages.  It  has 
long  been  known  that  it  is  prevented  by  the  use  of  lime  or  lemon- 
juice,  in  which  citric  and  a  trace  of  maUc  acid  are  contained,  and 
it  used  to  be  thought  that  it  was  the  organic  vegetable  acids  which 
were  the  important  thing.  Recent  researches  have  shown,  how- 
ever, that  scurw  is  only  one  of  a  group  of  diseases,  including  beri- 
beri, and  probablv  pellagra,  rickets,  and  others  which  are  induced 
by  deficiency  in  the  food  of  certain  substances  minute  in  amount 
but  essential  to  proper  nutrition. 

The  importance  of  such  accessory  components  in  the  food  has  been 
already  pointed  out,  in  discussing  the  influence  of  artificial  diets  upon 
the  growth  and  maintenance  of  animals  (p.  617).  These  substances  are 
sometimes  termed  '  vitamines.'  But  their  chemical  nature  is  im- 
perfectlv  known,  and  there  is  no  e\adence  that  the  bodies  which  exert 
the  beneficial  influence  belong  to  the  same  chemical  group.* 

McCollom  prefers  to  designate  provisionally  the  two  substances  or 
groups  of  substances  essential,  in  addition  to  a  diet  of  purified  proteins, 
carbohydrate,  fats  and  inorganic  salts,  for  growth  and  maintenance  of 
rats,  as  '  fat-soluble  A  '  and  '  water-soluble  B,'  rather  than  to  use  the 
unsatisfactory  term  vitamines.  The  first  is  soluble  in  fats  and  is 
abundant  in  butter-fat,  egg-fat,  and  ether  extract  of  kidney.  It  is  also 
found  in  considerable  amount  in  the  leaves  of  plants,  but  is  represented 
in  the  seed  in  too  small  amount  to  supply  the  needs  of  a  young  animal. 
The  second,  which  is  soluble  in  water  and  in  alcohol,  is  plentifullv 
present  in  wheat,  wheat  germ,  maize,  alfalfa  leaves,  cabbage,  and  in  a 
number  of  foods  of  animal  origin. 

One  representative  of  the  important  food  constituents  in  question  is  a 
basic  substance  separated  by  Funk  from  the  polishings  of  rice,  and 
named  by  him,  '  vitamine.'  Polished  rice  is  rice  deprived  of  the  outer 
coats  by  modem  milling  processes,  and  the  polishings  arc  the  coats  which 
have  been  removed.  Since  the  introduction  of  steel  rollers  instead  of  the 
primitive  millstones  which  used  to  crush  the  whole  grain,  beri-beri,  a 
disea.se  characterized  by  inflammatory  and  degenerative  changes  in  the 

*  It  might  be  better  in  the  present  state  of  our  knowledge  to  avoid  giving 
those  bodies  a  name  which  may  eaisily  mi.slead.  They  might  possibly  be  pro- 
visionally spoken  of  as  "  vitincs,"  a  term  involving  no  assumption  as  to  their 
chemical  nature,  and  imphnng  only  their  importance  in  the  nutritional  pro- 
cesses associated  with  the  life  (and  growth)  of  the  tissues. 


DIETETICS  633 

peripheral  nerves  (peripheral  nciinlis)  iti  d  consequent  paralysis,  has 
greatly  increased  among  the  rice-eating  Jiipaiic^c.  in  Bengal,  although 
much  rice  is  eaten,  there  is  practically  no  bcri-beri,  as  country  rice  and 
not  the  highly  polished  variety  is  consumed.  When  birrls-  e.g.; 
pigeons — arc  fed  on  polished  rice,  polyneuritis  similar  to  that  seen  in 
human  beri-beri  is  produced,  and  both  in  man  and  in  birds  the  condi- 
tion is  quickly  cured  by  reverting  to  rice  prepared  according  to  the 
old-fashioned  methods,  or  by  adding  the  polishings  or  an  alcoholic 
extract  of  them  containing  the  essential  substance,  or  the  isolated 
base  itself. 

The  addition  of  various  legumes  to  the  diet,  or  alcoholic  extracts 
of  these,  will  produce  the  same  beneficial  effect  (McCay).  Potatoes, 
carrots,  fresh  vegetables,  lime  and  other  fruit  juices,  also  certain 
animal  foods,  such  as  fresh  milk,  fresh  meat,  and  yolk  of  egg,  are 
all  valuable,  in  addition  to  their  ordinary  nutritive  constituents,  for 
their  content  of  vitamines.  Yeast  contains  them  in  exceptionally 
large  amount,  and  it  is  possible,  though  not  proved,  that  such  fer- 
mented liquors  as  beer,  or  some  varieties  of  it,  may  derive  some  part 
of  their  value  from  these  substances  liberated  both  from  the  yeast 
and  the  barley  and  not  destroyed  in  the  process  of  brewing. 

The  addition  of  yeast  to  artificial  diets  accelerates  the  growth  of 
young  rats.  Yeast  also  prevents  and  cures  polyneuritis  developed  in 
birds  by  a  diet  of  polished  rice.  It  is  not  known  whether  the  growth- 
promoting  component  is  identical  with  the  anti-neuritic  one  or  a  different 
substance. 

Since  vitamines  exert  so  great  an  effect  on  nutrition  and  growth, 
it  might  be  expected  that  their  absence  would  tell  on  those  glands 
of  internal  secretion  which  appear  to  be  concerned  in  the  metabolism 
of  growth.  As  a  matter  of  fact,  it  has  been  found  that  in  pigeons 
suffering  from  the  typical  deficiency  disease  beri-beri,  certain  of  these 
glands  show  marked  changes.  The  thymus  gland,  normally  very 
large  and  persistent  in  these  birds,  can  be  caused  to  atrophy  com- 
pletely by  a  diet  of  polished  rice.  Changes  also  occur  in  the 
pituitary,  and  decided  atrophy  in  the  testes  and  ovaries  (Funk  and 
Douglas). 

In  bringing  this  chapter  to  a  close,  it  may  be  useful  to  point  out 
again  that  indispensable  as  the  data  of  physiology  are  for  intelligent 
and  fruitful  criticism  of  the  dietetic  habits  of  individuals  or  communi- 
ties, they  must  be  applied  with  due  regard  to  the  other  factors. 
Nothing  is  more  sure  than  that  a  certain  minimum  number  of  calories 
must  be  supplied  to  an  average  man  of  given  weight  and  age,  living 
and  working  under  definite  conditions,  in  order  that  his  body  may 
be  maintained  in  health.  It  is  also  well  made  out  that  a  certain 
balance,  which,  however,  is  by  no  means  rigidly  fixed,  between  the 
great  groups  of  food-stuffs  is  of  the  essence  of  a  good  dietary.  Yet 
of  two  rations  each  containing  the  proper  number  of  calories,  and 
the  conventional  proportions  of  protein,  carbohydrate  and  fat,  one 
may  be  good  and  sufficient,  and  the  other  so  gravely  deficient  that 
malnutrition  or  disease  may  follow  the  use  of  it.  Where  natural 
foods  are  obtainable  in  abundance  and  variety,  there  is  seldom 
danger  of  a  lack  of  the  indispensable  accessories.  This  danger  in- 
creases when  economic  or  social  conditions  lead  to  an  excessive  use 


634  MIirABOLISM,  NUTRITION  AND  DIETETICS 

of  '  artificial  '  foods.  The  factor  of  safety,  however,  is  very  large 
and  the  dietary  of  an  individual  or  the  dietetic  habits  of  a  nation 
may  be  changed  from  top  to  bottom,  if  the  change  is  scientifically 
effected,  without  serious  detriment,  at  least  for  a  long  time.  The 
greatest  experiment  of  this  kind  in  the  history  of  the  world  is  now 
being  worked  out  over  a  large  part  of  Europe. 


CHAPTER  XI 

INTERNAL  SECRETION— ENDOCRINE  GLANDS 

It  is  long  since  Caspar  Friedrich  Wolff  expressed  the  idea  that 
'  each  single  part  of  tlie  body,  in  respect  of  its  nutrition,  stands  to 
the  whole  body  in  tiie  relation  of  an  excreting  organ,'  and  thus 
emphasized  the  importance  of  substances  produced  by  the  activity 
of  one  kind  of  cell  for  the  normal  metabolism  of  another.  But  it  is 
only  in  recent  years  that  it  has  become  possible  to  illustrate  this 
mutual  relation  by  any  large  number  of  experimental  facts. 

Certain  of  the  substances  taken  in  from  the  blood  by  the  liver 
find  their  way,  after  undergoing  various  changes,  into  the  biliary 
capillaries,  and  are  excreted  as  bile;  certain  other  substances,  such 
as  sugar  and  the  precursors  of  urea,  are  taken  up  by  the  hepatic 
cells,  transformed  and  sometimes  stored  for  a  time  within  them, 
and  then  given  out  again  to  the  blood.  Bile  we  may  callihe-^extetual 
secretion  of  the  hver.  glycogen,  and  urea  constituents  of  its  internal 
secretion.  In  one  sense  it  is  evident  that  all  tissues,  whether  glands 
in  the  morphological  sense  or  not,  may  be  considered  as  manufac- 
turing an  internal  secretion.  For  ever^^thing  that  an  organ  absorbs 
from  the  blood  and  lymph  it  gives  out  to  them  again  in  some  form 
or  other  except  in  so  far  as  it  forms  or  separates  a  secretion  that 
passes  away  by  special  ducts.  But  it  is  usual  to  employ  the  term 
only  in  relation  to  organs  of  glandular  build,  whether  provided  with 
ducts  or  not.  Typical  endocrine*  glands  (that  is,  glands  producing 
an  internal  secretion)  are  the  adrenals,  thyroid,  parathyroid, 
pituitary,  thymus,  etc.  For  convenience  the  action  of  extracts  of 
some  other  tissues,  such  as  nervous  tissue,  will  also  be  considered  here, 
although  there  is  no  reason  to  suppose  that  they  form  any  specific 
internal  secretion. 

The  capacity  of  manufacturing  internal  secretions  of  high  im- 
portance can  neither  be  attributed  to  all  glands  with  ducts  nor 
denied  to  all  other  organs.  For  the  salivary,  mammary,  and  gastric 
glands  may  be  completely  removed  without  causing  any  serious 
effects,  while  death  follows  excision  of  the,  so  far  as  mere  bulk  is 
concerned,  apparently  insignificant  masses  of  tissue  in  the  ductless 
thyroid,  parathyroid,  suprarenal  or  pituitary  bodies. 
*  From  iv^ov.  mthin,  and  Kpiva,  I  separate. 
635 


636  TNTERXAL  SECRETION— F.XDOCRINE  GLASDS 

It  is  known  that  in  the  case  of  the  Uver  the  internal  secretion  is 
more  important  than  the  external,  for  an  animal  cannot  survive 
without  its  liver,  wliilc  it  may  be  but  little  affected  by  the  con- 
tinuous escape  of  the  bile  through  a  fistulous  opening. 

Pancreas. — The  internal  secretion  of  the  pancreas  is  also  indis- 
pensable. For  when  the  pancreas  is  excised  death  follows  in  many 
species  of  animals,  and  especially  in  carnivorous  animals;  and  in 
man  severe  and  ultimately  fatal  diabetes  is  often  associated  with 
pancreatic  disease,  while  the  mere  loss  of  the  pancreatic  juice 
through  a  fistula  does  not  necessaril\'  shorten  life  although  the 
absorption  of  fat  is  seriously  interfer*  d  with. 

The  ultimate  cause  of  death  seems  to  he  a  profoimd  disturbance 
of  metabolism,  of  which  the  most  significant  token  is  the  increased 
proportion  of  sugar  in  the  blood,  and  its  speedy  appearance  in  the 
urine— in  dogs  always  within  twenty-four  hours  following  total 
removal  of  the  organ.  Associated  with  the  glycosuria  is  an  increase 
in  the  quantity  of  the  urine  (polyuria),  excessive  thirst  (polydipsia), 
and  a  ravenous  appetite  (polyphagia  accompanied  by  intense 
hunger  contractions  of  the  stomach — Luckhardt),  in  spite  of  which 
the  animal  becomes  more  and  more  emaciated — in  short,  the 
classical  symptoms  of  a  severe  type  of  pathological  diabetes  in  man, 
but,  of  course,  far  more  acute  in  their  onset,  and  far  more  rapid 
in  their  progress  towards  the  inevitable  end.  Dogs  rarely  survive 
more  than  two  or  three  weeks,  the  immediate  cause  of  the  rapidly 
fatal  result  being  perhaps  the  extensive  suppuration  which  is  apt 
to  ensue  on  slight  and  practically  unavoidable  superficial  injuries. 
The  resistance  of  the  tissues  to  bacterial  invasion  and  their  tendency 
to  spontaneous  healing  are  reduced  by  the  overloading  of  the  blood 
and  tissue  liquids  with  sugar.  Even  when  carbo-hydrates  are  ex- 
cluded from  the  food,  or  when  no  food  at  all  is  given,  sugar  continues 
to  be  excreted  in  large  amounts.  The  destruction  of  proteins  is 
increased.  It  is  a  significant  fact  that  glycosuria  does  not  appear 
or  is  only  transient  when  the  pancreas  is  partially  removed,  so  long 
as  a  comparatively  small  fraction  of  the  gland  (one-ciuarter  or  one- 
fifth)  is  left.  Even  when  such  a  remnant  is  dislocated  from  its 
original  position,  care  being  taken  not  to  interfere  with  its  circula- 
tion, and  sutured  in  the  peritoneal  cavity  or,  indeed,  under  the  skin, 
the  animal  remains  in  good  health.  In  the  dog  this  operation  can 
be  practised  on  the  lowest  part  of  the  descending  division  of  the 
pancreas,  which  is  not  united  with  the  duodenum,  but  lies  free  in 
the  mesenterv.  Removal  of  the  fragment  of  pancreas  is  followed 
by  the  whole  train  of  symptoms  associated  with  total  extirpation 
of  the  organ. 

When  the  portion  of  pancreas  left  is  smaller  than  is  sufficient  to 
completely  prevent  diabetes,  only  one-eighth  of  the  total  mass  of 
the  gland,  for  instance,  the  symptoms  come  on  more  gradually  than 


PASCREAS  637 

after  total  extirpation,  and  the  resemblance  to  human  diabetes 
becomes  closer.  The  animals  rapidly  deteriorate  if  supplied  with 
too  much  carbohydrate,  while  they  may  be  kept  alive  for  a  long 
time  in  good  licaltli  if  the  limit  of  their  tolerance  for  carboh\'drates 
is  not  exceeded  (Tliiroloix,  Allen  et  al.). 

Although  as  yet  we  are  ignorant  of  the  precise  manner  in  which 
the  pancreas  influences  the  metabolism  of  the  body,  it  is  impossible 
to  doubt,  in  view  of  the  facts  we  have  mentioned,  that,  like  the  liver, 
in  addition  to  carrying  on  the  exchanges  necessary  for  the  prepara- 
tion of  the  ordinary  or  external  secretion,  the  gland  has  other 
important  relations  with  the  circulating  fluids,  giving  to  them  or 
taking  from  them  substances  on  the  manufacture  or  destruction  of 
which  the  normal  metabolic  processes  depend.  It  has  been  sug- 
gested that  the  pancreas  neutralizes  or  renders  harmless  some 
toxic  substance  formed  elsewhere  in  the  body,  the  action  of  which 
produces  glycosuria.  But  no  evidence  of  the  existence  of  any  such 
substance  has  been  obtained,  and  the  transfusion  into  a  norma 
dog  of  blood  from  a  depancreatized  animal,  which  ought  to  be  laden 
wdth  the  hypothetical  toxic  material,  does  not  cause  glycosuria.  It 
is  much  more  probable  that  the  h^^perglycsemia  on  which  the 
glycosuria  depends  is  caused  by  the  absence  of  something  normally 
produced  by  the  pancreas,  and  which  is  indispensable  for  the  due 
regulation  of  the  sugar-content  of  the  blood.  This  something,  as 
already  pointed  out  in  discussing  pathological  diabetes,  may  be 
necessary  to  regulate  the  transformation  of  sugar  into  glycogen, 
or  eventually,  it  may  be,  into  fat,  so  that  too  great  a  surplus  oi 
sugar  does  not  remain  unchanged ;  or  to  regulate  the  transformation 
of  glycogen  into  dextrose,  and  prevent  too  hasty  and  too  extensive 
action  by  the  glycogenase;  or  to  regulate  the  production  of  sugar 
from  sources  other  than  the  carbo-hydrates;  or,  finally,  to  regulate 
and  to  aid  in  the  normal  utilization  of  the  sugar  in  the  organs 
(p.  553). 

While  the  liver  contains  less  than  the  normal  content  of  glycogen, 
its  power  to  form  glycogen  is  certainly  not  abolished.  On  the  con- 
trary, there  is  some  reason  to  think  that  a  great  deal  of  this  reserve 
carbo-hydrate  may  be  synthesized  in  the  diabetic  organism,  and 
that  the  comparative  poverty  of  the  hepatic  cells  in  glycogen  may 
be  due  to  rapid  glycogenolysis,  despite  the  hyperglycaemia,  in 
response  to  the  insistent  demand  for  sugar  on  the  part  of  the  tissues, 
which  in  the  midst  of  plenty  are  hungry  for  dextrose  on  account  of 
their  inability  to  utilize  it,  or  some  of  its  decomposition  products, 
in  the  normal  way.  It  has  indeed  been  sho\vn  b^^  numerous  ex- 
periments that  interference  with  the  formation  or  with  the  hydrol- 
ysis of  glycogen,  although  it  may  be  a  factor,  is  not  of  itself  sufficient 
to  explain  pancreatic  glycosuria. 

Failure  in  the  katabolism  of  dextrose,  as  already  mentioned 


638  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

(P-  554).  iias  been  asserted  by  some  observers  and  denied  by  others. 
A  great  production  of  sugar  from  proteins  {i.e.,  from  amino-acids) 
has  been  demonstrated,  but  it  is  quite  possible  that  just  as  much  is 
produced  from  this  source  in  the  normal  organism,  although  here 
its  formation  is  masked  by  a  corresponding  utilization. 

The  clearest  evidence  that  the  pancreas  produces  something  of 
high  importance  in  carbo-hydrate  metabolism  has  been  obtained 
by  experiments  in  which  animals  were  united  in  such  a  way 
that  substances  could  pass  from  one  to  the  other  (parabiosis,  see 
Chap.  XIX.).  Wlien  two  young  dogs  were  so  united  and  the  pancreas 
then  removed  from  one,  no  glycosuria  followed.  The  internal 
secretion  of  the  remaining  pancreas  was  sufficient  for  both  (Forsch- 
bach).  In  like  manner  the  removal  of  the  pancreas  from  pregnant 
bitches  not  far  from  full  term  caused  no  glycosuria  or  very  little 
till  the  pups  were  born,  when  the  usual  train  of  events  associated 
with  pancreatic  diabetes  ensued.  Obviously  the  pancreatic  tissue 
of  the  embryos  in  the  uterus  supplied  the  mother  with  the  indis- 
pensable secretion  (Carlson  and  Drennan). 

The  question  has  often  been  raised  why  it  should  not  be  possible 
to  supply  animals  or  human  beings  suffering  from  pancreatic  defi- 
ciency with  the  missing  material  by  administering  pancreas  or 
pancreatic  extracts.  Hitherto,  however,  little  if  any  success  has 
attended  attempts  of  this  kind,  perhaps  because  the  active  substance 
or  substances  are  very  easily  destroyed.  This  has  been  all  the  more 
disappointing,  as  in  the  case  of  the  internal  secretion  of  the  thyroid 
the  so-called  '  substitution  therapy  '  has  been  brilliantly  successful 
(p.  649)- 

The  seat  of  the  internal  secretion  of  the  pancreas  seems  to  be  the 
very  vascular  epithelioid  tissue  which  is  peculiar  to  this  gland,  and 
occurs  in  islands  between  or  imbedded  in  the  alveoh  (islands  or 
islets  of  Langerhans)  (Schafer).  For  animals  survive  the  complete 
atrophy  of  the  ordinary  secreting  epithelium  caused  by  the  injec- 
tion of  paraffin  into  the  ducts,  and  no  sugar  appears  in  the  urine. 
The  islets  remain  intact.  When  a  portion  of  the  pancreas  is 
separated  from  the  rest,  and  its  duct  ligated,  it  undergoes  extensive 
atrophy,  a  tissue  remaining  which  is  apparently  composed  of  en- 
larged islands  of  Langerhans  and  remains  of  pancreatic  ducts.  If 
the  rest  of  the  gland  is  now  removed,  no  glycosuria  occurs,  even 
when  considerable  quantities  of  dextrose  are  injected.  But  when 
the  atrophied  remnant  is  also  removed,  typical  pancreatic  glycosuria 
at  once  ensues  (W.  G.  MacCallum). 

As  further  evidence  that  the  islets  have  a  different  function  from 
the  pancreatic  alveoli  may  be  cited  the  statement  that  in  teleostean 
fishes,  in  which  the  islands  are  so  large  that  they  can  be  separated 
from  the  rest  of  the  tissue,  the  cells  of  the  islets,  instead  of  containing 
an  amylolytic  ferment  like  the  alveolar  cells,  contain  a  glycolytic 


PANCREAS  639 

ferment,  or  at  least  possess  the  power  of  destroying  sugar.  Yet  the 
question  of  the  significance  of  the  islets  can  hardly  be  considered 
settled,  although,  as  previously  mentioned,  the  supposed  experi- 
mental basis  of  the  theory  that  they  do  not  differ  essentially  from 
the  alveolar  tissue,  but  are  formed  by  certain  changes  in  the  arrange- 
ment and  properties  of  the  alveolar  elements,  appears  to  have 
collapsed  under  the  criticism  of  Bensley  and  others.  Far  from 
being  interchangeable  with  the  cells  of  the  acini,  the  islet  cells 
present  definite  and  permanent  criteria  by  which  they  can  be  sharply 
distinguished  from  the  alveolar  epithelium.  At  least  two  types  of 
islet  cells  may  be  identified  by  their  staining  reactions,  the  so-called 
A  and  B  cells  (Lane).  The  B  cells  are  the  most  abundant  in 
all  the  islets,  and  many  of  the  small  islets  are  composed  of  them. 
In  the  guinea-pig,  on  account  of  the  great  size  of  some  of  the  islets, 
and  because  many  of  them  are  situated  in  the  interstitial  tissue 
(between  the  acini),  it  is  not  difficult  to  pick  out  an  islet,  isolate  it 
from  the  surrounding  tissue,  and  examine  it  in  serum  or  salt  solu- 
tion. The  cells  are  crowded  with  very  fine  granules  exhibiting 
Brownian  movement.  In  the  fresh  preparation  the  granules  of  the 
A  cells  cannot  be  distinguished  from  those  of  the  B  cells. 
Both  varieties  stain  intensely  with  neutral  red  and  other  dyes,  and 
the  islet  tissue  can  in  this  way  be  easily  differentiated  from  the 
tissue  of  the  acini.  By  differences  in  their  staining  reactions  and 
certain  properties  of  their  nuclei,  which  need  not  be  gone  into  here, 
the  two  varieties  of  islet  cells  can  be  identified.  The  important 
point  for  our  purpose  is  that  by  an  appropriate  histological  tech- 
nique the  islet  tissue  can  be  studied  in  all  the  functional  vicissitudes 
of  the  gland.  When  this  is  properly  done,  it  is  not  found  that 
there  is  any  close  connection  between  the  secretory  activity  of  the 
cells  of  the  acini  and  the  islets.  Nor  is  there  any  evidence  that  the 
amount  of  islet  tissue  in  the  pancreas  is  ever  affected  by  the  forma- 
tion of  new  islets  out  of  acini.  On  the  other  hand,  it  seems  that  the 
islets,  or  the  great  majority  of  them,  consist  of  epithelial  cells  which 
are  in  direct  continuity  with  the  pancreatic  ducts,  and  that  after 
removal  of  a  portion  of  the  pancreas,  establishing  an  insufficiency  of 
islet  tissue,  new  islets  can  be  developed  from  the  duct  epithelium, 
in  addition  to  the  increase  by  interstitial  growth  in  the  size  of  islets 
already  existing  (Bensley,  etc.).  If  the  islets  are  connected  with 
the  ducts,  the  possibility  may  be  admitted  that  they  yield  some- 
thing to  the  external  secretion  of  the  pancreas  as  well  as  to  its 
internal  secretion.  But  if  this  be  so,  there  is  no  improbability  in 
the  idea  that  the  alveolar  epithelium,  which  is  undoubtedly  mainly 
concerned  in  the  preparation  of  the  pancreatic  juice,  may  also 
contribute  something  to  the  internal  secretion  of  the  gland.  While, 
then,  the  importance  of  the  pancreas  in  carbo-hydrate  metaboHsm 
is  certain,  and  the  dependence  of  this  function  upon  an  internal 


640  TNTERNAL  SECnETlOK—^E^^DOCRINE  GLANDS 

secretion  is  highly  probable,  it  is  not  yet  definitely  settled  whether 
this  secretion  is  formed  in  the  organ  as  a  whole,  or  only  in  the  islets. 
That  lesions  of  the  pancreas  may  be  concerned  in  pathological 
diabetes  is  well  estabhshed,  and  it  is  of  interest  in  connection  with 
the  question  we  have  just  been  discussing  that  in  a  certain  number 
of  cases  the  changes  observed  have  been  in  the  islands  (Opie).  And 
in  diabetes  accompanying  cirrhosis  of  the  liver,  which  has  usually 
been  considered  to  depend  upon  the  hepatic  changes,  it  has  been 
shown  that  in  many,  if  not  all,  of  the  cases  the  pancreas  is  also 
affected  by  a  growth  of  connective  tissue  outside  the  acini  (Stein- 
haus).  Some  authors,  indeed,  have  gone  so  far  as  to  say  that  in  all 
cases  of  diabetes  mellitus  there  is  disease  of  the  pancreas,  but  of  this 
there  is  no  evidence. 

Ligation,  or  the  establishment  of  a  fistula,  of  the  thoracic  duct, 
causes  glycosuria  in  dogs.  It  is  possible  that  this  is  really  a  mild 
form  of  pancreatic  diabetes,  due  to  interference  with  the  supply  oi 
the  internal  secretion  of  the  pancreas,  or  of  that  part  of  it  which 
reaches  the  blood  by  the  lymph-stream  (Tuckett). 

Pfliiger  long  maintained  that  it  is  not  the  removal  of  the  pancreas, 
as  such,  but  the  section  of  certain  nerves  running  into  or  through  it 
from  the  duodenum,  which  is  the  cause  of  the  glycosuria.  For, 
according  to  him, .when  these  nerves  are  divided  or  the  duodenum  re- 
moved while  the  pancreas  remains  untouched,  the  result  is  the  sam.e  as 
if  the  pancreas  itself  had  been  excised.  He  imagined  that  these  nerve! 
arc  '  antidiabetic  ' — that  is,  in  some  way  oppose  the  production  of 
sugar — while  nerves  coming  from  the  so-called  '  sugar  centre  '  in  the 
bulb  (the  centre  assumed  to  be  affected  in  the  puncture  experiment) 
favour  sugar  production.  Between  the.sc  the  normal  balance  is  struck 
in  health  ;  it  is  the  upsetting  of  this  balance  by  the  crippling  of  the 
duodenal  fibres  which  is  at  the  bottom  of  '  pancreatic  '  diabetes. 
But  it  has  been  shown  that  this  hypothesis  is  without  foundation, 
AJthough  in  frogs  removal  of  the  duodenum  does  cause  a  certain  degree 
of  glycos\iria,  this  is  not  the  case  in  dogs.  And  it  has  been  demon- 
strated clearly  in  the  dog,  by  special  experiments,  that  section  of  all  the 
old  connections  of  a  dislocated  remnant  of  the  pancreas  does  not  cause 
permanent  glycosuria,  whereas  removal  of  the  pancreatic  tissue  does. 

Sexual  Organs. — The  influence  of  castration  in  preventing  the 
development  of  the  sexual  characters,  and  especially  the  physical 
and  psychical  changes  that  normally  occur  at  puberty,  is  also  due 
to  the  loss  of  the  internal  secretion  of  the  generative  glands,  and 
does  not  appear  to  depend  at  all  upon  the  loss  of  nervous  impulses 
arising  in  these  organs.  In  Herdwick  sheep  an  outstanding  sexual 
difference  is  the  presence  of  horns  in  the  males,  their  absence  in 
the  females.  Removal  of  the  testes  from  ram  lambs  arrests  further 
growth  of  horns  forthwith  and  at  any  stage  of  development.  The 
retention  of  the  epididymes,  provided  that  the  testes  proper  are 
removed,  does  not  alter  the  result  of  castration  in  the  least.  The 
removal  of  one  testicle  slows  horn  growth  without  arresting  it 
(Marshall  and  Hammond).     In  partially  castrated  cocks  it  has  been 


SICXUAL  ORGANS  fi.^I 

seen  that,  so  Umg  as  a  portion  of  one  testicle  remains,  tlie  male 
characters  are  preserved,  but  after  removal  of  this  residue  the 
comb  and  wattles  wither  in  a  few  weeks  (Hanau).  At  the  breeding- 
time  the  muscles  of  the  forearm  of  the  brown  land  frog  {Rana 
fused)  become  hypertrophied  in  the  male,  so  that  it  can  more  tightly 
hold  the  female.  At  the  same  time  the  balls  of  the  toes  increase 
in  size,  and  become  covered  with  a  peculiar  black  growth.  After 
the  breeding  season  these  secondary  sexual  characters  disappear. 
If  the  male  frog  is  castrated,  the  periodic  return  of  these  phenomena 
does  not  occur,  but  the  prei^ence  of  one  testicle  suffices  for  their 
development  on  both  sides.  When  pieces  of  testicle  from  normal 
frogs  are  introduced  under  the  skin  of  the  castrated  frogs,  the 
phenomena  occur  just  as  if  the  animals  had  not  been  castrated 
(M.  Nussbaum). 

Many  facts  indicate  that  the  internal  secretion  is  not  furnished  by  the 
proper  reproductive  elements  (those  which  form  the  spermatozoa), 
but  by  the  interstitial  cells  of  Leydig,  which  are  distributed  in  groups 
throughout  the  substance  of  the  testes  between  the  seminal  tubules. 
The  spermatogenic  cells  may  be  atrophic  or  absent,  as  in  cryptorchids, 
or  after  ligation  of  the  vas  deferens  (Bouin  and  Anc«l) ;  or  they  may  be 
destroyed  by  X-rays,  without  interfering  with  the  development  of  the 
secondary  sexual  characters.  Steinach  has  shown  that  when  the  testes 
of  a  young  rat  or  guinea-pig  are  transplanted  to  another  part  of  its 
body  (the  peritoneal  cavity  or  subcutaneous  tissue),  the  animal  de- 
velops all  the  secondary  sexual  characters  at  the  proper  time.  The 
penis  grows  to  the  normal  size.  The  seminal  vesicles  and  prostate 
develop  in  the  ordinary  way,  and  yield  a  plentiful  secretion.  Sexual 
desire  and  potency  appear  in  due  season,  and  in  normal  or,  in  not  a  few 
cases,  indeed,  increased  intensity.  Yet  histological  examination  shows 
that  not  a  single  spermatocyte  or  spermatid  (Chapter  XIX.)  has  de- 
veloped, while  outside  the  seminal  tubules  the  interstitial  cells  ft)rm 
large  masses  which  much  surpass  in  size  the  interstitial  islands  of  the 
normal  testis.  Similar  clianges  are  observed,  though  with  less  cer- 
tainty and  after  a  longer  interval,  when  the  vas  deferens  is  ligated,  a 
method  often  recommended  and  occasionally  practised  for  the  steriliza- 
tion of  the  human  male.  On  account  of  the  influence,  thus  demon- 
strated, of  the  interstitial  cells  in  producing  the  sexual  development 
observed  at  puberty,  Steinach  designates  these  cells  collectively  as  the 
'puberty  gland.' 

When  the  ovaries  of  a  young  female  rat  or  guinea-pig  are  trans- 
planted into  the  peritoneal  cavity  or  under  the  skin  of  a  previously 
castrated  male  animal  of  the  same  kind  (preferably,  to  facilitate  acciirate 
comparison,  a  male  of  the  same  litter),  only  the  interstitial  cells 
survive  (in  about  half  the  cases).  There  is  this  difference  in  the  fate 
of  the  ovary  and  the  testis  when  auto-transplanted,*  that  the  genera- 
tive elements  of  the  former,  the  Graafian  follicles,  with  the  ova  contained 
in  them,  generally  develop  as  well  as  the  large  interstitial  cells  rich 
in  protoplasm  lying  in  the  stroma,  which  cells  appear  to  constitute 

*  An  auto-transplant  or  auto-graft  is  a  portion  of  tissue  transplanted  into 
another  part  of  the  same  animal's  body.  A  homceo-graft  is  a  portion  of  tissue 
transplanted  into  the  body  of  another  individual  of  the  same  species;  a  hetero- 
graft  is  a  portion  of  tissue  transplanted  into  an  animal  of  a  different  speciM. 

-41 


642  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

the  female  puberty  sl^"*^!-  l^t-'  strict  isolation  of  the  female 
])ubcrtv  ^'laiid  is  only  realized  in  those  cases  in  which  bv  some 
accident  of  healing  the  stroma  of  the  transplanted  ovary  maintains 
itself  while  the  generative  elements  disappear.  In  these  cases  the 
influence  of  the  ovary  on  the  development  of  the  sexual  characters 
is  the  same  as  when  the  reproductive  elements  proper  persist  and 
grow. 

A  more  general  influence  of  the  sexual  organs  on  metabolism 
seems  also  to  be  well  established.  The  exact  experiments  of  Loewy 
and  Richter  on  the  metabolism  of  bitches  before  and  after  cas- 
tration throw  light  upon  the  changes  which  follow  that  operation, 
and  afford  decisive  proof  that  tluy  are  connected  with  the  absence 
of  substances  specific  to  the  ovary.  They  conclude  that  in  the 
castrated  animal  the  oxidative  energy  of  the  cells  is  lessened.  The 
oxygen  consumption  sinks,  even  although  protein  is  laid  on  and  the 
total  amount  of  active  tissue  thus  increased.  Under  certain  cir- 
cumstances this  specific  diminution  of  metabolism  may  be  balanced 
by  conditions  which  cause  an  increase  in  the  metabolism.  The 
lessening  of  the  oxidative  power  is  due  to  the  loss  of  ovarian  sub- 
stance, for  the  administration  of  an  extract  of  the  ovary  (oophorin) 
not  only  neutralizes  it,  but  actually  causes  an  increase  in  the  gaseous 
metabohsm  to  far  above  the  original  amount,  while  it  has  no  effect 
on  the  metabolism  of  the  uncastrated  animal.  It  is  not  the  de- 
composition of  proteins,  but  of  non-nitrogenous  substances,  whicli 
is  accelerated.  Oophorin  also  brings  about  a  notable  increase  in 
metabolism  in  the  castrated  male  dog,  while,  curiously  enough, 
extract  of  testicle  causes  only  a  small  increase,  due  to  a  basic  sub- 
stance, spermin  (CgHj^Ng),  which  can  be  isolated  from  the  testicle. 
But  the  orchitic  extract  is  not  without  influence  in  other  ways. 
It  certainly  increases  the  capacity  for  muscular  work  (Zoth  and 
Pregl),  as  tested  by  the  ergograph  (p.  750),  and  this  distinct  physio- 
logical action  is  sufficient  to  encourage  the  hope  that  it  ma}'  possess 
some  therapeutic  value,  although  far  from  what  has  been  claimed 
for  it  by  its  more  enthusiastic  advocates.  The  only  constituent  of 
extracts  of  the  testicle  made  with  salt  solution  which  causes  any 
pronounced  effect  on  the  blood-pressure  when  injected  into  the 
circulation  is  a  nucleo-protein,  the  most  plentiful  of  the  protein 
substances.  The  pressure  falls,  mainly  owing  to  inhibition  of  the 
heart,  but  partly  through  vaso-dilatation  in  the  splanchnic  area 
(Dixon). 

The  testicles  also  influence  the  growth  of  the  bones.  In  eunuchs 
and  in  young  men  with  atrophy  of  the  testicles  a  tendency  has  been 
observed  for  the  long  bones  to  go  on  growing  far  beyond  the  usual 
period.  This  has  been  shown  by  the  Rontgen  rays  to  be  due  to 
delay  in  the  ossification  of  the  epiphyses.  The  same  has  been 
observed  in  animals,  and  is  supposed  to  be  caused  by  the  loss  of 


THYMUS  643 

some  substance  normally  toiinod  in  the  testicle  vvliicli  influences  tne 
metabolism  ol  the  bones  and  the  deposition  of  the  l)one  salts. 

A  temjiorarv  diminution  in  the  ha-moglobin  and  in  the  number 
of  the  erN-throcytes  has  been  observed  in  castrated  bitches,  an 
observation  which,  so  far  as  it  goes,  is  in  favour  of  the  view  that  an 
insufficient  internal  secretion  of  the  ovaries  is  the  cause  of  the 
form  of  anaemia  known  as  chlorosis. 

While  these  effects  on  general  metabohsm  and  nutrition,  as  well 
as  the  influence  on  the  development  of  the  sexual  characters,  are 
probably  to  be  ascribed  to  changes  in  the  internal  secretion  of  the 
interstitial  cells,  there  are  facts  which  indicate  that  other  elements 
may  be  concerned.  For  example,  evidence  has  been  brought 
forward  that  the  corpus  luteum  is  a  gland  with  an  internal  secretion, 
whose  function  is  connected  with  menstruation  and  with  the  im- 
plantation of  the  ovum  and  the  subsequent  growth  of  both  ovum 
and  uterus  in  pregnancy  (Born,  Fraenkel)  (Chapter  XIX.).  Removal 
of  the  corpora  lutea  occurring  during  the  first  half  of  pregnancy 
causes  abortion. 

Thymus. — Our  knowledge  of  the  function  of  the  thymus  is  very 
incomplete.  Even  its  histological  structure,  and  especially  the 
source  and  nature  of  its  cellular  elements,  have  long  been,  and  still 
are,  the  subject  of  controversy.  It  is  developed  as  a  pair  of  diver- 
ticula, mainly  from  the  ventral  part  of  the  third  branchial  cleft,  and 
to  a  slight  extent  from  the  fourth.  These  pouches  grow  downwards 
into  the  thorax.  At  this  stage  the  organ  is  a  purely  epithelial 
structure.  Soon  connective  tissue  and  bloodvessels  begin  to  grow 
into  it,  the  two  halves  coalesce  in  the  middle  line,  and  the  thvmus 
becomes  transformed  by  degrees  into  a  structure  with  a  general 
resemblance  to  a  big  lymph  gland,  and  consisting  mainly  of  small 
cells  like  lymphocytes.  Some  observers  beheve  that  these  cells 
are  true  lymphocytes,  derived  from  the  mesoderm,  which  have 
migrated  into  and  displaced  the  earher  epithelial  tissue.  Others 
maintain  that  the  resemblance  is  merely  superficial,  and  that  they 
are  simply  epithelial  cells  diminished  in  size  and  altered  in  shape, 
but  derived  from  the  original  epithelium  by  repeated  division,  and 
remaining  epithehal  to  the  end.  Any  theory  of  the  function  of 
the  thymus  must  needs  depend  largely  upon  the  view  adopted  as  to 
its  structure.  For  if  it  is  in  its  fully  developed  state  merely  a  large 
collection  of  lymphocytes,  it  would  appear  quite  unlikely  that  it 
should  possess  functions  very  different  from  those  of  other  collections 
of  lymphocjles.  On  the  other  hand,  if  the  essential  elements  in 
the  organ  are  epithelial,  they  may  well,  like  the  epithelial  elements 
of  the  thyroid  or  of  other  glands  with  an  internal  secretion,  be  con- 
cerned in  the  elaboration  of  substances  which  exercise  an  important 
influence  upon  nutrition  and  growth.  On  the  whole,  the  best  histo- 
logical evidence  seems  to  favour  the  view  that  the  thymus  cells  are 


644  [XTi:iy\AL  SECRETION— EN DOGKIXF.  GLANDS 

differrnt  liom  the  cells  ol  lympli  glands.  Chemical  differences  also 
exist.  For  example,  nuclein  substances  characteristic  of  the  nuclear 
framework  of  the  true  glands  are  much  more  abundant  in  the  thymus 
than  in  lymph  glands. 

After  a  period  of  further  development,  which  varies  in  duration  in 
different  animals,  the  organ  undergoes  involution.  In  mammals  (in- 
cluding man)  the  thymus  does  not  completely  disappear  in  the  adult. 
Islands  of  thymus  tissue  are  found  at  all  ages  among  the  fat  by  which 
the  bulk  of  the  organ  is  replaced.  In  certain  diseases,  as  exophthalmic 
goitre,  myxoadema  and  Addison's  disease,  an  actual  regeneration  of 
the  involuted  thymus  may  occur.  It  is  usually  stated  that  in  man 
the  thymus  begins  to  diminish  in  size  about  the  end  of  the  second  year, 
but  the  careful  observations  of  Hammar  indicate  that  this  is  incorrect. 
According  to  him,  the  organ  continues  to  grow  till  puberty  is  reached, 
weighing  on  the  average  13  grammes  at  birth,  37  grammes  at  eleven 
to  fifteen  years,  23  grammes  at  sixteen  to  twenty  years,  and  only  6 
grammes  at  sixty-six  to  seventy-five  years.  Besides  this  involution 
with  age,  great  changes  in  the  size  of  the  thymus  may  occur  at  any 
time  under  the  influence  of  toxic  substances  or  of  deficient  nutrition. 
In  starvation,  even  in  the  first  three  days  of  hunger,  the  weight  of  the 
thymus  in  rabbits  has  been  observed  to  shrink  to  one-halt,  and  during 
prolonged  underfeeding  even  to  one-thirtieth,  of  the  normal  (Jonson). 
The  opposite  effect,  namely,  cessation  of  the  involution  process,  or 
even  new  formation  of  thymus  tissue,  may  also  occur,  leading  to  the 
presence  of  an  unusually  large  so-called  persistent  thymus  in  the  adult 
— the  so-called  status  thymicus,  or  status  lymphaticus. 

The  point  most  clearly  established  in  the  physiology  of  the  thymus 
seems  to  be  its  relation  to  the  gonads  or  sex  glands.  It  is  well  known 
that  in  castrated  animals  the  thymus  is  larger  and  persists  longer  than 
in  entire  animals.  In  bulls  and  unspayed  heifers  the  normal  atrophy  of 
the  thymus,  which  begins  after  the  period  of  puberty,  is  greatly  acce- 
lerated when  the  bulls  have  been  used  for  breeding,  and  when  the 
heifers  have  been  pregnant  for  several  months.  There  is  a  reciprocal 
influence  of  the  thymus  on  the  testicles,  and  removal  of  the  thymus 
before  the  time  at  which  it  naturally  atrophies  is  followed  by  a  more 
rapid  growth  of  the  testes  (in  guinea-pigs)  (Paton).  The  remarkable 
atrophy  or  involution  of  the  gland  at  puberty  is  a  striking  indication 
of  this  relation.  That  the  nexus  between  the  thymus  and  the  gonads 
is  chemical  and  not  nervous  is  shown  by  the  fact  that  when  the  thymus 
is  autografted  under  the  skin  (a  situation  in  which  grafts  readily  take 
and  grow  after  removal  of  the  main  portion  of  the  gland  in  sexually 
immature  rabbits)  these  grafts  behave  in  the  same  way  as  the  gland 
in  situ,  showing  earlier  involution  both  in  the  male  and  in  the  female 
when  the  animals  arc  allowed  to  breed  (Marine  and  Manley).  The 
relation  of  the  thymus  to  the  growth  of  bones  is  less  well  established, 
but  according  to  some  observers  extirpation  of  the  gland  retards  their 
calcification. 

In  young  mammals  the  loss  of  the  thymus  is  said  to  cause  transient 
disturbances  of  nutrition,  as  temporary  decrease  in  the  number  of 
all  varieties  of  leucocytes,  and  a  diminished  resistance  to  the  pus- 
forming  micrococci,  probably  connected  with  the  relatively  feeble 
loucocytosis  (or  increase  in  the  number  of  leucocytes)  by  which  the 
animals  react  to  the  infection.  In  the  frog  the  thymus  persists  through- 
out life.  Yet  the  removal  of  it  is  not  fatal  if  precautions  against  in- 
fection be  taken.     The  contention  that  the  thvmus  is  indispensable  for 


THYROIDS  AND  PARATHYROIDS 


64; 


life  in  mammals,  and  that  its  removal  is  always  followed  by  a  characteris- 
tic cachexia  (Klose)  has  been  overthrown  by  later  experiments  on  the 
effects  of  extirpation  of  the  gland  (Pappenheim,  Ilowland,  etc.).  The 
thymus  of  young  mammals  can  be  readily  auto-grafted  into  the  subcu- 
taneous or  subperitoneal  tissues.  Such  grafts  involute  at  sexual 
maturity  with  the  main  thymus.  Homcco-grafts  are  not  permanently 
successful  in  mammals,  except  that  they  take  and  survive  for  two  or 
three  weeks  (Marine  and  Mauley). 

The  chief  effect  of  intravenous  injection  of  extract  of  human  or  ox 
thymus  is  a  lowering  of  blood-pressure;  but  there  is  nothing  specific 
in  this,  a  similar  effect  being  given  by  thyroid  extract  and  the  extracts 
of  many  other  tissues.  The  heart  may  be  at  the  same  time  accelerated. 
When  thymus  substance  is  fed  to  tadpoles,  growth  is  markedly  stimu- 
lated and  metamorphosis  delayed  (Gudernatsch),  the  opposite  of  the 
effect  produced  by  thyroid  substances.  This  direct  evidence  supports 
the  observations  on  mammals  above  referred  to  that  removal  of  the 
thymus  hastens  sexual  ditferentiation  ;  that  delayed  sexual  differentia- 
tion, as  in  myxccdema,  lymphatism,  etc.,  is  associated  with  enlarged 
thymus;  and  that  castration  delays  the  involution  of  the  thymus. 

Thyroids  and  Parathyroids. — The  thyroid  consists  of  two  lobes 
connected  by  an  isthmus  across  the  middle  Una  in  man  and  some 
animals,  but  often  separate. 
In  the  neighbourhood  of  the 
thyroid,  or  embedded  in  its 
tissue,  are  certain  bodies 
called  parathyroids,  consist- 
ing of  solid  columns  of  epi- 
thelial cells.  The  number 
and  situation  of  the  para- 
thyroids are  not  constant. 
As  a  rule,  there  are  four  in 
mammals,  two  on  each  side, 
but  this  number  is  subject 
to  variations  in  different 
individuals  of  the  same 
species.  The  variability  in 
their  anatomical  relations  to 
the  thyroid  is  of  greater 
significance.  For  much  of 
the  uncertainty  in  which  the 
whole  question  of  the  symp- 
toms following  extirpation 
of  the  thyroids  was  until 
lately  involved  arose  from 
ignorance  or  insufficient  re- 
cognition of  this  variabihty. 
In  most  animals  the  inferior,  anterior,  or  external  pair  of  para- 
thjToids  is  more  or  less  distinctly  separated  from  the  thyroid. 
The  separation  is  especially  evident  in  the  herbivcra,  in  the  monkey, 


Fig.  202. — Parathyroid  (Vincent  and  Jolly). 
A  small  portion  of  parathyroid  of  cat  em- 
bedded in  thyroid  tissue.  It  consists  for 
the  most  part  of  solid  colimins  of  epithelial 
cells  (3,  5,  8)  with  strands  of  vascular  con- 
nective tissue  (6).  A  thyroid  vesicle  (11) 
and  portions  of  two  others  (i,  10)  are  seen 
in  the  lower  part  of  the  figure,  separated 
from  the  parathyroid  by  a  fibrous  capsule 
(2).  4,  7,  bloodvessels;  9,  lower  boimdary 
of  the  parath3T:oid  tissue.     (  x  500.) 


646  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

and  in  man,  and  this  pair  of  jKirathyroids  is  nuirh  larger  than  the 
(tier.  In  carnivorous  animals,  as  the  dog  and  cat,  the  anterior 
pair  of  parathyroids  is  closely  adherent  to  the  thyroid  capsule. 
The  superior,  posterior,  or  internal  pair,  both  in  hcrbivora  and  carni- 
vora,  is  always  very  closely  associated  with  the  capsule  of  the 
thyroid,  and  frequently  embedded  in  the  substance  of  the  gland. 
The  consequence  of  this  arrangement  is  that  in  the  older  experiments 
the  chief  masses  of  parathyroitl  tissue  were  much  more  likely  to 
escape  removal  with  the  thyroid  in  the  case  of  herbivorous  than  in 
the  case  of  carnivorous  animals. 

But  even  in  one  and  the  same  species  considerable  variations  may 
exist.  It  is  easy  to  see,  then,  that  in  removing  the  th3Toid  the 
parathyroids  would  sometimes  be  completely  removed  as  well, 
while  at  other  times  all  or  some  of  the  parathyroid  tissue  would  be 
spared.  Add  to  this  that  sporadic  masses  of  thyroid  tissue  (acces- 
sory thyroids),  often  existing  as  far  down  as  the  root  of  the  aorta 
(always,  indeed,  in  certain  animals — e.g.,  the  dog),  must  necessarily 
be  spared  in  the  most  complete  thyroidectomy,  and  it  vAU  cease  to 
excite  surprise  that  the  symptoms  and  pathological  changes  de- 
scribed after  that  operation  should  have  been  so  various  and  so 
contradictory.  We  know  now  that  the  parathyroids  are  perfectly 
distinct  organs  from  the  thyroid  in  development,  in  structure,  in 
function,  and  in  the  consequences  of  their  removal.  The  para- 
thyroids, for  instance,  contain  no  iodine,  while  iodine  is  a  character- 
istic constituent  of  the  thyroid.  Nor  do  the  parathyroids  show  any 
compensatory  hypertrophy  when  the  thyroid  alone  is  excised,  or 
any  changes  which  would  indicate  a  definite  relation  to,  still  less,  an 
active  participation  in,  the  pathological  processes  occurring  in  the 
thyroid  in  goitre.  This  does  not  mean,  however,  that  there  are 
no  points  of  contact  between  the  functions  of  the  two  glands.  The 
more  the  matter  is  probed,  the  more  clearl}^  does  it  appear  that  none 
of  the  organs  is  quite  independent  of  the  rest,  and  the  reciprocal 
relations  of  the  ductless  glands  are  probably  of  exceptional  im- 
portance. But  the  premature  attempts  which  have  been  made, 
in  the  absence  of  a  sufficiency  of  exact  data,  to  represent  their 
mutual  influence  by  crude  schemata,  have  retarded  rather  than 
advanced  our  knowledge,  and  need  not  be  referred  to  here. 

Parathyroidectomy.— Total  extirpation  of  the  parath3'roids  is 
followed  by  a  train  of  acute  symptoms,  ending  fatally,  as  a  rule  in 
from  one  to  ten  days.  The  typical  nervous  symptoms  following  the 
operation  are  those  of  '  tetany  '  (tetania  parathyreopriva),  and  the 
tetany  which  used  to  be  included  among  the  consequences  of  re- 
moval of  the  thyroid  is  now  known  to  be  due  to  the  simultaneous 
excision  of  the  parathyroids  (Kocher).  A  cat,  after  the  combined 
operation,  is  perfectly  well  on  the  first  day.  On  the  second  day  a 
curious  shaking  of  the  paws  is  seen,  tremors  of  central  origin  soon 


THYROIDS  AND  PARATHYROIDS  647 

appear,  and  incii-asc  in  severity,  until  at  K'ngth  they  culminate  in 
general  spasmodic  attacks.  Even  when  the  animal  is  at  rest  the 
fore-legs  tend  to  be  ilexed,  while  the  hinrl-legs  are  extended,  and  this 
attitude  is  exaggerated  in  the  convulsions.  In  the  later  stages  un- 
consciousness is  associated  with  the  onset  of  the  convulsions.  Similar 
results  follow  excision  of  the  parathyroids  alone  in  dogs.  Although 
the  tetany  is  the  most  striking  symptom,  it  is  only  one  token  of  a 
profound  general  disturbance  of  nutrition.  The  pulse-rate  and  the 
rate  of  respiration  arc  markedly  increased.  There  is  fever  and  pro- 
fuse salivation,  with  dilatation  of  the  stomach  and  duodenum,  due 
to  the  loss  of  muscular  tonicity.  In  the  intervals  between  attacks 
the  tonus  returns  to  the  normal.  The  secretion  of  the  gastric 
juice,  pancreatic  juice,  and  bile  are  interfered  with  (Carlson,  etc.). 
The  excitability  of  the  vaso-constrictor  mechanism  is  said  to  be 
increased.  The  exact  significance  of  these  symptoms  is  unknown. 
It  has  been  suggested  that  the  loss  of  the  parathyroid  function  is 
in  some  way  associated  with  an  augmentation  of  the  irritability  of 
the  whole  sympathetic  system  (Hoskins).  The  administration  of 
calcium  completely  relieves  the  symptoms,  and  by  its  use  death  may 
be  long  or  perhaps  indefinitely  postponed  (W.  G.  MacCallum) .  The 
mode  of  action  of  the  calcium  has  not  been  made  clear  as  yet.  It 
does  not  seem  to  be  so  efficacious  in  rabbits  as  in  dogs  (Arthus) . 

A  suggestive  fact  is  the  increased  amount  of  guanidin,  methyl  and 
(Umethyl-guanidin  in  the  urine  of  dogs  after  parathyroidectomy  (Koch). 
Recently  the  hypothesis  has  been  put  forward  that  the  parathyroids 
regulate  the  metabolism  of  guanidin  in  the  body  and  bv  doing  so, 
probably  exercise  a  controlling  influence  on  the  tone  of  the  muscles. 
In  support  of  this,  it  is  pointed  out  that  in  tetania  parathyreopriva 
there  is  a  marked  increase  in  the  amount  of  guanidin  and  methyl- 
guanidin  in  the  blood,  as  well  as  in  the  urine.  This  is  also  true  of  the 
urine  of  children  suffering  from  the  disease  known  as  idiopathic  tetany, 
in  which  the  parathyroids  are  supposed  to  be  implicated  (Paton,  etal.). 
Symptoms  and  metabolic  changes  like  those  in  experimental  and  patho- 
logical tetany  are  said  to  be  caused  by  guanidin  and  methyl-guanidin. 

Thyroidectomy. — The  symptoms  that  follow  removal  of  the 
thjToid  alone  are  perfectly  different.  The  metabolic  disturbance  is 
eventually,  in  most  animals,  not  less  far-reaching  than  that  which 
ensues  when  the  parathyroids  are  alone  excised.  But  it  is  far  more 
chronic,  reveals  itself  by  totally  distinct  changes,  is  not  amenable 
to  calcium,  and  is  completely  corrected  by  the  administration  of 
thyroid  substance.  While  no  animals  which  have  been  examined 
survive  the  total  removal  of  the  parathyroids,  certain  species — 
e.g.,  the  goat — are  but  shghtly  affected  by  thyroidectomy,  and 
survive  indefinitely.  In  man,  before  the  consequences  of  th}Toid- 
ectomy  were  known,  the  whole  gland  was  not  infrequently  excised 
for  goitre.  If  the  parathyroids  happened  also  to  be  completely 
involved  in  the  operation,  death  quickly  followed.     But  where  only 


648  ISTERSAL  SECRIiiloS—LSUULRIM.  CLANDS 

the  thyroid  itself,  or  the  thyroid  plus  the  small  internal  pair  of 
parathyiviids,  was  cxtiipated,  the  condition  called  cachexia 
struniipii\a  was  observed  to  supervene.  The  symptoms  rcsf^mble 
those  of  the  disease  known  as  myxoedema,  in  which  the  charac- 
teristic anatomical  change  is  an  increase  (a  hyperplasia)  of  the 
connective  tissue  in  and  under  the  true  skin.  Newly-formed  connec- 
tive tissue  always  contains  an  excess  of  mucoids,  and  for  this  reason 
in  the  early  stages  of  myxoedema  there  is  somewhat  more  than  the 
usual  amount  of  these  substances  in  the  subcutaneous  tissue.  The 
skin  is  dry,  and  tlie  hair  falls  off.  The  features  are  swollen  and 
heavy,  and  movements  clumsy  and  trembling.  As  the  disease 
progresses  the  mental  powers  deteriorate  too;  the  patient  becomes 
stupid  and  slow,  and  perhaps,  at  last,  imbecile.  When  the  gland 
is  so  affected  in  early  life  that  extensive  atropliy  of  the  true  secreting 
tissue  occurs,  a  peculiar  condition  of  idiocy  (cretinism)  results. 

In  animals  there  is  a  great  difference  in  the  results  of  total  ex- 
cision of  the  thyroids,  both  between  different  groups  and  between 
different  individuals  of  the  same  group.  In  young  animals  the 
symptoms  come  on  more  rapidly  and  are  more  severe  than  in  old. 
Monkeys  develop  symptoms  resembling  those  of  myxoedema. 

The  older  descriptions  of  the  very  acute  onset  of  the  symptoms 
and  the  quickty  fatal  result  in  carnivorous  animals  were  vitiated 
by  the  circumstance  that,  for  the  anatomical  reason  already  alluded 
to,  the  parathyroids  were  also  involved  in  the  operation.  Never- 
theless, the  consequences  of  complete  removal  of  the  thyroid  proper 
are  in  general  more  serious  in  the  carnivora  than  in  the  herbivora. 
Muscular  weakness  soon  becomes  marked;  the  tissues  waste,  the 
temperature  becomes  subnormal,  and  this  is  associated  with  changes 
in  the  heat  regulation  (p.  699). 

If  a  portion  of  the  thyroid  be  left,  or  an  autograft  be  made  in  any 
part  of  the  body,  these  effects  are  permanently  obviated.  Homoeo- 
grafts,  although  they  take,  rarely  survive  and  function.  Working  with 
rabbits,  Marine  and  Manley  have  found  that  thyroid  autografts  take 
and  grow  when  placed  in  any  tissue,  spleen  and  bone  marrow  being  the 
least  favourable  tissues,  while  the  sex  glands  and  the  adrenals  are 
probably  the  most  favourable.  The  extent  of  the  growth  of  thyroid 
autografts  depends  on  the  age  of  the  animal,  being  more  marked  in 
young  animals,  on  the  amount  of  the  thyroid  gland  removed,  and  on  the 
administration  or  withholding  of  iodine.  Thyroid  homoeografts  rarely 
succeed.  In  a  series  of  5O7  thyroid  homoeografts  in  rabbits,  92  per  cent, 
underwent  absorption  in  ten  to  thirty  days;  (>  per  cent,  remained  active 
from  two  to  six  months  before  being  absorbed:  and  2  per  cent,  were 
permanent  and  beha\ed  in  all  respects  like  autografts.  The  outlook 
for  the  therapeutic  application  of  thyroid  grafts  in  the  treatment  of 
thyroid  insufficiencies  is  therefore  not  hopeful,  imlcss  some  means  is 
discovered  to  overcome  the  power  of  the  host  to  destroy  foreign 
proteins.  It  has  been  established  that  a  hetcro-thyroid  graft  does  not 
even  temporarily  succeed.  The  alien  thyroid  cells  arc  destroyed  by 
cytolysins  (p.  31)  in  the  scrum  and  tissue  liquids  of  the  animal. 


TUVROtnS  AND   PA  RAI  HY  IU)1 1)^  649 

When  a  small  part  of  a  thyroid  is  left,  it  may  undergo  gi  eat  hyper- 
trophy, and  the  same  is  true  of  the  accessory  thyroids.  The  ad- 
ministration of  extracts  of  the  thyroid  glands  or  the  glands  them- 
selves by  the  mouth  brings  about  a  cure,  permanent  so  long  as  the 
thyroid  treatment  is  continued,  in  cases  of  myxoedcma  in  man,  and 
prevents  the  development  of  the  symptoms  in  animals,  or  removes 
them  when  they  have  appeared.  The  same  is  true  of  a  compwund 
rich  in  iodine,  the  so-called  thyToiodin,  which  has  been  extracted 
from  the  organ.  Under  this  treatment  the  total  metabolism,  which 
in  myxcedema  is  below  the  normal,  is  markedly  increased.  This  is 
partly  due  to  an  increase  in  the  metabolism  of  protein.  An  increase 
in  the  destruction  of  protein  is  also  caused  in  normal  persons  and  in 
normal  animals  by  feeding  with  thyroid  or  with  thyroid  prepara- 
tions. The  excretion  of  nitrogen,  carbon  dioxide,  and  phosphoric 
acid,  and  the  intake  of  oxygen,  are  augmented.  But  in  spite  of  in- 
creased appetite  the  body-weight  falls  off,  and  diarrhoea  is  often 
caused.  For  these  reasons  the  use  of  thyroid  preparations  to  reduce 
weight  in  cases  of  obesity,  without  evidence  of  thyroid  insufficiency, 
is  a  dangerous  remedy.  For  while  a  fat  man  can  very  well  spare  a 
great  deal  of  his  fat,  he  cannot  spare  much  of  his  tissue-protein. 
That  the  gland  exerts  in  some  way  an  important  influence  on  the 
metabolism  of  proteins  is  also  indicated  by  other  facts.  The  ques- 
tion whether  the  thyroid  or  parathyroid  is,  in  addition,  concerned 
in  the  carbo-hydrate  metabolism  is  at  present  the  subject  of  dis- 
cussion, but  the  data  are  so  contradictory  that  it  would  not  be  advis- 
able to  enter  into  the  matter  here. 

The  ready  response  of  the  thyroid  by  hyperplasia  or  involution 
to  changes  in  the  nutritive  conditions  is  one  of  its  most  .striking 
characteristics,  and  further  illustrates  the  significant  role  which  it 
plays  in  the  chemical  activities  of  the  body.  The  thyroid  swells 
and  shrinks  almost  as  easily  and  under  almost  as  great  a  variety 
of  conditions  as  the  spleen.  One  of  the  most  interesting  of  the 
physiological  changes  is  the  hypertrophy  and  sometimes  hyperplasia 
of  the  gland,  which  is  a  normal  accompaniment  of  menstruation 
and  pregnancy.  This  is  a  classical  instance  of  a  definite  inter-rela- 
tion of  endocrine  functions.  Although  known  to  the  ancients  in  its 
crudest  manifestations,  the  underlying  physiology  of  the  condition 
is  as  yet  only  slightly  understood.  A  pathological  change  of  great 
interest,  because  of  the  careful  manner  in  which  it  has  been  studied, 
is  the  endemic  goitre  (sometimes  erroneously  termed  '  carcinoma  ') 
of  brook  trout  kc})t  under  artificial  conditions  in  hatcheries.  Marine 
has  shown  that  this  depends  upon  overfeeding  with  unsuitable  food 
(such  as  livers  of  cattle,  pigs,  or  sheep),  overcrowding,  and  insuffi- 
ciency of  water-supply,  and  that  the  goitre  can  be  readily  cured  or 
prevented  by  changing  the  conditions  in  these  respects.  Similar 
results  have  been  obtained  in  mammals  fed  exclusively  with  meat. 


6iO 


INTERNAL  SnCRRTlON— ENDOCRINE  GLANDS 


Thus,  lion  cubs  at  the  Zoological  Gardens  in  London  on  a  diet  con- 
sisting only  of  raw  aneat  de\'elo])cd  rickets  and  goitre,  as  did  pu])])ies 
fed  with  meat,  lungs,  liver,  or  heart,  and  nothing  else,  whereas  when 
milk,  bread,  and  bone  were  added  to  meat  the  puppies  grew  nor- 
mally (Marine).  A  meat  diet  caused  hyperplasia  of  the  thyroid  in 
rats  (Chalmers  Watson).  The  relation  of  the  disease  known  as 
exophthalmic  goitre  to  the  thyroid  has  been  much  debated.  The 
best  evidence  is  against  the  hypothesis  that  the  symptom  complex 
is  of  thyroid  origin.  The  increased  thyroid  activity  partially 
accounts  for  the  increased  metabolism  characteristic  of  the  disease; 
but  this  is  secondary  and  symptomatic.     All  attempts  to  produce 

anything     resembling     the 
pathological     condition    by 
the  administration  of  large 
amounts  of   thyroid    or    of 
thyroid  products  have  failed. 
Nor  has  it  ever  been  shown 
that    the    changes    in     the 
gland  are  the  primary  cause 
of    the   syndrome.     Indeed, 
no    specific    anatomical    or 
chemical    changes    have    as 
yet    been    demonstrated    in 
the  thyroid  in  this  condition. 
The   thyroid   gland   of    ex- 
ophthalmic   goitre    has   the 
same  action  on  animals  and 
on    patients   suffering   from 
exophthalmic  goitre  as  any 
other    thyroid    gland    with 
like  iodine  content  (Marine). 
The  relations  of  iodine  to 
the    gland    itself,    and    the 
modifications  in  its  structure  and  function  determined  by  the  giving 
or  withholding  of  iodine,  recently  studied  by  Marine,  are  of  great 
interest.     In  all  animals,  so  far  as  examined,  the  normal  thvroid 
contains  iodine.     The  amount  is  variable,  but  the  minimum  per- 
centage of  iodine  necessary,  if  the  normal  histological  structure  is 
to  be  maintained,  is  quite  constant  for  a  given  species.    So  also  the 
highest  percentage  of  iodine  associated  with  any  degree  of  active 
hyperplasia  (developing  goitre)  is  always  below  the  normal  minimum 
of  O'l  per  cent,  of  the  dried  gland  as  shown  by  Marine  in  the  dog, 
sheep,  man,  and  other  mammals.     As  active  hyperplasia  of  the 
thyroid  (goitre)  (Fig.  203)  develops,  the  iodine  content  of  the  gland, 
both  relative  and  absolute,  decreases,  until  in  extreme  degrees  of 
the  condition  there  may  be  no  demonstrable  iodine  present  at  all. 


Fig.  203. — Microphotograph  of  Active  Thyroid 
Hyperplasia  from  a  Case  of  Exophthalmic 
Goitre  (Marint^).  The  characteristic  changes 
in  the  hyperplastic  gland — the  infoldings 
and  plications  of  the  adveolar  epithelium, 
the  great  reduction  in  the  colloid,  and 
the  increase  in  the  stroma — are  shown. 


TlfVh'niDS  AND   P.lRATIlVI^OfnS 


G51 


vSincc  the  iodine  is  contiiiucd  in  the  colloid  as  an  io(lint'-])rot(in 
compound,  the  generahzation  may  be  made  that  in  the  thyroid 
the  iodine  varies  directly 
with  the  amount  of  colloid, 
and  inversely  with  the  de- 
gree of  hyperplasia.  The  ad- 
ministration of  any  iodine- 
containing  substance  to 
animals  with  actively  hyper- 
plastic thyroids  (goitres)  re- 
sults in  a  rapid  storage  of 
iodine  in  the  gland,  and 
quickly  (in  two  to  three 
weeks  in  dogs)  induces  a 
histological  change,  the  end 
stage  of  which  is  the  so-called 
colloid  goitre  (Fig.  204). 
This  is  an  involution  to  the 
normal  histological  structure 


Fig.  204.— Microphotograph  of  a  Colloid 
Gland  (Goitre)  (Marine).  The  effect  of  ad- 
iiiiuistration  of  iodine  is  shown  in  the  return 
towards  the  normal  structure  from  a  pre- 
ceding active  hyperplasia,  such  as  is  shown 
in  Fig.  203. 


(F"ig.  205),  SO  far  as  this  is 
possible  in  a  gland  which 
has  once  undergone  hyper- 
plasia. This  storage  of 
iodine  in  the  thyroid  is  of  unusual  interest  because  it  affords  the 
best  opportunity  for  the  quantitative  study  of  an  essential  inor- 
ganic constituent  of  the  body.     Iron  is  another  such  substance, 

but  it  is  impossible  to  follow 
its  absorption  quantitatively 
with  the  same  ease  and 
accuracy,  since  it  is  so  widely 
distributed.  Iodine  is  con- 
tained in  the  thyroid,  and  to 
all  intents  and  purposes  in 
the  thyroid  alone.  And  the 
tliyroid  is  so  situated  ana- 
tomically that  it  is  a  simple 
matter  to  remove  a  portion 
of  it  for  examination.  The 
extraordinary  affinity  of  the 
thyroid  for  iodine  and  its 
salts  has  been  demonstrated 
both  in  vivo  and  in  vitro. 
There  is  little  difference 
whether  the  iodine  salt  is 
injected  into  the  circulation  of  the  living  animal,  or  perfused 
through  the  excised  sur\i\-ing  gland,  so  long  as  the  gland  is  not 


Fig.  205. — Microphotograph  of  Normal 
Human  Thyroid  (Mca4ne). 


652  INTERNA L  SECRETION— ENDOCRINE  GLANDS 

already  saturated  with  iodine.  The  greatest  quantitative  absorption 
takes  place  in  those  glands  with  the  smallest  iodine  content,  or. 
what  comes  to  the  same  thing,  those  glands  with  the  most  marked 
hyperplasia. 

Thus,  a  dog's  thyroid  (in  early  hyperplasia)  weighing  i6  grammes, 
and  containing  0-54  milligramme  of  iodine  per  gramme  of  the  dry 
tissue  was  perfused  for  thirty  minutes  with  a  mixture  of  blood  and 
Ringer's  solution  to  which  was  added  5  milligrammes  of  potassium 
iodide.  The  gland  was  then  washed  out  thoroughly  with  Ringer's 
solution  to  remove  remaining  iodide.  It  was  now  found  to  contain 
I  38  milligramme  of  iodine  per  gramme  of  dry  tissue.  Ten  minutes 
after  the  injection  of  50  milligrammes  of  potassium  iodide  into  the 
femoral  vein  of  a  dog,  from  which  one  thyroid  lobe  had  been  removed 
as  a  control,  the  remaining  lobe  was  excised  and  all  loose  iodide  re- 
moved by  thorough  washing.  The  iodine  in  it  was  then  determined  and 
found  to  be  i  3S  milligramme  per  gramme  of  the  dry  tissue,  as  com- 
pared with  079  milligramme  in  the  control  lobe,  an  increase  of  75 
per  cent.  Only  traces  of  iodine  can  be  demonstrated  in  other  organs 
under  such  conditions,  even  when  they  have  not  been  washed.  Even 
m  five  minutes,  an  absorption  of  iodine  of  practically  the  same  magni- 
tude has  been  shown  to  occur.  So  that  the  thyroid  has  the  power  of 
taking  up  considerable  amounts  of  iodine  almost  instantaneously. 
While,  however,  the  time  required  for  the  absorption  of  iodine  by  the 
thyroid  from  the  blood,  and  the  binding  of  it  m  such  a  way  that  it 
cannot  be  washed  out,  is  so  short  as  to  be  measured  in  minutes,  the 
time  required  for  the  elaboration  of  the  iodine  into  the  active  iodine- 
containing  substance,  which  exhibits  the  specific  action  of  the  gland, 
is  much  greater.  In  dogs,  the  earliest  period  at  which  an  increase  in 
the  amount  of  active  iodine  could  be  made  out  was  eight  hours  after 
the  injection  of  an  iodine  salt  into  the  circulation. 

Summary  : — The  physiological  significance  of  iodine  in  the  thyroid 
mav  be  summed  up  as  follows  :  Iodine  is  absolutely  essential  for  the 
normal  activity  of  the  gland.  Tlie  amount  in  the  gland  at  any  given 
time  represents  the  store  or  reserve.  Iodine  prevents  spontaneous  hyper- 
plasia [goitre]  in  all  mammals,  and  also  the  compensatory  hyperplasia 
which  follouS  partial  removal  of  the  thvroid.  It  exercises  a  curative 
effect  on  CKtive  hyperplasias.  It  is  present  in  an  active  and  an  in- 
active form.  The  inactive  form  represents  the  newly  acquired  iodine, 
which  is  usually  a  very  small  fraction  of  the  total  content,  but  may 
undergo  a  great  temporary  increase  after  the  administration  of  iodine. 
Accordingly,  the  physiological  and  therapeutic  activity  of  thyroid 
substance  appears  in  general  to'  vary  with  the  total  amount  of  iodine 
in  it.  although  in  reality  with  the  amount  -which  exists  in  the  specific 
compound.     The  nature  of  this  compound  is  unknown. 

No  other  body  has  been  shown  to  possess  its  specific  activating  effect 
on  metabolism.  It  is  sometimes  spoken  of  as  the  iodine-containing 
hormone.  Kendall  has  been  able  to  separate  it  both  from  its  protein 
combination  and  from  the  inactive  iodine  by  alkaline  hydrolysis  of  the 
thyroid,  and  to  obta'n  it  in  a  cn,'stalline  form  containing  about  60  per 
cont  ,  by  weight,  of  iotlinc. 


THYh'niDS  AND   HA RATHY ROI DS  653 

Tlie  most  sensitive  and  accurate  test  object  for  estimating  the  pharma- 
cological activity  of  thyroid  substance,  or  of  its  hydrolytic  products,  is 
the  tadpole.  Its  growth  is  hindered  and  its  differentiation  accelerated 
by  the  active  iodine  compound,  so  that  the  limbs  grow  and  the  tail 
atrophies,  while  the  tadpole  remains  small  (Gudernatsch).  By  means 
of  this  test,  it  has  been  possible  to  demonstrate  the  presence  of  active 
and  inactive  iodine  in  the  gland,  and  to  estimate  the  rate  at  which  the 
thyroid  can  elaborate  the  active  iodine-containing  substance  from  the 
inactive  iodine  (Figs.  206,  207). 


Fig.  206. — Tadpoles  after  seven  days  feeding:  A,  with  iodine-free  hyperplastic  lamb 
thyroid  in  50  milligramme  doses  on  alternate  days;  B,  with  sheep  thyroid 
hydrolytic  product  (containing  17-9  milligrammes  of  iodine  per  gramme)  in  10 
milligramme  doses  on  alternate  days;  C,  with  ox  thyroid  hydrolytic  product 
(containing  14*8  milligrammes  of  iodine  per  gramme)  in  10  milligramme  doses 
on  alternate  days.  On  the  other  days  all  the  tadpoles  received  fresh  liver. 
In  A,  normal  growth  similar  to  control.  Great  emaciation  with  differentiation 
in  B  and  C  (Rogoff  and  Marine). 

While  the  precise  role  played  by  the  thyroid  in  the  economy  re- 
mains obscure,  it  is  evident  that  in  most  animals  and  in  man  its 
secretion  is  of  great  importance,  whether  it  be  solely  the  quasi- 
external  secretion  of  'colloid,'  with  its  specific  iodine-containing 
substance  that  collects  in  its  alveoli  and  slowly  passes  out  of  them 
by  the  lymphatics,  or  perhaps,  in  addition,  some  other  substance, 
which,  like  the  glycogen  of  the  liver,  never  finds  its  way  into  the 
lumen  of  the  gland-tubes  at  all.  It  may  also  be  admitted  that,  by 
aiding  in  the  maintenance  of  the  normal  level  of  general  nutrition, 
particularly  that  of  the  central  nervous  system,  the  ability  of  the 
organism  to  cope  with  toxic  substances  introduced  from  the  outside 
or  manufactured  in  the  body  is  favoured.  There  is,  however,  no 
e\adence  that  an  actual  destruction  or  neutralization  of  toxic  sub- 
stances occurs  in  the  gland  itself. 

It  is  uncertain  whether  the  secretion  of  the  thyroid  is  influenced  by 
nerves.  Section  of  most  of  the  nerves  entering  the  gland  does  not 
obviously  alter  its  activity.  Thyroid  tissue  may  be  transplanted  into 
any  part  of  the  body,  and  there  exhibit  all  the  morphological,  chemical, 
and  functional  changes  seen  in  the  gland  in  situ.  Transplantation  in 
the  same  nerve  field  as  the  original  thyroid  has  no  advantage  over 
transplantation  into  any  other  region  of  the  body  (Marine  and  Manley). 
This  is  an  indication  that  specific  secretory  nerves  are  not  indispensable 
for  thyroid  activity. 


Ov 


54 


INTERNAL  SECRETION— ENDOCRINE  GLANDS 


It  has  long  been  known  that  vaso-motor  fibres  for  the  dog's  thyroid  run 
up  in  the  cervical  sympathetic  to  the  superior  cervical  ganglion,  ami 


Sampl 


Thyroid. 


Fig.  207. — Effect  of  Desiccated  Human  Thyroid  on  Tadpoles  of  Different  Ages 
The  upper  row  shows  the  older,  the  lower  row  the  younger  tadpoles.  The  older 
ones  had  posterior  leg  buds  slightly  over  2  centimetres  long,  but  no  foreleg.  The 
younger  tadpoles  had  just  visible  posterior  leg  buds  and  no  foreleg  buds.  The  ind'- 
viduals  of  each  age  were  alike  at  the  beginning  of  the  experiment  as  to  size  ai  d 
condition  of  development.  One  of  each  age  was  killed  in  formalin  at  the  beginning 
of  the  experiment  (designated  as  '  Sample '  in  the  figure).  Another  of  each  a^^e 
was  used  for  control,  and  fed  fresh  liver  every  second  day.  A  third  specimen  nt 
each  age  (under  *  Thyroid'  in  the  figure)  was  fed  50  milligrammes  of  desiccated 
human  thyroid  every  second  day,  alternating  with  fresh  liver.  The  thyroid 
showed  the  condition  of  multiple  adenoma  and  contained  4-3  milligrammes  of 
iodine  per  gramme  of  the  dry  weight.  The  difference  at  the  end  of  the  experi- 
ment between  the  thyroid-fed  and  control  tadpoles  of  the  younger  set  is  especially 
seen  in  the  atrophy  of  the  tail  and  the  appearance  of  the  hind-legs  in  the  former. 
In  the  older  set,  at  each  stage  in  the  experiment  differentiation  was  more  ad- 
vanced in  the  thyroid-fed  specimen.  This  is  still  the  case  at  the  end,  especially 
in  the  much  greater  atrophy  of  the  tail.  The  difference  is  less  than  in  the  younger 
set,  simply  because  even  the  control  is  approaching  the  end  of  the  metamor- 
phosis  (Graham). 

thence  to  the  lobe  of  the  same  side.  These  were  first  discovered  bv 
the  eflfect  produced  b^-  their  stimulation  on  the  thyroid  circulation 
time  (p.  135^     Some  evidence  of  the  existence  of  secretory  fibres  has 


ADRENALS  055 

been  brought  forward  bj-  Aslier  and  Flack.  They  compared  the  excita- 
bihty  ol  the  depressor  nerve,  and  also  the  effect  on  the  bhjod-pressure 
of  the  intra\  enoiis  injection  of  adrenalin,  before  and  during  stimulation 
of  the  thyroid  nerves.  They  conclude  that,  when  all  the  other  con- 
ditions remain  unchanged,  both  the  effect  of  excitation  of  the  depressor 
and  the  effect  of  adrenalin  are  greater  during  stimulation  of  the  thyroid 
nerves  than  shortly  before  it  without  such  stimulation.  The  difference 
is  really  connected  with  the  internal  secretion  of  the  thyroid,  since  it  is 
not  obtained  if  the  thyroids  are  previously  extirpated,  and  injection 
of  thyroid  extracts  influences  the  result  exactly  in  the  same  way  as 
stimulation  of  the  thyroid  nerves.  Similar  indirect  evidence  has  been 
obtained  bv  other  observers  (Oswald,  Lew). 

Adrenal  Bodies. — It  had  been  observed  by  Addison  that  the 
malady  which  now  bears  his  name,  and  in  which  certain  vascular 
changes,  with  muscular  weakness,  anamia.  and  pigmentation  or 
'  bronzing  '  of  the  skin,  are  prominent  symptoms,  was  associated 
with  disease,  usually  tuberculous,  of  the  adrenal  bodies,  commonly 
called  in  human  anatomy  the  '  suprarenal  capsules.'  This  clinical 
result  was  soon  supplemented  by  the  discovery  that  extirpation  of 
the  adrenals  in  animals  is  incompatible  with  life  (Brown-Sequard). 
Our  knowledge  of  the  functions  of  these  hitherto  enigmatic  organs 
was  extended  by  the  experiments  of  Oliver  and  Schafer,  who  in- 
vestigated the  action  of  extracts  of  the  adrenals  (of  calf,  sheep, 
dog,  guinea-pig,  and  man)  when  injected  into  the  veins  of  animals. 
The  arteries  are  greatly  contracted,  and  this  mainly  through  direct 
action  on  the  vaso-motor  nerve-endings  or  some  structure  inter- 
mediate between  them  and  the  smooth  muscle  of  the  vessels,  but 
parth^  through  the  vaso-motor  centre.  The  blood-pressure  rises 
rapidly,  although  the  heart  may  be  inhibited  through  the  vagus 
centre.  The  heart  is  at  the  same  time  directly  stimulated,  so  that, 
although  it  beats  slowly,  the  beats  are  stronger  than  before.  When 
the  vagi  are  cut  the  action  of  the  heart  is  markedly  augmented, 
and  the  arterial  pressure  rises  enormously  (it  may  be  to  four  or  five 
times  its  original  amount) .  Stimulation  of  the  depressor  is  of  no  avail 
in  combating  this  increase  of  blood-pressure.  The  generalization 
may  be  made  that  the  active  principle  of  the  medulla — epinephrin 
or  suprarenin,  also  called  adrenin* — acts  upon  all  plain  muscle 
and  gland-cells  that  are  supplied  with  sj'mpathetic  nerve-fibres,  and 
the  result  of  the  action,  whether  augmentation  or  inhibition,  is  the 
same  as  would  be  produced  by  stimulation  of  the  sympathetic  fibres 
going  to  the  muscle  or  gland  in  question.  Yet  it  is  not  through 
excitation  of  these  fibres  that  epinephrin  acts,  for  its  effect  is  even 
more  pronounced  when  the  nerve-fibres  have  been  caused  to  de- 
generate, in  the  case  of  the  pupillo-dilator  fibres,  e.g.,  by  excision 
of  the  superior  cer\acal  ganglion.     Nor  is  the  effect  a  direct  one  on 

*  It  is  advisable  to  restrict  the  term  '  adrenalin  '  to  the  well-known  com- 
mercial preparation  of  the  active  substance. 


656  INTERNAL  SEC RETION— ENDOCRINE  GLANDS 

the  muscular  fibres.  For  smooth  nuisclc  which  is  not,  and  never  has 
been,  in  functional  miion  willi  symi)ath(tic  nerve-fibres  is  indifferent 
to  adrenalin  (KUiott).  It  seems,  then,  to  act  on  some  structure 
intermediate  between  the  nerve  and  the  muscle, but  so  related  to  the 
latter  that  it  continues  to  live  so  long  as  it  is  in  connection  with  the 
muscle-fibre.  Instead  of  a  definite  histological  structure,  the  seat 
of  the  action  may  be  a  special  '  receptive  '  substance  at  the  myo- 
neural junction.  Thus  adrenalin  causes  marked  diminution  of 
tone  in  the  small  intestine,  with  disappearance  of  the  peristalsis 
and  pendulum  movements.  The  same  effect  is  produced  on  an 
isolated  loop  of  intestine  immersed  in  Locke's  solution,  and  the  action 
is  therefore  local.  The  drug  is  effective  in  a  dilution  of  i :  10,000,000, 
or  even  in  much  greater  dilution.  A  similar  effect  has  been  ob- 
served on  the  stomach.  The  vessels  of  the  conjunctiva  are  con- 
stricted by  local  action  when  an  extract  of  the  capsules  is  dropped 
into  the  eye,  a  fact  which  has  proved  of  value  in  ophthalmological 
practice.  Inhibition  of  the  contraction  of  the  stomach,  intestine, 
urinary  bladder,  and  gall-bladder;  contraction  of  the  uterus,  vai 
deferens,  and  seminal  vesicles ;  dilatation  of  the  pupil  and  retraction 
of  the  nictitating  membrane ;  stimulation  of  the  salivary  and  lachry- 
mal secretions,  are  among  its  actions  (Langley). 

Meltzer  has  shown  that  the  dilatation  of  the  pupil  caused  by  the 
intravenous  injection  of  adrenalin  is  distinct,  though  fleeting,  in  cats, 
less  marked  in  rabbits.  Subcutaneous  injection  has  no  effect.  Instilla- 
tion of  the  drug  into  the  conjunctival  sac  is  without  effect  on  the  pupil 
in  the  normal  rabbit's  eye,  but  causes  dilatation  if  the  superior  cervical 
ganglion  has  been  removed. 

The  influence  of  adrenalin  in  increasing  the  sugar  content  of  the 
blood,  and  thus  causing  glycosuria,  has  been  previouslj'  discussed 
(p.  550).  A  new  and  interesting  action  has  been  added  to  the  already 
long  list  of  the  effects  of  adrenalin,  by  the  discovery  that  small  doses 
(0001  milligramme  per  kilo  of  body-weight)  injected  intravenously, 
and  larger  doses  injected  subcutaneously  into  cats  shorten  the  coagula- 
tion time  of  the  blood  to  one-half  or  one-third  of  its  previous  duration, 
probably  by  stimulating  the  liver  to  greater  activity  in  discharging 
some  substance  or  substances  concerned  in  clotting  (Cannon).  The 
injection  of  adrenalin  into  the  blood  is  said  to  cause  a  temporary  im- 
provement in  the  response  to  stimulation  of  a  fatigued  muscle  still  in 
connection  with  the  circulation,  and  this  improvement  does  not  seem 
to  be  entirely  due  to  augmentation  of  the  blood  fiow  (Gruber,  Cannon 
and  Nice). 

Methods  for  the  detection  and  the  assay  of  epinephrin  in  the  small 
quantities  in  which  it  can  only  be  supposed  to  be  present  in  physio- 
logical liquids  have  been  based  upon  certain  of  these  actions.  Such, 
for  example,  is  the  extraordinary  power  of  this  active  principle  that 
a  dose  of  one-millionth  of  a  gramme  per  kilo  of  body-weight  is  suflficient 
to  cause  a  distinct  effect  upon  the  heart  and  bloodvessels  (a  rise  of 
pressure  of  14  millimetres  of  mercury)  when  injected  into  the  veins 
of  a  mammal.  The  reaction  is  rendered  more  constant,  although  less 
dehcate,  when  the  brain  is  previously  destroyed  and  the  animal  used 
as  a  spinal   preparation.     In   pithed  cats  the  assay  can  be  accurately 


ADRENALS  657 

performed  to  001  niilligranimc.  Another  delicate,  and  for  certain  pur- 
poses a  con\cnicnt,  reaction  for  the  detection  and  the  physiological 
assay  of  epincphrin  is  the  perfusion  test  on  the  legs  of  frogs  already 
alluded  to  (p.  40).  The  dilatation  of  the  pupil  in  the  excised  eyeball 
of  the  frog,  the  contraction  of  stretched  artery  rings  (p.  66),  the  increase 
in  the  tone  of  isolated  segments  of  the  uterus  of  rabbits,  and  the  diminu- 
tion in  the  tone  of  isolated  segments  of  rabbits'  intestine  (Practical 
Exercises,  p.  453),  have  also  been  employed  as  physiological  tests. 

A  dilute  solution  of  adrenalin  chloride  is  used  in  medicine  as  a  styptic, 
and*  for  reducing  congestion  in  accessible  parts.  The  intense  loc^,! 
ana'mia  which  it  causes  when  given  subcutaneously  or  by  the  mouth 
is  one  reason,  perhaps  the  most  important,  for  the  slow  absorption  on 
which  depends  the  absence  of  its  general  effects,  including  that  on  the 
blood-pressure,  when  it  is  administered  in  this  way. 

Function  of  Epinephrin.  —The  striking  effects  produced  by  adrenalin 
have  naturally  led  to  the  assumption  tliat  the  function  of  epinephrin 
in  the  body  must  be  important.  But  there  is  perhaps  no  chapter  of 
recent  physiology  in  which  the  rash  appHcation  of  qualitative  data  to 
what  is  essentially  a  quantitative  problem  has  led  to  greater  errors. 
Because  adrenalin  in  a  certain  amount  and  concentration  raises  the 
blood-pressure  when  injected  intravenously  (a  fact  certainly  of  some 
pharmacological  interest),  it  has  been  assumed  that  the  naturally 
secreted  epii:.ephrin  must  be  an  important  factor  in  the  maintenance 
of  the  normal  vascular  tone  and  arterial  pressure.  From  this  assump- 
tion it  was  only  a  short  step  to  the  announcement  that  the  blood  in 
cases  with  permanently  increased  blood-pressure  (so-called  arterial 
hypertonus,  etc.),  and  even  the  urine  contained  truly  incredible  con- 
centrations of  epinephrin.  Because  the  injection  of  what  in  proportion 
to  the  normal  output  of  epinephrin  must  be  designated  as  monstrous 
doses  of  adrenalin  causes  an  increase  in  the  sugar  of  the  blood  and  the 
appearance  of  sugar  in  the  urine,  it  has  been  supposed  by  many  that  all 
the  experimental  hyperglycaemias  and  glycosurias  (p.  547)  are  directly 
due  to  increased  liberation  of  epinephrin  from  the  adrenals.  The  fallacy 
of  giving  a  physiological  value  to  the  details  of  the  pharmacology  and 
toxicology  of  a  substance  produced  in  the  body  or  known  to  exist  in 
the  blood  in  the  absence  of  information  as  to  its  amount  and  condition 
would  have  been  very' evident  in  the  case,  for  example,  of  ammonium 
or  potassium,  and  nobody  would  have  dreamt  that  the  effects  produced 
by  massive  injections  of  ammonium  or  potassium  compounds  of  various 
kmds  would  inform  us  of  the  role  played  by  the  ammonium  and  potas- 
sium compounds  circulating  in  normal  blood.  The  whole  question  of 
the  function  of  epinephri^i  turns,  therefore,  upon  the  quantity  wh'ch 
can  possibly  be  present  in  the  systemic  arteries  or  capillaries.  Direct 
assays  of  such  blood  by  trustworthy  observers  using  the  most  delicate 
methods  available  have  hitherto  yielded  negative  results,  both  in  health 
and  in  disease.  This  is  due  to  the  great  dilution  and  rapid  removal 
or  oxidation  of  the  epinephrin  known  to  be  given  off  bv  the  adrenal 
glands. 

That  epinephrin  is  continuously  liberated  into  the  blood  from  the 
adrenals  is  readily  shown  by  tving  off  a  long  segment  of  the  inferior 
vena  cava  in  such  a  way  that  only  the  adrenal  veins  discharge  into  it. 
The  cava  pocket  is  temporarily  clipped  above  the  level  of  the  orifices 
of  the  adrenal  veins  and  allowed  to  fill  with  adrenal  blood.  When  the 
blood  is  now  released  into  the  circulation  bv  removing  the  clip,  a  rise 
of  blood-pressure  (l"ig.  208)  is  produced,  beginning  after  an  interval 
sufficient  for  the  blood  from  the  pocket  to  pass  round  to  the  systemic 
arterioles.     Another  method  is  to  'i^^crve  the  effect  of  the  released  blood 

42 


b5b 


ISTERSAL  SECRET  JON— £S  DOCRI  >J  E  GLASDS 


in  causiiig  dilatation  of  the  pupil  and  retraction  of  tlic  nictitating  mem- 
brane of  the  eye  of  a  cat  from  which  the  superior  cervical  ganglion  on 
one  side  has  been  removed  a  week  or  two  before  the  experiment.  It  is 
well  known  that  alter  this  procedure  these  reactions  are  elicited  by 
adrenalin  with  great  ease. 


Fig.  2o3.^Showiag  Spoataaeous  Liberation  of  Epiaephrin  in  a  Cat.     8  to  9,  Pockst. 
Epinephrin  rise  on  release.     Time  trace   half-minutes  (^^  reduction). 

Or  the  adrenal  vein  blood  can  be  collected  directly  from  a  cannula 
in  the  cava  pocket,  and  then  tested  on  rabbit's  uterus  and  intestine 
segments  (.Fig.  209). 


209. — Inlestinr'  Segmont  Tracings  with  Adrenal  Blood  from  a  Cat.  At  30, 
Ringer's  solution  was  replaced  hy  indifferent  (jugnlar  vein)  blood,  and  this  at  31 
by  a  specimen  of  adrenal  vein  blood  collected  during  asphyxia.  At  3^,  Ringer's 
solution  was  replaced  by  jugular  blood,  and  this  at  33  by  a  specimen  ^f  adrenal 
vein  blood  collected  previously  without  asphy.\ia.  The  bloods  were  diluted 
with  eight  volumes  of  Ringer's  solution  The  concentration  of  epinephrin  in 
the  specimens  is  seen  to  be  about  the  same.  Time,  half-minutes  (reduced  to 
two-thirds). 

The  amount  of  epinephrin  in  the  blood  can  be  as.savcd  bv  comparing 
the  effects  produced  by  it  with  those  produced  bv  known' amounts  of 
adrenalin.     In  such  ways  it  has  been  shown  that  in  cats  the  amount  of 


ADRENALS 


659 


fpiiiephrin  given  off  per  minute  varied  from  0001  milligramme  to  0002 
nulligrammc.  All  the  epinephrin  seems  to  be  contained  in  the  plasma 
and  none  in  the  corpuscles  (Figs.  210,  z  11). 


Fig.  210- — Comparison  of  Effect  of  Adrenal  Vein  Blood  and  its  Sediment  on  Rabbit's 
Intestine  Segments.  11,  Ringer  replaced  by  indifferent  blood,  and  this  at  12 
by  adrenal  vein  blood.  13,  Ringer  replaced  by  sediment  of  indifferent  blood, 
and  this  at  14  by  sediment  of  adrenal  vein  blood.  The  bloods  and  sera  were 
diluted  with  2  volumes  Ringer.    Time-trace,  half-minutes  (reduced  to  one-half). 

If  we  suppose  chat  a  cat,  weighing  25  kilos,  and  containing  200  c.c. 
of  blood  was  giving  off  0001  milligramme  of  epinephrin  per  minute,  the 
concentration  which  this  output  would  maintain  in  the  mixed  blood, 
supposing  that  there  was  no  loss  in  passing  through  the  lungs  and  up  to 
the  systemic  capillaries,  would  be  at  most  only  i ;  400,000,000  or 
1 :  500,000,000.     For  at  Ica^t  400  or  500  c.c.  of  blood  would  pass  through 


/--^^--^^     ' 

' 

lb 

/(o 

f     f      r     .'      t     f' 

T    ■»    J     i    i    til 

Fig.  211. — Effect  of  Adrenal  Blood  (16),  Serum  (15),  and  Sediment  (iS),  on  Rabbit's 
Uterus  Segment.     All  the  specimens  were  diluted  with  5  volumes  Ringer. 

the  heart  in  one  minute.  Now.  with  such  concentration.!  of  adrenalin 
no  known  reaction  has  ever  been  demonstrated  in  the  normal  intact 
animal.  Of  course,  in  the  cava  pocket  experiments  described  above, 
the  concentration  in  the  blood  will  be  much  greater  because  a  relatively 
considerable  quantity  of  epinephrin-containing  blood  is  accumulated 
in  the  pocket  and  then  suddenly  discharged. 


660  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

The  function  of  the  spontaneously  liberated  epinephrin,  once  it 
has  entered  the  circulation,  is  accordingly  involved  in  doubt.  The 
common  view  that  it  exerts  an  important  physiological  action  u]>()n 
the  sympathetic  system,  contributing  especially  to  the  maintenance 
of  the  normal  blood-pressure  is  opposed  to  all  the  best  evidence. 
Whatever  influence  the  relatively  small  quantities  of  adrenalin  dis- 
charged from  time  to  time  may  have  upon  the  nutrition  of  the  smooth 
or  of  other  muscles,  it  is  quite  unlikely  that  such  amounts  are 
continuously  entering  the  blood  as  injection  experiments  have 
shown  to  be  necessary  for  the  maintenance  of  even  a  small  excess 
of  blood-pressure.  Statements  which  connect  the  increased  blood- 
pressure  in  such  conditions  as  chronic  nephritis  with  hypertrophy  of 
the  chromaffin  tissue  (p.  665),  an  increased  adrenalin  production, 
and  an  increased  adrenalin  content  of  the  blood,  must  be  received 
with  scepticism.  The  so-called  experimental  arteriosclerosis  pro- 
duced by  repeated  injections  of  adrenahn  into  the  blood  of  rabbits 
throws  little  light  upon  the  question,  for  the  vascular  changes,  in 
so  far  as  they  have  not  been  confounded  with  similar  lesions  occur- 
ring spontaneously  in  a  considerable  proportion  of  rabbits,  differ 
from  those  observed  in  pathological  arteriosclerosis  (M.  C.  Hill). 

Certain  facts  indicate,  indeed,  that  doses  of  adrenalin  considerably 
smaller  than  those  which  give  the  effects  described  above,  and 
usually  considered  the  '  normal  '  effects,  produce  a  reversal  of  the 
reaction,  very  small  doses  causing,  for  instance,  a  diminution  of 
blood-pressure  (Moore  and  Purington),  an  increase  in  intestinal 
tonus  and  peristalsis,  and  a  diminution  in  the  tone  of  uterine  seg- 
ments. The  actions  associated  with  these  small  doses  are  more 
likely  to  be  the  normal  actions  than  those  associated  with  the 
larger  doses,  and  the  normal  action  of  adrenalin,  if  it  is  a  continuous 
action,  would  therefore  more  probably  be  to  iphibit  than  to  excite 
the  sympathetic  mechanism.  But  there  is  no  evidence  that  even 
quantities  of  this  order  of  magnitude  are  continuously  discharged. 
The  continuous  introduct'on  of  epinephrin  at  a  vvvy  slow  rate 
produces  no  demonstrable  effect  at  all,  and  tlie  sudden  ligation  of 
all  the  adrenal  blv>odvessels  has  not  the  slightest  influence  upon 
the  blood-pressure  until  the  lapse  of  a  period  far  greater  than  would 
be  required  for  the  destruction  or  removal — a  quite  rapid  process — 
of  any  epinephrin  already  present  in  the  blood  or  tissues  (Tren- 
delenburg, Hoskins).  The  injection  of  a  quantity  of  adrenahn 
sufficient  to  cause  and  to  long  sustain  even  a  minimal  increase  of 
blood-pressure  creates  conchtions  highly  hazardous  to  life  or  in- 
compatible with  it — namely,  complete  inhibition  of  the  muscula- 
ture of  the  gastro-intestinal  tract. 

The  only  cttecl  of  interference  with  the  passage  into  the  blood  of 
the  spontaneously  liberated  epinephrin  which  has  hitherto  been  demon- 
strated is  upcm  a  mechanism  rendered  abnormally  sensitive — namely, 


ADRENALS  66l 

the  iris  of  the  cat's  eye  after  removal  of  the  superior  cervical  gangUon. 
When  the  pupil  has  been  dilated  by  epinephrin,  the  dilatation  passes  otf 
sooner  if  the  adrenal  vein  blood  is  prevented  from  entering  the  circula- 
tion. This  shows  that  the  dilatation  of  the  pupil  must  have  been  in 
jiart  sustained  by  the  epinephrin  continuously  entering  the  blood  from 
the  adrenal  veins. 

The  suggestion  that  enough  epinephrin  may  be  continuously  liberated 
to  exert  an  influence  upon  the  nutrition  and  metabolism  of  the  sym- 
pathetic system,  or  of  the  myoneural  junction,  which  is  necessar\'  for 
normal  excitability,  without  ever  rising  to  the  threshold  of  actual 
excitation,  is  a  mere  hypothesis,  and  a  hypothesis  which  does  not  seem 
easily  reconciled  with  the  result  of  Hoskins,  that  after  ligation  of  the 
adrenals  the  excitability  of  the  vaso-motors  remains  absolutely  un- 
diminished. 

It  has  been  supposed  by  some  that  although  usually  liberated  in  an 
amount  too  small  to  cause  demonstrable  effects,  epinephrin  can  be  dis- 
charged at  a  greatly  increased  rate  under  certain  conditions — for 
example,  under  emotional  stress  (the  so-called  emergencv  function  of 
epinephrin).  There  is  no  evidence,  however,  that  such  outbursts 
of  epinephrin  ever  occur,  and  experimentally  it  is  by  no  means  easy 
to  produce  decided  alterations  in  the  rate  of  discharge. 

Whatever  the  function  of  epinephrin  may  be,  it  is  not  indispens- 
able for  hfe  and  health.  For  cats  after  removal  of  one  adrenal  and 
section  of  the  nerves  which  govern  tlie  epinephrin  discharge  from 
the  other,  not  only  sur\-ive  indefinitely,  but  show  no  apparent  differ- 
ences from  normal  animals,  although,  when  the  nerve  section  is  com- 
plete, no  epinephrin  can  be  detected  by  the  most  delicate  tests  in  the 
adrenal  vein  blood,  and  the  possible  concentration  in  the  arterial 
blood  cannot  at  most  amount  to  i  :  loo  thousand  millions. 

Nervous  Mechanism  Controlling  the  Liberation  of  Epinephrin. 
— The  spontaneous  liberation  of  epinephrin  from  the  adrenals  is 
entirely  dependent  upon  nerve  fibres,  reaching  the  glands  from  the 
lower  dorsal  and  upper  lumbar  portions  of  the  sympathetic  chain. 
The  splanchnics  form  the  most  important  path.  When  in  the  cat 
the  fibres  coming  to  a  semilunar  ganglion  from  the  sympathetic, 
including  the  splanchnics,  are  cut,  the  secretion  of  epinephrin  by 
the  corresponding  adrenal  into  the  blood  comes  at  once  to  an  end. 
It  is  not  resumed  when  the  animal  is  allowed  to  survive.  When 
the  peripheral  ends  of  the  cut  splanchnics  are  stimulated  electrically, 
secretion  is  caused,  and  the  amount  of  epinephrin  discharged  per 
minute  may  exceed  that  spontaneously  liberated  (Figs.  212,  213). 

This  was  first  indicated  by  the  experiments  of  Dreyer,  w^ho  col- 
lected blood  from  the  adrenal  vein  of  a  dog  during  splanchnic  stimu- 
lation, and  caused  a  rise  of  blood-pressure  in  another  dog  by  injecting 
the  blood.  The  effect  of  stimulation  of  the  splanchnic  can  be  de- 
monstrated very  clear!}'  by  the  eye  reactions  already  alluded  to. 
After  the  interval  required  for  the  blood  to  pass  from  the  adrenals 
to  the  eye,  dilatation  of  the  pupil  and  retraction  of  the  nictitating 
membrane  are  seen  to  occur.     In  this  way  it  has  been  shown  that 


662 


INTERNAL  SECRETION— ENDOCRINE  GLANDS 


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ADRENALS 


663 


the  latent  period  of  the  secretion  is  so  short  that  the  reaction  follows 
the  cumnuncemcnt  of  stimulation  of  the  nerve  after  a  time-interval 
sensibly  the  same  as  when  it  is  elicited  by  the  corresponding  amount 


.^^\^vV%^^\\'l.ViMV;Jl^wuww«*lA;J^*ww\m'*^^' 


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Pi^     .J,  _^o    Pocket  Experiment  with  Stuualatiou  wf  ^Rii^ht    Splauclinic  111  Aljd(>- 
°"  meu  after  Section  of  Both  Splanchiiics.     21,  repetition  of  20,  but  with  a  shorter 
time  of  stimulation.     The  epiuephrin  rise  of  blood-pressure  after  20  is  consider- 
ably greater  than  after  21.     Time-trace,  hali-miuutes  (| reduction). 

of  adrenahn  injected  at  the  level  of  th?  adrenal  veins.  Even  when 
the  glands  have  ceased  to  respond  to  stimulation  of  the  nerves, 
epinephrin  can  still  be  liberated  into  the  blood  by  massaging  the 
ff'mds  with  the  fingers  (Fig.  214). 


-^.v.«^,'■•''''''••"■■■'■''»*'■■Vv^v^w^v.,.ww,,,^^^^^ 


Ficr  .T.— Showing  the  Effect  of  Massage  in  Liberating  Epinephrin  from  the  Left 
Adrenal  whose  Nerves  had  been  Cut  Five  Weeks  before.  27,  cava  pocket  wi  h 
massage,  the  left  adrenal  vein  being  open  to  the  pocket.  47  to  49,  POcket  with 
massage  the  left  adrenal  vein  having  been  closed  at  45  and  opened  at  48,  after 
dosure  of  the  pocket.  Massage  begun  at  45-A,  stopped  at  46.  Blood-pressure 
tracing  from  carotid  artery.     Time-trace,  half-minutes  (reduced  to  t). 

A  centre  for  epinephrin  secretion  seems  to  exist  in  the  upper  part 
of  the  thoracic  region  of  the  spinal  cord.  After  section  of  the  cord 
in  the  cervical  region,  even  as  low  as  the  level  of  the  last  cer\acal 
segment,  the  secretion  persists,  but  it  is  abolished  when  the  cord  is 
di\nded  at  the  third  or  fourth  dorsal  segment. 


o64  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

The  relation  of  the  nervous  system  to  the  adrenal  medulla  has  been 
further  illustrated  by  comparison  of  the  amount  of  epinephrin  which 
can  be  extracted  from  the  two  adrenals  when  the  nerves  of  one  have  been 
cut.  Under  the  influence  of  anaesthetics  and  some  other  drugs,  bac- 
terial toxins,  such  as  diphtheria  toxin,  etc.,  the  epinephrin  store  is 
markedly  diminished  in  the  gland  whose  nerve  supply  has  been  left 
intact  as  compared  with  the  other. 

For  example,  in  a  cat  the  fibres  coming  from  the  sympathetic  to  the 
left  semilunar  ganglion,  including  the  left  splanchnic  nerves,  were  cut, 
and  the  animal  allowed  to  recover.  Several  days  later  when  it  is  kno^n 
that  equality  of  epinephrin  load  in  the  two  adrenals  would  have  been 
restored,  morphin  was  administered  to  the  animal,  and  after  a  few 
hours  it  was  killed,  and  the  epinephrin  in  the  adrenals  assayed.  The 
left  gland  contained  028  milligramme,  the  right,  01 1  milligramme.  If 
the  animal  had  been  suddenly  killed  without  morphin,  the  two  ac'.renals 
would  have  been  found  to  contain  equal  amounts  of  epinephrin.  There- 
fore the  deficiency  in  the  right  gland  must  have  been  due  to  the  fact 
that  it  was  not  protected  by  section  of  its  nerves. 

A  similar  deficiency  has  been  found  in  the  unprotected  gland  aftei 
administration  of  a  drug,  /3-tetrahydronaphthylamine,  after  surgical 
operations  (post-operative  deficiency),  and  in  many  other  conditions. 
When  the  animal  recovers  the  deficiency  is  gradually  made  good,  the 
adrenal  having  the  power  of  forming  and  storing  epinephnn  up  to  a 
cc  tain  point  in  the  absence  of  its  nerve  supply,  although  it  is  unable 
to  liberate  it  into  the  blood. 

There  is  no  foundation  for  the  statement  that  emotional  disturb- 
ances, as  fright  or  anger,  cause  a  depletion  of  the  epinephrin  store  of  the 
adrenals. 

Summary  : — The  existence  of  a  nervous  mechanism  through  which 
the  gland  is  stimulated  to  secrete  epinephrin  info  the  blood  can  there- 
fore be  considered  as  definitely  established.  It  is  the  function  of  the 
epinephrin,  once  it  has  entered  the  circulation  that  is  involved  in  doubt. 
Although  it  is  highly  improbable  that  the  concentrations  necessary  for 
direct  stimulation  of  sympathetic  endings  ever  e.xist  in  the  general  mass 
of  the  blood,  it  is  quite  possible  that  a  '  sensitizing  '  influence  is  exerted 
by  epinephrin  upon  the  sympathetic  peripheral  mechanisms  which 
renders  them  more  susceptible  to  nerve  impulses  originating  in  other 
wavs.  The  possibility  of  a  more  direct  action  of  epinephrin  upon  the 
chemistry  of  carbo-hydrate  metabolism,  particularly  upon  glycogenolysis 
or  even  upon  glycogen  formation  has  been  emphasized  by  some  writers. 
But  glycogen  can  be  formed  abundantly,  and  certain  experimental 
hvperglyccBmias  which  depend  upon  the  rapid  transformation  of 
glycogen  into  dextrose  can  be  produced  after  the  epinephrin  secretion 
of  the  adrenals  has  been  abolished. 

Chemistry  and  Formation  of  Adrenalin  .—It  has  been  shown  (Stolz. 
Dakin)  that  adrenalin  (CgHjgXOg)  is  a  dioxyphenyl-ethauol-methy- 
lamin, 

CH 
OH.C/\C.CH(OH).CH,NH.CH, 

!       ! 

OH.C\/CH 
CH 


ADRENALS  665 

It  has  been  prepared  synthetically,  and  in  the  body  appears  to  be 
formed,  probably  by  the  introduction  of  a  methyl  (CHg)  group,  from 
a  compound  arising  from  an  aromatic  amino-acid  (tyrosin  or  phenyl- 
alanin).  While  the  natural  adrenalin  rotates  the  plane  of  polarization 
to  the  left,  the  artificial  substance  is  optically  inactive.  This  is  because 
it  consists  of  equal  parts  o."  laevo-rotatory  and  dextro-rotatory  adrenalin. 
The  artificial  adrenalin  has  approximately  half  the  effect  of  the  natural 
on  the  blood-pressure,  from  which  it  may  be  inferred  that  the  dextro- 
rotatory isomer  has  only  a  very  slight  j^ressor  effect.  1  he  left  and  right 
rotatory  moieties  have  been  separated.  The  former  has  exactly  the 
same  power  of  raising  the  blood-pressure  as  the  natural  adrenalin,  the 
latter  only  yV,-  to  j^.  as  mvich.  Practically  the  same  proportion  holds 
when  the  power  of  the  two  isomers  in  producing  glycosuria  is  compared. 
This  constitutes  important  corroboration  of  the  view  already  referred 
to  (p.  550),  that  adrenalin  glycosuria  is  caused  by  an  action  on  the 
sympathetic  system,  for  the  effect  on  the  blood-pressure  is  known 
to  be  thus  produced  (Cushny). 

It  is  in  the  medulla  of  the  adrenals  that  the  epinephrin  is  formed. 
The  medullary  cells  contain  a  substance  which  gives  a  yellow  or  brown 
stain  with  chromic  acid  or  chromates,  and  for  this  reason  the  cells  are 
called  chromaffin  or  chromaphil.  Similar  cells  are  found  elsewhere  in 
the  body — e.g.,  within  the  sympathetic  ganglia,  and  also  strung  out 
in  clumps  along  the  course  of  the  abdominal  aorta  below  the  level  of 
the  adrenal  glands  (Vincent).  These  outlying  masses  of  chromaffin 
tissue  appear  to  contain  epinephrin,  or  a  substance  with  similar  physio- 
logical actions,  so  that  the  formation  of  this  compound  seems  to  be  a 
property  common  to  chromaphil  tissue,  no  matter  what  its  situation 
may  be.  A  remarkable  fact,  and  one  calculated  to  induce  caution 
in  assigning  a  physiological  function  to  epinephrin,  is  that  the  so-called 
parotid  gland  of  a  Jamaican  toad  secretes  it  in  a  concentration  not 
much  short  of  5  per  cent.  (Abel). 

Function  of  the  Adrenal  Cortex. — The  function  of  the  cortical  cells  is 
obscure,  but  there  is  evidence  that  they,  and  not  the  chromaffin  cells 
of  the  medulla,  are  concerned  in  the  production  of  the  internal  secretion, 
whatever  its  nature  may  be,  the  loss  of  which  leads  so  speedily  to  death 
on  removal  of  the  adrenals.  For  example,  the  period  of  survival  after 
this  operation  is  practically  unaffected  by  the  continuous  intravenous 
administration  of  adrenalin,  although  the  loss  of  the  medulla  might 
be  supposed  to  be  compensated  in  this  way.  Still  more  convincing 
is  the  fact  already  referred  to  that  after  removal  of  one  adrenal  and 
denervation  of  the  other  in  cats,  epinephrin  ceases  to  be  discharged 
in  detectable  amount,  and  yet  the  animal  survives  in  good  health.  In 
Addison's  disease  adrenalin  is  likewise  powerless. 

The  weakness  (asthenia)  of  the  skeletal,  and  to  some  extent  of  the 
cardiac,  musculature  which  is  characteristic  of  Addison  s  disease,  is 
produced  experimentally  within  a  few  hours  by  ligation  of  both  adrenals, 
and  all  the  evidence  goes  to 'show  that  it  is  the  cortical  and  not  the 
medullary  region  which  is  related  to  this  disease.  When  the  adrenals 
are  not  completely  extirpated,  compensatory  hypertrophy  of  the  re- 
maining portions  may  occur,  and  the  animal  survive  indefinitely.  In 
such  cases  it  has  been  found  that  the  hypertrophy  is  confined  to  the 
cortex. 

In  animals  like  the  rabbit  in  which  accessory  adrenals  are  not  un- 
common, when  these  are  present  complete  removal  of  both  adrenals 
does  not  cause  death.  Now,  the  accessory  adrenals  consist  of  cortical 
substance  without  medulla.  Portions  of  the  adrenal  are  readily- 
grafted  under  the  skin,  but  only  the  cortex  survives  and  grows. 


666  TNTERWAL  SF.CRETTOS'—EXDOCRTXr.  CI  AXDS 

The  functional  difference  between  cortex  and  medulla  is  easily  under- 
stood when  we  reflect  that  the  morphological  history  of  the  two  tissues 
is  (^uite  different.  The  medulla  is  developed  from  cells  which  push 
their  way  into  the  gland  from  the  rutlim  jnts  of  the  sympathetic  ganglia 
at  that  level,  and  is  therefore  of  cctodermic  origin.  The  cortex  is 
(.lerived  from  the  same  mesodermic  structure  which  gives  rise  to  the 
kidneys  and  genital  organs. 

Embryologicallv,  the  cortical  cells  are  related  to  the  interstitial  cells 
of  the  ovaries  and  of  the  testes,  and  like  these  are  characterized  by  their 
richness  in  lipins  (or  lipoids).  There  is  some  evidence  of  an  inter- 
relation between  the  thyroid  and  all  these  groups  of  sex  cells  (interstitial 
cells  of  ovary  and  testes,  cortex  of  adrenal).  Removal  of  a  large  part 
of  the  adrenals  in  the  rabbit  causes  slight  though  defuiite  hypertrophy 
of  the  thyroid  and  lymphoid  hyperplasia.  This  is  also  seen  in 
Addison's  (li>eHse  in  man. 


^f^^ 


^^'>'    Pituitary  Body  or  Hypophysis.— In  the  pituitary  body  two  parts 

r^d-y^' essentially  different  in  origin  and  function  may  be  distinguished: 

^  V^Ov  (^)  The  large  anterior  lobe,  or  pars  anterior,  consisting  of  epithehal 

?9^    9\^  cells,  many  of  whicli  are  filled  with  granules  of  the  type  seen  in 

^trf  -i^  glandular  epithelium,  and  abundantly  provided  with  bloodvessels; 

^  (2)  the  smaller  posterior  or  ner\ous  lobe,   or  pars   nervosa,   also 

called  the  infundibular  portion,  consisting  chiefly  of  neuroglia,  the 

whole  connected  with  the  floor  of  the  third  ventricle  by  a  stalk 

called  the  infundibulum. 

A  further  subdivision  of  the  epithelial  portion  is  made  into  the 
anterior  lobe  proper  and  the  pars  intermedia  or  intermediate  lobe,  con- 
sisting of  epithelial  cells,  less  granular  and  less  richly  supplied  with 
bloodvessels  than  those  of  the  pars  anterior.  Ttie__pars  intermrdia 
forms  an  epithelial  investment  of  the  pars  nervosa,  almost  completely 
surrounding  it  and  throwing  out  offshoots  of  epithelial  cells  into  its 
substance,  which  is  also  invaded  by  colloid  material  secreted  by  the 
cells  of  the  intermediate  lobe.  The  differences  in  the  structure  of  the 
anterior  and  posterior  lobes  of  the  pituitary  body  correspond  to  a 
difference  in  their  development.  The  anterior  lobe  is  developed  (in 
man  in  the  fourth  week  of  intra-uterine  life)  from  an  ectodermal  pouch 
(Kathke's  pouch),  which  is  pushed  up  from  the  roof  of  the  bucco- 
pharyngeal cavity  towards  the  mid-brain.  The  posterior  lobe  is 
developed  from  an  extension  of  the  neural  ectoderm,  which  grows  back- 
wards as  the  infundibular  process  till  it  meets  and  blends  with  that 
portion  of  the  buccal  pouch  which  gives  rise  to  the  pars  inic  media. 
The  pars  intermedia  is  separated  from  the  anterior  lobe  proper  by  a 
cleft  which  represents  what  is  left  of  the  lumen  of  Kathkc's  pouch. 
In  connection  with  the  interpretation  of  the  results  of  exjx^riments  on 
removal  of  the  pituitary  body,  it  is  of  consequence  to  remember  that 
a  residue  of  the  same  epithelium  which  develops  into  the  anterior  lobe 
appears  always  to  get  cut  off  in  the  vault  of  the  pharynx,  constituting 
the  so-called  pharyngeal  hypophysis,  and  consisting  of  a  cord  of  cells 
identical  with  those  of  the  anterior  lolie  (Haberfeld).  Kmbryonic 
'  rests  '  of  hypophyseal  tissue  are  also  often  found  in  the  dura  of  the 
sella  turcica,  in  which  the  pituitary  body  lies,  and  in  the  body  of  the 
sphenoid  bone.  Cells  of  the  intermediate  lolx>  also  run  up  the  stalk 
of  the  infundibulum,  and  even  stretch  for  a  little  distance  along  the 
floor  of  the  third  ventricle.     Add  to  this  the  formidable  nature  of  the 


operations  required  for  the  extirpation  of  the  hypophysis  from  its 
sheltered  position  within  the  skull,  and  it  will  not  be  wondered  at  that 
complete  liarmonv  has  not  been  attained  as  to  the  ccjnsequences  of  its 
removal.     The  best  evidence  at  present  is  to  the  following  effect: 

When  the  pituitary  body  is  completely  removed,  death  speedily 
and  in\ariably  ensues,  in  clogs,  on  the  average  within  twenty-four 
to  forty-eight  hours.  Puppies  often  live  as  long  as  two  or  three 
weeks.  The  mucii  longer  periods  of  survival  occasionally  witnessed 
are  due  to  failure  to  remove  some  small  portion  of  the  hypophyseal 
epithehum.  On  the  day  after  the  operation  the  animals  may  be 
able  to  walk  about,  to  eat  and  drink,  and  may  show  an  interest  in 
their  surroundings.  The  temperature,  pulse,  and  respiration  at 
this  time  may  be  normal.  Soon,  however,  they  become  lethargic, 
then  comatose,  with  characteristically  incurved  spine,  slow  respira- 
tion, with  long-drawn  inspiration,  a  feeble  pulse,  perfectly  hmp 
muscles,  and  often  a  subnormal  temperature,  and  the  appearance 
of  sugar  in  the  urine.  This  deep  coma  passes  into  death,  wdth  no 
perceptible  transition,  and  without  a  struggle  (Paulesco,  Gushing). 
The  ablation  of  a  part  of  the  cortical  substance  of  the  anterior 
(epithelial)  lobe  of  the  hypophysis  is  compatible  with  permanent 
surxival,  and  gives  rise  to  no  symptom  of  disorder.  The  same  is 
true  when  only  the  posterior  lobe  is  removed.  This  does  not  seem 
to  be  followed  by  an3^  recognizable  symptoms.  In  some  animals, 
however,  kept  under  observation  for  long  periods  after  partial 
removal  of  the  anterior  lobe,  a  marked  tendency  to  accumulate 
fat  has  been  noted,  accompanied  by  hypoplasia  of  the  generative 
organs  in  adults  or  the  persistence  of  the  infantile  condition  in 
immature  animals.  On  the  other  hand,  complete  removal  of  the 
anterior  lobe  causes  death,  just  as  if  the  whole  gland  had  been 
taken  away.  Of  all  the  structures  included  in  the  pituitary  body, 
the  most  important  from  the  functional  point  of  view  appears  to  be 
the  superficial  layer  of  the  anterior  lobe. 

Mere  separation  of  the  stalk  of  the  hypophysis  may  produce 
effects  sometimes  as  serious  as  those  of  total  removal  of  the  gland, 
probably  o\^'ing  to  the  disturbance  caused  in  the  circulation.  It  is 
stated,  indeed,  by  some  observers  that  the  vulnerable  point  is  the 
base  of  the  infundibulum,  and  that  if  this  is  not  injured  extirpation 
of  the  hypophysis  is  not  incompatible  with  continued  existence, 
and  that  in  adult  animals  the  resultant  changes  are  only  shght, 
although  much  more  pronounced,  especiallv  as  regards  the  disturb- 
ances in  metabolism  and  development  in  young  animals.  It  has 
been  asserted  that  the  pituitary  undergoes  (compensatory  ?)  hyper- 
trophy after  thyroidectom5^  Some  observers  have  accordingly 
assumed  a  similarity  of  function  for  these  organs.  It  has  even  been 
stated  that  the  production  of  colloid  material  bv  the  cells  of  the  pars 
intermedia   is    increased,    and    that    colloid    accumulates    in    the 


568  INTERNAL  SECRETION— ENDOCRINE  GLANDS 

nervous  portion  of  the  posterior  lobe.  But  this  colloid,  whatever 
its  function  may  be,  is  very  different  from  that  of  the  thyroid 
aheoU,  for  the  (sheep's)  pituitary  contains  no  iodine  after  extir- 
pation of  the  thyroid  any  more  than  before  (Simpson  and 
Hunter).  And  in  man  pathological  changes  (tumours)  in  the 
pituitary  body  are  associated,  not  with  myxoedcma,  or  other 
disease  connected  with  changes  in  the  thyroid,  but  frequently  with 
another  condition,  called  acromegaly,  in  which  the  bones  of  the 
limbs  and  face,  especially  the  hands  and  feet  and  the;  lower  jaw, 
become  hypertrophied. 

Another  condition  often  associated  with  tumours  of  the  pituitary- 
is  gigantism — a  condition  occurring  before  the  normal  growth  of 
the  bones  is  completed,  and  resulting  in  a  great  increase  in  the 
length  of  the  bones  both  in  the  limbs  and  the  trunk. 

Action  of  Intravenous  Injection  of  Extracts  of  the  Pituitary. — 
The  effects  on  the  vascular  system  of  intravenous  injection  of 
extracts  of  the  pituitary  gland  are  also  very  different  from  those 
caused  by  thyroid  extracts.  The  posterior  lobe,  or  infundibular 
body,  including  the  pars  intermedia,  contains  two  active  substances, 
one  pressor  and  the  other  depressor.  The  former  is  soluble  in  salt 
solution,  but  insoluble  in  absolute  alcohol  and  ether;  while  the 
latter  is  soluble  in  salt  solution  as  well  as  in  alcohol  and  ether.  The 
pressor  substance  (obtained  in  fairty  pure  form  in  the  preparation 
called  pituitrin,  and  in  still  greater  concentration  in  a  preparation 
to  which  the  name  hypophysin  has  been  given)  causes  a  rise  of 
blood -pressuie,  due  partly  to  constriction  of  the  arterioles  and 
partly  to  an  increase  in  the  force  of  the  heart-beat,  both  of  which 
are  brought  about  by  direct  action.  This  rise  of  pressure  lasts  for 
a  considerable  time,  and  is  sometimes  accompanied  by  a  slowing 
of  the  heart.  A  second  dose  injected  before  the  effect  of  the  first 
has  passed  off  is  inactive;  and  this  distinguishes  the  pituitary  from 
the  suprarenal  extract.  Associated  with  the  pressor  effect  is  an 
increase  in  the  flow  of  the  urine.  Whether  this  is  due  to  a  separate 
diuretic  substance,  as  some  maintain,  has  not  been  definitely  settled. 

Indeed,  the  factors  on  which  the  diuretic  action  depends  are 
complex,  and  sometimes  in  spite  of  an  increase  of  general  arterial 
pressure,  and  of  the  volume  of  the  kidney,  there  is  no  increased  flow  of 
urine.  In  diabetes  insipidus  pituitrin  has  been  found  to  produce  pre- 
cisely the  opposite  effect — namely,  diminution  in  the  excessive  urinarv 
flow.  The  pressor  substance,  unlike  adrenalin,  directly  stimulates 
smooth  muscle  fibres  (especially  the  arteries,  uterus,  and  spleen)  irrespec- 
tive of  their  innervation  ^Dale). 

Many  other  points  of  difference  exist  between  the  pressor  principles 
of  the  infundibular  body  and  the  adrenal  medulla.  For  example, 
pituitrin  constricts  the  pupil  and  diminishes  the  flow  of  saliva  from  the 
submaxillary  gland,  whereas  adrenalin  dilates  the  pupil  and  causes  an 
increased  flow  of  saliva.  Hypophy.sin  and  other  preparations  of  the 
posterior  lobe  have  been  employed  to  stimulate  the  uterine  contractions 
in  obstetrical  practice,  but  their  use  does  not  seem  to  be  free  from 


i^'l 


^/s 


669 


danger.  When  injected  intramuscularly,  regular  and  powerful  con- 
tractions of  the  uterus  are  excited  in  two  or  three  minutes  at  any  stage 
in  parturition.  Another  effect  of  extracts  of  the  infundibular  body  is 
on  the  mammary  gland.     An  increased  flow  of  milk  follows  the  injec- 


Pig.  215. — Action  of  Extract  of  Infundibular  Lobe  (Pars  Nervosa  of  Ox  Pituitaiy). 
P,  Carotid  pressure;  K,  kidney  volume;  U,  drops  of  urine;  S,  signal  showing  point 
at  which  pituitary  extract  was  injected;  T,  time-trace  in  lo-second  intervals. 
T  is  also  the  zero  of  the  blood-pressure  (Hering). 

tion  of  pituitrin  (Simpson).  But  it  is  in  doubt  whether  this  is  due  to 
increased  secretion  and  not  solely  to  stimulation  of  the  smooth  muscle 
of  the  organ  with  expulsion  of  milk  already  formed.  The  depressor 
substance  produces  a  marked  fall  of  blood-pressure,  even  when  it  is 
injected  during  the  rise  of  pressure  caused  by  an  injection  of  the  pressor 


Fig.  216. — Action  of  Extract  of  Hypophyseal  Lobe  of  Pituitary  on  the  Blood- Pressure 
(W.  VV.  Hamburger).  The  signal  line  at  the  top  shows  the  time  and  length  of 
injection  of  the  saline  extract  into  the  blood.  Time-trace  (at  bottom)  shows 
second  intervals.     The  figure  is  to  be  read  from  left  to  right. 

substance.  The  anterior  lobe,  or  hypophysis,  also  contains  a  depressor 
substance.  Intravenous  injection  of  a  sahne  extract  causes  a  distinct 
fall  of  blood-pressure,  accompanied  usually  by  acceleration  and  weaken- 
ing of  the  heart  (Fig.  216).  A  second  injection  immediately  following 
the  first  produces  no  change  in  the  pressure  (W.  W.  Hamburger). 


070  INTERNAL  SECRET tON— ENDOCRINE  GLANDS 


An  active  substance  which  lias  l)ccn  termed  '  tcthehn,'*  because  of  its 
influence  on  growth,  has  been  separated  from  the  anterior  lolx>.  On 
intravenous  injection  into  rabbits,  it  causes  a  slight  fail  of  blood  pres- 
sure and  rto  diuresis.     Its  eriects  are  therefore  quite  different  from  those 

of  the  posterior  lobe.  Mixefl  with  the  food 
of  mice,  it  has  lieen  fountl  to  exert  a  charac- 
teristic influence  upon  their  growth,  retarfl- 
ing  it  at  certain  stages,  and  accelerating  it 
"1  at  other  stages  (Robertson). 

It  is  not  at  present  possible  to  deduce 
from  such  clinical  and  experimental 
observations  as  those  described  any  co- 
herent theory  of  the  function  of  the 
pituitary.  That  there  is  some  connection 
between  the  normal  action  of  the  gland, 
and  in  particular  of  its  interior  lobe,  and 
the  normal  growth  and  nutrition  of  the 
body,  including  the  skeleton,  is  scarcely 
to  be  doubted.  The  fact  that  administra- 
tion of  the  dried  gland  substance  to  dogs 
causes  an  increased  excretion  of  calcium 
on  a  diet  rich  in  calcium  is  a  further 
indication  of  its  influence  on  the  meta- 
bolism of  bone  (Malcolm).  But  so  far 
is  the  precise  nature  of  this  influence,  if 
it  exists,  from  being  fully  understood, 
that  authorities  of  repute  are  still  divided 
on  the  question  whether  the  symptoms 
of  acromegaly  and  gigantism  are  due  to 


iniiimiiimiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 
30' 

Fig.  217. — Action  of  hifundi- 
bular  Extract  upon  Virfjiii 
Uterus  of  Guinea- Pig.  Tlie 
same  dose  was  applied  three 
times  in  succession  to  an  iso- 
lated segment,  at  the  points 
marked  by  the  arrows  at 
the  bottom  of  the  curves. 
After  each  application  the 
segment  was  washed  with 
Ringer's  solution  at  R.  The 
tracings  have  been  made  to 
overlap.  (Reduced  to  one- 
half.)     (Dale.) 


atrophy  or  to  hypertrophy  of  the  active 
elements  of  the  gland,  to  loss  of  its  internal  secretion,  or  to  its 
manufacture  in  excessive  amount.  There  is  evidence  that  the 
colloid  secretion  of  the  posterior  lobe,  probably  formed  by  the 
epithelial  cells  of  the  pars  intermedia,  passes  through  the  nerxous 
portion  to  enter  the  infundibulum  and  the  third  ventricle  of  the  brain, 
where  it  breaks  down  in  the  cerebro-spinal  fluid  (Hering).  And 
it  has  been  suggested  that  in  virtue  of  the  action  of  the  hormones 
(p.  404)  in  this  secretion  on  the  vascular  system  in  general,  and  on 
the  renal  cells  and  the  renal  circulation  in  particular,  the  posterior 
lobe  constitutes  a  mechanism  for  the  control  of  the  secretion  of  urine. 
But  this  suggestion  is  still  in  the  realm  of  h\pot  liesis.  Some  support 
is  given  to  it  by  the  observation  that  continued  irritation  of  the 
posterior  lobe  by  a  plug  of  the  gutta-percha  compound  used  by 
dentists  for  temporarily  filling  teeth  introduced  through  the  floor 
of  the  sella  turcica  caused  permanent  polyuria  in  dogs,  analogous 
to  the  diabetes  insipidus  seen  in  man  (Matthews). 
*  i'l'om  Ti$i]\ws,  growing,  tiounshing. 


^ 


671 


Pineal  Gland. — Extracts  of  the  pineal  gland  injected  into  the  circula- 
tion have  10  citcct  other  than  that  due  to  the  inorganic  constituents 
of  the  calcareous  concretions  or  '  brain  sand,'  which  are  its  cliaractcr- 
istic  feature.  Since  in  early  life  the  organ  has  a  glandular  structure 
which  is  later  replaced  bv  librous  tissue,  it  has  been  supposed  that  it 
may  exercise  some  function  in  connection  with  growth.  But  so  far 
the  physiology  of  the  pineal  body  is  practically  a  blank  sheet,  or,  at 
best,  a  budget  of  contradictory  statements  from  which  nothing  certain 
can  be  deduced.  Thus  in  two  of  the  niost  recent  papers,  each  based 
on  a  large  number  of  carefid  experimeiLs,  one  author  concludes  that 
removal  of  the  gland  in  male  guinea-pigs  is  associated  with  hastened 
development  of  the  sexual  organs,  and  ni  females  with  a  tendency  to 
breed  earlier  than  the  normal  conti'ols  (Horrax).  The  other  observer 
finds  that  feeding  young  guinea-pigs  with  pineal  tissue  from  young 
animals  determines  an  earlier  sexual  maturity  than  normal,  and  in- 
creases the  rate  of  growth  of  the  body  (McCord). 

The  alleged  influence  of  the  invasion  of  the  gland  in  young  children 
by  pathological  growths  in  accelerating  the  development  of  the  skeleton 
and  reproductive  organs,  which  has  been  supposed  to  indicate  that  it 
normally  exerts  a  restraining  or  regulative  influence  on  this  develop- 
ment, is  at  present  purely  fanciful. 

Kidney. — The  experiments  of  Bradford,  which  seemed  to  indicate 
that  the  kidney,  in  addition  to  its  function  as  an  excretory  organ,  plays 
an  important,  and  indeed  indispensable,  part  in  protein  metabolism, 
possibly  by  forming  something  of  the  nature  of  an  internal  secretion. 


1-ig.  218.— Effect  of  b.me-.Marrow  on  Blood-Prcs.^uie.  Intravenous  Injection  of 
Saune  Extract  V  ag.  Intact.  The  uppermost  line  is  a  signal  trace  showing  the 
time  and  lenglli  ot  nijection.  Below  this  is  the  record  of  the  respirai  -v  move- 
ments, and  lowest  the  blood-pressure  tracing.     To  be  read  from  leii  10  right. 

have  not  been  confirmed.  He  stated  that,  when  the  half  or  two-thirds 
of  one  kidney  and  the  whole  of  the  other  have  been  removed  from  a 
dog  by  successixe  operations.,  death  ensues,  although  the  quantity  both 
of  water  and  urea  excreted  by  the  fragment  of  renal  substanc'e  that 
remains  is  far  above  the  normal.  In  spite  of  the  increased  elimination 
of  urea,  that  substance  was  said  to  accumulate  in  the  tissues  showin- 
that  the  destruction  of  protein  was  increased-a  conclusion  which 
seemed  to  derive  support  from  the  wasting  of  the  animal.  It  has  since 
been  shown  that  an  increased  output  of  nitrogen  is  not  of  constant 
occurrence,  and  only  takes  place  under  the  same  condii  ons  a  m 
starvation  (p.  603).     As  a  matter  of  fact,  the  animals  waste  and  d"e 


67 J  IXTERXAL  SECRETION— ENDOCRINE  GLANDS 

within  a  few  days  or  weeks  largely  t>ecaiisc  they  refuse  to  eat.  Polyuria 
(increase  of  urine  beyond  the  normal)  does  not  necessarily  occur.  It 
is  well  known  that,  when  only  one  kidney  is  extirpated  the  other  hyjjer- 
trophios,  and  no  ill-effects  ensue. 

The  statement  that  extracts  of  the  kidney  when  injected  into  the 

veins  of  an  animal  cause  a  rise  of  arterial  blood-pressure,  essentially 

through  direct  action  on  the  peripheral  vaso-motor  mechanism,  is  of 

considerable  interest,  for  it  may  possibly  have  some  bearing  on  the  rise 

of  pressure  and  consequent  hypertrophy  of  the  heart  associated  with 

certain  renal  diseases.     But  there  is  not  as  yet  sufficient  evidence  that 

the   hv]iothctical   pressor  sub.-itance,   to  which  the  name   '  renin  '  has 

been  given,  in  anv  sense  represents  an  internal  secretion  of  the  kidney. 

^L^^^  The    pressor    substance    (so-called 

^d||PW||L  '  urohypertensine  ')   which  can  be 

J0r  Tk  extracted    by   ether    from    normal 

,^Jr  \  human  urine  (Abelous)  is  probably 

^laL^gfr  \|  only  excreted  by  the  kidney,  and 

PIP^^  ^^    »».«A      perhaps  arises  from  the  putrefac- 

\jM|N  ^''^*"   "^  proteins  in   the  intestine. 

^^  lor  it  has  been  shown  that  in  the 

putrefaction  of  fhorse-^  meat  bases 

•"^MJM^^iW^^  unraveS.llv,^'cause^'a"    riie'^ol 

_^ , ■■ blood-pressure.      The  most  active 

Fig.  219.— Injection  ol  Extract  of  Bone-  of  these  is  a  body  known  as 
Marrow  with  the  Vagi  Cut.  To  be  read /J-hydroxyphenylethylamine, 
from  left  to  right.  formed  from  tyrosin   (Barger  and 

Walpole).  Whether  the  pressor 
(vaso-constrictor)  substance  which  appears  to  be  liberated  from  the 
platelets  when  blood  is  shed,  and  may  therefore  be  presumed  to  be  more 
slowly  liberated  from  such  platelets  as  normally  break  down  in  the 
circulating  blood,  has  any  relation  to  the  pressor  substance  of  urine 
is  unknown.  It  is  also  quite  uncertain  whether,  as  has  been  stated  by 
some  observers,  extracts  of  the  kidney  or  blood  from  the  renal  vein 
stave  off  for  a  time  the  onset  of  the  uraemic  symptoms  that  follow 
removal  of  both  kidneys  or  ameliorate  them  when  they  have  already 
appeared. 

Spleen. — The  spleen  does  not  produce  an  internal  secretion 
necessary  to  life,  for  it  can  be  removed  both  in  animals  and  in 
man,  without  the  development  of  serious  symptoms.  Its  blood- 
forming  and  blood-destroying  functions  (p.  22)  are  taken  on  by 
other  structures  (particularly  the  red  bone-marrow). 

The  most  definite  changes  following  splenectomy  are  transient 
anaemia,  increased  resistance  to  haemolytic  agents,  and  an  increase 
in  the  content  of  cholesterol  in  the  blood  (Pcarce).  These  effects 
are  more  pronounced  in  the  young.  This  is  intclHgible  if  the  spleen 
normally  plays  a  considerable  part  in  the  destruction  of  worn-out 
erythrocytes  with  liberation  of  hiemoglobin,  the  source  of  the  bile- 
pigment.  The  formation  of  the  bile-pigment  is  said  to  be  inter- 
fered with,  and  its  amount  reduced  by  more  than  50  per  cent. 
(Pugliese). 

The  spleen  can  be  auto-transplanted  readily  into  the  subcutaneous 
tissues  of  animals.     There  is  a  great  difference  in  the  behaviour  of 


f>7^ 

such  transplants  according  to  the  age  of  the  animal  (Marino  and 
Manley).  In  young  rabbits,  the  transplants  grow  rapidly  if  the 
spleen  is  removed  at  the  time  of  transplantation,  while  in  sexuallv 
mature  rabbits  they  do  not  grow  and  often  undergo  gradual  absorp- 
tion. Likewise,  transplants  which  have  grown  rapidly  in  young 
animals  decrease  in  size  after  adult  life  is  reached,  indicating  that 
the  function  of  the  spleen  is  more  necessary  in  young  than  in  older 
animals ;  or  that  its  function  is  more  easily  and  completely  assumed 
by  other  tissues,  probably  the  bone  marrow,  in  adults.  A  further 
and  very  suggestive  fact,  is  that  a  subcutaneous  spleen  graft  which 
has  '  taken,'  but  is  not  growing,  in  a  young  animal  whose  spleen  has 
not  been  removed,  can  be  made  to  grow  by  removal  of  the  spleen. 
These  results  indicate  that  splenic  insufficiency  is  a  necessar}^  con- 
dition of  growth  of  a  splenic  transplant,  just  as  thyroid  insufficiency 
is  a  necessary  condition  of  growth  of  a  thyroid  transplant.  The 
stimulus  to  growth  in  the  one  case,  as  in  the  other,  must  be  assumed 
to  be  a  chemical  stimulus  transmitted  through  the  blood,  and  not 
dependent  upon  the  nervous  system. 

The  salivary  glands  may  be  extirpated  without  any  sensible  change 
being  produced  in  the  normal  metabolism.  It  has  been  stated  how- 
ever, that  the  secretion  of  the  gastric  juice  is  diminished.  It  has  been 
supposed  that  this  may  be  due  to  the  absence  of  a  hormone  (p.  404) 
normally  produced  in  the  salivary  glands.  A  temporary  increase  in 
the  gastric  secretion  is  said  to  be  caused  when  extracts  of  the  glands 
of  normal  dogs  are  injected  into  the  veins  or  into  the  peritoneal  cavitv 
of  dogs  deprived  of  their  salivary  glands  (HemmiCter).  But  later 
experiments  contradict  the  theorv  r;f  the  existence  of  a  hormone  in  the 
salivary  glands,  which  stimulates  the  secretion  of  gastric  juice.  The 
average  rate  of  secretion  into  a  Pawlow  gastric  pouch  (p.  403)  was  not 
diminished  in  dogs  after  extirpation  of  the  glands  (Swanson.) 

Extracts  of  nervous  tissue  (sciatic  nerve,  white  matter  of  brain,  and 
spinal  cord,  but  especially  grey  matter  of  brain)  cause,  on  injection  into 
the  veins,  a  decided  fall  of  arterial  blood-pressure,  which  soon  passes 
off,  and  can  he  renewed  by  a  fresh  injection.  The  fall  of  pressure  is 
due  to  direct  action  upon  the  bloodvessels  of  a  depressor  substance  in 
the  extracts,  and  not  to  the  action  of  vaso-motor  nerves.  It  can  be 
obtained  after  section  of  the  vagi. 

Extracts  of  muscular  tissue  also  cause  a  distinct  though  transient 
fall  of  pressure,  but  not  so  great  a  fall  as  in  the  case  of  extracts  of 
nervous  tissue.  Saline  decoctions  of  other  tissues  (testis,  kidney, 
spleen,  pancreas,  liver,  mucous  membrane  of  stomach  and  intestine, 
lung,  and  mammary  gland)  all  produce  a  fall  of  blood-pressure  (Osborne 
and  Vincent).  The  same  is  true  of  bone  marrow  (Brown  and  Guthrie; 
Figs.  218,  219).  It  must  be  repeated  that  there  is  no  evidence  that 
these  depressor  substances  are  specific  internal  secretions  in  the  same 
sense  as  epinephrm. 


43 


CHAPTER    XTI 

ANIMAL  HEAT 

From  the  earliest  ages  it  must  have  been  noticed  that  the  bodies  of 
many  animals,  and  particularly  of  men,  are  warmer  than  the  air 
and  than  most  objects  around  them.  The  '  vulgar  opinion  '  of 
Bacon's  time,  '  that  fishes  are  the  least  warm  internally,  and  birds 
the  most,'  if  it  does  not  imply  a  very  extensive  knowledge  of  animal 
temperature,  at  least  shows  that  the  fundamental  distinction  of 
warm  and  cold-blooded  animals,  which  is  to-day  more  accurately 
expressed  as  the  distinction  between  animals  of  constant  tempera- 
ture (homoiothermal)  and  animals  of  variable  temperature  (poikilo- 
thermal),  had  been  grasped,  and  was  even  popularly  known.  Since 
that  time  the  accumulation  of  accurate  numerical  results,  and  the 
advance  of  physical  and  physiological  doctrine,  have  given  us 
definite  ideas  as  to  the  relation  of  animal  heat  to  the  metabohc 
processes  of  the  body.  It  is  impossible  to  understand  the  present 
position  of  the  subject  without  an  elementary  knowledge  of  the 
science  of  heat.  For  this  the  student  is  referred  to  a  textbook  of 
physics.  All  that  can  be  done  here  is  to  preface  the  physiological 
portion  of  the  subject  by  a  few  remarks  on  the  physical  methods  and 
instruments  employed: 

Section  I. — Thermometry  and  Calorimetry. 

Temperature. — Two  bodies  are  at  the  same  temperature  if,  when 
placed  in  contact,  no  exchange  of  heat  takes  place  between  them. 
They  are  at  different  temperatures  if,  on  the  whole,  heat  passes  from 
one  to  the  other,  and  that  body  from  which  the  heat  passes  is  at  the 
higher  temperature.  It  is  known  by  experiment  that  if  two  bodies  of 
different  temperature  are  placed  in  contact,  heat  will  pass  from  one  to 
the  other  till  they  come  to  have  the  same  temperature.  If,  then,  we 
have  the  means  of  finding  out  the  temperature  of  any  one  body,  we 
can  arrive  at  the  temperature  of  any  other  by  placing  the  t^^-o  in  con- 
tact for  a  sufficiently  long  time,  under  the  proviso  that  the  quantity  of 
heat  necessary  to  bring  the  temperature  of  the  first  body,  which  may  be 
called  the  '  measuring  '  body,  to  equality  with  that  of  the  second  is  so 
small  as  not  to  make  a  sensible  difference  in  the  latter.  This  is  the 
principle  on  which  thermometric  measurements  depend.  A  mercurial 
thermometer  consists  of  a  quantity  of  mercur\'  ordinarily  contained  in 
a  thin  glass  bulb,  the  cavity  of  which  is  continued  into  a  tube  of  very 

674 


THERMOMETRY  AND  CALORIMETRY  675 

fine  bore  in  the  stem.  Like  most  other  substances,  mercury  expands 
when  the  temperature  rises,  and  contracts  when  it  sinks,  and  the  amount 
of  expansion  or  contraction  is  shown  by  the  rise  or  fall  of  the  mercurial 
column  in  the  stem  of  the  thermometer.  The  point  at  which  the 
meniscus  stands  when  the  bulb  is  immersed  in  melting  ice  or  ice-cold 
water  is,  on  the  centigrade  scale,  taken  as  zero ;  the  point  at  which  it 
stands  when  the  thermometer  is  surrounded  by  the  steam  rising  from 
a  vessel  of  boiling  water  is  taken  as  100  degrees.  The  intermediate 
portion  of  the  stem  is  divided  into  degrees  and  fractions  of  degrees. 
When,  now,  we  measure  the  temperature  of  any  part  of  an  animal  with 
such  a  thermometer,  we  place  the  bulb  in  contact  with  the  part  until 
the  mercury  has  ceased  to  rise  or  fall.  We  know  then  that  the  mercury 
has  ceased  to  expand  or  contract,  and  therefore  that  its  temperature 
is  stationary,  and  presumably  the  same  as  that  of  the  part.  It  is  to 
be  noted  that  we  have  gained  no  information  whatever  as  to  the  amount 
of  heat  in  the  body  of  the  animal.  We  have  only  observed  that  the 
mercury  of  the  thermometer  when  its  temperature  is  the  same  as  that 
of  the  given  part  expands  to  an  extent  marked  by  the  division  of  the 
scale  at  which  the  column  is  stationary.  And  we  know  that  if  the 
mercury  rises  to  the  same  point  when  the  thermometer  is  applied  to 
another  part,  the  temperature  of  the  latter  is  the  same  as  that  of  the 
first  part ;  if  the  mercury  rises  higher,  the  temperature  is  greater ;  if 
not  so  high,  it  is  less.  The  thermometer,  then,  only  informs  us  whether 
heat  would  flow  from  or  into  the  part  with  which  it  is  in  contact  if 
the  part  were  placed  in  thermal  connection  with  any  other  body  of 
which  the  temperature  is  known.  In  other  words,  the  temperature  is 
a  measure  of  the  heat  '  tension,'  so  to  speak;  and  difference  of  tempera- 
ture between  two  bodies  is  analogous  to  difference  of  potential  between 
the  poles  of  a  voltaic  cell  (p.  724),  or  to  difference  of  level  between  the 
surface  of  a  mill-pond  and  the  race  beiow  the  wheel. 

The  temperature  of  an  animal  is  measured  in  one  of  the  natural 
cavities,  as  the  rectum,  vagina,  mouth,  or  external  ear,  or  in  the  axilla, 
or  at  any  part  of  the  skin.  For  the  cavities  a  mercury  thermometer 
is  nearly  always  used ;  the  ordinarj^  little  maximum  thermometer  is  most 
convenient  for  clinical  purposes.  The  temperature  of  the  skin  may  be 
measured  by  an  ordinary  mercury  thermometer,  the  outer  portion  of 
the  bulb  of  which  is  covered  by  some  badly  conducting  material.  An 
uncovered  thermometer,  heated  nearly  to  the  temperature  expected, 
will  also  give  results  sufficiently  accurate  for  most  purposes,  especially 
if  the  bulb  is  flat  or  in  the  form  of  a  flat  spiral,  which  can  be  easily 
applied  to  the  surface.  A  theoretically  better  method,  but  more 
laborious  in  practice,  is  the  use  of  a  thermo-electric  junction,  or  a  resist- 
ance thermometer  formed  of  a  grating  cut  out  of  thin  lead-paper  or  tin- 
foil (Fig.  220).  This  is  especially  useful  for  comparing  the  temperature 
of  two  portions  of  skin .  The  temperature  of  the  solid  tissues  and  liquids 
of  the  body  may  also  be  measured  or  compared  by  the  insertion  of  mer- 
curial or  resistance  thermometers  or  thermo-electric  junctions  (p.  764). 

Calorimetry. — The  quantity  of  heat  given  off  by  an  animal  is  generally 
measured  by  the  rise  of  temperature  which  it  produces  in  a  known 
mass  of  some  standard  substance.  Sometimes,  however,  as  in  the  ice- 
calorimeter  of  Lavoisier  and  Laplace,  and  the  ether  calorimeter  of 
Rosenthal,  a  physical  change  of  state — in  the  one  case  liquefaction  of 
ice,  in  the  other  evaporation  of  ether — is  taken  as  token  and  measure 
of  heat  received  by  the  measuring  substance,  the  number  of  imits  of 
heat  corresponding  to  liquefaction  of  unit  mass  of  ice  or  evaporation  of 
unit  mass  of  ether  being  known.  The  unit  generally  adopted  in  the 
measurement  of  heat  is  the  quantity  required  to  raise  the  temperature 


r.76 


ANIMAL  HEAT 


G 


of  a  kilogramme  of  water  1°  C,  which  is  called  a  calorie,*  or  kilocalorie 
or  large  calorie.  The  thousandth  part  of  this,  the  quantity  needed  to 
raise  the  temperature  of  a  gramme  of  water  by  1°,  is  termed  a  small 
calorie  or  millicalorie  or  gramme-calorie. 

In  the  calorimeters  which  have  been  chiefly  used  in  physiology  either 
water  or  air  has  been  taken  as  the  measuring  substance.  The  simplest 
form  of  water  calorimeter  is  a  box  with  double  walls,  the  space  between 
whi'  h  is  filled  with  a  weighed  quantity  of  water.  The  animal  is  placed 
inside  the  vessel,  and  the  temperature  of  the  water  notetl  at  the  begin- 
ning and  end  of  the  experiment.  Suppose  that  the  quantity  of  water 
is  10  kilos,  and  that  the  temperature  rises  1°  in  thirty  minutes,  then  the 
amount  of  heat  lost  by  the  animal  is 
ID  calories  in  the  half -hour,  or  480 
calories  in  the  twenty-four  hours;  and 
if  the  rectal  temperature  is  unchanged, 
this  will  also  be  the  amount  of  heat 
produced. 

Here  we  assume  (i)  that  all  the  heat 
lost  by  the  animal  has  gone  to  heat  the 
water  and  none  to  heat  the  metal  of  the 
calorimeter;  (2)  that  none  has  been 
radiated  away  from  the  outer  surface  of 
the  latter.  The  first  assumption  will 
seldom  introduce  any  sensible  error  in  a 
prolonged  physiological  experiment ;  but 
it  is  very  easy  to  determine  by  a  separate 
observation  the  water-equivalent  of  the 
calorimeter — that  is,  the  quantity  of 
water  whose  temperature  will  be  raised  i  ° 
by  a  quantity  of  heat  which  just  suffices 
to  raise  the  temperature  of  the  metal  by 
1°  (p.  721).  Then  the  water-equivalent 
is  added  to  the  quantity  of  water  actu- 
ally present,  and  the  sum  is  multiplied  by 
the  rise  of  temperature.  If  the  tempera- 
ture of  the  room  is  constant,  as  will  be 
approximately  the  case  in  a  cellar,  any 
error  due  to  interchange  of  heat  between 
the  calorimeter  and  its  surroundings  may  be  eliminated  by  making  the 
initial  temperature  of  the  water  as  much  less  than  that  of  the  air  as  the 
final  temperature  exceeds  it.  Then  if  the  loss  of  heat  by  the  animal  is 
uniform,  as  much  heat  is  gained  during  the  first  half  of  the  experiment 
by  the  calorimeter  from  the  air  as  is  lost  by  it  to  the  air  during  the  last 
half.  Or,  without  lowering  the  temperature  of  the  water,  the  amount 
of  heat  lost  by  the  calorimeter  during  an  experiment  may  be  previously 
determined  by  a  special  observation,  and  added  to  the  quantity  cal- 
culated from  the  observed  rise  of  temperature.  Or,  finally,  two  similar 
calorimeters  may  be  used,  one  containing  the  animal  and  the  other  a 
hydrogen  flame,  or  a  coil  of  wire  traversed  by  a  voltaic  current,  which 
is  regulated  so  as  to  keep  the  temperature  the  same  in  the  two  calorim- 
eters. From  the  quantity  of  hydrogen  burnt,  or  electricity  passed, 
the  heat-production  of  the  animal  can  be  calculated. 

In  Atwater's  great  respiration  calorimeter  (Fig.  221)  both  the  heat 
production  and  the  respiratory  exchange  are  measured.  The  heat  pro- 
duced by  the  person  in  the  calorimeter  is  carried  away  from  it  by  a 

*  The  student  should  carefully  note  that  when  the  term  '  calorie '  is  used 
without  qualification,  a  large  calorie,  i.e.,  1,000  gramme-calories,  is  meant. 


w 

Fig.  220. — Resistance  Thermom- 
eter for  measuring  Temperature 
of  Skin.  G,  grating  of  lead- 
paper,  attached  to  a  cover -slip, 
and  mounted  on  a  holder;  W, 
W,  wires  to  the  Wheatstone's 
bridge.  An  increase  of  tem- 
perature causes  an  increase  in 
the  resistance  of  the  lead.  The 
balance  of  the  bridge  is  thus  dis- 
turbed. By  experimental  grad- 
uation the  temperature  value 
of  the  deflection,  or  of  the  change 
of  resistance  that  balances  it,  is 
known  (p.  725). 


THERMOMETRY  ASf)  CALORIMETRY 


677 


stream  of  water  nowinf^  tlirou^h  llic  c  li.unl)cr  in  a  scries  of  tubes,  the 
temperature  within  the  calorimeter  beiiiK  kept  constant  by  regulating 
the  temperature  and  vch)city  of  the  entering  stream  of  water.  The 
quantity  of  the  escaping  water  and  tlie  increase  in  its  temperature  are 
measured,  and  the  heat-prochiction  can  tlien  be  calculated.  The 
apparatus  consists  of  a  chamber  in  wlucii  a  human  being  can  liv^c  for 
several  days  and  nights.  A  stream  of  air  is  supplied,  and  the  chemical 
changes  produced  in  this  arc  investigated  in  the  manner  already 
described  (p.  J 40). 


Fig-  -21- — Respiration  Calorimeter  (Atwater).  Interior  of  chamber.  A  corner  (f 
the  inner  copper  wall  is  supposed  to  be  taken  away.  The  ventilating  air-current 
enters  the  chamber  at  the  lower  end  of  W,  and  leaves  the  chamber  through  the- 
long  tube  fastened  above  W.  The  copper  tubes  H,  H  are  surrounded  by  copper 
discs  I,  I,  fastened  on  them  like  a  string  of  beads  to  increase  the  surface.  These 
tubes  constitute  the  arrangement  through  which  the  stream  of  water  flows  which 
removes  the  heat  formed  in  the  chamber.  J,  J  are  copper  troughs  which  receive 
the  water  dropping  from  H,  H.  M,  .M,  M  are  electrical  thermometers  which  show 
the  temperature  of  the  chamber;  N,  N,  similar  thermometers  which  show  the 
temperature  of  the  copper  wall. 


This  calorimeter,  improved  in  various  ways,  has  served  as  the  model 
for  all  subsequent  constructions  used  for  calorimetrical  studies  in  man. 
A  large  amount  of  work  of  fundamental  importance,  both  on  normal 
and  diseased  persons,  has  already  been  carried  out,  especially  by  Bene- 
dict and  by  Lusk  with  their  numerous  co-workers,  and  our  quantitative: 
knowledge  of  the  energy  transformations  in  the  body  has  been  notably 
extended. 


678 


AXIMAL  HEAT 


All  the  modern  respiration  calorimeters  permit  the  direct  estimation 
not  only  of  the  carbon  dioxide  produced,  but  also  of  the  oxygen  con- 
sumed. This  allows  the  amount  of  heat  to  be  calculated  indirectly 
(so-called  indirect  calorimetry),  as  well  as  measured  directly.  For  if  we 
know  how  much  of  the  oxygen  taken  in  goes  to  oxidize  protein,  fat  and 
carbohydrates,  respectively,  we  can  calculate  the  amount  of  heat  pro- 
duced in  the  body  with  a  given  consumption  of  oxygen.  The  amount  of 
protein  oxidized  is  easily  obtained  from  the  nitrogen  excretion.  The 
respiratory  quotient  (corrected  for  the  influence  of  the  protein  meta- 
bolized) informs  us,  with  certain  limitations,  as  to  the  proportions  of  fat 


Fig.  222. — Qinical  Respiration  Calorimeter.  The  patient  is  shown  on  the  Led  half 
way  in.  The  tube  of  a  stethoscope  strapped  over  the  heart  is  seen.  Coiled  up 
on  the  wall  is  the  (electric  resistance)  rectal  thermometer  not  yet  inserted.  To 
the  right  of  this  is  shown  a  telephone  for  communicating  with  the  patient  if 
necessary  (Lusk,  et  al-)- 

and  carbohydrates  being  consumed.  Thus,  a  respiratory  quotient  of 
070  represents  the  oxidation  of  fat  alone,  a  quotient  of  i-oo  the  oxida- 
tion of  carbohydrate  alone  (p    241). 

If  the  respiratory  quotient  is  intermediate  between  these  extremes — 
e.g.,  0-85,  it  would  represent  the  oxidation  of  fat  and  carbohydrate  in 
such  a  proportion  that  49  per  cent,  of  the  number  of  calories  produced 
are  due  to  the  burning  of  carbohydrate,  and  51  per  cent,  to  the  oxidation 
of  fat.  With  this  respiratorv  quotient,  the  absorption  of  1  litre  of 
oxygen  would  indicate  that  4,^63  gram-calories  had  t^en  produced  in  the 
b©dy.     In  a  similar  way  the  amount  of  heat  produced  can  be  calculated, 


THERMOMETRY  AND  CALORIMETRV 


670 


although  in  general  with  less  accuracy,  from  the  amount  of  carbon 
dioxide  given  off.  With  careful  technifjue,  the  results  obtained  by 
indirect  agree  closely  with  those  obtained  by  direct  calorimetry,  which 
is  tantamount  to  saying  that  the  law  of  conservation  of  energy  holds 
in  the  animal  body  (Rubner). 

Air  calorimeters  have  sometimes  been  used  for  physiological  pur- 
poses, but  at  present  they  have  little  more  than  historical  interest. 
A  diagram  of  one  is  shown  in  Fig.  223.  Such  calorimeters  are  really 
thermometers  with  an  immense  radiating  surface,  for  only  a  small 
proportion  of  the  heat  given  off  by  the  animal  goes  to  heat  the  measuring 
substance.  The  heat  required  to  raise  the  temperature  of  a  litre  of  air 
by  1°  is  very  small  in  comparison  with  that  required  to  raise  the  tern- 


Fig.  223. — Air  Calorimeter:  (/.)  Cross-Section;  (//.),  Longi- 
tudinal Section.  A,  cavity  of  calorimeter  for  animal  ;  B,  copper 
cylinder  corrugated  so  as  to  increase  the  radiating  surface;  C,  air 
space  enclosed  between  B  and  a  concentric  copper  cylinder  F  ; 
C  is  air-tight,  and  is  connected  by  the  tube  2  with  the  manometer  M.  The 
other  end  of  the  manometer  is  connected  with  an  exactly  similar  calorimeter,  in 
which  a  hydrogen  flame  is  burnt  in  the  space  corresponding  to  A,  or  in  which  the  air 
in  A  is  heated  by  a  coil  of  wire  traversed  by  an  electrical  current.  The  flame  or 
current  is  regulated  so  as  to  keep  the  coloured  petroleum  or  mercury  in  the  manometer 
M  at  the  same  level  in  both  limbs;  the  amount  of  heat  given  off  to  the  one  calorimeter 
by  the  flame  or  current  is  then  equal  to  that  given  off  by  the  animal  to  the  other. 
D  is  an  external  cylinder  of  copper  or  tin  perforated  by  holes  (6,  7)  at  intervals.  The 
purpose  of  it  is  to  prevent  draughts  from  affecting  the  loss  of  heat  from  F;  4,  5,  are 
tubes  through  which  thermometers  can  be  introduced  into  C;  i  is  the  terminal  of  a 
spiral  tube,  which  is  coiled  in  the  end  portion  of  the  air  space  C.  The  sections  of  the 
coils  are  indicated  by  small  circles.  The  other  end  of  the  spiral  tube  is  3;  through 
this  tube  air  is  sucked  out,  and  so  the  proper  ventilation  of  the  animal  is  kept  up. 
The  object  of  the  spiral  arrangement  is  that  the  air  aspirated  out  of  A  may  give  up 
its  heat  to  the  air  in  C  before  passing  out.     E  is  a  door  with  double  glass  walls. 


perature  of  a  litre  of  water  by  the  same  amount.  Hence  a  given 
quantity  of  heat  raises  the  temperature  of  an  air  calorimeter  much  more 
than  that  of  a  water  calorimeter  of  the  same  dimensions ;  and  the  loss 
of  heat  to  the  surroundings  being  proportional  to  the  elevation  of  tem- 
perature, in  the  water  calorimeter  the  chief  part  of  the  heat  is  actuallv 
retained  in  the  water,  while  in  an  air  calorimeter  the  greater  portion 
passes  through  the  air  space,  and  is  radiated  away.  When  the  amount 
of  heat  lost  by  the  calorimeter  becomes  equal  to  that  gained  from  the 
animal,  the  '  steady  '  reading  of  the  instrument  is  taken,  and  from  this 
the  heat-production  can  be  deduced  by  an  experimental  graduation  of 
the  apparatus.  The  one  advantage  of  an  air  calorimeter  is  that  it 
follows  more  closely  rapid  variations  in  th«   heat-production  of  th« 


68o  AXJMAL  1 1  LAV 

animal,  or,  to  spc.iU  more  conccUy,  in  the  heat  loss.  It  .should  be 
carefully  noted  that  in  calorimctry  what  is  directly  measured  is  the 
(}uantity  of  heat  fj;i\en  out  by  the  animal,  not  the  quantity  produced. 
The  t\vo(juantities  are  identical  only  when  the  temperature  of  the  animal 
has  remained  unchanged  throughout  the  experiment.  If  the  tempera- 
ture has  fallen,  the  quantity  of  heat  produced  is  equal  to  the  quantity 
measured  by  the  calorimeter  minus  the  difference  between  the  quantity 
in  the  animal  at  the  beginning  and  at  the  end  of  the  observation.  This 
difference  is  equal  to  the  average  specific  heat  of  the  animal  multiplied 
by  its  weight  and  by  the  fall  of  temperature.  It  can  Ije  approximately 
found  by  multiplying  the  weight  (in  kilogrammes  or  grammes)  by  the 
fall  of  rectal  temperature  (in  degrees),  since  the  average  specific  heat 
of  the  body  is  not  \'ery  difficult  from  that  of  water,  and  the  specific 
heat  of  water  is  taken  as  unity. 

The  diticrential  micro-calorimeter  of  A.  \'.  Hill  Is  the  most  accurate 
apparatus  for  measurjug  \cry  small  quantities  of  heat — e.g.,  the  heat 
given  off  by  resting  muscles,  or  by  muscles  during  the  process  of  heat 
rigor,  or  in  such  reactions  as  the  souring  of  milk  by  the  lactic  acid 
bacillus.  It  consists  of  a  pair  of  Dewar  flasks  (ordinary  thermos  oi 
vacuum  bottles),  in  which  loss  of  heat  to  the  surroundings  is  greatly 
hindered  by  exhausting  the  air  from  the  space  enclosed  by  the  double 
wall  of  the  flask.  The  bottles  are  packed  in  sawdust  in  cylindrical  tins. 
The  tissue  or  liquid  experimented  with  is  put  into  one  flask,  and  water 
into  the  other  (control)  flask,  and  the  amount  of  the  water  is  adjusted 
so  that  the  change  of  temperature  of  each  flask  due  to  conduction  and 
radiation  to  or  from  the  outside  is  the  same.  Loss  of  heat  is  thus 
automaUcally  eliminated,  and  from  the  excess  of  temperature  of  the 
experimental  over  that  of  the  control  flask  the  heat  production  in  the 
former  can  be  calculated.  The  temperatures  are  measured  by  thermo- 
electric junctionsof  an  alloy  called  constantan  and  copper,  one  junction 
being  in  each  flask.  To  economize  time  in  making  such  observations, 
a  number  nf  pairs  of  flasks  can  be  simultaneously  employed.  The 
apparatus  is  so  sensitive  that  a  liberation  in  ten  hours  of  i  gramme- 
calorie  per  gramme  of  contents  of  the  flask  can  be  followed  and  esti- 
mated with  an  error  not  exceeding  3  per  cent. 

Body-Temperature. — All  the  higher  aninials  (mammals  and  birds) 
have  a  practically  constant  internal  temperature  (fowl  41°  to  44°  C, 
mouse  37*^  to  '^^°,  dog  38°  to  39°,  man  37°  in  the  rectum),  but  a  few 
hibernating  mammals,  such  as  the  marmot,  are  homoiothermal  in 
summer,  poikilothermal  during  their  winter  sleep.  In  the  lower 
forms  the  body-tem])erature  follows  closely  the  temperature  of  the 
environment,  and  is  never  very  much  above  it  (frog  0-5°  to  2°  above 
external  temperature).  Both  in  a  frog  and  in  a  pigeon  heat  is 
evolved  as  long  as  life  lasts;  but  per  unit  of  weight  the  amphibian 
produces  far  less  than  the  bird,  and  loses  far  more  readily  what  it 
does  produce.  The  temperature  of  the  frog  may  be  25°  C.  in  June 
and  5°  in  January.  The  structure  of  its  tissues  is  unaltered,  and 
their  vitality  unimpaired  by  such  violent  fltictuations.  But  it  is 
necessary,  not  only  for  health,  but  even  for  life,  that  the  internal 
temperature  (the  temperature  of  the  blood)  of  a  man  should  vary 
only  within  relatively  narrow  limits  around  the  mean  of  '^y'^  to 
38°  C. 


INCOME  AND  EXPENDITURE  OF  THE  BODY  68 1 

Why  it  is  that  a  comparatively  high  temi^erature  slio'ild  be 
needed  for  the  full  physiological  activity  of  the  tissues  of  a  mammal, 
while  the,  in  many  respects,  similar  tissues  of  a  ftsh  work  perfectly, 
although  perhaps  more  sluggishly,  at  a  much  lower  temperature,  is 
not  quite  clear.  Nor  do  we  know  the  precise  significance  of  that 
relative  constancy  of  temperature  in  the  warm-blooded  animal, 
which  is  as  important  and  peculiar  as  its  absolute  height.  The 
higher  animals  must  possess  a  superior  delicacy  of  organization, 
hardly  revealed  by  structure,  which  makes  it  necessary  that  they 
should  be  shielded  from  the  shocks  and  jars  of  varying  temperature 
that  less  highly  endowed  organisms  endure  with  impunity.  Leaving 
the  discussion  of  the  local  differences  and  periodic  variations  of  the 
temperature  of  warm-blooded  animals  to  a  future  page,  let  us 
consider  now  the  mechanism  by  which  the  loss  of  heat  is  adjusted 
to  its  production,  so  that  upon  the  whole  the  one  balances  the  other. 

Section  II. — Income  and  Expenditure  of  the  Body  in  Terms 

OF  Energy. 

Heat-Loss. — Heat  is  lost  (i)  from  the  surfaces  of  the  body  by 
radiation,  conduction,  and  convection;  (2)  as  latent  heat  in  the 
watery  vapour  given  off  by  the  skin  and  lungs;  and  (3)  in  the 
excreta.  Even  in  the  bulky  excrement  of  herbivora  a  compara- 
tively trifling  part  of  the  total  heat  is  lost.  The  second  channel 
of  elimination  is  much  more  important;  the  first  is  in  general  the 
most  important  of  all. 

The  loss  of  heat  by  direct  radiation  from  a  portion  of  the  skin  or 
clothes,  or  from  hair,  fur,  or  feathers  covering  the  skin,  may  be  measured 
by  means  of  a  thermopile  or  a  resistance  radiometer  (bolometer).  Tlie 
latter  instrument  is  similar  in  principle  and  allied  in  construction  to  the 
resistance  thermometer  used  in  measuring  superficial  temperatures, 
and  already  described  (Fig.  220,  p.  676).  It  may  consist  of  a  grating 
of  lead-paper  6r  tinfoil  fixed  vertically  in  a  small  box  which  protects 
it  from  draughts.  The  box  has  a  sliding  lid,  which  is  kept  closed  till 
the  moment  of  the  observation,  when  it  is  withdrawn  and  the  portion 
of  skin  applied  to  the  opening  at  a  fixed  distance  (5  to  10  cm.)  from  the 
grating.  The  intensity  of  radiation  depends  on  the  excess  of  tempera- 
ture of  the  radiating  surface  over  that  of  the  surroundings,  as  well  as 
on  the  nature  of  the  surface.  The  uncovered  parts  of  the  skin  (face 
and  hands  in  man)  radiate  more  per  unit  of  area  than  the  clothes  or 
hair;  and  the  warm  forehead  mare  than  the  comparatively  cool  lobe 
of  the  ear  or  tip  of  the  nose.  When  a  man  is  sitting  at  rest  in  a  still 
atmosphere,  pure  radiation  plays  a  greater,  and  conduction  and  con- 
vection play  a  smaller,  part  in  the  total  loss  of  heat  from  the  skin  than 
when  he  is  walking  about  or  sitting  in  a  draught.  The  more  rapidly 
the  air  in  contact  with  the  skin  and  clothes  is  renewed,  the  lower,  other 
things  being  equal,  the  temperature  of  the  radiating  surfaces  is  kept, 
the  greater  is  the  loss  of  heat  by  conduction  to  the  adjacent  portions  of 
air,  and  the  smaller  the  loss  by  radiation  to  the  walls  of  the  room,  the 
furniture,  and  other  surrounding  objects.     It  is  probable  that,  under 


6^7 


ANIMAL  HEAT 


the  moot  favourable  conditions,  the  amount  of  heat  lost  from  the  sur- 
face by  true  radiation  does  not  exceed  the  amount  lost  by  conduction 
and  convection. 

The  loss  of  heat  by  evaporation  of  water  from  the  skin  can  be  calcu- 
lated if  we  know  the  quantity  of  water  so  given  off.  For  a  gramme  of 
water  at  the  ordinary  temperature  (say  15°  C.)  needs  0-555  calorie  to 
convert  it  into  aqueous  vapour  at  the  average  temperature  of  the  skin. 
If  we  take  the  average  quantity  of  water  excreted  as  sweat  in  twenty- 
four  hours  as  750  c.c,  this  will  be  equivalent  to  a  heat-loss  of  416*25 — 
say,  in  round  numbers,  400  larg^  calories. 

The  quantity  of  heat  given  off  by  the  lungs  may  be  also  deduced 
from  calculation,  the  data  being  (i)  the  weight,  temperature,  and 
specific  heat  of  the  expired  air,  and  (2)  the  excess  of  water  it  contains 
in  the  form  of  aqueous  vapour  over  that  contained  in  the  inspired  air. 
Helmholtz  calculated  the  quantity  of  heat  needed  to  warm  the  air 
expired  by  a  man  in  twenty-four  hours  from  an  initial  temperature  oi 
20°  to  body-temperature,  at  70  calories,  and  that  required  to  evaporate 
the  water  given  off  by  the  lungs  at  397,  making  the  total  heat-loss  by 
the  lungs  in  these  processes  from  400  to  500  calories.  A  certam  amount 
of  heat  is  also  absorbed  in  connection  with  the  escape  of  the  carbon 
dioxide.  The  reason  why  a  great  deal  more  water  and  therefore  more 
heat  is  not  given  off  by  the  lungs  with  their  enormous  surface,  and  the 
high  degree  of  imbibition  (p.  426)  of  the  epithelium  of  the  alveoli,  is 

Fig.  224. — Calorimeter  for 
Measuring  Heat  given  off  in 
Respiration.  B,  copper  tube 
with  mouthpiece,  connected  with 
the  thin  brass  capsule  4;  4  is 
connected  with  a  similar  capsule 
3  by  a  short  tube,  which  passes 
out  from  it  at  the  side  opposite 
to  that  at  which  B  enters;  2  and 
I  are  similar  capsules.  From  i 
an  outlet  tube  C  passes  off. 
The  whole  is  set  in  a  copper 
cylinder  A  filled  with  water. 
A  piece  is  supposed  to  be  cut  out 
of  .\  in  order  to  show  the  cap- 
sules. A  is  placed  in  another 
wider  copper  cylinder. 

that  the  air  is  already  saturated  with  aqueous  vapour,  or  nearly  so, 
before  it  reaches  the  alveoli.  By  direct  calorimetric  observations  it 
was  found  that  a  man  of  70  kilos  weight  gave  off  in  normal  breathing, 
with  an  air-temperature  of  12°  to  15°  C,  from  350  to  450  calories. 
Forced  respiration,  as  might  be  expected,  increased  the  amount  often 
to  double  or  even  treble.  A  diagram  of  a  calorimeter  for  measuring 
the  heat  given  off  in  respiration  is  shown  in  Fig.  224.  (Se«  Practical 
Exercises,  p.  721) 

The  following  table  gives  an  analysis  of  the  heat-loss  of  an  average 
man.  It  must  be  understood  that  the  figures  are  only  approximate. 
In  round  numbers  we  may  say  that  two-thirds  of  the  heat-loss  is 
due  to  radiation,  conduction,  and  convection,  and  one-third  to  the 
evaporation  of  water. 


INCOME  AND  EXPENDITURE  OF  ENERGY  G83 


(Evaporation  of  water 
Radiation*     -         -         -         - 
Conduction  (and  convection) 
_  I  Evaporation  of  water     - 

l-ungs|p^^^^^g  the  expired  air  - 

Heating  the  excreta 


Per  Cent. 

Calories 

25     '      80 
40    J 

400 

650 

1,000 

%]     .7-5 

.400 
I    70 

2-5 

70 

2 


590 


In  the  rabbit,  according  to  Nebelthau,  the  heat  lost  by  evaporation 
of  water  is  about  16  per  cent,  of  the  whole,  or  about  half  the  proportion 
in  man,  according  to  the  above  calculation.  This  is  not  surprising 
when  we  reflect  that  the  rabbit  does  not  sweat,  and  drinks  comparatively 
little  water. 

Sources  of  the  Heat  of  the  Body — Heat  Production. — Some  heat 
enters  the  body  as  such  from  without — in  the  food,  and  by  radiation 
from  the  sun  and  from  fires.  The  ultimate  source  of  all  the  heat 
produced  in  the  body  is  the  chemical  energy  of  the  food  substances. 
For  this  reason,  the  distinction  between  much  of  the  subject  matter 
of  this  chapter  and  that  of  Chapter  X.  is  scarcely  even  a  formal 
one.  Whatever  intermediate  forms  this  energy  may  assume— 
whether  the  mechanical  energy  of  muscular  contraction;  the  energy 
of  electrical  separation  by  which  the  currents  of  the  tissues  are 
produced;  the  energy  of  the  nerve  impulse;  or  the  energy,  be  it 
what  it  may,  which  enables  the  living  cells  to  perform  their  chemical 
labours — it  all  ultimately,  except  so  far  as  external  mechanical 
work  may  be  done,  appears  in  the  form  of  heat.  As  already  pointed 
out  (p.  544),  the  fraction  of  the  total  energy  liberated  in  the  pro- 
cesses of  hydrolytic  cleavage  is  comparatively  small.  Most  of  the 
heat  is  set  free  in  the  oxidative  processes  which  accompany  or  follow 
the  hydrolytic  changes. 

Thus  the  energy-value  of  a  gramme-molecule  (p.  426)  of  maltose, 
cane-sugar,  or  lactose  is  a  little  more  than  1,350  calories;  that  of  the 
two  gramme-molecules  of  dextrose  formed  by  hydrolysis  of  the  maltose 
is  I347'4  calories;  that  of  the  gramme-molecule  each  of  dextrose  and 
levulose  formed  from  the  cane-sugar,  i349'6;  and  that  of  the  gramme- 
molecule  each  of  dextrose  and  galactose  formed  from  the  lactose, 
1 343-6  calories.  That  is  to  say,  the  hydrolysis  of  these  disaccharides 
to  monosaccharides,  which  is  the  first  step  in  their  metabolism,  is  accom- 
plished with  the  liberation  of  very  little  heat.  The  same  is  true  of  the 
splitting  of  the  fats  and  proteins.  The  dried  residue  of  a  filtered  pan- 
creatic digest  was  found  to  yield,  when  burned  in  the  calorimetric 
bomb,  only  10  per  cent,  less  heat  than  the  same  weight  of  dry  meat. 
Much  the  greater  part  of  this  deficiency  was  accounted  for  by  the  leucin 
and  tyrosin  which  had  crystallized  out,  and  the  derivatives  of  higher 
fatty  acids  in  the  meat,  as  these  would  be  removed  from  the  digest 
by  filtration. 

It  has  been  shown  that  the  law  of  the  conservation  of  energy  holds 
for  the  animal  body;  in  other  words,  there  is  a  practically  exact 

*  ITie  relative  amounts  lost  by  radiation  and  conduction  cannot  b«  accur- 
ately fixed.     The  proDortion  is  extremely  variable. 


684  AXIMAL  HEAT 

agreement  between  the  potential  energy  of  the  food  and  the  kinetic 
energy  into  which  it  is  transformed  in  the  body  both  during  rest 
and  during  work.  This  kinetic  energy  is  represented  by  the  heat 
'given  off  plus  the  heat-equivalent  of  any  mechanical  work  done 
(Atwater).  In  other  words,  the  food,  whether  it  is  burned  in  a 
calorimeter  to  simple  end-products  hke  carbon  dioxide  and  water, 
or  more  slowly  oxidized  in  the  body,  yields  the  same  amount  of 
heat,  provided  alwa3^s  that  in  both  cases  it  is  entirely  consumed,  and 
that  no  work  is  transferred  to  the  outside.  In  the  body  the  com- 
bustion of  carbo-hydrates  and  fats  is  complete;  but  the  nitrogenous 
residues  of  the  proteins — urea,  uric  acid,  etc. — can  be  further 
oxidi/.ed,  and  the  remnant  of  energy  which  they  yield  must  be 
taken  into  account  in  any  calculation  of  the  total  heat-production 
founded  on  the  heat  of  combustion  of  the  food  substances.  Froni 
careful  experiments,  it  has  been  found  that  a  gramme  of  dry  protein 
(egg-albumin),  when  burned  in  a  calorimeter,  yields  5735  calorics 
of  heat,  a  gramme  of  dextrose  3742,  and  a  gramme  of  animal  fat 
9-500  calories  (Stohmann). 

Calories. 

Heat-equivalent  of  i  gramme  of  albumin  -  5 "735 

Albumin  (minus  urea  produced  from  it)     -  -  4*949 

Cane-sugar  -----  3'955 

Kreatin  (water-free)  -  -  -  -  4*275 

Starch  ------  4-182 

In  applying  such  results  to  the  calculation  of  the  heat-production  of 
the  bodv,  it  is  not  sufficient  to  deduct  from  the  heat  of  combustion  of 
the  proteins  the  heat  which  the  residual  urea  would  yield  if  fully 
oxidized.  For  other  incompletely  oxidized  products  arise  from  pro- 
teins when  consumed  in  the  body,  and  Rubner  has  shown,  by  actually 
determining  the  heat  of  combustion  of  the  urine  and  faeces,  that  the 
real  equivalent  of  a  gramme  of  albumin  is  at  most  only  4'4-o  calories. 
The  heat-equivalent  of  our  less  liberal  spccunen  diet  (p.  625)  will  be 
approximately:  ^,^^.^^ 

Protein,  95  grammes  x        4*420  =  41 9*9 

Fat,  80  grammes  x        9*500  =  760-0 

Carbo-hydrate     (reckoned    as 

dextrose),  320  grammes  x        3*74-  =  ^'^97*4 

2, 377  "3 

The  heat-equivalent  of  the  more  generous  specunen  diet  (p.  627)  would 
be  2,878  calories. 

But  this  is  the  diet  of  a  man  doing  a  fair  day  s  work,  and  to  get  the 
quantitv  of  energy  which  actually  appears  as  heat,  the  heat-equivalent 
of  the  inechanica'l  work  performed  must  be  deducted.  A  fair  day's 
work  is  about  150,000  kilogramme-metres— that  is,  an  amount  equal 
to  the  raising  of  150,000  kilogrammes  to  the  height  of  a  metre.  Now. 
a  kilogramme-degree  or  calorie  of  heat  is  equivalent  to  425-5  kilo- 
gramme-metres of  work,  and  a  kilo  gramme -metre  to  -.-;Tr:  calorie. 
The  heat-equivalent  of  the  day's  work  is,  therefore,i50,ooox  —  7_  = 
352  calories.     Deducting  this  from  the  heat-equivalent  of  the  food. 


INCOME  AND  EXPENDITURE  OF  ENERGY 


685 


we  get  in  round  numbers  2,520  large  calorics  as  the  heat  given  off  on 
the  more  liberal  diet.  This  corresponds  fairly  well  with  the  calculated 
heat-loss  (p.  081). 

The  table  on  this  page,  based  on  the  direct  calorimetric  observations 
of  Atwater  and  Benedict,  shows  the  average  heat-production  in  a  large 
number  of  experiments  on  several  individuals  at  rest  and  doing  measured 
amounts  of  work,  with  a  stationary  bicycle,  for  instance.  This  was 
connected  with  a  small  dynamo,  which  transformed  the  greater  part 
of  the  work  into  electrical  energy.  Tlie  electrical  energy  in  its  turn 
was  changed  into  heat,  the  current  passing  through  a  lamp. 

1  he  heat-production  during  the  hours  of  sleep,  in  the  second  night 
period,  is  much  less  than  in  the  waking  hours  of  rest,  and  of  course 
enormously  less  than  in  the  hours  of  work.  After  work  the  heat  pro- 
duction in  the  period  of  sleep  is  only  a  little  greater  than  after  rest. 

As  already  indicated  (p.  683),  it  is  permissible  to  calculate  the  heat- 
production  from  the  diet,  and  Rubner  has  done  this  for  various  classes 
of  men,  reducing  everything  to  the  standard  of  a  body-weight  of 
67  kilos.  The  fasting  man,  of  67  kilos  body-weight,  produces  2,303  calo- 
ries in  the  twenty-four  hours.  The  class  of  brain-workers,  represented 
by  physicians  and  of&cials,  produce  only  a  little  more  heat  than  the 
fasting  man,  viz.,  2,445  calories.  The  second  class,  represented  by 
soldiers  (presumably  in  time  of  peace)  and  day-labourers  (probably  of 
a  cautious  and  conservative  type),  work  up  to  2,868  calories.  The 
third  class,  composed  of  men  who  work  with  machines  and  other  skilled 
labourers,  attain  a  heat-production  of  3,362  calories.  The  fourth  class, 
typified  by  miners  (who  are  engaged,  usually  by  the  piece  and  not  by 
the  day,  in  severe  and  exhausting  toil),  produce  as  much  as  4,790  calo- 
ries. In  the  fifth  and  last  class,  represented  by  lumberers  and  other 
out-of-door  labourers  (who,  in  addition  to  excessive  exertion,  have 
often  to  face  intense  cold),  the  heat-production  rises  to  5,360  calories. 
The  diet  of  ordinary  prisoners  in  Scotland,  doing  light  work,  chiefly  of 
a  sedentary  character,  was  found  to  correspond  to  3,115,  and  that  of 
convicts  on  '  hard  labour  '  to  3,707  calories.  It  is  a  fair  presumption 
that  in  Scotch  prisons  the  total  heat  value  supplied  is  not  excessive. 
From  the  general  agreement  of  calculated  results  with  actual  measure- 
ments we  can  safely  conclude  that  most  healthy  adults  produce  between 
2,000  and  3,000  large  calories  (35  to  40  per  kilo  of  body-weight)  on  a  '  rest' 
day,  or  a  day  of  light  labour,  and  between  3,000  and  4,000  (45  to  60  per 
kilo  of  body-weight)  on  a  day  of  hard  manual  work. 


.si 

So 
K.S 

1  = 
Ha 

Heat  eliminated  per  Hour. 

Percentage  of  Total  Heat 
in  24  Hours. 

Day-time. 

Night-time. 

Average 

per  Hour 

for  24 

Hours. 

Day-time. 

Night-time. 

7  a.m. 

to 
I  p.m. 

I  p.m. 

to 
7p.m. 

7  p.m. 

to 
I  a.m. 

I  a.m. 

to 
7  a.m. 

7  a.m. 

to 
I  p.m. 

I  p.m. 

to 
7  p.m. 

7  p.m. 

to 
I  a.m. 

I  a.m. 

to 
7  a.m. 

Rest  experi- 
ments - 

Work  experi- 
ments - 

Heat-equiva- 
lent of  work 

Total  for  work 
experiments 

2,262 
4.225 

4,676 

Io6'3 
2317 

58-5 
290-2 

104.4 

235-6 
56-8 

292-4 

98-3 
I18-I 

iiS-i 

67-9 

78-4 

78.4 

94-3 
166-6 

194-8 

28-2 

37-5 

27.7 

37-2 

26-1 
15-2 

18-0 
lO-I 

686  ANIMAL  HEAT 

^^^  at  has  been  already  said  in  connection  with  standard  dietaries 
(p.  624)  indicates  that  the  work  of  the  world  might  possibly  be  accom- 
plished as  well  with  a  smaller  transformation  of  energy  in  the  human 
machine,  at  least  in  the  more  prosperous  countries,  and  that  in  the 
body,  as  in  an  engine,  more  careful  '  stoking  '  might  result  in  a  saving 
of  fuel.  It  is  extremely  improbable,  however,  that  any  argument  of 
tliis  sort  will  have  much  effect  upon  the  deep-rooted  dietetic  habits  of 
mankind. 

In  any  case  it  must  be  carefully  remembered  that  the  question  of 
the  minimum  amount  of  protein  necessary  in  a  permanent  diet  is 
quite  distinct  from  the  question  of  the  minimum  heat  value  of  the  diet 
for  a  man  of  given  body-weight  doing  a  definite  amount  of  work  under 
definite  conditions.  Whether  the  protein  allowance  be  scanty  or  liberal, 
the  total  heat  value  cannot  be  permanently  reduced  below  a  certain 
minimum  depending  on  the  work  done,  the  climate,  and  other  conditions. 

Basal  Metabolism.— The  total  metabolism  of  a  normal  man  or  animal 
as  measured  by  the  heat-production  is  so  greatly  affected  by  the  taking 
of  food,  by  the  kind  as  well  as  the  quantity  of  the  food,  by  the  amount 
and  nature  of  the  work  done,  even  by  the  position  of  the  body,  that  for 
many  pui poses  it  is  necessary  to  simplify  the  conditions  in  order  to 
disentangle  the  various  factors.  The  greatest  degree  of  simplification 
which  is  practicable  is  attained  when  the  observations  are  made  upon  a 
subject  a  considerable  time  (at  least  twelve,  but  better  eighteen  hours) 
after  the  last  meal,  in  the  recumbent  posture,  and  in  a  condition  of  rest 
as  absolute  as  possible.  The  metabolism  under  those  conditions  is 
termed  the  basal  metabolism.  In  89  normal  men,  the  basal  metabolism, 
indirectly  calculated  from  the  calorific  value  of  the  oxygen  consumed, 
was  found  to  vary  from  08  to  13  calories  per  kilo  of  body- weight,  and 
from  28-9  to39  0  calories  per  square  metre  of  surface  per  hour  (Benedict). 
The  average  heat-production  per  square  metre  of  surface  was  34-7 
calories  per  hour  (or  calculated  on  surface  measurements  made  by  newer 
methods,  40  calories  per  hour).  This  agrees  very  closely  with  the 
average  obtained  by  direct  determination  of  the  heat  with  the  '  bed ' 
calorimeter  (Du  Bois). 

Specific  Dynamic  Action  of  the  Food-Stuffs. — The  old  idea  that  the 
increase  in  the  metaboHsm  above  the  basal  level  which  follows  the  inges- 
tion of  food  is  chiefly  due  to  increased  work  of  the  alimentary  canal 
in  digestion  and  absorption  has  been  disproved.  A  large  meal  of  meat 
given  to  a  dog  may  cause  the  heat-production  to  be  nearly  doubled. 
This  phenomenon  is  spoken  of  as  the  specific  dynamic  action  of  the 
food-stuffs.  It  is  especially  well  marked  in  the  case  of  the  proteins. 
The  best  evidence  is  that  the  action  is  due  to  some  kind  of  stimulation 
of  the  protoplasm  by  decomposition  products  of  the  amino-acids;  in 
the  case  of  alanin,  for  instance,  probably  lactic  acid  produced  in  the 
process  of  deaminization.  It  is  not  merely  the  oxidation  of  the  amino- 
acids  themselves  which  is  mainly  responsible  for  the  increase  in  meta- 
bolism. P'or  it  has  been  found  that  glycoco'.l  and  alanin  when  fed  to 
phlorhizinized  animals,  in  which  they  do  not  yield  energy  by  oxidation, 
being  excreted  as  sugar  and  urea,  still  exert  the  specific  dynamic  action, 
and  increase  the  heat-production  (Lusk). 

The  Seats  of  Heat-Production. — We  have  already  recognized  the 
skeletal  muscles  as  important  seats  of  heat-production.  A  frog's 
muscle,  contracting  under  the  most  favourable  conditions,  does  not 


INCOME  AND  EXPENDITURE  OF  ENERGY 


6«7 


convert  at  most  more  than  one-fourth  or  one-fifth  of  the  energy  it 
expends  into  mechanical  work;  at  least  three-fourths  or  four-fifths 
of  the  energy  appears  as  heat.  The  muscles  of  mammals  and  of 
man  in  the  intact  body  work,  upon  the  whole,  more  economically 
than  the  excised  frog's  muscles  at  their  maximum  efficiency.  Under 
the  best  conditions — ^that  is.  when  the  work  is  moderate  and  not  too 


NOTPiiNTS.        ■;o,vs  


i      PCTENTIAL    ENCR-Y.      CALORIES 


i  DIETARY     STANDARDS.        


jUBSistence  diet  (playfaib) 


VAN   AT    MODERATE     WORK^OIt) 


MAN    AT    HARD    WORK  cATWATEr") 


'.^AN    WITH    MODERATE  EXERCISE  CpLAYFAIR) 


ACTUAL       DIETARIES. 


■i^s^^il 

l^l 

■■■ 

Hiiini^^^ 

^kH 

1  I^B^^^HI 

Wlillli^^^^^^^ 

Fig.  aas. — Diagram   showing    the    Heat-equivalent   of  various  Dietaries. 
A,  proteins;  B,  fats;  C,  carbo-hydrates;  D,  heat -equivalent, 

rapidly  done — about  one-third  of  the  chemical  energy  expended 
may  be  transformed  into  mechanical  work,  and  only  two-thirds  into 
heat  (Zuntz).  In  hard  work  three-quarters  of  the  energy  may  be 
changed  into  heat;  but  even  then  the- efficiency  of  the  muscles  far 
outstrips  that  of  the  best  steam-engines,  which  convert  only  an 
eighth  of  the  total  energy  into  work. 

Notwithstanding  the  splendid  efficiency  of  the  muscular  machine, 
the  gaseous  metabolism  easily  rises  during  muscular  work  to  five 
times,  and  in  severe  labour  to  nine  times  its  resting  value,  although 
persons  inured  to  toil  work  more  economically  than  amateurs. 
In  one  of  Atwater's  '  severe  work '  experiments  the  work  done  in 
twenty-four  hours  had  a  heat-equivalent  of  1,482  calories  (equal  to 


688 


ANIMAL  HEAT 


over  630,000  kilogramme-metres).  The  total  heat-production  (in- 
cluding the  equivalent  of  the  work)  was  9,314  calories.  It  is  not 
difficult  to  show  that  the  greater  part  of  the  metabolism  and  heat- 
production  of  a  man  doing  ordinary  work  is  accounted  for  by  the 
contraction  of  the  voluntary  and  involuntary  muscles. 

Even  in  muscles  completely  at  rest  metabolism  goes  on.  and  some 
heat  is  produced.  In  resting  frogs,  newts,  and  snakes,  the  rate  of  heat- 
production  per  gramme  of  tissue  is  about  0'5  gramme-calorie  per  lioiir 
with  a  room  temperature  of  20°  C,  or  about  a  third  of  that  of  a  resting 
man  (Hill).  Of  course,  this  must  be  above  tlie  heat-production  of 
muscles  of  these  poikilothermal  animals  absolutely  at  rest.  For  not 
only  must  the  active  heart  and  glands  contribute  something,  but  the 
muscles  of  frogs  lying  huddled  in  a  micro-calorimeter  not  only  maintain 
the  normal  tonus,  but  are  certainly  liable  to  contract  acti\-ely  from 
time  to  time.  By  analyzing  the  gases  of  the  arterial  and  venous  blood, 
Zuntz  compared  the  oxygen  consumption  and  carbon  dioxide  produc- 
tion in  the  hind-legs  of  dogs  when  the  sciatic  and  anterior  crural  nerves 
were  divided  and  intact.  In  both  cases  the  muscles  were  at  rest  in 
the  ordinary'  sense.  But  in  the  second  experiment  the  central  '  tonus  ' 
(p.  917)  was  preserved,  while  in  the  first  it  was  abolished.  In  one 
experiment  in  which  the  nerves  were  intact  the  oxygen  consumed 
amounted  to  122  c.c,  and  the  carbon  dioxide  produced  to  1*32  c.c, 
per  kilo  of  tissue  per  minute.  In  the  experiment  in  which  the  nerves 
were  severed,  the  corresponding  numbers  were  0-68  c.c.  for  the  oxygen, 
and  0'63  c.c.  for  the  carbon  dioxide.  Although  it  is  probable,  from 
the  results  of  Chauveau  and  Kauffmann  already  referred  to  (p.  271), 
that  these  figures  are  too  low  for  the  normal  resting  muscle,  they  still 
demonstrate  that,  even  in  the  absence  of  innervation  from  the  central 
nervous  system,  the  metabolism,  and  therefore  the  heat-production  of 
the  muscles,  are  by  no  means  negligible;  0'68  c.c.  of  oxygen  per  minute 
corresponds  to  40-8  c.c.  per  hour,  or  more  than  one-tenth  of  the  oxygen 
consumption  per  kilo  per  hour  of  a  fasting  dog  lying  at  rest  (Zuntz). 

If  the  work  of  the  heart  is  taken  as  16.600  kilogramme-metres  in 
twenty-four  hours  (p.  138),  the  total  heat  produced  by  this  organ  will 
be  equi\-alent  (on  the  assumption  that  it  converts  one-third  of  its 
energy  into  work)  to  about  50,000  kilogramme-metres,  or  not  much 
less  than  120  calories,  since,  practically,  the  whole  work  is  expended 
in  overcoming  the  friction  of  the  vessels,  and  finally  appears  as  heat. 
Enough  energy  is  transformed  in  twenty-four  hours  in  the  heart  of  the 
colonel  of  a  regiment  of  1,000  men  to  lift  the  whole  regiment  to  the 
height  of  the  mess-table,  if  it  could  be  all  changed  into  mechanical 
work.  Barcroft  and  Dixon  have  calculated  the  energ>^  of  the  heart's 
contraction  on  the  assumption  that  it  is  derived  from  the  oxidation 
of  a  carbo-hydrate  by  the  oxygen  absorbed  bv  the  organ.  They  con- 
cluded that  the  energy  set  free  in  the  heart  of  a  dog  weighing  12  kilos 
corresponds  on  the  average  to  7-86  kilogramme-metres  per  minute, 
which  is  equivalent  to  26*6  calories  in  twenty-four  hours.  Allowing  for 
the  fact  that  the  heart  of  a  small  animal  pumps  more  blood  in  propor- 
tion to  the  body-weight  than  the  heart  of  a  large  animal  (p.  139).  this 
result  agrees  very  well  with  that  deduced  from  the  work  of  the  heart. 
The  work  of  the  inspiratory  muscles  may  be  reckoned  at  13,000  kilo- 
gramme-metres, equal  to  30-5  calories,  and  the  heat  produced  by  them 
at,  say,  90  calories.     In  sum,  the  muscular  work  of  the  circulation  and 


INCOME  AND  EXPENDITURE  OF  ENERGY  689 

respiration  is  responsible  for  the  production  of  about  210  calories 
(without  including  the  heat  produced  by  the  smooth  muscle  of  the 
bronchi  and  bloodvessels),  or  nearly  one-twelfth  of  the  total  produc- 
tion of  a  man  doing  ordinary  labour. 

The  glands,  and  then  the  central  nervous  system,  rank  after  the 
muscles,  though  at  a  great  distance,  as  seats  of  heat-production. 
The  liver  and  brain  (?)  are  the  hottest  organs  in  the  body;  and  that 
this  is  not  altogether  due  to  their  being  well  protected  against  loss 
of  heat  is  shown,  in  the  case  of  the  hver,  by  the  excess  of  tempera- 
ture of  the  blood  of  the  hepatic  over  that  of  the  portal  vein.  In 
view,  however,  of  the  exaggerated  importance  which  some  have 
given  to  these  organs  as  foci  of  heat-production,  it  may  be  well  to 
point  out  that  although  many  of  the  chemical  changes  in  the  animal 
body  are  undoubtedly  associated  with  the  setting  free  of  heat 
(exothermic  reactions),  other,  and  not  less  weighty  and  character- 
istic, reactions  may  cause  the  absorption  of  heat  (endothermic 
reactions) ;  and  it  is  possible  that  some  of  the  syntheses  which  many 
of  the  tissues  are  capable  of  performing  may  be  included  in  this 
latter  category.  For  example,  when  urea  is  decomposed  so  as  to 
yield  ammonium  carbonate  (p.  478),  heat  is  set  free.  We  must 
assume  that  if  ammonium  carbonate  were  transformed  into  urea  in 
the  liver,  an  equal  amount  of  heat  would  be,  on  the  whole,  absorbed. 
So  that  the  heat-production  of  an  organ  may  depend,  not  only  upon 
the  quantity,  but  also  upon  the  quality,  of  its  chemical  activity. 
In  all  the  tissues,  including  the  muscles,  it  is  necessary  to  assume 
that  some  of  the  energy  transformed  is  expended  in  so-called  '  resti- 
tution '  processes — that  is,  in  replenishing  the  store  of  nutritive 
material  within  the  cells  and  in  building  up  the  protoplasm.  Claude 
Bernard  observed  an  excess  of  06°  C  in  the  temperature  of  the 
blood  of  the  hepatic  vein  over  that  of  the  portal  during  hunger,  and 
as  much  as  i-6°  at  the  height  of  digestion,  although  at  the  beginning 
of  digestion  the  portal  blood  was  the  hotter  by  0-4°.  But  such 
observations,  like  the  corresponding  ones  on  the  salivary  glands,  are 
open  to  many  errors,  and  when  we  consider  the  enormous  tide  of 
blood  which  during  digestion  sets  through  the  portal  system,  we 
shall  look  with  suspicion  upon  results  that  announce  a  difference 
of  more  than  a  small  fraction  of  a  degree  in  the  temperature  of  the 
incoming  and  outgoing  blood  of  the  liver.  Probably  not  less  than 
200  litres  of  blood  pass  in  twenty-four  hours  through  the  hver  of  a 
2-kilo  rabbit.  If  the  temperature  of  this  blood  is  raised  even  one- 
tenth  of  a  degree  in  its  passage  through  the  hepatic  capillaries,  this 
would  correspond  to  a  heat-production  of  20,000  small  calories,  or 
one-tenth  of  the  whole  heat  produced  in  the  animal. 

In  the  case  of  the  brain  there  is  some  evidence,  obtained  b^-  com- 
parison of  the  gases  of  blood  taken  from  the  carotid  and  from  the  venous 
sinuses  (torcula  Herophili),  that  the  metabolism  is  feeble  as  compared 

44 


690  ANIMAL  HEAT 

even  with  that  of  resting  muscles  (Hill).  Nor  is  it  possible  to  demon* 
stratc  any  marked  or  constant  increase  when  the  cerebral  cortex  is 
roused  to  such  an  active  discharge  of  impulses  as  leads  to  general 
epileptiform  convulsions.  The  rise  of  temperature  of  certain  regions, 
especially  the  occipital  portion,  of  the  scalp,  which  some  observers  have 
stated  to  take  place  during  mental  activity,  cannot  be  due  to  con- 
duction of  heat  from  the  brain  through  the  skull.  It  might  be  caused 
by  vaso-motor  changes  in  the  scalp,  associated  with  corresponding 
changes  in  related  areas  of  the  cortex.  The  alleged  increase  in  the 
temperature  of  the  brain  during  intense  psychical  activity,  sometimes 
to  o'2°  C,  or  0'3°  C.  above  the  rectal  temperature  (Mosso),  may  also, 
if  genuine,  be  due  to  vascular  changes.  And  if  we  remember  how 
large  a  proportion  of  the  central  nervous  system  is  made  up  of  nerve- 
fibres,  in  which  no  sensible  production  of  heat  has  ever  been  demon- 
strated, it  will  not  appear  surprising  if  even  a  considerable  increase 
in  the  metabolism  of  the  really  active  elements  should  fail  to  make 
itself  felt. 

Section  III. — Regulation  of  Temperature  or  Thermotaxis. 

What,  now,  is  the  mechanism  by  which  the  balance  is  maintained 
in  the  liomoiothermal  animal  between  heat-production  and  heat- 
loss  ?  In  answering  this  question  we  have  to  recognize  that  both 
of  these  quantities  are  variable,  that  a  fall  in  the  production  of  heat 
may  be  compensated  by  a  diminution  of  heat-loss,  and  an  increase 
in  the  loss  of  heat  balanced  by  a  greater  heat-production. 

The  loss  of  heat  from  the  surfaces  of  the  body  may  be  regulated 
both  by  involuntary  and  by  voluntary  means.  It  is  greatly  affected 
by  the  state  of  the  cutaneous  vessels,  and  these  vessels  are  under  the 
influence  of  nerves.  A  cold  skin  is  pale,  and  its  vessels  are  con- 
tracted. In  a  warm  atmosphere  the  skin  is  flushed  with  blood,  its 
vessels  are  dilated,  its  temperature  is  increased;  an  effort,  so  to 
speak,  is  being  made  by  the  organism  to  maintain  the  difference  of 
temperature  between  its  surface  and  its  surroundings  on  which  the 
rate  of  heat-loss  by  radiation  and  conduction  depends.  A  still 
more  important  factor  in  man,  and  in  animals  like  the  horse,  which 
sweat  over  their  whole  surface,  is  the  increase  and  decrease  in  the 
quantity  of  water  evaporated  and  of  heat  rendered  latent.  It  is 
owing  to  the  wonderful  elasticity  of  the  sweat-secreting  mechanism, 
and  to  the  increase  of  respiratory  activity  and  the  consequent 
increase  in  the  amount  of  watery  vapour  given  off  by  the  lungs, 
that  men  are  able  to  endure  for  days  an  atmosphere  hotter  than  the 
blood,  and  even  for  a  short  time  a  temperature  above  that  of  boiling 
water.  The  temperature  of  a  Turkish  bath  may  be  as  high  as 
65"  to  80°  C.  Blagden  and  Fordyce  exposed  themselves  for  a  few- 
minutes  to  a  temperatiu-e  of  nearly  127°  C  Although  meat  was 
being  cooked  in  the  same  chamber  by  the  heat  of  the  air,  they 
experienced  no  ill-effects,  nor  was  tlieir  body-temperature  even 
increased.     But  a  far  lower  temperature  than  this,  if  long  con- 


THERMOTAXIS  691 

tinued,  is  dangerous  to  life.  During  the  '  hot  waves  '  not  infre- 
quently experienced  in  summer  in  the  United  States,  hundreds  of 
persons  have  died  within  a  few  days  from  the  excessive  heat.  It  is 
stated  that  during  the  unusually  hot  summer  of  1819  the  tempera- 
ture at  Bagdad  ranged  for  a  considerable  time  between  108°  and 
120°  F.  (42°  to  49°  C),  and  there  was  great  mortahty.  A  much 
higher  temperature  may  be  borne  in  dry  air  than  in  air  saturated 
with  watery  vapour.  A  shade  temperature  of  100°  F.  (377°  C.)  in 
the  dry  air  of  the  South  African  plateaux  is  quite  tolerable,  while  a 
temperature  of  85°  F.  (294°  C.)  in  the  moisture-laden  atmosphere 
of  Bombay  may  be  oppressive.  The  reason  is  that  in  dry  air  the 
sweat  evaporates  freely  and  cools  the  skin,  while  in  moist  air, 
although  according  to  Rubner  the  loss  of  heat  by  radiation  and 
conduction  is  increased,  the  loss  of  heat  by  evaporation  of  sweat  is 
diminished  in  a  still  greater  degree.  In  saturated  air  at  the  body- 
temperature  no  loss  of  heat  by  perspiration  or  by  evaporation  from 
the  pulmonary  surface  is  possible ;  the  temperature  of  an  animal  in 
a  saturated  atmosphere  at  35°  to  40°  C.  soon  rises,  and  the  animal 
dies.  In  animals  like  the  dog;  which  sweat  little  or  not  at  all  on 
the  general  surface,  the  regulation  of  the  heat-loss  by  respiration  is 
relatively  more  important  than  in  man. 

The  observations  of  Boycott  and  Haldane  in  a  deep  mine,  in  the 
incubating-room  of  a  laboratory,  and  in  a  Turkish  bath  illustrate  the 
important  influence  of  the  humidity  of  the  air.  In  still  air  the  body- 
temperature  rose  above  normal  when  the  wet-bulb  thermometer  rose 
above  31*  C.  (88°  F.),  and  it  remained  normal  whatever  the  external 
temperature  might  be  so  long  as  the  reading  of  the  wet-bulb  thermo- 
meter did  not  exceed  that  level.  The  more  the  wet-bulb  thermometer 
rose  above  31°  the  more  rapid  was  the  increase  in  the  body-temperature. 
In  moving  air  a  greater  degree  of  humidity  could  be  borne  without 
increase  in  the  body-temperature,  which  did  not  occur  till  the  tem- 
perature shown  by  the  wet-bulb  thermometer  exceeded  35°  C.  The 
great  increase  in  the  evaporation  of  sweat  when  the  temperature  of  the 
air  is  high  is  shown  by  the  observation  that  on  a  warm  day  (dry  bulb, 
79"  F. ;  wet  bulb,  67*5°  F.)  the  average  loss  of  moisture  from  the  body 
was  1,816  grammes  for  four  soldiers  during  a  march  of  seven  miles, 
while  on  a  cold  day  (dry  bulb,  45°  F. ;  wet  bulb,  38°  F.)  it  was  only 
419  grammes  during  the  same  march  by  the  same  men  (Pembrey). 

The  winter  fur  of  Arctic  animals  is  a  special  device  of  Nature  to 
meet  the  demands  of  a  rigorous  climate,  and  combat  a  tendency  to 
excessive  loss  of  heat.  The  experiments  of  Hosshn,  and  the  experi- 
ence of  squatters  in  Australia,  go  to  show  that  even  domesticated 
animals  have  a  certain  power  of  responding  to  long-continued 
changes  in  external  temperature  by  changes  in  the  radiating  surfaces 
which  affect  the  loss  of  heat.  It  is  said  that  in  the  hot  plains  of 
Queensland  and  New  South  Wales  the  fleeces  of  the  sheep  show  a 
tendency  to  a  progressive  decrease  in  weight.  And  Hosslin  found 
that  a  young  dog  exposed  for  eighty-eight  days  to  a  temperature 


69t  ANIMAL  HEAT 

of  5°  C  developed  a  thick  coat  of  tine  woolly  hairs.  Another  dog 
of  the  same  Utter,  exposed  for  the  same  length  of  time  to  a  tem- 
perature of  315°  to  ^2°  C,  had  a  much  scantier  covering.  The 
increased  protection  against  heat-loss  in  the  case  of  the  '  cooled  ' 
dog  was  not  sufficient  fully  to  compensate  for  the  lowered  external 
temperature.  The  metabolism — ^that  is  to  say,  the  heat-production 
— was  also  increased.  And  although  the  food  was  exactly  the  same 
for  both  animals  in  quantity  and  quahty,  the  dog  at  5°  C.  put  on 
less  than  half  as  much  fat  in  the  period  of  the  experiment  as  the 
'  heated  '  dog,  but  the  same  amount  of  '  flesh.' 

The  voluntary  factor  in  the  regulation  of  the  heat-loss  is  of  great 
importance  in  man.  Clothes,  hke  hair  and  other  natural  coverings, 
retai  d  the  loss  of  heat  from  the  skin  chiefly  by  maintaining  a  zone 
of  still  air  in  contact  with  it,  for  air  at  rest  is  an  exceedingly  bad 
conductor  of  heat.  A  man  clothed  in  the  ordinary  way  has  two  or 
three  concentric  air-jackets  around  him.  The  air  in  the  intervals 
between  the  inner  and  outer  garments  is  of  importance  as  well  as 
that  in  the  pores  of  the  clothes  themselves ;  and  it  is  for  this  reasou 
that  two  thin  shirts  put  on  one  above  the  other  are  warmer  than  the 
same  amount  of  material  in  the  form  of  a  single  shirt  of  double 
thickness.  When  a  man  feels  himself  too  hot  and  throws  off  his 
coat,  he  really  removes  one  of  the  badlj'  conducting  layers  of  air, 
and  increases  the  rate  of  heat-loss  by  radiation  and  conduction. 
At  the  same  time  the  water-vapour,  which  practically  saturates 
the  layer  of  air  next  the  skin,  is  allowed  a  freer  access  to  the  surface, 
and  the  loss  of  heat  by  the  evaporation  of  the  sweat  becomes  greater. 
The  power  of  voluntarily  influencing  the  heat-loss  must  be  looked 
upon  in  man  as  one  of  the  most  important  means  by  which  the 
equilibrium  of  temperature  is  maintained.  In  the  lower  animals 
this  powei  also  exists,  but  to  a  much  smaller  extent.  A  dog  on  a 
hot  day  puts  out  its  tongue  and  stretches  its  limbs  so  as  to  increase 
the  surface  from  which  heat  is  radiated  and  conducted.  The  mere 
placing  of  a  rabbit  on  its  back,  Nnth  its  le.ss  apart,  may  cause  in  an 
hour  or  two  a  fall  of  1°  to  2°  C  in  the  rectal  temperature.  The 
power  of  covering  themselves  with  straw  or  leaves,  of  burrowing 
and  of  forming  nests,  may  be  included  among  the  voluntary  means 
of  regulation  of  the  heat-loss  possessed  by  animals.  A  man  opens 
the  window  when  he  is  too  hot,  and  pokes  the  fire  when  he  feels 
cold.  Both  actions  are  a  tribute  to  his  status  as  a  homoiothermal 
animal,  and  illustrate  the  importance  of  the  voluntary  element  in 
the  mechanism  by  wliich  his  temperature  is  controlled. 

The  production  of  heat,  hke  the  loss,  is  to  a  certain  extent  under 
voluntary  control.  Rest,  and  especially  sleep,  lessen  the  pro- 
duction; work  increases  it.  The  inhabitants  of  the  tropics,  human 
and  brute,  often  tide  ov^er  the  hottest  part  of  the  day  by  a  siesta; 
and  it  is  as  natural,  and  as  much  in  accordance  with  physiological 


THERMOTAXIS  693 

laws,  that  a  man  overpowered  by  the  heat  should  lie  down,  as  it  is 
that  he  should  walk  about  and  stamp  his  feet  or  clap  his  hands  on 
a  cold  winter  morning.  In  the  one  case  a  diminution,  in  the  other 
an  increase,  in  the  heat-production  is  aimed  at  by  a  corresponding 
change  in  the  amount  of  muscular  contraction.  The  quantity  and 
quality  of  the  food  also  influence  the  production  of  heat.  The 
Eskimo,  who  revels  in  train-oil  and  tallow-candles,  unconsciously 
illustrates  the  experimental  fact  that  the  heat  of  combustion  of  fat 
is  high;  the  rice  diet  of  the  ryot  of  the  Carnatic,  with  its  low  heat- 
equivalent,  seems  peculiarly  adapted  to  the  dweller  in  tropical 
lands.  But  it  would  be  easy  to  attach  too  much  weight  to  con- 
siderations such  as  these.  The  Arctic  hunter  eats  animal  fat,  and 
the  Indian  peasant  vegetable  carbo-hydrate,  not  only  because  fat 
has  a  high  and  carbo-hydrate  a  low  heat-equivalent,  but  because 
in  the  climate  of  the  Far  North  animals  %vith  a  thick  coating  of 
badly-conducting  fat  are  plentiful,  and  vegetable  food  scarce; 
whereas  in  the  river-valleys  of  India  Nature  favours  the  growth  of 
rice,  and  religion  forbids  the  killing  of  the  sacred  cow. 

The  production  of  heat  is  also  controlled  by  an  involuntary  nervous 
mechanism,  through  which  the  '  chemical  '  regulation  of  the  body- 
temperature  is  achieved,  as  the  '  physical '  regulation  is  accom- 
plished by  the  nervous  mechanisms  that  control  the  circulation, 
the  sweat-glands,  and  the  respiratory  movements.  It  is  a  matter 
of  everyday  experience  that  cold  causes  involuntary  shivering — 
involuntary  muscular  contractions — ^the  object  of  which  seems  to  be 
a  direct  increase  in  the  heat-production.  But  besides  this  visible 
mechanical  effect,  the  apphcation  of  cold  to  a  warm-blooded  animal, 
when  not  carried  so  far  as  to  greatly  reduce  the  rectal  temperature, 
is  accompanied  by  a  marked  increase  in  the  metabolism,  as  shown 
by  an  increased  production  of  carbon  dioxide  and  consumption  of 
oxygen.  In  cold-blooded  animals  like  the  frog  the  metabolism, 
on  the  other  hand,  rises  and  falls  with  the  external  temperature; 
there  is  no  automatic  mechanism  which  answers  an  increased  drain 
upon  the  stock  of  heat  in  the  body  by  an  increased  supply.  Or,  in 
the  light  of  recent  experiments,  we  ought  rather  to  say  that, 
although  the  rudiments  of  a  heat-regulating  mechanism  may  exist 
in  such  animals  as  the  frog,  the  newt,  and  even  the  earthworm 
(Vernon),  it  is  only  able  to  modify  to  a  certain  extent  the  effects  of 
changes  of  external  temperature,  not  to  balance  or  even  override 
them,  as  in  the  homoiothermal  animal.  In  resting  frogs  and  snakes 
the  rate  of  heat-production,  as  measured  by  the  micro-calorimeter, 
increases  two  to  three  times  when  the  temperature  rises  10"  C. 
(Hill).  The  warm-blooded  animal  loses  its  heat-regulating  power 
when  a  dose  of  curara  sufficient  to  paralyze  the  voluntary  muscles 
is  given.  A  curarized  rabbit,  kept  alive  by  artificial  respiration, 
reacts  to  changes  of  external  temperature  like  the  cold-blooded 
frog.     Now,  the  only  action  of  curara  adequate  to  account  for  this 


694  ANTMAL  HEAT 

effect  is  its  power  of  paralyzing  the  motor  innervation,  and  so 
cutting  off  from  the  skeletal  muscles  impulses  which  in  the  intact 
animal  would  have  reached  them.  The  excitation  by  cold  of  the 
cutaneous  nerves,  or  some  of  them,  which  in  the  unpoisoned  animal 
is  reflected  along  the  motor  nerves  to  the  muscles,  and  causes  the 
increase  of  metaboHsm,  is  now  blocked  at  the  end  of  the  motor 
path;  and  the  muscles,  the  great  heat-producing  tissues,  are  aban- 
doned to  the  direct  influence  of  the  external  temperature  (Pfliiger). 
How  is  it,  then,  that  nervous  impulses  from  the  skin  produce  in 
the  intact  animal  their  effect  upon  the  chemical  processes  in  the 
muscles  ?  We  know  that  the  heat-production  of  a  muscle  is  greatly 
increased  when  it  is  caused  to  contract;  but  it  has  not  hitherto  been 
possible  by  artificial  stimulation  to  demonstrate  that  any  chemical 
or  physical  effect  is  produced  in  a  muscle  by  excitation  of  its  motor 
nerve  unless  as  the  accompaniment  of  a  mechanical  change.  When 
the  gastrocnemius  of  a  frog  poisoned  with  not  too  large  a  dose  of 
curara  is  laid  on  a  resistance  thermometer  (p.  783),  and  its  nerve 
stimulated  from  time  to  time  as  the  curara  paralysis  deepens, 
heating  of  the  muscle  is  observed  as  long  as,  and  only  as  long  as, 
there  is  any  visible  contraction.  The  gaseous  metabolism  of  a 
rabbit  immersed  in  a  bath  of  constant  temperature  may  sink  by 
as  much  as  30  to  40  per  cent,  when  curara  is  given.  One  obvious 
cause  of  this  is  the  complete  muscular  relaxation.  And  the  whole 
secret  of  the  regulation  of  the  heat-production  might  be  plausibly 
supposed  to  lie  in  the  bracing  effect  of  cold  upon  the  skeletal  muscles 
and  the  relaxing  effect  of  heat.  Indeed,  in  man  it  has  been  observed 
that  exposure  to  moderate  cold  causes  no  metabolic  increase  when 
shivering  is  prevented  by  a  strong  effort  of  the  will  (Loewy). 
Nevertheless,  the  explanation  is  inadequate  in  the  case  of  small 
animals,  such  as  guinea-pigs,  rabbits,  and  cats;  for  very  great 
changes  in  the  metaboUsm  may  be  brought  about  by  external  cold 
without  any  outward  token  of  increased  muscular  activity.  In  a 
man  also  a  fall  in  the  external  temperature  from  23°  to  15°  C.  caused 
a  certain  increase  in  the  output  of  carbon  dioxide  (from  27-9  to 
32  3  grammes  per  hour),  although  no  shivering  was  observed.  As 
the  temperature  of  the  air  is  lowered,  the  point  is  soon  reached  at 
which  shivering  can  no  longer  be  suppressed,  and  then  it  is  neither 
practicable  nor  perhaps  very  important  to  distinguish  clearly  the 
portion  of  the  increased  heat-production  associated  with  the  visible 
muscular  contractions  and  the  portion  due  to  quickened  muscular 
metaboUsm  without  contraction.  Lefevre  found  that  in  man  a 
marked  increase  in  the  heat-loss,  such  as  is  caused  by  immersion 
for  a  considerable  time  (one  to  three  hours)  in  cold  water  (at  a  tem- 
perature of  7°  to  15°  C),  was  accompanied  by  a  great  increase  in 
the  production  of  heat,  so  that  the  axillarj^  temperature  fell  com- 
paratively little — e.g.,  only  1°  C.  during  a  stay  of  three  hours  in  a 
bath  at  15°  C.     With  short  periods  of  immersion,  a  characteristic 


THERMOTAXIS  695 

reaction  occurs  after  the  person  comes  out  of  the  bath.  The  rectal 
temperature  falls  to  a  minimum,  which  is  reached  in  twenty  to 
thirty  minutes  after  exit  from  the  bath,  and  then  gradually  returns 
to  normal.  This  fall  of  internal  temperature  is  due  to  the  heating 
of  the  superficial  portions  of  the  body  at  the  expense  of  the  central 
portions.  By  training,  the  fall  of  temperature  is  greatly  lessened, 
the  heat-regulating  mechanism  acquiring,  so  to  speak,  with  practice, 
greater  promptitude  and  precision  of  adjustment. 

It  must  be  admitted,  then,  that  the  metabolic  changes  normally 
going  on  in  the  resting  muscles  may  be  reflexly  increased — especially 
in  the  smaller  homoio-thermal  animals- — without  the  usual  accom- 
paniment of  mechanical  contraction,*  and  that  such  an  increase  of 
'  chemical  tone  '  is  an  important  means  by  which  the  temperature 
is  regulated.  It  is  possible  that  other  organs  besides  the  muscles 
may  be  concerned,  though  not  to  a  sufficient  extent  to  secure  the 
due  regulation  of  temperature  during  curara  paralysis.  It  is 
obvious  that  in  man,  whose  environment  is  so  much  under  his  own 
control,  a  mere  automatic  regulation  is  less  required  than  in  the 
inferior  animals,  and  that  a  regulative  power,  if  present  in  rudiment, 
would  tend  to  '  atrophy  '  by  disuse,  or,  at  all  events,  to  become  less 
sensitive  to  slight  changes  of  temperature.  In  the  larger  animals, 
again,  mere  bulk  is  an  important  safeguard  against  any  sudden 
change  of  internal  temperature.  To  reduce  the  temperature  of  a 
horse  or  an  elephant  by  1°,  a  considerable  quantity  of  heat  must 
be  lost,  while  a  very  slight  loss  would  suffice  to  cool  a  mouse  by 
that  amount.  Not  only  so,  but  the  surface  by  which  heat  is  lost  is 
greater  in  proportion  to  the  mass  of  the  body  in  small  than  in  large 
rnimals.  The  power  of  rapidly  increasing  the  heat-production  to 
meet  a  sudden  demand  is,  therefore,  far  more  important  to  the 
mouse  than  to  the  horse;  and  the  fact  (p.  628)  that  the  metabolism 
of  an  animal  varies  approximately  as  its  surface,  and  not  as  its 
mass,f  is  an  illustration  of  the  nice  adjustment  by  which  heat- 

*  Increased  tonus  of  the  muscles  might,  however,  account  for  a  portion 
of  the  increased  heat-production. 

t  The  relation  between  mass  (M)  and  surface  (S)  in  man  is  approximately 

S-v/M 
given  by  the  equation      ^      =  K,  and  the  relation  between  surface,  mass, 

length  of  body  (L),  and  circumference  of  chest  (C)  just  above  the  nipples  in 

Sv'M*  L*  C3 
the  '  mean  '  position  of  respiration,  by  the  equation  — vr~T~?^   ~  =K'.    M  is 

expressed  in  grammes,  S  in  square  centimetres,  L  and  C  in  centimetres.  K  is 
a  constant  whose  mean  value  is  I2'3,  and  K'  a  constant  whose  mean  value  is 
4*5  (Meeh). 

It  has  been  shown  that  this  formula  gives  somewhat  too  high  results.  In 
any  case,  a  formula  of  this  nature  is  accurate  only  for  objects  of  similar  shape. 
Many  other  formulae  ha\-e  been  proposed.  A  more  accurate  '  height-weight ' 
formula  is  A  =  W^^^x  Ro  725^  C,  where  A  is  the  surface  area  in  square 
centimetres,  W,  the  weight  in  kilograms,  and  C,  a  constant  7i'84.  Another 
method  is  based  on  the  principle  of  raultipljang  the  length  by  the  average  cir- 


696 


ANIMAL  HEAT 


equilibrium  is  niaiutaincd.  There  is  reason  to  believe  that  at  a 
tt-mprraturc  equal  to  that  of  the  human  body,  the  heat-production 
of  a  frog  })cr  unit  of  inass  would  equal  that  of  a  man  or  other  large 
mammal,  although  it  would  be  far  less  than  that  of  a  small  homoio- 
thermal  animal.  This  is  in  favour  of  the  view  that  in  the  larger 
mammals  a  nervous  regulation  of  the  intensity  of  the  metabohsm 
is  not  of  prime  importance. 

Relations  between  Heat-Production,  Surface  Area,  and  Blood-Flow. — 

The  t\)!l()wing  tabic  shows  how  close  is  the  agreement  in  the  heat- 
production  per  unit  of  surface  for  animals  of  different  species  and  very 
different  body-weight: 


Weight  in 
Kilos. 

Calories  produced  in  34  Hours. 

Per  Kilo. 

Per  Sq.  Metre 
of  Surface. 

948 
1,042 
1,036 

917 

943 
1,188 

Horse     -         -    '     - 

Man        ----- 

Dog 

Rabbit  (without  ears)     - 
Fowl       -         .         -         -         - 
Mouse              .         .         .         - 

441 
64-3 

2-3 

2 

o-oiS 

II-3 
32-1 

51-5 
75-1 
71-0 

212-0 

The  relation  between  heat-production  and  surface  area  has  been  rein- 
vestigated by  modern  method.s.  Some  observers,  notably  Benedict, 
are  inclined  to  deny  that  any  simple  proportion  exists  between  the 
basal  metabolism  and  the  area  of  the  skin.  They  consider  that  the 
magnitude  of  the  metabolism  is  related  rather  to  the  mass  of  active 
protoplasm,  w^hich  is  a  different  quantity  from  the  w'eight  of  the  body, 
the  fatty  tissues — e.g.,  contributing  largely  to  the  body-weight,  but 
little  to  the  metabolism.  On  the  other  hand,  Lusk,  Du  Bois,  and  their 
fellow-workers,  believe  that  when  the  surface  area  is  accurately  cal- 
culated there  is  no  reason  to  doubt  the  hitherto  accepted  view  of  a 
proportionalit}'  between  heat-production  and  area  of  surface.  It  must 
be  remembered  that  it  is  only  for  subject.s  in  the  same  general  physio- 
logical state  that  the  proportionality  is  supposed  to  hold.  Nobody 
imagines,  for  instance,  that  a  patient  with  exophthalmic  goitre  will 
have  the  same  heat-production  per  unit  of  surface  as  a  normal  indi- 
vidual. Nor  can  an  infant  be  expected  to  be  exactly  comparable  with 
an  adult,  since  it  differs  so  much  not  only  in  the  proportions  of  the 
body  and  the  relative  size  of  the  various  organs,  but  also  in  its  meta- 
bolism.    It  has  been  found,  as  a  matter  of  fact,  that  the  heat-produc- 


cumference  or  width  of  each  of  the  characteristic  parts  of  the  body.  Con- 
stants have  been  worked  out  for  each  part  by  comparison  of  the  actual  area 
of  a  mould  applied  to  the  skin  with  the  data  obtained  by  the  measurements. 
This  so-called  '  linear  formula  '  docs  not  involve  the  body-weight,  and  gives 
good  results  with  bodies  of  very  dilferent  size  and  shape  (Du  Bois).  Bene- 
dict has  also  developed  a  photographic  method  of  obtaining  the  surface  area. 
The  main  interest  of  such  measurements  hes  in  their  bearing  upon  the  relation 
between  the  metabohsm  and  the  body-surface. 


THF.IJMOT.IXIS 


697 


tion  per  square  uK^tre  of  body-surface,  which  is  low  at  birth,  increases 
rapidly  during  the  hrst  year,  reaches  a  maximum  between  the  ages 
of  one" and  six,  then  falls  steeply  until  tlie  age  of  twenty,  and  thereafter 
very  slowly.  The  basal  metabolism  of  boys  of  twelve  or  thirteen  years 
old  per  unit  of  suiface  is  25  per  cent,  higher  than  that  of  the  adult. 

The  next  table,  calculated  by  Kubner  from  the  quantity  of  tissue- 
protein  and  fat  consumed,  gives  the  relative  intensity  of  heat-produc- 
tion in  fasting  dogs  of  different  sizes:  and  along  with  it  is  given  for 
comparison  some  of  the  results  on  the  output  of  the  heart  in  dogs  of 
different  weight,  obtained  by  the  method  of  injecting  salt  solution 
into  the  ventricle  described  on  p.  139. 


Weight  in 
Kilos. 

Calories  per  Kilo 
per  Hour. 

Weight  in  Kilos. 

Output  per  Kilo 
per  Second  inc.c. 

31 

1-58 

27-89 

1-92 

24 

1-70 

18-20 

2-31 

20 

1-87 

12-82 

3-28 

18 

1-92 

11-68 

3-56 

10 

2-55 

10-32 

3-86 

6 

2.84 

7-165 

4-13 

3 

3-78 

4-975 

5-36 

Number  of 
Dogs. 

Range  of  Weight  in 
Kilos. 

Average  Weight. 

Average  Output 
per  Second  in  c.c. 

Average  Output 

per  Kilo  per 

Second. 

2'40 

3-25 
3-55 

3-69 
4-42 

3 

2 
2 

34*5  to  27-9 

i8'2  ,,  ii'7 

10-3  ..     9-3 

8-4  ,.     7-2 

6*5  ..     5-0 

31-5 
14-3 

9-8 
7-8 
5-7 

75-7 

46-6 

34-8 
28-8 
25-2 

It  is  obvious  that  the  two  quantities,  heat-production  (or  loss)  and 
heart-output,  vary  in  the  same  general  way.  The  reason  is  clear. 
Oxygen  must  be  absorbed  by  the  lungs  in  proportion  to  the  heat 
produced,  and  where  more  oxygen  is  to  be  absorbed,  more  blood  passe? 
through  the  lungs  to  take  it  up.*     It  is  interesting  to  inquire  whether 

*  For  sirapHcity,  the  possibility  that  the  coefficient  of  utilization  of  the  oxy- 
gen-carrying capacity  of  the  blood  {i.e.,  the  quantity  of  oxygen  absorbed  by 
a  litre  of  blood  during  its  passage  through  the  lungs  divided  by  the  total 
quantity  of  oxygen  which  it  can  take  up)  may  vary,  is  disregarded.  This 
possibility  would  imply  that  the  average  oxygen  content  of  the  venous  blood 
coming  to  the  right  side  of  the  heart  varied  in  animals  of  different  size,  more 
oxygen  being  abstracted,  for  example,  from  the  blood  in  passing  through  the 
tissues  of  small  animals  than  of  large.  The  greater  the  utilization  of  the 
oxygen  the  smaller  would  the  quantity  of  blood  passing  through  the  lungs 
require  to  be.  There  is  no  evidence,  however,  that  such  differences  exist  be- 
tween animals  of  the  same  species  of  different  size,  although  it  has  been  sug- 
gested that  a  higher  coefficient  of  utilization  coupled  with  a  proportionately 
smaller  heart  output  may  be  one  way  in  which  training  diminishes  the  diffi- 
culty and  discomfort  of  hard,  muscular  effort. 


698  ANIMAL  HEAT 

in  the  smaller  animals  the  contact  of  the  alveolar  air  with  the  rela- 
tively increased  quantity  of  blood  is  obtained  by  a  similar  increase  in 
the  area  covered  by  capillaries  (or  in  what  is  doubtless  approximately 
proportional  to  this  area,  the  mass  of  the  lung  tissue),  or  by  a  shortening 
of  the  pulmonary  circulation  time  (p.  137).  The  answer  is  that  the  pul- 
monary circulation  time  is  markedly  shortened  as  the  size  of  the 
animal  diminishes,  although  not  in  proportion  to  the  diminution  in 
weight,  but  rather  in  proportion  (roughly  speaking)  to  the  square  root 
of  the  surface.  This  could  not  be  the  case  if  the  area  of  the  pulmonary 
surface  bore  the  same  proportion  to  the  area  of  the  skin  as  the  output 
of  the  heart  does.  For  in  this  case  the  vascular  capacity  of  the  lungs 
(or  the  quantity  of  blood  contained  in  them)  would  be  proportional  to 
the  heart  output,  and  the  time  required  for  the  blood  discharged  by 
the  right  ventricle  to  displace  the  whole  of  the  blood  contained  in  the 
lungs  at  any  given  moment — that  is  to  say,  the  average  pulmonary 
circulation  time — would  be  the  same  for  animals  of  all  sizes.  But  it 
may  very  well  be  the  case  if  the  vascular  capacity  of  the  lungs  (or 
the  mass  of  the  lung  tissue)  decreases  more  rapidly  than  the  surface 
decreases,  say  in  proportion  to  the  body-weight.  At  first  thought  it 
might  appear  advantageous  that  the  area  of  the  surface  through  which 
oxygen  is  absorbed  should  be  proportional  to  the  area  through  which 
the  heat  produced  in  the  oxidations  of  the  body  is  chiefly  eliminated, 
so  that  the  greater  the  necessary  heat  loss,  the  greater  should  be  the 
facilities  for  absorption  of  oxygen.  We  have,  however,  already  seen 
(p.  251)  that  the  blood,  even  when  it  passes  through  the  pulmonary 
capillaries  at  its  maximum  speed,  has  still  sufficient  time  to  practically 
saturate  itself  with  oxygen.  Within  the  limits  where  this  holds  good 
there  would  be  no  advantage  in  increasing  the  relative  size  of  the 
lungs  rather  than  in  increasing  the  linear  velocity  of  the  blood  passing 
through  them — that  is,  diminishing  the  pulmonary  circulation  time — 
and  on  general  principles  it  may  be  assumed  that  a  larger  pulmonary 
reservoir  than  is  necessary  for  the  maximum  possible  intake  of  oxygen 
would  not  be  provided.  For  if  the  pulmonary  reservoir  holds  an  ex- 
cessive amount  of  blood,  some  other  tissues  must  have  too  little.  It 
has  been  stated,  indeed,  that  in  animals  of  different  size  in  the  same 
species  the  total  quantity  of  blood  in  the  body  is  a  function  not  of  the 
body-weight,  but  of  the  surface,  so  that  the  smaller  animals  have 
a  relatively  larger  amount  of  blood  (p.  56).  If  this  be  so,  it  is  probably 
related  to  the  greater  intensity  of  metabolism  and  the  greater  loss  of 
heat  from  the  surface  of  small  animals,  which  entails  a  greater  cir- 
culation through  the  skin.  This  greater  cutaneous  circulation  means 
the  permanent  withdrawal  of  blood  from  the  rest  of  the  body,  which 
can  be  compensated  by  a  corresponding  increase  in  the  total  circulating 
mass.  The  fact  that  the  blood  contained  in  the  living  skin  must 
form  a  substantial  fraction  of  the  total  blood,  and  a  fraction  rela- 
tively more  important  in  the  smaller  than  in  the  larger  animals, 
would  of  itself  help  to  establish  a  relation  between  surface  area 
and  total  quantity  of  blood.  The  greater  volume  of  the  blood 
will  contribute  to  the  increased  output  of  the  heart  in  the  smaller 
animals.  In  this  connection  the  fact  already  alluded  to  more  than 
once  may  be  again  emphasized,  that  it  is  not  the  quantity  of  blood  con- 
tained in  an  organ  or  an  organism,  but  the  quantity  passing  through 
the  capillaries  in  a  given  time,  wliich  is  the  important  thing  for  its 
function,  in  the  case  of  the  lungs  for  the  function  of  the  gaseous  ex- 
change, in  the  case  of  the  skin  for  the  regulation  of  the  heat-loss. 


THERMOTAXIS  699 

There  is  reason  to  suppose  that  the  average  amount  of  blood  contained 
in  the  cutaneous  vessels,  as  well  as  the  average  amount  flowing  through 
them  per  unit  of  time,  is  greater  in  proportion  to  the  total  area  of  the 
skin  in  animals  like  man,  with  a  skin  devoid  of  fur  and  well  supplied 
with  sweat  glands,  than  in  animals  well  protected  by  hair  and  with 
few  sweat  glands.  For  in  the  latter  the  cutaneous  circulation  cannot 
take  as  great  a  share  in  the  regulation  of  the  heat-loss  as  in  the  former, 
although,  of  course,  the  nutrition  of  the  hair  itself  requires  a  certain 
supply  of  blood.  The  relatively  insignificant  proportion  of  the  total 
bk)od  usually  assigned  to  the  skin  of  such  an  animal  as  the  rabbit 
(p.  56)  probably  gives  quite  an  erroneous  idea  of  the  proportion  in 
the  skin  of  a  living  man.  It  must  be  remembered  that  such  determin- 
ations as  have  been  carried  out  have  been  made  on  dead  animals  whose 
skin  under  ordinary  conditions  contains  less  blood  than  during  life. 

Rubner  has  found  that  animals  abundantly  fed  do  not  show  so  much 
change  in  the  production  of  heat  when  the  external  temperature  is 
varied  as  starving  animals,  perhaps  because  the  thicker  coat  of  sub- 
cutaneous fat  so  steadies  the  rate  at  which  heat  is  lost  that  it  becomes 
easy  for  the  vaso-motor  mechanism  alone  to  hold  the  balance  between 
loss  and  production.  In  well-fed  animals  it  is  the  heat-loss  which  is 
chiefly  affected,  and  it  may  be  that  this  has  something  to  do  with  the 
explanation  of  Loewy's  results  on  man  (p.  694). 

Lorrain  Smith  discovered  the  interesting  fact  that  after  removal  of 
the  thyroid  glands  (in  cats),  the  heat-production,  as  measured  by  the 
amount  of  carbon  dioxide  given  off,  is  more  sensitive  to  changes  of 
external  temperature  than  in  the  normal  animal. 

Effect  of  Excessive  Loss  of  Heat — Varnishing  of  the  Skin. — it 
must  not  be  imagined  that  the  production  of  heat  can  be  in- 
creased indefinitely  to  meet  an  increased  heat-loss.  The  organism 
can  make  considerable  efforts  to  protect  itself,  but  the  loss  of  heat  may 
easily  become  so  great  that  the  increase  of  metabolism  fails  to  keep 
pace  with  it.  The  internal  temperature  then  falls,  and  if  the  fall  be 
not  checked,  the  animal  dies.  A  mammal,  when  cooled  artificially 
to  the  temperature  of  an  ordinary  room  (15°  to  20°  C),  does  not  recover 
of  itself,  but  may  be  revived  by  the  employment  of  artificial  respiration 
and  hot  baths,  even  when  the  rectal  temperature  has  sunk  to  5°  to 
10°  C.  If  the  skin  of  a  rabbit  be  varnished,  and  the  air  which  it  is 
the  function  of  the  fur  to  maintain  at  rest  around  it  be  thus  expelled, 
the  animal  dies  of  cold,  unless  the  loss  of  heat  is  artificially  prevented. 
If,  without  varnishing  at  all,  the  greater  portion  of  the  skin  of  a  rabbit 
or  guinea-pig  be  closely  clipped  or  shaved,  similar  phenomena  are 
observed.  Prevented  from  covering  itself  with  straw,  the  animal  dies, 
sometimes  in  twenty-four  hours.  The  radiation  from  the  skin,  as 
measured  by  the  resistance-radiometer  (p.  681),  is  greatly  increased; 
the  animal  shivers  constantly,  and  the  rectal  temperature  falls.  Placed 
in  a  warm  chamber  before  the  temperature  in  the  rectum  has  fallen 
below  25°,  the  animal  recovers  perfectly.  If  the  fall  is  allowed  to  go 
on,  it  dies.  If  it  is  kept  from  the  first  in  the  warm  chamber,  no  faU  of 
temperature  occurs.  When  the  increased  loss  of  heat  is  less  perfectly 
compensated — when,  for  example,  the  animal  is  left  at  the  ordinary 
temperature,  but  supplied  with  sufficient  straw  to  cover  itself,  or 
allowed  to  crouch  among  other  animals — a  curious  phenomenon  may 
sometimes  be  seen.  The  rectal  temperature,  which  has  fallen  sharply 
during  the  operation,  remains  subnormal  (as  much  as  2°  to  3°  below 
the  ordinary  temperature)  for  a  time  (a  week  or  more),   and  then 


700  ANIMAL  HEAT 

gradually  rises  as  the  coat  again  begins  to  grow.  The  meaning  of  this 
seems  to  be  that  the  power  of  regulating  the  temperature  by  increasing 
the  metabolism  is  overtasked  by  the  removal  of  the  natural  protective 
covering,  unless  the  escape  of  heat  is  artificially  diminished.  When  the 
loss  of  the  fur  is  entirely  compensated,  no  fall  of  temperature  occurs; 
when  it  is  not  compensated  at  all,  the  animal  cools  till  it  dies ;  when  it  is 
partially  compensated,  the  increased  metabolism  may  only  suffice  to 
maintain  a  temperature  lower  than  the  normal,  although  constant 
muscular  contractions  (shivering)  are  brought  in  to  supplement  the 
efforts  of  the  regulative  chemical  processes. 

Hitherto  we  have  only  spoken  of  a  reflex  regulation  of  the  heat- 
production  called  into  play  by  external  cold.  It  might  be  sup- 
posed— and,  indeed,  has  often  been  assumed — that  heat  would  lessen 
the  metabolism,  as  cold  increases  it;  and  there  are  indications  that 
in  the  smaller  animals  this  is  the  case,  although  the  influence  of 
heat  seems  to  be  much  smaller  than  the  influence  of  cold.  But 
neither  experimental  results  nor  general  reasoning  have  as  yet 
shown  that  in  man,  either  in  the  tropics  (Eykman)  or  in  the  north 
temperate  zone  (Loewy),  the  chemical  tone  is  diminished  by  a  rise 
of  external  temperature  much  above  the  mean  of  an  ordinary 
English  summer,  apart  from  the  effect  of  the  muscular  relaxation 
which  heat  induces.  In  a  man,  indeed,  at  rest  in  a  hot  atmosphere, 
the  production  of  carbon  dioxide  and  consumption  of  oxygen  are, 
if  an3i:hing,  greater  than  at  the  ordinary  temperature.  The  regu- 
lation of  temperature  in  an  environment  warmer  than  the  normal 
seems,  in  fact,  to  be  brought  about  more  by  an  increase  in  the  loss 
than  a  decrease  in  the  production  of  heat.  Evaporation  from  the 
skin  and  lungs  is  an  automatic  check  upon  overheating  as  important 
as  the  involuntary  increase  of  metabolism  upon  excessive  cooling. 

Nervous  Mechanism  of  Thermotaxis. — While  the  skeletal 
muscles,  and  perhaps  the  glands,  are  at  one  end  of  the  reflex  arc  by 
which  the  impulses  pass  that  regulate  the  temperature  through  the 
metabolism,  we  are  as  yet  ignorant  of  the  precise  paths  by  which 
the  afferent  impulses  travel,  of  the  nerve-centres  to  which  they  go, 
and  even  of  the  end-organs  in  which  they  arise.  There  are  nerves 
in  the  skin  which  minister  to  the  sensation  of  temperature 
(Chap.  XVIII.).  A  change  of  temperature  is  their  '  adequate  '  and 
suflicient  stimulus;  and  it  is  a  tempting  hypothesis  that  these  are 
the  afferent  nerves  concerned  in  the  reflex  regulation  of  temperature 
— that  impulses  carried  up  by  them  to  some  centre  or  centres  in 
the  brain  or  cord  are  reflected  down  the  motor  nerves  to  control 
the  metabolism  of  the  skeletal  muscles,  and  down  the  vaso-motor 
nerves  to  control  the  loss  of  heat  from  the  skin. 

It  is  more  than  doubtful,  however,  whether  the  whole  chemical  regu- 
lation can  be  attributed  to  such  stimuli.  For  it  has  been  found  that  the 
relation  between  heat-production  and  extent  of   surface    in    animals 


THERMOTAXJS  701 

(guinea-pigs)  of  different  size  is  unaltered  wh^  the  air  temperature  is 
made  so  nearly  the  same  as  that  of  the  skin  that  the  temperature  nerves 
can  hardly  be  supposed  to  be  excited. 

There  is  some  evidence  that  the  bioplasm — the  living  substance — of 
different  animals,  even  when  the  external  conditions  are  the  same,  may 
differ  specifically  in  the  average  intensity  of  metabolism  to  which  it  is 
pitched.  When  exposed  to  a  temperature  about  equal  to  that  of  warm- 
blooded animals,  the  green  lizard  [Lacerta  viridis)  and  the  bull-frog, 
which  live  in  the  temperate  zone,  and  for  which  a  temperature  of 
37*  C.  is  highly  abnormal,  double  their  heat-production,  and  soon  die. 
Tropical  poikilothermal  animals,  such  as  the  alligator,  also  double 
their  heat-production,  but  the  highest  values  reached  are  only  one-half 
that  of  the  lizard  at  25°  C.  Apparently  the  bioplasm  of  the  tropical 
animals  has  adapted  itself  to  a  high  external  temperature,  and  works 
very  economically  even  at  the  highest  temperatures  (Krehl). 

Heat  Centres. — It  is  known  that  certain  injuries  of  the  central 
nervous  system  are  related  to  disturbance  of  the  heat-regulating 
mechanism.  Injury  to  various  portions  of  the  cortex  cerebri  in 
the  dog  and  other  animals,  and  lesions  of  the  pons,  medulla  oblongata 
and  cord  in  man,  may  be  followed  by  increase  of  temperature. 
When  the  spinal  cord  is  cut  below  the  level  of  the  vaso-motor  centre, 
the  increased  loss  of  heat  from  the  skin  due  to  dilatation  of  the 
cutaneous  vessels  masks  any  increase  of  the  heat-production  which 
may  possibly  have  taken  place,  and  the  internal  temperature  falls; 
but  if  the  loss  of  heat  is  diminished  by  wrapping  the  animal  in 
cotton-wool  the  temperature  may  rise.  From  such  phenomena  it 
has  been  surmised  that  certain  '  centres  '  in  the  brain  have  to  do 
with  the  regulation  of  temperature  by  controlHng  the  metabolism 
of  the  tissues;  that  they  cause  increased  metabohsm  when  the 
internal  temperature  threatens  to  sink,  diminished  metabolism 
when  it  tends  to  rise.  The  cutting  off,  it  is  said,  of  the  influence 
of  the  '  heat  centres  '  by  section  of  the  paths  leading  from  them 
allows  the  metabolism  of  the  tissues  to  run  riot,  and  the  temperature 
to  increase.  But  diversity  of  opinion  still  reigns  as  to  the  existence 
or,  if  they  exist,  as  to  the  precise  location  of  the  nervous  centres 
which  preside  over  this  function.  It  is  stated  by  some  workers 
that  animals  deprived  of  the  cerebral  hemispheres,  the  corpora 
striata  and  one  of  the  optic  thalami,  still  maintain  to  a  remarkable 
degree  a  body  temperature  independent  of  their  environment,  but 
that  when  both  optic  thalami  have  been  removed  they  become 
poikilothermal  (Krehl,  etc.).  The  greatest  mass  of  evidence  points, 
however,  to  the  corpora  striata  as  structures  more  intimately  con- 
cerned in  temperature  regulation  than  any  other.  Puncture  of  the 
median  portion  of  the  corpus  striatum  in  the  rabbit  by  a  needle 
thrust  through  a  trephine  hole  in  the  skull  is  followed  in  a  few- 
hours  by  a  rise  of  temperature  in  the  rectum  (1°  to  2°),  and  still 
more  in  the  duodenum,  which  is  normally  the  hottest  part  of  tht 
body  in  this  animal.     The  heat-production,  the  respiratory  exchange 


7oa  ANIMAL  HEAT 

and  the  nitrogen  excretion  are  increased.  These  phenomena  mav 
last  for  several  days  (Ott,  Richet,  Aronsohn,  and  Sachs),  and  are 
due  to  stimulation  of  the  portions  of  the  brain  in  the  immediate 
neighbourhood  of  the  injury.  Electrical  stimulation  of  this  region 
has  a  similar  effect.  When  the  temperature  has  returned  to 
normal,  a  fresh  puncture  may  again  cause  a  rise. 

As  to  the  manner  in  which  these  centres  are  excited,  there  is 
some  evidence  that,  in  addition  to  any  influence  exerted  on  them 
by  afferent  nerves,  they  are  capable  of  being  directly  affected  by 
the  temperature  conditions  of  the  blood  passing  through  them,  as 
well  as  by  numerous  drugs.  Thus  it  is  stated  by  Barbour  and  Wing 
that  direct  application  of  cold  to  the  region  of  the  corpus  striatum, 
especially  its  caudate  nucleus,  in  rabbits  causes  a  rise  in  the  rectal 
temperature,  associated  with  shivering  and  consequent  increase  of 
heat-production  in  the  contracting  muscles,  and  with  peripheral 
vaso-constriction  and  consequent  diminution  in  the  heat-loss. 
The  application  of  warmth  has  the  opposite  effect :  the  peripheral 
bloodvessels  dilate,  the  animal  becomes  quiet,  and  the  rectal  tern 
perature  falls.* 

Some  observers  hold  that  the  chief  seat  of  the  increased  metab- 
olism in  the  puncture  fever  is  the  skeletal  muscles,  others  the  Hver. 
The  question  turns  largely  upon  the  success  of  the  puncture  ex- 
periment after  the  previous  administration  of  curara  on  the  one 
hand,  and  of  strychnine  on  the  other.     For  curara  cuts  out  the 
motor  innervation  of  the  skeletal  muscles,  and  strychnine  convul- 
sions exhaust  the  store  of  hepatic  glycogen.     Certain  investigators 
have  found  that  after  an  adequate  dose  of  curara  no  puncture  fever 
can  be  obtained,  and  they  locate  the  increased  metabolism  asso- 
ciated with  the  fever  in  the  muscles.     Others  maintain  that  even 
after  curara  the  puncture  is  followed  by  fever,  but  is  not  followed 
by  fever  if  strychnine  has  first  been  given.     They  accordingly  con- 
clude that  the  rapid  combustion  of  the  glycogen  (or  the  dextrose 
derived  from  it)  is  the  primary  factor  in  the  increased  metabolism. 
It  may  be  pointed  out,  however,  that  neither  experiment  is  a  crucial 
test.     For  if  strychnine  reduces  the  liver  glycogen,  it  also  reduces 
the  glycogen  of  the  muscles.     And  if  in  the  puncture  fever  the  liver 
glycogen  is  transformed  into  dextrose  more  rapidly  than  usual^  the 
dextrose  is  probably  in  great  part  used  up  in  the  muscles  more 
rapidly  than  usual,  eh?,  it  would  appear  in  the  urine.     The  effect 
of  strychnine  on  the  puncture  fever,  then,  is  no  proof  that  the 
muscles  are  not  essentially  concerned  in  it.     On  the  other  hand,  the 
alleged  absence  of  the  fever  after  curara  is  not  sufficient  to  show 
that  the  muscles  are  alone  concerned.     For  curara  causes  a  lowering 
of  the  body-temperature,  which,  if  it  be  not  overcompensated,  may 

*   Other  observers,  however,  have  failed  to  coa&rm  these  results  (Cloetta 
and  Waser). 


PEVER  703 

mask  the  fever.  The  positive  result  of  the  puncture  in  curarized 
animals,  which  some  observers  say  they  have  obtained,  would,  if 
animals,  which  some  observers  say  they  have  obtained,  would,  if 
confirmed,  be  important  evidence  that  the  primary  effect  is  not  on 
the  muscles,  or,  at  least,  not  solely  on  them,  but  would  not  prove 
that  it  is  on  the  liver.  That  the  liver  is  concerned,  however,  is  more 
directly  indicated  by  the  fact  that  during  the  puncture  fever  the 
hver  continues  to  be  what  it  is  under  normal  conditions,  the  warmest 
organ  in  the  body,  warmer  than  the  blood  in  the  root  of  the  aorta 
by  about  1°  C.  The  most  probable  conclusion  is  that  the  increased 
production  of  heat  in  this  form  of  experimental  fever  is  due  to  an 
increased  metabolism  of  carbo-hydrate  (glycogen)  both  in  the  liver 
and  in  the  muscles. 

Temperature  Regulation  in  Hibernating  Animals. — The  behaviour 
of  hibernating  mammals,  such  as  the  marmot,  dormouse,  hedgehog, 
and  bat,  is  of  interest  in  connection  with  the  temperature  regulation. 
In  the  active  waking  state  these  animals  are  homoiothermal,  but  in 
profound  winter  sleep  they  are  poikilothermal,  the  body-tempera- 
ture rising  and  falHng  with  that  of  the  air.  The  rectal  temperature 
may  be  as  low  as  2°  C.  There  is  an  intermediate  state  in  which  the 
animal  is  partially  awake,  though  inactive,  and  its  temperature  is 
much  below  the  normal,  but  considerably  above  that  of  its  environ- 
ment. In  this  condition  it  has  an  imperfect  thermotaxis,  something 
Hke  that  of  an  ordinary  mammal  (including  the  human  infant)  in 
the  period  of  immaturity,  immediately  after  birth.  When  the 
hibernating  mammal  awakes  the  rise  of  temperature  is  enormous 
and  abrupt.  The  temperature  of  a  dormouse  rose  in  an  hour  from 
135°  C  to  357°  C,  and  that  of  a  bat  in  fifteen  minutes  from  17°  C. 
to  34"  C.  (Pembrey). 

Fevers. — Fever  is  a  pathological  process  generally  caused  by  the 
poisonous  products  of  bacteria,  and  characterized  by  a  rise  of 
temperature  above  the  Hmit  of  the  daily  variation  (p>  712).  It  is 
further  associated  with  an  increase  in  the  rate  of  the  heart  and  the 
respiratory  movements,  and  a  diminution  in  the  alkalies  and  carbon 
dioxide  of  the  blood.  The  total  excretion  of  nitrogen  is  increased, 
at  least  in  proportion  to  the  amount  of  protein  ingested,  indicating 
an  increase  in  the  consumption  of  tissue-protein.  The  distribution 
of  the  nitrogen  among  the  urinary  constituents  is  altered.  The 
ammonia  (in  the  form  of  ammonium  salts  of  organic  acids),  the 
uric  acid,  and  to  a  smaller  extent  the  creatinin  (Leathes),  are  in- 
creased, while  the  urea  is  relatively  decreased,  evon  when  its  abso- 
lute amount  is  greater  than  normal.  Creatin,  which  is  not  normally 
present  in  urine,  unless  the  food  contains  it,  may  also  appear  in 
fever  (Shaffer).  It  has  been  suggested  that  the  proximate  cause  of 
fever  is  the  action  of  bacterial  poisons  or  of  other  substances  on  the 
*  heat  centres,'  and  that  antipyretics,  or  drugs  which  reduce  the 
temperature  in  fever,  do  so  by  restoring  the  centres  to  their  normal 


704  ANIMAL  HEAT 

State,  by  preventing  the  development  of  the  poisons,  aiding  their 
elimination,  or  antagonizing  their  action.     In  favour  of  this  view, 
it  has  been  stated  that  when  the  basal  ganglia  are  cut  off,  by  section 
of  the  pons,  from  their  lower  nervous  connections,  fever  is  no  longer 
produced  by  injection  of  cultures  of  bacteria  which  readily  cause  it 
in    an    intact    animal,    while    antipjTin    has   no   influence    upon 
the  temperature  (Sawadowski).     And  while  it  is  almost  certain 
that  some  pyrogenic  or  fever-producing  agents — cocaine,  e.g. — act 
indirectly,  through  the  brain  or  cord,  it  is  quite  possible  that  others 
affect  directly  the  activity  of  the  tissues  in  general,  just  as  some 
antipyretics  or  fever-reducing  agents,  such  as  quinine,  act  imme- 
diately upon   the   heat-forming  tissues,   so   as  to   diminish   their 
metabohsm,  while  others,  like  antipyrin,  affect  them  through  the 
nervous  system.     Quinine  has  no  influence  upon  '  puncture  '  fever 
in  rabbits.     A  still  more  important  action   of  antip}Tin,  and  the 
group  of  antipyretics  to  which  it  belongs,  is  the  increase  in  the  heat- 
loss  which  they  bring  about  by  the  dilatation  of  the  bloodvessels 
of  the  skin.   This  effect  is  also  produced  through  the  nervous  system. 
Fever  is  a  condition  so  interesting  from  a  physiological  point  of 
view,  and  of  such  importance  in  practical  medicine,  that  it  will  be 
well  to  consider  a  little  more  closely  the  possible  ways  in  which  a 
rise  of  temperature  may  occur.     It  must  not  be  forgotten  that  the 
febrile  increase  of  temperature  is  always  accompanied  by  other 
departures  from  the  normal,  and  that  all  the  fundamental  febrile 
changes  may  even,  in  certain  cases,  be  present  without  elevation, 
and  even  with  diminution  of  temperature.     But  here  we  have  only 
to  do  with  the  disturbance  of  the  normal  equilibrium  between  the 
loss  and  the  production  of  heat;  and  it  is  evident  that  any  of  the 
five  conditions  illustrated  in  the  diagram  (Fig.  226)  may  give  rise 
to   an   increase  of  temperature.     It   is   not   necessary  to   discuss 
whether  cases  of  fever  can  actually  be  found  to  illustrate  every  one 
of  these  possibihties.     It  is  probable  that  not  infrequently  dimin- 
ished loss  and  increased  production  may  be  both  involved;  and  it 
ought  to  be  remembered  that  the  healthy  standard  with  which  the 
heat-production  of  a  fever  patient  should  be  compared  is  not  that 
of  a  man  doing  hard  work  on  a  full  diet,  but  that  of  a  healthy  person 
in  bed,  and  on  the  meagre  fare  of  the  sick-room.     When  this  is  kept 
in  view,  the  comparatively  low  heat-production  and  respiratory 
exchange  which  have  sometimes  been  found  in  fever  cease  to  excite 
surprise.     But  in  any  case,  no  mere  change  in  the  absolute  quantities 
of  heat  formed  and  lost  is  sufficient  to  explain  the  febrile  rise  of 
temperature;  there  must  be  a  change  in  the  relative  proportion. 
That  an  increase  in  heat-production  is  not  of  itself  enough  to  produce 
fever  is  proved  by  the  fact  that  severe  muscular  work,  which  in- 


FEVER 


705 


creases  the  metabolism  more  than  high  fever,  only  causes  in  a 
healthy  man  a  rise  of  about  1°  C.  in  the  rectal  temperature.  When 
the  work  is  over,  the  temperature  comes  rapidly  back  to  normal. 
The  essence  of  the  change  in  fever  is  a  derangement  of  the  mechanism 
by  which  in  the  healthy  body  excess  or  defect  of  average  metab- 
olism, or  of  average  heat- 
loss,  is  at  once  compensated 
and  the  equilibrium  of  tem- 
perature maintained. 

This  derangement  only  lasts 
as  long  as  the  temperature 
is  rising.  When  it  becomes 
stationary  at  its  maximum 
we  have  again  adjustment, 
again  equality  of  production 
and  escape  of  heat;  but  the 
adjustment  is  now  pitched 
for  a  higher  scale  of  tempera- 
ture. A  rough  analogy,  so 
far  as  one  part  of  the  process 
is  concerned,  may  be  found 
in  the  behaviour  of  the 
ordinary  gas-regulator  of  a 
water-bath.  It  can  be  '  set ' 
for  any  temperature.  That 
temperature,  once  reached, 
remains  constant  within  nar- 
row limits  of  oscillation;  but 
the  regulator  can  be  equally 
well  adjusted  for  a  higher  or 
a  lower  temperature.  It  is, 
however,  important  to  note  that  the  equilibrium  is  more  unstable 
in  fever  than  in  health,  so  that  changes  of  external  temperature  more 
easily  depress  or  increase  the  temperature  of  a  fever  patient  than  of 
a  healthy  man. 

Rosenthal  has  concluded  from  calorimetric  observations  that,  in 
the  first  stage  of  fever,  while  the  temperature  is  rising,  there  is 
always  increased  retention  of  heat.  Maragliano  actually  found 
evidence,  by  means  of  the  pletliysmograph,  that  the  cutaneous 
vessels  are  at  this  stage  constricted,  and  that  the  constriction  may 
even  precede  the  rise  of  temperature.  The  blood-flow  in  the  feet 
in  cases  of  typhoid  fever  investigated  by  the  calorimetric  method 
(p.  122)  was  not  found  to  exceed  the  normal  flow,  and  was  usually 
decidedly  below  the  normal.  Hyperexcitability  of  the  vaso-con- 
strictor  mechanism  of  the  peripheral  parts,  especially  of  the  skin, 

45 


Fig.  226. — Diagram  to  show  the  Possible 
Relations  between  Heat- Production  and 
Heat-Loss  in  Fever. 


706  AXIMAL  HEAT 

was  present.  All  these  observations  lend  support  to  the  famous 
'  retention  '  theory  of  Traube.  It  has  been  suggested  that  the 
significance  of  the  increased  action  of  the  cutaneous  vaso-constrictor 
mechanism  in  typhoid  fever  is  that  the  peripheral  vaso-constriction 
is  a  compensatory  arrangement  which  secures  for  the  organs  mainly 
suffering  from  the  infective  process  an  increased  flow  of  blood  to 
combat  the  infection.  On  this  hypothesis  the  rise  of  temperature 
in  so  far  as  it  depends  upon  diminished  loss  of  heat  is  a  secondary 
phenomenon  inevitably  following  the  redistribution  of  the  blood, 
and  unavoidable  except  by  a  corresponding  diminution  in  the  total 
metabolism.  In  the  great  majority  of  cases  the  production  of  heat 
is  also  increased,  on  the  average  by  20  to  30  per  cent,  of  the  normal 
production  of  a  resting  man.  The  increase  may  be  much  greater 
during  the  chill  which  ushers  in  so  many  infections  on  account  of 
the  muscular  contractions  in  shivering.  During  the  period  of  rising 
temperature  the  production  of  heat  is  not  necessarily  increased. 
At  the  height  of  the  fever  there  is  often,  though  apparently  not 
always,  an  increase  in  the  heat-production.  After  the  crisis,  while 
the  fever  is  subsiding,  the  rate  at  which  heat  is  lost  rises  sharply. 
As  to  the  explanation  of  the  increase  of  metabolism  in  fever, 
and  especially  of  the  increased  metabolism  of  tissue-protein, 
various  \news  have  been  held.  Some  have  gone  so  far  as  to  say 
that  the  increase  is  merely  the  consequence,  not  the  cause,  of 
the  rise  of  temperature.  But  the  rebutting  evidence  which  has 
been  brought  against  this  view  is  strong  and,  indeed,  overwhelming. 
It  is  perfectly  true  that,  when  the  temperature  of  the  body  is 
artificially  raised  by  preventing  the  free  loss  of  heat  for  a  sufficient 
time  (so-called  ph3-siological  fever),  the  destruction  of  protein  is 
augmented.  A  fasting  dog  whose  temperature  was  increased  to 
40°  or  41°  C  for  twelve  hours  eliminated  ^y  per  cent,  more  nitrogen 
than  when  the  body-temperature  was  normal.  But  this  increase 
in  the  protein  metabolism  could  be  entirely  prevented  by  gi\nng 
the  animal  a  sufficient  amount  of  carbo-h\-drate.  Similar  r^^sults 
have  been  obtained  in  man.  The  carbon  dioxide  excretion  and 
oxygen  absorption  are,  of  course,  also  markedly  increased.  But  the 
increase  in  the  nitrogen  excretion  is  often  much  greater  in  fever  than 
any  increase  which  can  be  brought  about  by  artificially  raising  the 
temperature  of  a  health}'  individual  by  means  of  hot  baths.  A 
typhoid  patient  was  found  to  lose  10  8  grammes  of  nitrogen  a  day 
(corresponding  to  318  grammes  of  muscle)  during  eight  days  of 
fever  (F.  Miiller).  A  portion  of  the  loss  of  nitrogen  on  the  routine 
fever  regimen  may  be  due  to  the  fact  that  the  ordinary  typhoid 
patient  is  really  on  a  semi-starvation  diet,  the  heat-equivalent  of 
which  is  not  much  more  than  half  his  heat-production.  Yet  it 
has  not  been  found  possible  to  completely  prevent  the  loss  of 


FEVER 


707 


nitrogen  by  putting  the  fever  patient  on  a  diet  rich  in  protein,  or 
on  a  diet  containing  a  moderate  amount  of  protein  with  a  large 
quantity  of  fat  and  carbo-hydrate,  even  when  the  total  heat- value 
of  the  diet  is  much  in  excess  of  the  32  or  33  calories  per  kilo  of  body- 
weight  which  corresponds  to  the  heat-production  of  a  resting  man. 
Another  suggestive  fact  is  that  the  excessive  excretion  of  nitrogen 
does  not  run  parallel  with  the  rise  of  temperature  in  fever,  but  is 
often  most  marked  after  the  crisis.  During  the  stage  of  defer- 
vescence an  enormous  amount  of  urea  is  sometimes  given  off.  In  a 
case  of  typhus,  in  the  mixed  urine  of  the  third  and  fourth  days  after 
the  crisis,  no  less  than  160  grammes  of  urea  was  found  (Naunyn),  or 
nearly  three  times  the  normal  amount  for  a  man  on  full  diet.  Again, 
when  fever  is  caused  by  the  injection  of  bacteria  or  their  products, 
the  increase  in  the  carbon  dioxide  eliminated  and  oxygen  consumed 
occurs  even  when  the  temperature  is  prevented  from  rising  by  cold 
baths.  It  seems  perfectly  clear,  then,  that  the  increase  of  metab- 
olism is,  in  many  cases  at  least,  a  primary  phenomenon  of  fever. 
Its  course  and  incidence,  falling  as  it  does  so  largely  upon  the 
proteins,  the  steady  loss  of  tissue  nitrogen,  and  the  inability  of  the 
tissues  to  recoup  their  losses  from  the  protein  of  the  food  or  to 
shield  their  own  protein  by  burning  more  carbo-hydrate  or  fat,  all 
suggest  that  the  cells  are  poisoned  by  toxic  products  of  the  infective 
process.  The  poisoned  bioplasm  falls  an  easy  prey  to  the  hydro- 
lysing  and  oxidizing  agents  always  present  in  the  tissues.  It  breaks 
down  more  rapidly  and  builds  itself  up  more  slowly  than  normal 
bioplasm.  This  increased,  and  to  some  extent  perverted,  metab- 
olism, far  from  being  occasioned  by  the  febrile  temperature,  is  quite 
probably  the  cause  of  the  thermo-regulative  upset  which  we  call  fever. 
For  Mandel  has  shown — (i)  that  one  of  the  purin  bases  (xanthin) 
causes  fever  in  monkeys;  (2)  that  the  purin  bases  in  the  urine  are 
increased  both  in  infective  fevers  and  the  so-called  aseptic  or  surgical 
fever — 'that  is,  in  cases  where  the  temperature  rises  after  such  injuries 
as  extensive  crushing  of  tissues  without  infection.  There  is  a  con- 
stant relation  between  the  height  of  the  fever  and  the  quantity  of 
purin  bases  excreted.  The  source  of  the  purin  bases  in  aseptic  fever 
is  presumably  the  autolysis  of  the  injured  tissue,  from  which  they 
pass  into  the  blood  without  being  oxidized  to  uric  acid.  The  xanthin 
fever  can  be  prevented  by  salicylates,  though  not  by  antipyrin. 

It  has  been  very  generally  admitted  that  the  chief  seat  of  excessive 
metabohsm  in  fever  is  the  muscles;  but  U.  Mosso  has  stated  that 
cocaine  fever — the  marked  rise  of  temperature  produced  by  injec- 
tion of  cocaine — can  be  obtained  in  animals  paralyzed  by  curara. 
This,  even  if  true,  would  not  support  the  conclusion  that  a  '  nervous 
fever  ' — that  is  to  say,  a  fever  due  solely  to  increased  metabolism 
in  the  nervous  system — exists;  for  in  a  curarized  animal  a  large 


7o8  ANIMAL   HEAT 

amount  of  'active'  tissue  (glands,  heart,  smooth  muscle)  still 
remains  in  i)hysiol()gical  connection  with  the  brain  and  cord.  But, 
as  a  matter  of  fact,  in  an  animal  under  a  dose  of  curara  sufficient 
to  completely  paralyze  the  skeletal  muscle  cocaine  causes  no  appre- 
ciable rise  of  rectal  temperature;  and  this  is  strongly  in  favour  of 
tlie  view  that  the  fever  produced  in  the  non-curarized  animal  is 
connected  with  excessive  muscular  metabolism. 

Significance  of  the  Increased  Temperature  in  Fever. — It  remains 
to  ask  whether  the  rise  of  temperature  is  unytliing  more  than  a 
superticial  and,  so  to  speak,  an  accidental  circumstance.  The 
question  has  already  been  raised  in  discussing  the  changes  in  the 
circulation  in  fever  (p.  706).  The  orthodox  view  for  many  ages 
has  undoubtedly  been  that  the  increase  of  temperature  is  in  itself 
a  serious  part  of  the  pathological  process,  a  symptom  to  be  fought 
with  and,  if  possible,  removed.  And,  indeed,  it  is  not  denied  by 
anyone  that  the  excessive  rise  of  temperature  seen  in  some  cases  of 
febrile  disease  (to  43°  C.,  or  even  to  45")  is,  apart  from  all  other 
changes,  a  most  imminent  danger  to  life,  unless,  as  is  sometimes  the 
case  (in  influenza,  e.g. ,  where  a  temperature  of  44°  has  been  observed) , 
the  high  temperature  lasts  only  a  short  time.  Experimental  heat 
paralysis,  a  condition  in  which  all  voluntary  and  reflex  movements 
are  abolished,  is  produced  in  frogs  by  raising  the  internal  tempera- 
ture to  about  34°  C.  On  cooling,  the  animal  recovers.  A  similar 
condition  can  be  induced  in  mammals,  but,  of  course,  at  a  higher 
temperature.  The  central  nervous  system  succumbs  before  the 
peripheral  structures.  The  superior  cervical  ganglion  in  the  cat  or 
rabbit  loses  the  power  of  transmitting  nerve  impulses  at  50°  C 
But  some  evidence  has  been  brouglit  forward,  mostly  from  the  field 
of  bacteriology,  to  support  the  idea  that  in  infective  processes  the 
rise  of  temperature  is  of  the  nature  of  a  protective  mechanism,  that 
the  fever  is,  indeed,  a  consuming  fire,  but  a  fire  that  wastes  the  body, 
to  destroy  the  bacteria.  The  streptococcus  of  erysipelas,  for  ex- 
ample, does  not  develop  at  39°  to  40°  C,  and  is  killed  at  39'5°  to 
41°  C,  and  erysipelas  infections  in  rabbits  are  less  virulent  if  the 
body -temperature  be  artificially  raised.  Anthrax  bacilli,  kept  at 
42°  to  43°  C.  for  some  time,  are  attenuated,  and  when  injected  into 
animals  confer  immunity  to  the  disease.  Heated  for  several  days 
to  41°  to  42°  C,  pneumococci  render  rabbits  immune  to  pneumonia, 
and  in  rabbits  in  which  '  puncture  '  fever  has  been  induced  pneumo- 
coccus  infections  run  a  milder  course.  These  bacteriological  results 
are  sup])orted  to  a  certain  extent  by  clinical  experience.  For  it  has 
been  observed  that  a  cholera  patient  witli  distinct  fever  has  a 
better  chance  of  recovery  than  a  case  which  shows  no  fever.  But 
too  much  weight  ought  not  to  be  given  to  isolated  facts  of  this  sort, 
and  adverse  evidence  can  be  produced  both  from  the  laboratory 


TEMPI'. HA  TURE  TOPOGh'A  J'UY 


709 


and  tlie  hospital.  For  although  hens  are  immune  to  anthrax  under 
ordinary  conditions,  but  can  be  infected  by  inoculation  when 
artificially  cooled,  frogs,  equally  immune  at  the  temperature  of  the 
air,  become  susceptible  when  artificially  heated.  And  it  is  impos- 
sible to  deny  that  the  use  of  cold  baths  in  typhoid  fever  is  sometimes 
of  remarkable  benefit.  This  benefit,  however,  while  very  unlikely 
to  be  connected  with  any  directly  unfavourable  action  of  the  reduced 
body-temperature  on  the  growth  of  the  bacilli,  may  perhaps  be  due, 
in  some  part  at  least,  to  an  increase  in  the  cutaneous  vaso-con- 
striction  which  helps  to  send  through  the  infected  intestine  a  more 
copious  stream  of  blood. 

Section  IV. — Distribution  of  Heat — -Temperature 
Topography. 

The  great  foci  of  heat-formation — the  muscles  and  glands — would, 
if  heat  were  not  constantly  leaving  them,  in  a  short  time  bcconn; 
much  warmer  than  the  rest  of  the  body;  while  structures  like  the 
bones,  skin,  and  adipose  tissue,  in  which  chemical  change  and  heat- 
production  are  slow,  would  soon  cool  down  to  a  temperature  not 
much  exceeding  that  of  the  air.  The  circulation  of  the  blood 
insures  that  heat  produced  in  any  organ  shall  be  carried  away  and 
speedily  distributed  over  the  whole  body;  while  direct  conduction 
also  plays  a  considerable  part  in  maintaining  an  appro.ximately 
uniform  temperature.  The  uniformity,  however,  is  only  approxi- 
mate. The  temperature  of  the  liver  is  several  degrees  higher  than 
that  of  the  skin,  and  the  temperature  of  the  brain  several  degrees 
higher  than  that  of  the  cornea.  The  blood  of  the  superficial  veins 
is  colder  than  that  of  the  corresponding  arteries. 

The  crural  vein,  for  example,  carries  colder  blood  than  the  crural 
artery,  and  the  external  jugular  than  the  carotid.  The  heat  produced 
in  the  deeper  parts  of  the  regions  which  they  drain  is  more  than  counter- 
balanced by  the  heat  lost  in  the  more  superficial  parts.  When  loss  of 
heat  from  the  surface  is  sufficiently  diminished  by  an  artificial  covering, 
or  prevented  by  the  protected  situation  of  any  organ  with  an  active 
metabolism,  the  venous  blood  leaving  it  is  warmer  than  the  arterial 
blood  coming  to  it.  The  temperature  of  the  blood  passing  from  the 
levator  labii  superioris  muscle  of  the  liorse  during  mastication  may  be 
sensibly  higher  than  that  of  the  blood  which  feeds  it ;  the  blood  in  the 
vena  profunda  femoris,  and  in  the  crural  vein  of  a  dog  with  the  leg 
wrapped  in  cotton- wool,  is  warmer  byO'i°to  0*3°  than  of  the  crural 
artery.  The  difference  is  due  to  the  heat  produced  in  the  muscles,  and  it 
ought  to  be  of  this  order  of  magnitude.  The  quantity  of  blood  in  a 
7-kilo  dog  is  about  J  kilo ;  J  of  this,  or  ^  kilo,  is  in  the  skeletal  muscles, 
and  the  average  circulation-time  through  them  may  be  taken  as  ten 
seconds.  Six  times  in  the  minute,  or  360  times  in  the  hour,  |  kilo  of 
blood  passes  through  the  muscles,  and  is  heated  on  the  average  by  0-2°. 

This  represents  a  heat-production  of  about  '-q- x — ,  or  9  calories  per 

hour.     Now,    the    total    heat-production   of   a    7-kilo    dog   is   about 


yio  ANIMAL  HEAT 

1 1)  calorics  per  hour,  of  which  somewhat  less  than  one-half  is  formed 
in  tne  skeletal  muscles. 

The  blood  of  the  inferior  vena  cava  at  the  le\cl  of  the  kidneys  may 
be  o*i°  colder  than  that  of  the  abdominal  aorta,  but  is  warmer  than 
the  blood  of  the  superior  cava.  The  right  heart,  therefore,  receives 
two  streams  of  blood  at  different  temperatures,  which  mingle  in  its 
cavities.  A  controversy  was  long  carried  on  as  to  the  relative  tem- 
perature of  the  blood  of  the  two  sides  of  the  heart ;  but  the  researches 
of  Heidenhain  and  Korner  have  shown  that  a  thermometer  passed  into 
the  right  ventricle  through  the  jugular  vein  stands,  as  a  rule,  slightly 
higher  than  a  thermometer  introduced  through  the  carotid  into  the 
left  ventricle.  The  method  gives  not  so  much  the  temperature  of  the 
blood  in  the  two  cavities  as  that  of  their  walls.  The  thin-walled  right 
ventricle  is  heated  by  conduction  from  the  warm  liver,  from  which  it  is 
only  separated  by  the  diaphragm,  while  the  left  ventricle  loses  heat 
to  the  cooler  lungs.  The  difference  of  temperature  is  not  caused  by 
cooling  of  the  blood  in  its  passage  through  the  pulmonary  capillaries, 
for  even  when  respiration  is  suspended,  a  difference  of  temperature 
between  the  two  sides  of  the  heart  is  found.  Under  ordinary  circum- 
stances, the  inspired  air  is  already  heated  almost  to  body-temperature 
before  it  reaches  the  alveoli.  But,  while  this  is  the  case,  a  fall  of  less 
than  ^■\y°  in  the  temperature  of  the  blood  passing  through  the  lungs 
would  account  for  all  the  heat  lost  by  the  expired  air.  If  half  of  the 
loss  took  place  in  the  upper  air-passages,  less  than  ;^V)''  would  be  suffi- 
cient. A  slight  difference  of  temperature  in  the  blood  of  the  two  ven- 
tricles might  be  caused,  even  in  the  absence  of  respiration,  by  the  heat 
developed  in  the  cardiac  muscle  itself  during  contraction,  a  large  pro- 
portion of  which  must  be  conveyed  by  the  coronary  veins  into  the  right 
heart. 

The  surface  temperature  varies  between  rather  wide  limits  with  the 
temperature  of  the  environment.  The  temperature  of  cavities  like 
the  rectum,  vagina,  and  mouth,  and  of  secretions  like  the  urine,  approxi- 
mates to  that  of  the  blood  in  the  great  vessels  or  the  heart,  and  under- 
goes only  slight  changes.  An  increase  in  the  velocity  of  the  blood  causes 
the  internal  and  surface  temperatures  to  come  nearer  to  each  other, 
the  former  falling  and  the  latter  rising.  When  the  loss  of  heat  from 
a  portion  of  the  surface  is  prevented,  the  temperature  of  this  portion 
approaches  the  internal  temperature.  For  this  reason  a  thermometer 
placed  in  the  axilla  approximately  measures  the  internal  temperature, 
and  not  that  of  the  skin;  and  a  thermometer  in  tlie  groin  of  a  rabbit, 
and  completely  covered  by  the  flexed  thigh,  may  stand  as  high  as,  or, 
it  is  said,  even  higher  than,  a  thermometer  in  the  rectum  (flale  White). 
The  temperature  in  the  mouth  is  not  a  very  reliable  index  of  the  deep 
temperature  of  the  body,  especially  in  cold  weather  or  after  exercise, 
as  it  is  apt  to  be  influenced  by  the  inspired  air.  The  mouth  must,  of 
course,  be  kept  closed  during  the  measurement.  On  the  average  its 
temperature  is  about  the  same  as  that  of  the  axilla,  and  0*4°  C.  below 
that  of  the  rectum.  The  rectal  temperature  is  o->°  or  0-3°  alx)ve  that 
of  the  urine.  In  point  of  accuracy  rectal  observations  are  the  best,  and 
next  to  them  determinations  of  the  temperature  of  the  stream  of  urine. 
The  latter  method,  although  subject  to  obvious  limitations,  is  rapid  and 
free  from  the  danger  of  conveying  infection  to  the  person  (Pembrey). 

The  surface  temperature  is  a  rough  index  of  the  rate  of  heat-loss; 
the  internal  temperature,  of  the  rate  of  heat-production.  A  normal 
skin  temperature  and  a  rising  rectal  temperature  would  probably  in- 
dicate increased  production  of  heat;  an  increased  rectal  temperature, 


TEMPERATURE  TOPOGRAPH  Y  7H 

in  conjunction  with  a  diminished  surface  temperature,  as  in  the  cold 
stage  of  ague,  might  he  duo  cither  to  diminished  heat-loss  while  the 
heat-production  remained  normal,  or  to  diminished  heat-loss  plus 
increased  heat-production. 

Tlie  following  tables  illustrate  the  differences  of  temperature  found 
in  the  body.  It  should  be  remembered  that  the  numbers  are  not 
strictly  comparable  with  each  other;  the  temperature  of  the  mammals 
in  which  direct  observations  have  been  made  on  the  blood  is  not 
exactly  the  same  as  that  of  man,  the  temperature  of  the  dog.  for 
example,  being  a  little  (about  i°  C.)  higher.  Then  in  the  same  animal 
there  is  no  very  constant  ratio  between  the  temperature  of  the  blood 
in  two  vessels  or  of  the  skin  at  two  points.  Even  in  the  same  vessel 
the  temperature  may  vary  with  many  circumstances,  such  as  the 
velocity  of  the  stream,  and  the  state  of  activity  of  the  organ  from  which 
it  comes.  Apart  from  physiological  variations,  experimental  fallacies 
sometimes  cause  a  want  of  constancy,  especially  in  measurements  of 
blood  temperature.  The  insertion  of  a  mercurial  thermometer  into  a 
vessel  is  very  likely  to  obstruct  the  passage  of  the  blood;  and  if  the 
blood  lingers  in  a  warm  organ,  it  will  be  heated  beyond  the  normal. 
In  man  the  blood-temperature  in  the  arteries  at  the  wrist  has  been 
estimated  indirectly  by  the  calorimetric  method  of  measuring  the 
blood-flow  in  the  hand  (p.  122),  probably  with  greater  accuracy  than 
would  be  attainable  by  the  direct  insertion  of  a  thermometer,  were 
this  permissible.  The  temperature  of  the  calorimeter  is  determined  at 
which  it  neither  imparts  heat  to  the  blood  nor  gains  heat  from  the  blood. 
On  the  assumption  that  the  heat-production  of  the  resting  hand  is 
negligible  for  this  purpose,*  the  temperature  so  fixed  will  be  that  at 
which  the  blood  enters  the  hand — i.e.,  the  temperature  of  the  arterial 
blood  at  the  wrist. 

Blood.     {Dog.) 

Right  heart         -         .         .         .     38-8°  C. 

Left         ,,    -         -         -         -         -     38-6 

Aorta 38-7 

Superior  vena  cava       -         -         _     36-8 

Inferior  ,,  -         -         -     38-1 

Crural  vein  -         -         _         .         _     37-21 
,,      artery        -         .         .         _     38'o 

Profunda  femoris  vein         -         -     38-2 

Portal  vein  -         -         -         -  38-39     "I  Varies  with  activity 

Hepatic  vein         -         .         .       38'4-39'7  J  of  digestive  organs. 

Arterial  blood  at  wrist  in  man      -        0-5  below  rectal  temperature. 

*  Since,  of  course,  some  heat  is  produced  in  the  hand  even  at  rest,  although 
doubtless  less  per  unit  of  weight  than  in  the  resting  body  as  a  whole,  the 
arterial  blood  temperature  as  thus  determined  must  be  somewhat  too  high. 
No  error  is  caused  by  this  in  the  calculation  of  the  blood-flow  in  the  hand 
(p.  122) ;  for  while  the  factor  T — T'  in  the  denominator  is  somewhat  too  great, 
thv  corresponding  quantity  of  heat  produced  in  the  hand  is  included  in  H  in 
the  numerator. 

t  The  following  numbers  were  obtained   (in  an  anaesthetized  dog  whose 
rectal  temperature  had  fallen  2°  C.)  for  the  temperature  of  the  walls  of  the 
crural  artery  and  vein,  as  measured  by  an  electrical  resistance  thermometer. 
Leg  of  dog  lightly  wrapped  in  wool.  '\ 

Crural  artery 34'95 

vein     ------     34-761  Rcclum,  36*2 

Leg  more  carefully  wrapped  up.  [Air,  i6'3 

Crural  artery  -----     34' 70 

vein     -         -         -         -         -         -     34' 82  J 


712 


ANIMAL  HEAT 


Tissues. 

Bniin 

Liver    ------ 

Subcutaneous  tissue  2-i  lower  than 

tliat  of  subjacent  muscles  (man). 

Anterior  chamber  of  eye 

Vitreous  humour 


40°  C 
4o*6-40*9 


-     3 


3^';;}(rabbit). 


Cavities. 
Axilla  -  -  -  . 
Rectum  -  -  -  - 
Moutli  -  -  -  - 
Vagina  -  .  -  _ 
Uterus  -  -  -  - 
External  auditory  meatus  - 
Bladder  (temperature  of  the 
escaping  urine) 


(Man.) 

36-3-37-5° 

36-37-8 

37'-5 

37-5-38 

37-7-38-3 

37-3-37-8 


C.  (97-3-99-5"  F-). 


36-0-37-5 


Air 

temperature, 

4-5"  " 


trachea  - 


C. 


[Horse.) 

-  ^3-4°  C. 

-  32-4  in  inspiration. 

-  34'4  in  expiration. 


(Man) 

Room 

temperature. 

I/O 


Respiratory  Passages. 
TMiddle  of  nasal  cavity 

I  ::    " ' 


Natural  Surfaces. 
Cheek  (boy,  immediately  after  running) 
'Anterior  surface  of  forearm 
Posterior 

Skin  over  biceps  -         .         -         _ 

head  of  tibia  -  -  . 
immediately  below  xiphoid  carlik; 
over  sternum  -  -  -  - 
On  hair  (boy)  ----- 
Under  hair  over  sagittal  suture  (boy) 
Shaved  skin  of  neck  (rabbit) 
On  hair 

,,       between  eyes        ,, 


Artificial  Surfaces. 

k       '  Surface  of  trousers  over  thigh 

Room  ,  ° 

,  .         -  ,,  coat  over  arm    - 

temperature.  waistcoat     -        - 

17-5  I 


36-23° 

33-5-34-4 

34-0 

35-0 

31-9 

34-7 

33  2 

30-0 

33-7-34-0 

36-5 

31-5 

30-7 


23-7- 
j6-8 
26-0 


2ii-r 


Normal  Variations  in  the  Temperature. — The  internal  tempera- 
ture, as  has  been  already  said,  is  not  strictly  constant.  It  varies 
with  the  time  of  day;  with  the  taking  of  food;  with  age;  to  some 
extent  with  violent  changes  in  the  external  temperature,  such  as 
those  produced  b}^  hot  or  cold  baths;  and  possibly  with  sex.  On 
the  average  the  range  of  variation  in  tlie  temperature  of  the  rectum 
or  urine  of  a  healthy  man  is  from  36-0°  C.  (96-8°  F.)  to  37*8°  C. 
(100-0°  F.). 

In  the  monkey  a  very  distinct  and  constant  diurnal  variation  has 
been  observed,  and  the  range  is  much  wider  than  in  man  (as  much 
as  5-4°  F.),  the  maximum  falling  between  6  and  8  p.m.  and  the 
minimum  between  2  and  4  a.m.  (Simpson). 


TEMPERA T URE   TOPOGRAPH  Y 


713 


The  daily  curve  of  temperature  shows  a  niininiuin  in  the  early 
morning,  between  two  and  six  o'clock  (36-3°  C),  and  a  maximum 
in  the  evening,  between  five  and  eight  o'clock  (37*5°  C)  (Fig.  227). 
The  daily  range  in  health  may  be  taken  as  a  little  over  i"  C,  01 
about  2°  F.  In  fever  it  is  generally  greater,  but  the  maximum  and 
minimum  fall  at  the  same  periods;  and  it  is  of  scientific,  and  also 
of  practical,  interest  that  the  early  morning,  when  the  temperature 
and  pulse-rate  are  at  their  minimum,  is  often  the  time  at  which  the 
flagging  powers  of  the  sick  give  way.  From  two  to  six  o'clock  in 
the  morning  the  daily  tide 
of  life  may  be  said  to  reach 
low- water  mark.  Even  in 
a  fasting  man  the  diurnal 
temperature  curve  runs  its 
course,  but  the  variations 
are  not  so  great.  The  ta- 
king of  food  of  itself  causes 
an  increase  of  temperature, 
although  in  a  healthy  man 
this  rarely  amounts  to  more 
than  half  a  degree.  The  rise 
of  temperature  is  certainly 
due  in  part  to  the  increased 
work  of  the  alimentary 
canal,  but  it  is  in  the  main 
connected  with  the  increase 
of  metabolic  activity  which  the  entrance  of  the  products  of  digestion 
into  the  blood  brings  about.  The  heat-production  is  especially 
increased  by  proteins. 

A  dog  weighing  I5'3  kilos,  the  heat-production  of  which  was  22-3  calo- 
ries during  an  hour  previous  to  feeding,  was  given  1,200  grammes  of 
meat  at  noon.  The  heat-production  rose  to  36  calories  in  the  2nd  hour, 
and  42  calories  in  the  3rd.  It  remained  above  40  calories  per  hour 
beyond  the  loth  hour,  and  in  the  14th  hour  it  had  only  fallen  to  37  calo- 
ries, to  reach  25  calories  in  the  21st  hour.  On  the  whole,  the  increase 
in  heat-production  ran  parallel  with,  and  was  proportional  to,  the 
increase  in  the  excretion  of  nitrogen  (Williams,  Richie  and  Lusk). 
The  relati\-ely  unimportant  share  taken  by  the  increased  work  of  the 
gastro-intestinal  tract  in  the  augmentation  of  the  metabolism  is  illus- 
trated by  the  fact  that  a  high  rate  of  heat-production  was  maintained  till 
the  14th  hour,  even  although  by  this  time  three-quarters  of  the  nitrogen 
corresponding  to  the  food  protein  had  been  eliminated  in  the  urine,  and 
the  work  of  digestion  and  absorption  must  have  been  largely  completed. 

The  rise  of  temperature  during  digestion  is  gradual,  the  maximum 
being  reached  during  the  fourth  hour,  or  even  later. 

The  cause  of  the  daily  variation  of  temperature  has  been  much 
discussed.  There  is  no  doubt  that  several  factors  are  concerned, 
among  the  most  important  being  the  variation  in  the  amount  of 
contraction  of  the  skeletal  muscles  and  the  influence  of  food.     Mus- 


2?7. 


Curve  showing  the  Daily  Variation 
of  Body-Temperature. 


7M 


ANIMAL  HEAT 


d2S 
38 


36 


J^ 


32 


■5i5     4iJ      i25     M5     S6 


\—r 

'     "'\ 

^, 

\| 

\, 

ip  t& 

\ 

^ 

cular  exercise  is  capable  of  causing  a  considerable  rise  in  the  tem- 
perature of  the  rectum  and  urine,  to  38'5°  C.  (101-3°  F.)  or  even 
38-9°  C.  (102°  F.)  without  producing  any  feeling  of  distress.  Other 
unknown  influences  seem  also  to  be  involved,  as  is  shown  by  the 
fact  that  in  persons  who  work  at  night  and  sleep  during  the  day 
the  curve  of  temperature,  although  greatly  altered,  is  not  reversed. 
Recent  observations  on  this  subject  are  those  of  Benedict.  By 
means  of  a  resistance  thermometer  in  the  rectum,  readings  were 

taken  usually  every  four  minutes. 
With  such  a  thermometer  no  disturb- 
ance of  the  person's  sleep  is  n<*cessary 
to  obtain  a  reading.  He  can  sit  with- 
out discomfort  in  any  position,  walk 
about  the  room  (returning  to  the  ob- 
server's table  for  the  observations), 
and  even  ride  a  stationary  bicycle. 
Even  years  of  night-work  do  not  elim- 
inate the  tendency  to  a  fall  of  tempera- 
ture at  night,  a  minimum  in  the  early 
morning,  and  a  morning  rise. 

As  to  the  relation  of  age  and  se.x  to 
temperature,  it  is  only  necessary  to 
remark  that  the  mean  temperature 
both  of  the  young  child  and  of  the 
old  man  is  somewhat  higher  than 
that  of  the  vigorous  adult;  but  a 
point  of  more  importance  is  the  rela- 
tive imperfection  of  the  heat-regulation 
in  infancy  and  age,  and  the  greater 
effect  of  accidental  circumstances  on 
the  mean  temperature.  Thus,  old  people  and  young  children  are 
specially  liable  to  chills,  and  a  fit  of  crying  may  be  sufficient  to 
send  up  the  temperature  of  a  baby.  In  infants  an  hour  or  two  old 
the  temperature  may  be  as  low  as  34°  C.  (93*2°  F.)  or  33*0°  C. 
(91-4°  F.)  even  when  they  are  fully  clothed  in  a  room  at  15°  C 
(59°  F.).  It  rises  gradually  during  the  first  day  or  two,  but  shows 
marked  variations.  On  the  fifth  day  after  birth,  e.g.,  the  rectal 
temperature  ranged  from  36-2°  C  (97*  16°  F.)  to  33*5°  C.  (92-3°  F.) 
in  a  child  weighing  ^\  pounds  (Babak).  The  temperature  of  women 
is  generally  a  little  higher  than  that  of  men,  and  is  also  somewhat 
more  variable.  A  fall  of  temperature,  rarely  amounting  to  more 
than  1°  F.,  is  associated  with  the  menstrual  jx-riod. 

After  death  the  body  cools  at  first  rapidly,  then  more  slowly 
(Fig.  2:8).  But  occasionally  a  post-mortem  rise  of  temperature 
may  take  place.  In  certain  acute  diseases  (like  tetanus)  associated 
with  excessive  muscular  contraction  this  has  been  especially  noticed ; 
in  bodies  wasted  by  prolonged  illness  it  does  not  occur.     Nearly  an 


30 


28 

Fig.  228. — Curve  of  Cooling  after 
Death  :  Guinea  -  Pig.  Time 
marked  along  horizontal,  and 
temperature  along  vertical  axis. 
At  a  ether  and  chloroform 
given  to  kill  animal;  death,  as 
indicated  by  stoppage  of  the 
heart,  took  place  at  h.  The 
dotted  line  shows  the  course 
the  curve  would  have  taken  if 
death  had  occurred  at  the 
moment  the  anx-sthetics  were 
given.     Air  of  room  I7-6"'. 


PRACTICAL  EXERCISES  715 

hour  after  death,  in  a  case  of  tetanus,  the  temperature  was  found 
to  be  45*3°,  while  before  death  it  was  447°  (Wunderhch).  In  dogs 
a  shght  post-mortem  rise  may  be  demonstrated,  especially  when 
the  body  is  wrapped  up;  but  when  an  animal  has  been  long  under 
the  influence  of  anaesthetics  no  indication  whatever  of  the  phenom- 
enon may  be  obtained.  The  explanation  of  post-mortem  rise  of 
temperature  is  to  be  found:  (i)  In  the  continued  metabolism  of  the 
tissues  for  some  time  after  the  heart  has  ceased  to  beat,  for  the  cell 
dies  harder  than  the  body.  (2)  In  the  diminished  loss  of  heat,  due 
to  the  stoppage  of  the  circulation.  (3)  To  a  small  extent  in  physical 
changes  (rigor  mortis,  coagulation  of  blood)  in  which  heat  is  set  free. 


PRACTICAL  EXERCISES  ON  CHAPTERS  X.,  XL,  AND  XII. 

I.  Glycogen* — (i)  Preparation. — {a)  Cut  an  oyster  into  two  or  three 
pieces,  throw  it  into  boiling  water,  and  boil  for  a  minute  or  two.  Rub 
up  in  a  mortar  with  clean  sand,  and  again  boil.  Filter.  Precipitate 
any  proteins  which  have  not  been  coagulated,  by  adding  alternately 
a  drop  or  two  of  hydrochloric  acid  and  a  few  drops  of  potassio-mercuric 
iodide  so  long  as  a  precipitate  is  produced.  Only  a  small  quantity  of 
these  reagents  will  be  required,  as  the  greater  part  of  the  proteins  has 
been  already  coagulated  by  boiling.  Filter  if  any  precipitate  has  formed. 
The  filtrate  is  opalescent.  Precipitate  the  glycogen  from  the  filtrate  (after 
concentration  on  the  water-bath  if  it  exceeds  a  few  c.c.  in  bulk)  by  the 
addition  of  four  or  five  times  its  volume  of  alcohol.  Filter  off  the  precipi- 
tate, wash  it  on  the  filter  with  alcohol,  and  dissolve  it  in  a  little  water. 
To  some  of  the  solution  add  a  drop  or  two  of  iodine ;  a  reddish-brown 
(port  wine)  colour  is  produced,  which  disappears  on  heating,  returns  on 
cooling,  is  removed  by  an  alkali,  restored  by  an  acid.  Add  saliva  to  some 
of  the  glycogen  solution,  and  put  in  a  bath  at  40°  C.  In  a  few  minutes 
reducing  sugar  (maltose)  will  be  found  in  it  by  Trommer's  test  (p.  10). 

Note  that  dextrin  (erythrodextrin)  gives  the  same  colour  with  iodine 
as  glycogen  does.  Dextrin  is  also  precipitated  by  alcohol,  but  a 
greater  proportion  must  be  added  to  cause  complete  precipitation. 
Glycogen  is  completely  precipitated  by  saturation  with  magnesium 
sulphate  or  ammoniuni  sulphate,  so  that  the  filtrate  no  longer  gives 
the  reddish  colour  with  iodine.  A  pure  solution  of  erythrodextrin  is 
not  precipitated.  On  the  addition  of  a  drop  or  two  of  a  solution  of 
basic  lead  acetate  to  a  solution  of  glycogen  in  distilled  water,  a  pre- 
cipitate forms  immediately.  When  the  same  reagent  is  added  to  a 
solution  of  dextrin  in  distilled  water  there  is  no  immediate  precipitate. 
Maltose  is  formed  when  dextrin  is  digested  with  saliva. 

{b)  Cut  another  oyster  into  pieces,  throw  it  into  boiling  water  acidu- 
lated with  dilute  acetic  acid,  and  boil  for  a  few  minutes.  Rub  up  in  a 
mortar  with  sand,  boil  again,  and  filter.  Test  a  portion  of  the  fil- 
trate with  iodine  for  glycogen.  Precipitate  the  rest  with  alcohol, 
filter,  dissolve  the  precipitate  in  water,  and  test  again  for  glycogen. 
On  boiling  some  of  the  opalescent  solution  for  a  few  minutes  after  the 
addition  of  a  few  drops  of  sulphuric  acid  the  opalescence  disappears,  and 

*  For  the  quantitative  estimation  of  glycogen  in  organs,  Pfliiger's  method 
is  the  best.  The  organ  is  minced  and  heated  with  strong  (60  per  cent.)  potas- 
sium hvdroxide.  The  glycogen  is  precipitated  with  alcohol,  and  then,  after 
hydrolysis  with  hj^drochloric  acid,  estimated  as  dextrose. 


7l6  METABOLISM  AND  ANIMAL  HEAT 

when  the  solution  has  been  neutralized  with  sodium  hydroxide  it  gives 
Tronimer's  test,  owing  to  the  hydrolysis  of  the  glycogen  into  dextrose. 
(j)  Deeply  etherize  a  dog  or  rabbit  five  hours'after  a  meal  rich  in 
carbo-hydrates — e.g.,  rice  and  potatoes  in  the  case  of  the  dog,  carrots 
in  the  case  of  the  rabbit.  Fasten  it  on  a  holder.  Clip  off  the  hair 
over  the  abdomen  in  the  middle  line.  Make  a  mesial  incision  through 
the  skin  and  abdominal  wall  from  the  ensiform  cartilage  to  the  pubis. 
The  liver  will  now  be  rapidly  cut  out  (by  the  demonstrator)  and  divided 
into  two  portions,  one  of  which  will  be  (distributed  among  the  class 
and)  treated  as  in  (a)  or  {b) ;  the  other  will  be  kept  for  an  hour  at  a 
temperature  of  40°  C.,  and  then  subjected  to  process  (a)  or  (b).  Little, 
if  any,  sugar  and  much  glycogen  will  be  found  in  the  portion  which 
was  boiled  immediately  after  excision.  Abundance  of  sugar  will  be 
found  in  the  jiortion  kept  at  40°  C. ;  it  may  or  may  not  contain  glycogen. 

2.  Catheterism. — In  many  physiological  experiments  it  is  necessary' 
to  obtain  urine  from  the  bladder  by  means  of  a  catheter.  It  is  possible 
to  pass  a  fine  rubber  catheter  into  the  bladder  of  a  male  dog.  A 
larger  one  is  easily  passed  in  a  male  rabbit,  and  a  still  larger  in  a  bitch, 
which  is  often  used  for  experiments  on  metabolism.  Even  in  the  bitch 
the  opening  of  the  urethra  lies  entirely  concealed  within  the  vagina, 
much  deeper  than  the  cul-de-sac  in  the  mucous  membrane,  into  which 
the  beginner  usually  tries  to  force  the  catheter.  For  a  first  attempt 
tile  animal  should  be  etherized  and  fastened  on  a  holder.  The  little 
or  index  finger  of  the  left  hand  is  passed  into  the  vagina  till  the  sjmi- 
physis  pubis  can  be  felt.  A  little  below  this  is  the  opening  of  the 
urethra.  With  the  riglit  hand  the  point  of  a  catheter  of  suitable 
calibre  is  directed  along  the  finger,  and  after  a  little  '  guess  and  trial  ' 
it  slips  into  the  bladder,  its  entrance  being  announced  by  the  escape  of 
urine.  A  glass  tube  drawn  out  to  a  sufticiently  small  calibre  and  bent 
near  the  point  is  the  easiest  form  of  catheter  to  pass  in  a  bitch.  The 
point  must,  of  course,  be  rounded  in  the  flame.  The  insertion  of  the 
catheter  is  much  facilitated  by  the  use  of  a  speculum. 

When  the  bitch  is  to  be  used  in  a  long  series  of  experiments  an 
operation  is  sometimes  performed  first  of  all  to  render  the  urethral 
orifice  more  accessible. 

3.  Glycosuria. — (i)  (o)  Weigh  a  dog  (female  by  preference)  or  rabbit. 
Fasten  on  a  holder,  and  etherize.  Insert  a  glass  cannula  into  the 
femoral  or  saphena  vein  of  the  dog,  or  into  the  jugular  of  the  rabbit 
(p.  214).  Fill  a  burette  with  a  2  per  cent,  solution  of  dextrose  in 
physiological  salt  solution,  connect  it  with  the  cannula  bv  means  of  an 
indiarubber  tube,  taking  care  that  there  are  no  air-bubbles  in  the  tube, 
and  sloivly  inject  as  much  of  the  solution  as  will  amount  to  |-  or  J  grm. 
of  sugar  per  kilo  of  body-weight.  Tie  the  vein,  remove  the  cannula,  and 
in  half  an  hour  evacuate  the  bladder  by  passing  a  catheter,  by  pressure 
on  the  abdomen,  or.  if  both  of  these  methods  fail,  by  tapping  the  bladder 
with  a  trocar  pushed  through  the  linea  alba  (suprapubic  puncture). 
In  an  hour  again  draw  off  the  urine.     Test  both  specimen"  for  sugar. 

In  this  experiment  the  opportunity  may  also  be  taken  to  demon- 
strate that  egg-albumin,  when  injected  into  the  blood,  is  excreted  by 
the  kidneys,  a  filtered  solution  containing  the  albumin  of  one  egg  and 
sugar  in  the  quantity  mentioned  being  injected. 

The  catheter  may  be  inserted  before  the  injection  is  begun,  and  the 
bladder  evacuated.  After  the  injection  the  urine  that  drops  from  the 
catheter  may  be  collected  in  test-tubes,  first  every  two  minutes,  and 
then,  as  soon  as  sugar  is  found,  every  ten  minutes.  Determine  the 
interval  between  injection  and  the  appearance  of  the  first  trace  of 
sugar  and  albumin.     If  a  sufficient  amount  of  urine  is  obtained,  the 


PRACTICAL  EXERCISES  71? 

quantity  of  sugar  in  successive  specimens  may  be  estimated  and  com- 
pared. The  rate  of  How  of  the  urine  as  measured  by  the  number  of 
drops  falling  from  the  catheter  may  also  be  estimated  from  time  to  time 
in  order  to  determine  whether  diuresis  is  taking  place. 

If  a  rabbit  is  used  for  this  experiment,  the  sugar  solution  may  be 
injected  into  the  ear  vein.  The  vein  is  caused  to  swell  up  by  pressing 
on  it  with  the  finger  and  thumb,  and  the  hypodermic  needle  is  then 
inserted  towards  the  heart. 

{b)  Instead  of  collecting  the  urine  by  a  catheter  in  the  bladder,  the 
abdomen  of  the  dog  may  be  opened,  and  a  cannula  tied  into  each  ureter. 
The  two  cannuke  are  then  connected  by  sliort  rubber  tubes  with  a 
glass  Y-piece,  on  the  stem  of  which  a  test-tube  is  tied  for  collecting  the 
urine.  Replace  the  test-tube  by  a  fresh  one  from  time  to  time.  The 
urine  already  in  the  bladder  is  removed  by  pressure  or  by  a  trocar,  and 
tested  for  sugar,  since  the  anaesthetic  itself  may  cause  a  certain  amount 
of  glycosuria.  Test  the  samples  of  urine  obtained  from  the  ureters 
for  sugar,  and  in  those  in  which  it  is  present  estimate  its  amount.  Note 
also  any  changes  in  the  rate  of  secretion  of  urine,  and  any  abnormal 
constituents,  as  albumin. 

(2)  Phlorhizm  Glycosuria. — Dissolve  ^  grm.  of  phlorhizin  in  warm 
water,  and  inject  it  subcutaneously  into  a  rabbit.  Obtain  a  sample  of 
the  urine  at  the  end  of  two  hours,  by  pressure  on  the  abdomen  with 
the  thumb  or  by  passing  a  catheter,  and  test  for  sugar.  If  none  is 
present,  wait  some  time  longer,  and  again  test  the  urine. 

This  experiment  can  also  be  performed  without  risk  on  man.  One 
grm.  of  phlorhizin  has  been  injected  twice  a  day  without  disturbing  the 
individual.  Much  sugar  is  found  in  the  urine,  but  it  disappears  the 
day  after  the  administration  of  phlorhizin  is  stopped.  The  phlorhizin 
may  also  be  given  by  the  mouth,  but  more  is  required,  and  it  is  not 
very  easily  absorbed,  and  often  causes  diarrhoea  (v.  Mering). 

(3)  Aliynentary  Glycosuria. — The  urine  having  been  tested  for  sugar 
for  two  successive  days,  and  none  being  found — • 

(fl)  A  large  quantity  of  dextrose  is  to  be  taken  in  the  form  which  is 
most  agreeable  to  the  student  some  hours  after  a  meal.  The  urine  of 
the  next  twenty-four  hours  is  to  be  collected  and  measured.  A  sample 
of  it  is  then  to  be  tested  for  reducing  sugar  by  Trommer's  and  the 
phen^d-hydrazine  test.  If  any  sugar  is  found,  the  reducing  power  of  a 
definite  quantity  of  the  urine  is  to  be  determined  by  titration  wath 
Fehling's  solution  (p.  326). 

{b)  Instead  of  dextrose  use  cane-sugar  and  proceed  as  in  {a).  But 
estimate  the  reducing  power  of  the  urine  («)  before  and  (/3)  after  boiling 
with  hydrochloric  acid  (p.  465). 

(c)  A  large  meal  of  rice  and  arrowroot,  sweetened  with  as  much  dex- 
trose as  the  observer  can  induce  himself  to  swallow,  is  to  be  taken,  and 
the  urine  treated  as  in  {a). 

(d)  A  large  number  of  sweet  oranges  may  be  eaten.* 

4.  Esfimation  of  the  Sugar  in  Blood — Method  of  Lewis  and  Benedict, 
somewhat  modified. — The  blood  must  be  used  immediately  after  being 
drawn.  When  only  a  single  sample  is  required  it  can  be  obtained  by 
puncturing  a  vein  with  a  large-sized  hypodermic  needle.  If  a  number 
of  students  have  to  be  provided  with  blood  an  animal  may  be  killed 
by  decapitation.  Long  anaesthetization  is  to  be  avoided,  as  this  causes 
hyperglycaemia.  To  take  blood  from  a  vein,  place  a  few  crystals  of 
potassium  oxalate  in  the  tip  of  a  2  c.c.  pipette,  and  having  punctured  the 
vein  with  a  needle,  draw  up  blood  into  the  pipette  to  a  little  above  the 

*  These  experiments  may  be  distributed  among  the  class  so  that  each 
student  does  one. 


7i8  METABOLISM  AND  ANIMAL  HEAT 

m^rk.  Allow  the  blood  to  run  back  just  to  the  mark,  and  immediately 
discharge  the  contents  of  the  pipette  into  a  large  test  tidie  (about  50  c.c. 
capacity)  containing  8  c.c.  of  distilled  water.  Shake  until  haemolysis 
is  complete.  Then  add  15  c.c.  of  saturated  aqueous  solution  of  pure 
picric  acid;  shake  thoroughly  to  precipitate  the  proteins  of  the  blood, 
and  filter  through  a  small  filter  paper.  Into  each  of  two  long  narrow 
test  tubes  (capacity  ab(jut  23  c.c),  which  have  been  marked  accurately 
with  a  tile  at  10  c.c,  measvire  7  c.c.  of  the  fdtrate,  add  2  c.c.  of  the 
saturated  solution  of  picric  acid  and  i  c.c.  of  a  10  per  cent,  solution  of 
anhydrous  sodium  carbonate.  A  duplicate  determination  will  thus  be 
made.  The  test  tubes  are  placed  in  an  autoclave  (according  to  Pearce's 
modification  of  the  method),  and  the  pressure  gradually  brought  up  to 
20  to  25  pounds  to  the  scjuare  inch  (2 '5  kilogrammes  to  the  square  centi- 
metre), and  kept  at  this  level  for  twenty-five  minutes,  j^icramic  acid  is 
formed  by  the  reducing  action  of  the  sugar,  and  from  the  amount  of 
picramic  acid  estimated  by  a  colorimeter  the  amount  of  sugar  is  de- 
duced. Let  the  autoclave  cool  down  till  the  pressure  is  zero,  remove 
the  tubes  and  allow  them  to  cool  to  room  temperature.  Sufficient 
water  is  now  added  to  each  tube  to  bring  the  volume  back  to  the  10  c.c. 
mark,  and  after  shaking  the  contents  are  filtered  through  cotton  into 
the  (Duboscq)  colorimeter  bottles.  The  determination  is  made  by 
comparison  with  a  solution  containing  a  known  amount  of  pure  dex- 
trose which  has  been  carried  through  the  same  process,  or  with  a 
picramic  acid  standard  solution.* 

A  solution  of  pure  dextrose  may  be  used  as  a  standard  instead  of  the 
picramic  acid,  as  follows  :  Into  a  test  tube  place  4  c.c.  of  a  solution, 
corresponding  to  o*56  milligramme  dextrose ;  add  5  c.c.  of  the  saturated 
picric  acid  solution,  and  i  c.c.  of  10  per  cent,  solution  of  anhydrous 
sodium  carbonate.  Place  in  the  autoclave  and  proceed  as  above 
described,  bringing  the  final  volume  again  to  10  c.c,  and  filtering 
through  cotton  into  one  of  the  colorimeter  bottles. 

Calculation  : 
Reading  of  standard     mgm.  dextrose  in  standard'k      mgm.  dextrose  per 
Reading  of  unknown  c.c.  blood  used  )  "         c.c.  blood. 

The  amount  of  blood  taken  for  each  of  the  duplicate  determinations 
is  2^5X2  c.c.=o-56  c.c.  The  standard=o-5()  milligramme  dextrose  in 
10  'c.c,  so  that  the  second  fraction  on  tlie  left  sick-  of  the  eqiiation 
becomes  unity,  and  the  reading  of  the  standard  divided  by  the  reading 
of  the  unknown  gives  at  once  the  number  of  millignimmes  of  dextrose 
in  I  c.c.  of  blood. 

5.  Milk. —  (i)  Examine  a  drop  of  fresh  cow's  milk  with  the  micro- 
scope.    Note  the  fat  globules  of  various  sizes. 

(2)  Determine  the  specific  gravity  of  the  milk  with  a  hydrometer 
(lactometer).  Then  centrifugalize  some  of  the  milk  to  separate  the 
cream,  which  rises  to  the  top  of  the  tubes.  Remove  the  cream  and 
determine  the  specific  gravity  of  the  skimmed  milk.  It  will  be  found 
to  have  increased,  since  the  fat  is  of  lower  specific  gravity  than  the 
rest  of  the  milk.  Normal  cow's  milk  has  a  specific  gravity  of  1,028 
to  1,034,  skimmed  milk  i,o33"to  1,037. 

*  Picramic  acid,  56  milligrammes,  anhydrous  sodium  carbonate,  roo 
milligrammes,  and  distilled  water  to  make  up  1,000  c.c.  Dissolve  the  sodium 
carbonatr  in  about  30  c.c.  of  water,  add  the  picramic  acid  and  dissolve  it 
with  the  aid  of  heat.  When  cooled  to  room  temperature  add  onough  water 
to  make  1,000  c.c.  Picramic  acid  obtained  on  the  market  varies  in  the  amount 
of  colour  produced  in  the  preparation  of  this  sohition.  The  standard  sliould 
thereiore  be  compared  with  a  solution  of  pure  dextrose  which  has  been  standard- 
ized  by  another  method,  and  then  treated  by  the  Lewis  and  Benedict  method. 


PRACTICAL  EXIUtCISES 


719 


(3)  Test  the  reaction  of  the  milk  to  litnuis-iKiiicr.    J t  is  slightly  alkaline. 

(4)  {a)  Put  10  c.c.  of  milk  in  a  test-tube,  and  nearly  fill  it  up  with 
water.  Add  strong  acetic  acid  drop  by  drop.  A  precipitate  of  casein- 
ogen  is  thrown  down  wliich  entangles  the  fat,  and  carries  it  down 
mechanically  along  with  it.  Filter  olt  the  precipitate.  Keep  the 
filtrate  for  (b).  Wash  the  precipitate  with  water,  scrape  a  portion  of 
it  off  the  filter,  and  add  to  it  .some  2  per  cent,  sodium  carbonate  solution. 
The  caseinogen  dissolves,  while  the  fat  remains  in  suspension.  The 
solution  gives  the  colour  reactions  for  proteins  (p.  8). 

[h)  lest  st)me  of  the  filtrate  (p.  10)  for  lactose.  Add  dilute  sodium 
carbonate  solution  to  another  portion  till  it  is  only  slightly  acid.  Boil, 
and  lactalbumin  is  coagulated.  Remove  the  lactalbumiu  by  liltering, 
and  test  this  tiltrate  for  earthy  {i.e.,  calcium  and  magnesium)  phos- 
phates by  adding  a  few  drops  of  ammonia,  which  precipitates  them  as 
a  slight  cloud. 

(c)  To  5  c.c.  of  milk  add  an  equal  volume  of  saturated  ammonium 
sulphate  solution.  The  caseinogen  is  precipitated,  entangling  the  fat. 
Filter  off.  The  filtrate  may  be  used  to  test  for  lactalbumin  by  boiling. 
The  addition  of  water  to  the  precipitate  of  caseinogen  (and  fat)  on  the 
filter  causes  the  caseinogen  to  dissolve,  as  it  is  soluble  in  weak  salt 
solutions.  Caseinogen  can  also  be  precipitated  by  saturating  milk 
with  sodium  chloride  or  magnesium  sulphate. 

(5)  To  5  c.c.  of  milk  add  a  couple  of  drops  of  20  per  cent,  sodium  or 
potassium  hydroxide,  and  then  a  few  c.c.  of  ether.  Shake  up.  The 
ether  dissolves  the  fat,  and  the  opacity  of  the  milk  diminishes.  Take 
off  the  ether  with  a  pipette,  evaporate  away  most  of  it  on  a  water-bath, 
and  place  a  drop  or  two  of  the  remainder  on  a  filter-paper.  A  greasy 
stain  is  left,  showing  the  presence  of  the  fat  of  the  milk,  or  butter. 

(6)  Clotting  of  Milk. — (a)  To  a  few  c.c.  of  milk  in  a  test-tube  add  a 
few  drops  of  rennet.  Place  the  tube  in  a  bath  at  40°  C.  In  a  short 
time  a  clot  or  curd  is  formed,  consisting  of  casein,  which  is  derived  from 
the  caseinogen.  The  fat  is  entangled  in  the  clot.  On  standing  some 
time  the  clot  contracts,  and  exudes  the  whey.  Boil  some  of  the  whey 
after  slight  acidulation  with  acetic  acid;  the  lactalbumin  and  whey- 
protein  are  coagulated.  Test  another  portion  of  whey  for  proteins  by 
one  of  the  general  protein  tests  (p.  8) — e.g.,  the  xanthoproteic. 

lb)  Repeat  (a)  but  use  rennet  which  has  been  previously  boiied.  The 
milk  is  not  curdled,  because  the  ferment  has  been  inactivated  by  boiling. 

(c)  To  10  c.c.  of  milk  add  3  c.c.  of  i  per  cent,  potassium  oxalate. 
Divide  the  oxalated  milk  into  three  portions — A,  B,  and  C.  To  A  add 
a  few  drops  of  rennet,  to  B  i  c.c.  of  2  per  cent,  calcium  chloride  solu- 
tion and  a  little  rennet,  and  to  C  i  c.c.  of  2  per  cent,  calcium  chloride 
solution  alone.  Put  the  tubes  at  40°  C.  Clotting  will  occur  in  B,  but 
not  in  A  or  C. 

0.  Cheese. — (i)  Rub  up  some  finely-grated  cheese  in  a  mortar  with 
2  per  cent,  sodium  carbonate  solution.  Filter.  The  filtrate  contains 
casein,  which  can  be  precipitated  by  adding  dilute  acetic  acid  by  drops 
to  a  portion  of  the  filtrate.  The  precipitate  is  soluble  in  excess  of  the 
acid.  With  another  portion  of  the  filtrate  perform  some  of  the  general 
protein  tests  (p.  8). 

(2)  Shake  up  some  finely-grated  cheese  in  a  dry  test-tube  with  ether. 
Take  off  the  ether  with  a  pipette,  and  evaporate  on  a  water-bath  till 
only  a  few  drops  remain.  With  a  glass  rod  put  a  drop  of  the  ether  on 
a  piece  of  filter-paper.     A  greasy  spot  is  left,  showing  that  fat  is  present. 

7.  Flour. — (i)  Mix  some  wheat-flour  with  a  little  water  into  a  stiff 
dough.  Let  it  stand  for  a  few  minutes  at  body-temperature  to  facilitate 
the  formation  of  gluten.     Wrap  a  piece  in  cheese-cloth,  forming  a  kind 


720  METABOLISM  AND  ASIMAL  HEAT 

of  bag,  and  knead  it  with  the  fingers  in  a  capsule  of  water.  The 
starch  grains  come  througli  the  cheese-cloth.  Pour  the  water  into  a 
beaker.  It  is  opaque,  and  on  standing  the  starch  grains  sink  to  the 
bottom,  (fl)  Test  for  starch  with  the  iodine  test,  and  also  examine 
microscopically.  The  grains  are  round,  with  a  central  hilum,  and  are 
smaller  than  those  of  potato  starch  (p.  ii).  (6)  Test  for  sugar  by 
Trommer's  test  (p.  lo).  None  is  present  unless  the  flour  has  been  made 
from  inferior  grain  in  which  some  germination  has  taken  place. 

(2)  Go  on  kneading  the  dough  till  no  more  starch  comes  through. 
The  sticky  mass  which  remains  in  the  bag  is  a  protein  called  gluten, 
which  is  formed  from  certain  globulins  and  other  proteins  in  the  flour 
on  addition  of  water.  Oatmeal,  ground  rice,  and  other  grains  poor  in 
gluten-forming  globulins  do  not  form  dough  when  mixed  with  water. 
Suspend  some  of  the  gluten  in  water  in  a  test-tube,  and  apply  to  it  the 
general  protein  colour  tests  (p.  8). 

8.  Bread. — (i)  Rub  up  a  small  piece  of  the  crumb  of  a  stale  loaf  in  a 
mortar  w^ith  water.  Strain  through  cheese-cloth.  The  fluid  which 
passes  through  contains  starch  grains,  (a)  Filter  it,  and  test  a  portion 
of  the  filtrate  for  dextrose  by  Trommer's  test.  A  positive  result 
is  obtained.  Test  another  portion  with  iodine  for  erythrodextrin. 
(fc)  Test  a  portion  of  the  residue  of  the  bread  which  has  not  passed 
through  the  cheese-cloth  for  protein  by  the  general  protein  tests — e.g., 
the  xanthroproteic  or  Millon's  tests. 

(2)  Repeat  (i)  using  the  crust  of  the  bread.  Both  dextrose  and 
er^^throdextrin  are  present  in  the  cold-water  extract,  but  the  dextrose 
is  less  plentiful  than  in  the  crumb,  having  been  converted  into  caramel 
in  the  baking.  The  sugar  and  dextrin  are  formed  from  the  starch  of  the 
flour  by  the  ferments  of  the  yeast  employed  to  make  the  bread  rise. 

9.  Variations  in  the  Total  Nitrogen  (p.  521)  and  in  the  Quantity  of 
Urea  excreted,  with  Variations  in  the  Amount  of  Proteins  in  the  Food. — 
The  student  should  put  himself,  or  somebody  else  if  he  can,  for  two  days 
on  a  diet  poor  in  proteins,  then  (after  an  interval  of  forty-eight  hours 
on  his  ordinary  food)  for  two  ds-ys  on  a  diet  rich  in  proteins.  A  suitable 
table  of  diets  will  be  supplied.  The  urine  should  be  collected  on  ths 
six  days  of  the  period  of  experiment,  on  the  day  before  it  begins,  and 
on  the  day  after  it  ends.  Small  samples  of  the  mixed  urine  of  the 
twenty-four  hours  for  each  of  these  eight  days  should  be  brought  to  the 
laboratory',  and  the  quantity  of  urea  determined  by  the  hypobromite 
method.  The  volume  of  the  urine  passed  in  each  interval  of  twenty- 
four  hours  being  known,  the  total  excretion  of  urea  for  the  twenty-four 
hours  can  be  calculated,  and  a  curve  plotted  to  show  how  it  varies 
during  the  period  of  experiment.*  If  sufficient  time  is  available,  the 
experiment  will  be  made  still  more  instructive  by  determining  the 
total  nitrogen  in  each  sample  in  addition  to  the  urea.  A  curve  showing 
the  variation  in  the  total  nitrogen  can  then  be  p>lotted  on  the  same  paper 
as  the  urea  curve,  and  a  table  calculated  giving  the  percentage  of  the 
total  nitrogen  contained  in  the  urea  for  eacli  day  of  the  experiment. 

10.  Action  of  Epinephrin  (Adrenalin). — Several  experiments  to  illus- 
trate this  are  given  in  the  Practical  Exercises  following  other  chapters, 
but  may  equally  well  be  performed  here.  (See  Experiment  8,  p.  66; 
Experiment  3,  p.  453;) 

*  In  17  healthy  students  the  average  amount  of  urea  excreted  in  twenty 
four  hours  on  the  ordinary  diet  was  29-51  grammes  (minimum  1935  grammes 
maximum  4601  grammes) ;  on  a  diet  poor  in  protein,  average  20- 75  grammes 
(minimum  9-52  grammes,  maximum  32- 86  grammes) ;  on  a  diet  rich  in  protein, 
average  38'83  grammes  (minimum  2326  grammes,  maximum  67'82  grammes). 


PRACTICAL  EXERCISES  721 

11.*  Measurement  of  the  Quantity  of  Heat  given  off  in  Respiration. — • 

This  may  be  done  approximately  as  follows:  Put  in  the  inner  coi)j)er 
vessel,  A,  of  the  calorimeter  shown  in  Fig.  224  (p.  682)  a  measured 
quantity  of  water  sufficient  to  completely  cover  the  series  of  brass  discs. 
Place  A  in  the  wide  outer  cylinder,  the  bottom  of  which  it  is  prevented 
from  touching  by  pieces  of  cork.  The  outer  cylinder  hinders  loss  of 
heat  to  the  air.  Suspend  a  thermometer  in  the  water  through  one  of  the 
holes  in  the  lid.  In  the  other  hole  place  a  glass  rod  to  serve  as  a  stirrer, 
Read  off  the  temperature  of  the  water.  Put  the  glass  tube  connected 
with  the  apparatus  in  the  mouth,  and  breathe  out  through  it  as  regu- 
larly and  normally  as  possible,  closing  the  opening  of  the  tube  with 
the  tongue  after  each  expiration  and  breathing  in  through  the  nose. 
Continue  this  for  live  or  ten  minutes,  taking  care  to  stir  the  water  fre- 
quently. Then  read  off  the  temperature  again.  If  W  be  the  quantity 
of  water  in  c.c,  and  t  the  observed  rise  of  temperature  in  degrees  Centi- 
grade, W^  equals  the  quantity  of  heat,  expressed  in  small  calories 
(p.  675),  given  off  by  the  respiratory  tract  in  the  time  of  the  experiment, 
on  the  assumptions  (i)  that  all  the  heat  has  been  absorbed  by  the  water, 
(2)  that  none  of  it  has  been  lost  by  radiation  and  conduction  from  the 
calorimeter  to  the  surrounding  air.  Calculate  the  loss  in  twenty-four 
hours  on  this  basis;  then  repeat  the  experiment,  breathing  as  rapidly 
and  deeply  as  possible,  so  as  to  increase  the  amount  of  ventilation. 
The  quantity  of  heat  given  off  will  be  found  to  be  increased. "f" 

In  an  experiment  of  short  duration  (2)  is  approximately  fulfilled. 
As  to  (i),  it  must  be  noted  that  in  the  first  place  the  metal  of  the 
calorimeter  is  heated  as  well  as  the  water,  and  the  water-equivalent 
of  the  apparatus  must  be  added  to  the  weight  of  the  water  (p.  676). 
The  water-equivalent  is  determined  by  putting  a  definite  weight  of 
water  at  air  temperature  T  into  the  calorimeter,  and  then  allowing  a 
quantity  of  hot  water  at  known  temperature  T'  to  run  into  it,  stirring 
well,  and  noting  the  temperature  of  the  water  when  it  has  ceased  to 
rise.  Call  this  temperature  T".  Enough  hot  water  should  be  added 
to  raise  the  temperature  of  the  calorimeter  about  2°  C.  The  quantity 
run  in  is  obtained  by  weighing  the  calorimeter  before  and  after  the 
hot  water  has  been  added.  Suppose  it  is  m.  Let  the  mass  of  the  cold 
water  in  the  calorimeter  at  first  be  M,  and  let  M'=the  mass  of  water 
which  would  be  raised  1°  C.  in  temperature  by  a  quantity  of  heat  suffi- 
cient to  increase  the  temperature  of  all  the  metal,  etc.,  of  the  calorimeter 
by  i" — in  other  words,  the  water-equivalent  of  the  calorimetor. 

The  mass  ni  of  hot  water  has  lost  heat  to  the  amount  of  m  (T' — T"), 
and  this  has  gone  to  raise  the  temperature  of  a  mass  of  water  M, 
and  metal  equivalent  to  a  mass  of  water  M',  by  (T" — T)  degrees. 
.-.  m  (T'— T")  =  M(T"— T)  +  M'(T"— T).  Everything  in  this  equation 
except  M'  is  known,  and  .".  M',  the  water-equivalent  of  the  calorimeter, 
can  be  deduced,  and  must  be  added  in  all  exact  experiments  to  the  mass 
of  water  contained  in  it. 

Secondly,  all  the  excess  of  heat  in  the  expired  over  that  in  the  inspired 
air  is  not  given  off  to  the  calorimeter,  for  the  air  passes  out  of  it  at  a 
slightly  higher  temperature  than  that  of  the  atmosphere.  At  the 
beginning  of  the  experiment  this  excess  of  temperature  is  zero.  If 
at  the  end  it  is  i"  C,  the  mean  excels  is  0*5°  C.     Now,  when  respiration 

*  This  experiment  is  given  as  an  example  of  a  simple  calorimetric  measure- 
ment, which  can  be  easily  performed  with  sufficient  accuracy  by  students, 
and  involves  the  essential  principles  of  such  determinations. 

f  The  average  heat-loss  by  the  lungs  for  51  men  (calculated  for  the  24  hours) 
was  312,000  small  calories  for  normal,  919,000  for  the  fastest,  and  195,000  for 
the  slowest  breathing. 


METABOLISM  AND  AMMAL  NF.AT 


is  carried  on  in  a  room  at  a  temperature  ol  lo"  C,  the  expired  air  has 
its  temperature  increased  by  nearly  30°  C.  About  ^  of  the  heat 
given  oil  by  the  respiratory  tract  in  raising  the  temperature  of  the  air 
of  respiration  would  accordingly  be  lost  in  such  an  experiment.  But 
since  the  portion  of  the  heat  lost  by  the  lungs  which  goes  to  heat  the 
expired  air  is  only  ^  of  the  whole  heat  lost  in  respiration  (p.  682).  the 
error  would  only  amount  to  ;.vj,j  of  the  whole,  and  this  is  negligible. 

Thirdly,  the  air  leaves  the  calorimeter  saturated  with  watery  vapour 
at,  say.  iO'5°,  while  the  inspired  air  is  not  saturated  for  10°  C.  Now, 
the  quantity  of  heat  rendered  latent  in  the  evaporation  of  water  suffi- 
cient to  Stiturate  a  given  quantity  of  air  at  40°  C.  (the  expired  air  is 
saturated  for  body-temperature)  is  six  times  that  required  to  saturate 
the  same  quantity  of  air  at  10°.  If,  then,  the  inspired  air  is  half 
saturated,  the  error  under  this  head  is  ^.^.  or  8^  per  cent.  If  theinspired 
air  is  three-quarters  saturated,  the  error  is  .}i.  or  about  4  per  cent.  If  the 
air  is  fully  saturated  before  inspiration,  as  is  the  case  when  it  is  drawn 
in  through  a  water-valve  (Fig.  229)  by  a  tube  fixed  in  one  nostri),  the 
only  error  is  that  due  to  the  slight  excess  of  temperature  of  the  air 
leaving  the  calorimeter  over  that  of  the  inspired  air.  The  latent  heat 
of  the  aqueous  vapour  in  saturated  air  at  10-3°  C.  is  about  ^^j  more 
tha  n  the  latent  heat  of  the  aqueous  vapour  in  the  same 
mass  of  saturated  air  at  10°  C,  or  about  jl„  of  the 
latent  heat  in  saturated  air  at  40°.  The  error  in  this 
case  would  therefore  be  under  i  percent.  Th.c  tubes 
must  be  wide  and  tiie  bottle  large. 

12.  In  the  observations  on  the  blood-flow  in  the 
hands  (Experiment  31,  p.  219)  data  on  the  quantity 
of  heat  given  off  by  the  hands  when  immerhed  in  water 
at  a  given  temperature  have  already  been  obtained. 
.'Vdditional  data  should  be  got  by  putting  the  hand 
into  the  calorimeter  without  previous  immersion  in 
the  bath,  and  comparing  the  heat  given  off  during 
the  period  when  the  hand  is  acquiring  the  temperature 
of  the  calorimeter  with  that  sjiven  off  when  the  steady 
state  has  been  reached.  Different  calorimeter  trni- 
peratures  should  be  employed.  It  will  be  found  that 
as  the  calorimeter  temperature  is  diminished  the 
quantity  of  heat  given  off  maybe  increased  although 
the  blood-flow  is  diminished,  each  gramme  of  blood  passing  through 
the  hand  giving  off  more  heat  the  lower  the  calorimeter  temperature. 

The  quantity  of  heat  lost  by  the  hand,  at  a  given  temperature 
of  the  calorimeter,  per  square  centimetre  of  skin  surface  can  be  cal- 
culated. If  no  special  instrument  for  measuring  the  area  of  irregular 
surfaces  is  available,  the  surface  of  the  hand  can  be  arrived  at  ap- 
proximately by  covering  it  with  strips  of  gummed  paper  of  known 
breadth,  and  noting  the  length  used  to  cover  the  whole  hand  up  to  the 
lower  level  of  the  styloid  process  of  the  ulna.  Or  an  old  thin  glove 
which  fits  the  hand  can  be  cut  off  at  this  level  and  weighed.  As  large 
a  piece  as  possible  of  regular  shape  is  then  cut  from  the  glove,  weighed, 
and  its  area  deduced  by  measuring  it  with  a  rule.  The  area  of  the 
whole  glove,  on  the  assumption  that  it  is  of  uniform  thickness,  is  thus 
known.  Or,  without  cutting  the  glove,  it  may  be  laid  flat  on  a  piece 
of  paper,  an  outline  of  it  traced,  and  the  paper  cut  out.  The  weight 
of  the  paper  cut  out  is  compared  with  that  of  a  piece  of  i)aper  of  known 
area,  and  its  area  deduced.  Obviously  this  is  approximately  equal  to 
half  the  surface  of  the  hand. 


Fig.  229.  — Bottle 
arranged  for 
Water-Valve. 


CHAPTER  XIII 

THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Section    I.  —  Preliminary   Observations  —  Physical  and 
Technical  Data. 

In  all  the  great  functions  of  the  body  muscular  movements  play 
an  essential  part.  The  circulation  and  the  respiration,  the  two 
functions  most  immediately  essential  to  life,  are  kept  up  by  the 
contraction  and  relaxation  of  muscles.  The  movements  of  the 
digestive  canal,  the  regulation  of  the  blood-supply  to  its  glands  and 
to  all  parts  of  the  body,  and  that  immense  class  of  movements 
which  we  call  voluntary,  are  all  dependent  upon  muscular  action, 
which,  again,  is  indebted  for  its  initiation,  continuance,  or  control, 
to  impulses  passing  along  the  nerves  from  the  nerve-centres. 
Hitherto  we  have  not  gone  below  the  surface  fact,  that  muscular 
fibres  have  the  power  of  contracting,  either  automatically,  or  in 
response  to  suitable  stimuH.  In  this  chapter  and  the  two  next  we 
shall  consider  in  detail  the  general  properties  of  muscle,  nerve,  and 
the  other  excitable  tissues. 

Lying  deeper  than  the  pecuharities  of  individual  muscles,  muscular 
tissue  has  certain  common  properties — physical,  chemical,  and 
physiological.  The  biceps  muscle  flexes  the  arm  upon  the  elbow, 
and  the  triceps  extends  it.  The  external  rectus  rotates  the  eyeball 
outwards.  The  intercostal  muscles  elevate  the  ribs.  The  sphincter 
ani  seals  up  by  a  ring-Hke  contraction  the  lower  end  of  the  ahmentary 
canal.  These  actions  are  very  different,  but  the  muscles  that  carry 
them  out  are  at  bottom  very  similar.  And  it  cannot  be  doubted 
that  the  functional  differences  are  due  entirely,  or  almost  entirely, 
to  differences  of  anatomical  connection,  on  the  one  hand  with  bones 
and  tendons,  on  the  other  with  the  nerve-cells  of  the  spinal  cord  and 
brain.  The  common  properties  in  which  all  the  skeletal  muscles 
agree  are  the  subject-matter  of  the  general  physiology  of  striated 
muscle. 

The  cardiac  muscle  differs  more,  both  in  structure  and  in  function, 
from  the  skeletal  muscles  than  these  do  among  themselves;  the 
smooth  muscle  of  the  intestines  and  bloodvessels  still  more.  But 
every  muscular  fibre,  striped  or  unstriped,  resembles  every  other 

723 


724       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


muscular  fibre  more  than  it  does  a  nerve-fibre  or  a  gland-cell  or  an 
epithelial  scale.  The  properties  common  to  all  muscle  make  up  the 
general  physiology  of  muscular  tissue. 

A  nerve-fibre  is  at  first  sight  very  different  from  a  muscular  fibre. 
It  has  diverged  more  widely  from  the  primitive  type  of  undiffer- 
entiated protoplasm,  but  it  retains,  in  common  with  the  muscle- 
fibre,  susceptibility  to  stimulation,  or  excitability,  the  capacity  for 
growth,  and  to  a  limited  extent  the  capacity  for  reproduction  ;  and 
while  it  has  lost  the  power  of  contraction  or  contractility,  it  has 
developed  in  a  higher  degree  than  any  Other  tissue  the  power  of 
conducting  the  excited  state.  This  inheritance  of  primitive  pro- 
perties, retained  aliko  by  both  tissues,  is  the  basis  of  the  general 
physiology  of  muscle  and  nerve. 

The  electrical  organ  of  Torpedo  oi  Malapterurus  is  inter- 
mediate in  some  respects  between  muscle  and  nerve,  and  has 
properties  common  to  both.  In  the  gland-cell  the  chem'cal  powers 
of  native  protoplasm  have  been  specialized  and  developed.  Con- 
tractility has  been,  in  general,  entirely  lost ;  but  excitabihty  remains. 
The  idea  that  certain  common  en- 
dowments find  expression  in  the 
action  of  muscle,  nerve,  electrical 
organ,  gland,  etc.,  in  the  midst 
of  all  their  apparent  differences,  is 
the  basis  of  the  general  physiology 
of  the  excitable  tissues. 

It  is  impossible  to  understand  the 
general  physiology  of  muscle  and 
nerve  without  some  acquaintance 
with  electricity.  It  would  be  out  of 
place  to  give  even  a  complete  sketch 
of  this  preliminary  but  essential 
knowledge  here;  and  the  student  is  expressly  warned  that  in  this  book 
the  elementary  facts  and  principles  of  physics  are  assumed  to  be  part 
of  his  mental  outfit.  But  in  describing  some  of  the  electrical  apparatus 
most  commonly  used  in  the  study  of  this  portion  of  our  subject,  and 
which  are  employed  in  the  Practical  Exercises,  it  may  be  useful  to  recall 
some  of  the  pliysical  facts  involved. 

Batteries. — The  Daniell  cell  is  perhaps  better  suited  for  physiological 
work  than  any  other  voltaic  element,  although  for  special  purposes 
Grove,  Leclanchc,  bichromate  of  potassium  or  dry  batteries  may  be 
employed  (p.  197).  Storage  batteries  or  current  from  the  street  supply 
may  also  be  used. 

Inside  the  Daniell  cell  the  current  (the  positive  electricity)  passes 
from  zinc  to  copper;  outside,  from  copper  to  zinc.  The  copper  is  called 
the  positi\e.  the  zinc  the  negati%c.  pole.  When  the  current  is  passed 
through  a  tissue,  the  electrode  by  which  it  enters  is  termed  the  anode, 
and  tliat  by  whicli  it  leaves  the  tissue  the  kathode.  The  anode  is, 
therefore,  the  electrode  connected  with  the  copper  of  the  Daniell's  cell; 
the  kathode  is  connected  with  the  zinc. 

Potential — Current  Strength— Resistance. — We  do  not  know  what 
in  reality  electricity  is,  but  we  do  know  that  when  a  current  flows  along 


Fig.  230. — Daniell  Cell.  A,  outer  vessel; 
B,  copper;  C,  porous  pot;  D,  zinc  rod; 
D  is  supposed  to  be  raised  a  little  so  as 
to  be  seen. 


PRELIMINARY  DATA 


725 


a  wire  energy  is  expended,  just  as  energy  is  expended  when  water  flows 
from  a  higlier  to  a  lower  level.  Many  of  the  phenomena  of  current 
electricity  can,  in  fact,  be  illustrated  by  the  laws  of  flow  of  an  incom- 
pressible liquid.  The  difference  of  level,  in  virtue  of  which  the  flow 
of  liquid  is  maintained,  corresponds  to  the  difference  of  electrical  level, 
or  potential,  in  virtue  of  which  an  electrical  current  is  kept  up.  The 
positive  pole  of  a  voltaic  cell  is  at  a  higher  potential  than  the  negative. 
When  they  are  connected  by  a  conductor,  a  flow  of  electricity  takes 
place,  which,  if  the  difference  of  level  or  potential  were  not  constantly 
restored,  would  soon  equalize  it,  and  the  current  would  cease;  just  as 
the  flow  of  water  from  a  reservoir  would  ultimately  stop  if  it  was  not 
replenished.  If  the  reservoir  was  small,  and  the  discharging-pipe  large, 
the  flow  would  only  last  a  short  time;  but  if  water  was  constantly  being 
pumped  up  into  it,  the  flow  would  go  on  indefinitely.  This  is  prac- 
tically the  case  in  the  Daniell  cell.  Zinc  is  constantly  being  dissolved, 
and  the  chemical  energy  which  thus  disappears  goes  to  maintain  a 
constant  difference  of  potential  between  the  poles.  Electricity,  so  to 
speak,  is  continually  running  down  from  the  place  of  higher  to  the  place 
of  lower  potential,  but  the  cistern  is  always  kept  full. 

The  difference  of  electrical  potential  between  two  points  is  called 
the  electromotive  force ;  and  from  its  analogy  with  difference  of  pressure 
in  a  liquid,  it  is  easy  to  understand  that  the  intensity  or  strength  of  the 
current — that  is,  the  rate  of  flow  of  the  electricity  between  two  points  of 
a  conductor — does  not  depend  upon  the  electromotive  force  alone, 
any  more  than  the  rate  of  discharge  of  water  from  the  end  of  a  long 
pipe  depends  alone  on  the  difference  of  level  between  it  and  the  reser- 
voir. In  both  cases  the  resistance  to  the  flow  must  also  be  taken  account 
of.  With  a  given  difference  of  level,  more  water  will  pass  per  second 
through  a  wide  than  through  a  narrow  pipe,  for  the  resistance  due  to 
friction  is  greater  in  the  latter.  In  the  case  of  an  electrical  current,  a 
wire  connecting  the  two  poles  of  a  Daniell's  cell  will  represent  the  pipe. 
A  thick  short  wire  has  less  resistance  than  a  thin  long  wire;  and  for  a 
given  difference  of  potential,  of  electric  level,  a  stronger  current  will 
flow  along  the  former.  But  for  a  wire  of  given  dimensions,  the  in- 
tensity of  the  current  will  vary  with  the  electromotive  force.  The 
relation  between  electromotive  force,  strength  of  current,  and  resistance 

were  experimentally  determined   by   Ohm,    and   the  formula    C=  ^5. 

which  expresses  it,  is  called  Ohm's  Law.  It  states  that  the  current 
varies  directly  as  the  electromotive  force,  and  inversely  as  the  resist- 
ance. 

For  the  measurement  of  electrical  quantities  a  system  of  units  is 
necessary.  The  common  unit  of  resistance  is  the  ohm,  of  current 
the  ampire,  of  electromotive  force  the  volt.  The  electromotive  force 
of  a  Daniell's  cell  is  about  a  volt.  An  electromotive  force  of  a  volt, 
acting  through  a  resistance  of  an  ohm,  yields  a  current  of  one  ampere. 
But  the  current  produced  by  a  Daniell's  cell,  with  its  poles  connected 
by  a  wire  of  i  ohm  resistance,  would  be  less  than  an  ampere,  because 
the  internal  resistance  of  the  cell  itself — that  is,  the  resistance  of  the 
liquids  between  the  zinc  and  the  copper — must  be  added  to  the  external 
resistance  in  order  to  get  the  total  resistance,  which  is  the  quantity 
represented  by  R  in  Ohm's  Law. 

Measurement  of  Resistance. — To  find  the  resistance  of  a  conductor, 
we  compare  it  with  known  resistances,  as  a  grocer  finds  the  weight  of  a 
packet  of  tea  by  comparing  it  with  known  weights.  The  Wheatstone's 
bridge  method  of  measuring  resistance  depends  on  the  fact  that  if  four 
resistances,  AB,  AD,  BC,  CD,  are  connected,  as  in  Fig.  231,  with  each 


726         THE  PHYSIOLOGY  Of  THE  COSTRACTILE  TISSUES 
other,  and  with  a  galvanometer    G,  and  a  battery,  F,  no  current  will 
flow  through  the  galvanometer  wl.cn  Ars^rns- 

In  making  the  measurement,  a  resistance  box,  containing  a  large 
number  of  coils  of  wire  of  different  resistances,  is  used.  The  resistances 
conospondini;  to  AB  and  AD  may  be  made  equal,  or 
may  stand  to  each  other  in  a  ratio  of  i  :  lo,  i  :  loo, 
etc.  Then,  the  unknown  resistance  being  CD,  BC 
is  adjusted  by  taking  plugs  out  of  the  box  till,  on 
closing  the  current,  there  is  either  no  deflection,  or  the 
deflection  is  as  small  as  it  is  possible  to  make  it  with 
the  ,L;i\en  arrangement. 

Galvanometers. — A  galvanometer  is  an  instrument 
used  to  detect  a  current,  to  determine  its  direction, 
anfl  to  measure  its  intensity.  Since,  bv  Ohm's  law, 
electromotive  force,  resistance,  and  current  strength 
are  connected  together,  any  one  of  them  may  be 
measured  by  the  galvanometer.  A  galvanometer  of 
Fig.  231.  Wheat-  fhe  kind  ordinarily  used  in  physiology  consists  es.scn- 
stone's  Bridge,  tially  of  a  small  magnet  suspended  in  the  axis  of  a 
coil  of  wire,  and  free  to  rotate  under  the  influence 
of  a  current  passing  through  the  coil.  The  most  sensitive  instruments 
possess  a  small  mirror,  to  which  the  magnet  is  rigidly  attached.  A  ray 
of  light  is  allowed  to  fall  on  the  mirror,  from  which  it  is  reflected  on 
to  a  scale  ;  and  the 
rotation  ol  the  mir- 
ror is  magnified  and 
measured  by  the  ex- 
cursion of  the  spot 
of  light  on  the  scale. 
The  method  of  read- 
ing by  a  telescope 
can  be  applied  to  any 
mirror  galvanometer, 
and  is  often  extreme- 
ly convenient  in 
physiological  work. 
Sometimes  a  small 
scale  is  fastened  on 
the  mirror  itself,  and 
ol). -served  directly 
through  a  low-power 
microscope. 

Fig.  232. — Diagram  of  String  Galvanometer.  The  string  or  fibre  CC  is  stretched  be- 
tween the  poles  of  a  powerful  electromagnet.  When  a  current  passes  down  the 
string  it  is  deflected  in  the  direction  of  the  larg»  arrow  a — i.e.,  at  right  angles  to 
the  magnetic  field  NS.  When  tha  current  is  reversed,  the  string  moves  in  the 
opposite  direction.  The  movements  of  the  string  can  be  observed  by  a  micro- 
scope, A  (objective  E),  passing  through  a  hole  bored  through  the  centre  of  the 
magnet  poles.  For  obtaining  records  a  source  of  light  is  placed  at  B  and  con- 
centrated on  the  fibre  by  a  condenser,  F,  and  the  movements  of  the  shadow  are 
recorded  by  photography. 

In  the  d'Arsonval  galvanometer  the  current  passes  through  a  small 
coil  of  fine  wire  suspended  in  the  field  of  a  strong  magnet.  When 
the  current  passes  the  coil  is  deflected,  carrying  with  it  a  small  mirror 
attached  to  the  suspending  filament.  A  great  advantage  of  this  galvano- 
meter in  many  situations  is  that  it  is  unaffected  by  neighbouring  currents. 


PRELIMINARY  DATA 


7V 


The  string  galvanometer  of  Einthoven  has  peculiar  merits  for  certain 
physiological  purposes.  It  consists  of  a  silvered  quartz-  or  glass-fibre 
stretched  in  a  very  strong  magnetic  field.     When  traversed  by  a  current 

the  fibre  is  deflected,  and  by  means 
of  a  beam  of  light  the  deflection  is 
greatl\-  iiKignificfl  (Fig-  -3-2). 

.\  rheocord  is  an  instrument  by 
means  of  wliicli  a  current  may  be 
divided,  and  a  definite  portion  of  it 
sent  through  a  tissue  (Fig.  233). 

A  compensator  is  simply  a  rheo- 
cord from  whii.  liabranchof  a  current 
is  led  off,  to  balance  or  '  compen- 
sate '  any  electrical  difference  in  a 
tissue,  like  that  which  gives  rise  to 
the  current  of  rest  of  a  muscle,  for 
example  (Fig.  234). 

An  electrometer  is  an  instrument 
for  measuring  electromotive  force — 


Fig.  233  — Diagram  of  Rheocord  (after 
Du  Bois-Reymond's  Model). 


Fig.  234. — Compensator. 


Description  of  Fig.  233 :  I  to  VII  are  pieces  of  brass  connected  with  the  wires  a  to  / 
in  such  a  way  that,  by  taking  out  any  of  the  brass  plugs  i  to  5.  a  greater  or  less 
resistance  may  be  interposed  between  the  binding-screws  A  and  B.  The  two  wires 
a  are  connected  by  a  slider  s,  filled  with  mercury  or  otherwise  making  contact  between 
the  wires.  The  current  from  the  battery  B  divides  at  A  and  B,  part  of  it  passing 
through  the  rheocord,  part  through  N,  the  nerve,  muscle,  or  other  conductor  which 
forms  the  alternativ-e  circuit.  When  a  sufficient  resistance  R  is  interposed  in  the 
chief  circuit  to  make  the  total  strength  of  the  current  independent  of  changes  in  the 
resistance  of  the  rheocord.  the  strength  of  the  current  passing  through  N  will  vary 
inversely  as  the  resistance  of  the  rheocord.  When  all  the  plugs  are  in,  and  the  slider 
close  up  to  A,  there  is  practically  no  resistance  in  the  rheocord,  and  all  the  current 
passes  across  the  brass  pieces  and  plugs  to  B,  and  thence  back  to  the  battery.  As  s 
is  moved  father  away  from  A,  the  resistance  of  the  rheocord  is  increased  more  and 
more,  and  the  intensity  of  the  current  passing  through  N  becomes  greater  and  greater. 
The  scale  S  shows  the  length  of  wire  interposed  for  any  position  of  s,  and  this  gives  a 
rough  measure  of  the  fraction  of  the  current  passing  through  N.  When  plug  i  or  2  is 
taken  out,  a  resistance  equal  to  that  of  the  two  wires  a  is  interposed;  plug  3,  twice 
that  of  a  ;  plug  4,  five  times;  plug  5,  ten  times. 

Description  of  Fig.  234 :  W  is  a  wire  stretched  alongside  a  scale  S.  A  battery  B  is 
connected  to  the  binding-screws  at  the  ends  of  the  wire.  A  pair  of  unpolarizable 
electrodes  are  connected,  one  with  a  slider  moving  on  a  wire,  the  other  through  a 
galvanometer  with  one  of  the  terminal  binding-screws.  In  the  figure  a  nerve  is 
shown  on  the  electrodes,  one  of  which  is  in  contact  with  an  uninjured  portion,  the 
other  with  an  injured  part.  The  slider  is  moved  until  the  twig  of  the  compensating 
current  just  balances  the  demarcation  current  of  the  nerve  and  the  galvanometet 
shows  no  deflection. 


728        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

tluit  is,  differences  of  electric  potential.  Lippmann's  capillary  elec- 
trometer has  been  much  employed  in  physiology.  A  simj)le  form, 
suitable  for  students  working  in  a  class  where  a  consiflerable  number  of 
copies  of  the  instrument  is  needed,  can  be  eoiueniently  made  as  fcjUows: 
A  glass  tube  is  drawn  out  to  a  capillary  at  one  end  and  filled  with  mer- 
cury. The  tube  is  inserted  into  a  small  glass  bottle,*  and  fastened  in 
its  neck  by  a  cork  or  a  plug  of  sealing-wax  which  does  not  quite  fill  the 
opening,  so  that  the  interior  of  the  bottle  is  still  in  communication  with 
the  external  air.  The  upper  end  of  the  tube  is  connected  by  a  short 
piece  of  rubber  tubing  with  a  glass  T-tube  as  in  Fig.  235.  The  bottle 
is  partially  filled  with  5  to  10  per  cent,  sulphuric  acid,  under  which  the 
capillary  dips.  By  means  of  a  small  reservoir  made  from  a  piece  of 
glass  tubing  filled  with  mercury,  and  connected  with  the  stem  of  the 
T-tube,  a  little  mercury  is  forced  through  the  capillary  so  as  to  expel 
the  air  in  it.  When  the  pressure  is  lowered  again,  sulphuric  acid  is 
drawn  up,  and  now  lies  in  the  capillary  in  contact  with  the  meniscus 
of  the  mercury.  A  platinum  wire  fused  through  the  tube,  or  simply 
inserted  through  its  upper  end,  dips  into  the  mercury.  Another, 
passing  through  the  cork,  or,  better,  fused  through  the  bottom  of  the 
bottle,  makes  contact  witli  the  sulphuric  acid  through  some  mercury. 
The  bottle  is  fastened  on  the  stage  of  a  microscope,  the  capillary  brought 
into  focus,  and  the  meniscus  adjusted  by  raising  or  lowering  the  reser- 
voir. When  the  platinum  wires  are  connected  with  points  at  different 
potential,  a  current  begins  to  pass  through  the  instrument,  and  the 
meniscus  of  the  mercury  in  the  capillary  tube,  where  the  current  density 
is  the  greatest,  becomes  polarized  by  the  ions  sejmrated  from  the 
sulphuric  acid  at  the  surface  of  contact  between  the  acid  and  the  mer- 
cury, so  that  the  meniscus  is  no  longer  in  ecjuilibrium  in  the  tube. 
The  surface  tension  (p.  429)  is  diminished  when  the  direction  of  the 
current  is  from  mercury  to  acid  (mercury  at  a  higher  potential  than 
acid),  and  is  no  longer  able  to  counterbalance  the  hydrostatic  pressure 
of  the  mercury.  The  meniscus  therefore  moves  down  in  the  tube. 
Witfi  the  opposite  direction  of  current  (mercury  at  a  lower  potential 
than  acid)  the  surface  tension  is  increased,  and  the  meniscus  moves 
up.  The  polarization  develops  itself  almost  instantaneously,  and  thus 
an  electromotive  force  is  at  once  established  in  the  opposite  direction  to 
that  between  the  points  connected  with  the  electrometer,  and  equal  to 
it  so  long  as  the  external  electromotive  force  is  not  sufiiciently  great  to 
cause  continuous  electrolysis  of  the  acid — that  is,  so  long  as  it  is  below 
about  2  volts.  The  external  current  is  therefore  at  once  compensated, 
and  after  the  first  moment  no  current  passes  through  the  instrument, 
which  is  accordingly  not  a  measurer  of  current,  but  of  electromotive 
force. 

Induced  Currents.  —When  a  coil  of  wire  in  which  a  current  is  flowing 
is  br(juglit  uj)  suddenly  to  another  coil,  a  momentary  current  is  developed 
in  the  stationary  coil  in  the  opposite  direction  to  that  in  the  moving 
coil.  Similarly,  if  instead  of  one  of  the  coils  being  moved  a  current  is 
sent  through  it,  while  the  other  coil  remains  at  rest  in  its  neighbour- 

*  A  parallel-sided  bottle  is  best,  as  it  gives  the  clearest  image  of  the  menis- 
cus. But  it  is  easiest  to  make  a  cylindrical  boitlc  from  a  piece  of  wide  glass 
tubing,  and  to  insert  a  platinum  wire  into  it  before  closing  it  at  the  bottom  in 
the  blow-pipe  flame.  The  tube  can  then  be  firmly  fastened  with  sealing  wax 
in  a  dej)ression  in  a  piece  of  wood,  the  wire  being  brouglit  out  Ihrougli  a 
hole  in  the  wood.  Onee  the  instrument  is  arranged,  there  is  little  chance 
of  the  capillary  getting  broken,  and  there  is  very  httle  evaporation  of  the 
acid. 


PRELIMINARY  DATA 


729 


hood,  a  transient  oppositely-directed  current  is  set  up  in  the  latter. 
When  the  current  in  the  hrst  coil  is  broken,  a  current  in  the  same 
direction  is  induced  in  the  other  coil. 


Fig.  236. 


Pi„  2,,  __\  Simple  Capillary  Elec  romettr.  R  bottle  containing  sulpnuric  acid  ; 
ii"  mercury  E  E' ,  platinum  wires.  E  dips  into  tlie  mercury  in  the  vertical 
tube  and  £''is  fused  through  the  bottom  of  B,  so  as  to  make  contact  with  the 
merc'urv  in  B,  the  other  end  of  it  passing  out  through  a  small  hole  in  the 
wooden  platform  F,  on  which  B  rests.  F  is  fastened  to  the  stage  of  the 
microscope  S  by  a  pin,  G,  passing  through  one  of  the  clip-holes,  and  to 
L  wooden  upright  D  by  the  pin  H.  D  fits  tightly  over  the  microscope 
stage  but  can  be  moved  laterally  a  little  so  as  to  brmg  the  capillary  mto  the 
middle  of  the  field.  /.  stem  of  glass  T-tube  passing  through  a  hole  in  £). 
L  rubber  tube  connecting  the  capillary  point  with  the  vertical  portion  of  the 
T-tube  ^  is  a  reservoir  containing  mercury  connected  by  tlie  rubber  tube 
M  to  /.  A  can  be  raised  or  lowered  by  sliding  it  in  the  clips  A .  C,  magnified 
portion  of  the  capillary  tube  showing  the  meniscus. 

Fig.  236.— Capillary  Electrometer  (after  Frey). 

Du  Bois-Reymonds  Sledge  Inductorium  (Fig.  237)— This  consists  of 
tNvo  coils  the  primary  and  the  secondary,  the  former  havmg  a  com- 
paratiyely  small  number  of  turns  of  fairly  thick  copper  wire,  the  latter 
alar-e  number  of  turns  of  thin  ^y ire.  The  object  of  this  is  that  the 
resistance  of  the  primary,  which  is  connected  with  one  or  more  voltaic 


730       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


cells,  may  not  cut  down  the  current  too  much;  while  the  currents 
induced  in  the  secondary',  having  a  high  electromotive  force,  can  readily 
pass  througii  a  iiigh  resistance,  and  are  directly  proportional  in  intensity 
to  the  number  of  turns  of  the  wire. 

By  means  of  various  binding-screws  and  the  electro-magnetic  inter- 
rupter or  Necf's  hammer,  shown  in  the  figure  and  explained  below  it, 
the  current  can  be  made  once  in  tlic  primary  or  broken  once,  or  a  con- 
stant alternation  of  make  and  break  can  be  kept  up.  We  can  thus  get 
a  single  make  or  break  shock  in  the  secondary,  or  a  series  of  shocks, 
sometimes  called  an  interrupted  or  faradic  current.  Such  a  series  of 
stimuli  can  also  be  got  by  making  and  breaking  a  voltaic  current  at  any 
given  rate. 

A  '  self-induced  '  current  can  also  be  obtained  from  a  single  coil;  for 
instance,  from  the  primary  coil  alone  of  tlie  induction  apparatus.     The 


Fig.  237. — Du  Bois-Reymond's  Inductorium.  B,  primary,  B',  secondary,  coil, 
H,  guides  in  which  B'  slides,  with  scale;  1),  electro-magnet;  E.  vibrating  spring; 
i,  wire  connecting  wire  of  I)  to  end  of  primary;  v,  screw  with  platinum  point, 
connected  with  other  end  of  primary ;  A,  A',  binding-screws,  to  which  are  attached 
the  wires  from  battery.  A'  is  connected  with  the  wire  of  the  electro-magnet  D; 
and  through  it  and  i  with  the  primary. 

reason  of  this  is,  that  when  a  current  begins  to  flow  through  any  turn 
of  a  coil  of  wire  it  induces  in  all  the  other  turns  a  current  in  the  opposite 
direction,  and,  when  it  ceases  to  flow,  a  current  in  the  same  direction 
as  itself.  The  former  current,  '  the  make  extra  shock,'  being  in  the 
opposite  direction  to  the  inducing  current,  is  retarded  in  its  develop- 
ment, and  reaches  its  maximum  more  slowly  than  '  the  break  extra 
shock.'  But,  as  we  shall  see,  the  suddenness  with  which  an  electrical 
change  is  brought  about  is  one  of  the  most  important  factors  in  elec- 
trical stimulation,  and  therefore  the  break  extra  shock  is  a  much  more 
powerful  stimulus  than  the  make.  Owing  to  these  self-induced  cur- 
rents, the  stimulating  power  of  a  voltaic  stream  may  be  much  in- 
creased by  putting  into  the  circuit  a  coil  of  wire  of  not  too  great 
reristance. 

The  self-induction  of  the  primary  also  affects  the  stimulating  power 
of  the  currents  induced  in  the  secondary;  the  shock  induced  m  the 
secondary  by  break  of  the  primary  current  is  a  stronger  stimulus  than 
that  caused  "at  make  of  the  primary.  The  reason  is  that  with  a  given 
distance  of  primary  and  secondary,  and  a  given  intensity  of  the  voltaic 
current  in  the  primary,  the  abruptness  with  which  the  induced  current 


PRELIMINARY  DATA  731 

In  tHe  secondary  is  developed  depends  upon  the  rapidity  with  which  the 
primary-  current  reaches  its  maximum  at  closing,  or  its  minimum  (zero) 
at  opening.  Now,  the  make  extra  current  retards  the  development  of 
the  primary  current,  while  in  tlie  opened  circuit  of  the  primary  coil  the 
current  intensity  falls  at  once  to  zero. 

The  inequality  between  the  make  and  break  shocks  of  the  secondary 
coil  can  be  greatly  reduced  by  means  of  Helmholtz's  wire.  Connect  one 
pole  of  the  batter^'  witli  i'  (Fig.  2J7),  and  the  other  with  A'.  Join  A 
and  A'  by  a  short,  thick  wire.  With  this  arrangement  tlie  primary  cir- 
cuit is  never  opened,  but  the  current  is  alternately  allowed  to  flow- 
through  tlie  primary,  and  short-circuited  when  the  spring  touches  v. 
The  '  make  '  now  corresponds  to  the  sudden  increase  of  intensity  of 
the  current  in  the  primary-  when  the  short-circuit  is  removed,  and  the 
'  break  '  to  its  sudden  decrease  when  the  short-circuit  is  established. 
In  both  cases  self-induced  currents  are  developed,  and  therefore  both 
shocks  are  weakened.  But  the  opening  stimulus  is  now  slightly  the 
weaker  of  the  two,  because  the  opening  extra  shock  has  to  pass  th-ough 
a  smaller  resistance  (the  short-circuit)  than  the  closing  extra  shock 
(which  passes  by  the  batter^'),  and  therefore  opposes  the  decline  of 
current  intensity  on  short-circuiting  more  than  the  closing  shock 
opposes  the  increase  of 
current  intensit}-  on  long- 
circuiting  through  the 
primary^ 

By  means  of  wires  con- 
nected with  the  terminals 
of    the    secondary     coil, 
and  leading  to  electrodes, 
a    nerve  or  muscle   may     pjg     238.  — Unpolarizable   Electrodes.     A,    hook- 
be  stimulated.    It  is  usual         shaped;    B,    U-tubes;    C,    straight;    D.    clay   in 
to  connect    the   wires   to         contact  with    tissue;   S,  saturated  zinc  sulphate 
a     short-circuiting     key         solution;  Z,  amalgamated  zinc  wire. 
(Fig.    240),    by    opening  •   .     .u      .■  ^      k        ^• 

which  the  induced  current  is  thrown  mto  the  tissue  to  be  stimu- 
lated. For  some  purposes  the  electrodes  may  be  of  platinum; 
but  all  metals  in  contact  with  moist  tissues  become  polarized  when 
currents  pass  through  them — that  is,  have  decomposition  products  of 
the  electrolysis  of  the  tissues  deposited  on  them.  And  as  any  slight 
chemical  difference,  or  even  perhaps  a  difference  of  physical  state,  be- 
tween the  two  electrodes  will  cause  them  and  the  tissues  to  form  a 
battery  evolving  a  continuous  current,  it  is  often  desirable  to  use  t<«- 
polarizable  electrodes. 

Unpolarizable  Electrodes. — Some  convenient  forms  of  these  are 
represented  in  Fig.  238.  A  piece  of  amalgamated  zinc  wire  dips  into 
saturated  zinc  sulphate  solution  contained  in  the  upper  part  of  a  glass 
tube.  The  lower  end  of  the  tube  may  be  straight,  but  drawn  out  so 
as  to  terminate  in  a  not  very  large  opening,  or  it  may  be  bent  into  a 
hook,  in  the  bend  of  which  a  hole  is  made.  Before  the  tube  is  filled 
with  the  zinc  sulphate  solution,  the  lower  part  of  it  is  plugged  with 
china  clay  made  up  with  physiological  salt  solution.  The  clay  just 
projects  through  the  opening,  and  thus  comes  in  contact  with  the 
tissue.  When  these  electrodes  are  properly  set  up,  there  is  ver>-  little 
polarization  for  several  hours,  but  for  long  experiments,  U-shaped 
tubes,  filled  with  saturated  zinc  sulphate  solution,  are  better.  The 
amalgamated  zinc  dips  into  one  limb,  and  a  small  glass  tube  fiUed  with 
clav,  on  which  the  tissue  is  laid,  into  the  other. 


732         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Pohl's  Commutator  or  Reverser  (Fig.  239)  consists  of  a  block  of  paraf- 
fin or  wood  witli  six  mercury  cups,  each  in  connection  with  a  binding- 
screw  (not  sliown  in  the  figure).  Cups  i  and  6  and  2  and  5  are  connected 
by  copper  wires,  which  cross  each  other  without  touching.  The  bridge 
consists  of  a  glass  or  vulcanite  cross-piece  a,  to  which  are  attached  two 
wires  bent  into  semicircles,  each  connected  with  a  straight  wire  dip- 
ping into  the  cups  3  and  4  respectively.  With  the  bridge  in  the  posi- 
tion shown  in  the  figure,  a  current  coming  in  at  4  would  pass  out  by 
the  wire  connected  with  i,  and  back  again  by  that  connected  with  2,  in 
the  direction  shown  by  the  arrows.  When  the  bridge  is  rocked  to  the 
other  side  so  that  the  bent  wires  dip  into  5  and  6,  the  direction  of  the 
current  is  reversed.  The  cross-wires  may  be  taken  out  altogether,  and 
the  commutator  used  to  send  a  current  at  will  through  either  of  two 
circuits,  one  connected  with  i  and  2,  and  the  other  with  5  and  6. 

Du  Bois -Raymond's  Short- 
circuiting  Key. — A  cheap  and 
convenient  form  is  shown  in 
Fig.  240. 

Time  -  Markers  —  Electric  Sig- 
nal.— It  is  of  importance  to  know 
the  time  relations  of  many 
physiological  phenomena  which 
are    graphically    recorded  ;     for 


Fig.  239. —  Pohl's  Commutator. 


Fig.  240. —  Short-Circuiting  Key. 


example,  the  contraction  of  a  skeletal  muscle  or  the  beat  of  a  heart. 
For  this  purpose  a  tracing  showing  the  speed  of  the  travelling  sur- 
face in  a  given  time  is  often  taken  simultaneously  with  the  record 
of  the  movement  under  investigation.  For  a  slowly-moving  surface 
it  is  sufficient  to  mark  intervals  of  one  or  two  seconds,  and  this  is 
very  readily  done  by  connecting  an  electro-magnetic  marker  (such 
as  the  electric  signal  of  Deprez)  with  a  circuit  which  is  closed  and 
broken  by  the  seconds  pendulum  of  an  ordinary  clock  or  ,1  metronome 
(Fig.  88,  p.  195).  Special  clocks  have  also  been  constructed  which 
permit  of  the  time  intervals  being  varied.  For  shorter  intervals  a 
tuning-fork  is  used,  which  makes  and  breaks  a  circuit  including  an 
electromagnetic  marker,  or  writes  on  the  drum  directly  by  means  of 
a  writing-point  attached  to  one  of  the  prongs. 


Amoeboid  movement  (p.  16)  is  the  most  primitive,  the  least 
elaborated  form  of  contraction.  The  maximum  velocity  of  the 
movement  has  been  reckoned  at  o  008  millimetre  a  second.     Stimu- 


CILIA  733 

lation  with  the  constant  current  or  induction  shocks  causes  the 
whole  of  the  pseudopodia  to  be  drawn  in.  This  ilkistrates  a 
universal  property  of  protoplasm,  excitability,  or  the  power  of  re 
sponding  to  certain  influences,  or  stimuli,  by  manifestations  of  the 
pecuhar  kind  which  we  distinguish  as  vital  or  physiological.  Many 
unicellular  organisms  and  the  chief  varieties  of  the  white  blood- 
corpuscles  possess  the  power  of  amoeboid  movement ;  and  we  have 
aJready  dwelt  upon  some  of  the  important  functions  fulfilled  bv 
such  movement  in  the  higher  animals  and  in  man.  A  great  dis- 
tinction between  this  kind  of  contraction  and  that  of  a  muscular 
fibre  is  that  it  takes  place  in  any  direction. 

Cilia. — Cilia  possess  a  higher  and  more  speciaHzed  grade  of 
contractility.  They  are  very  widely  distributed  in  the  animal 
kingdom;  and  analogous  structures  are  also  found  in  manv  low 
plants,  such  as  the  motile  bacteria. 

In  the  human  subject  ciliated  epithelium  usually  consists  of 
several  layers  of  cells,  the  most  superficial  of  which  are  pear-shaped, 
the  broad  end  being  next  the  surface,  and  covered  with  extremely 
fine  processes,  or  ciha,  about  8  ^  in  length,  which  are  planted  on 
a  clear  band.  It  lines  the  respiratory  passages,  the  middle  ear  and 
Eustachian  tube,  the  Fallopian  tubes,  the  uterus  above  the  middle 
of  the  cer\nx,  the  epidid^'mis,  where  the  cilia  are  extremelv  long, 
and  the  central  cavity  of  the  brain  and  spinal  cord. 

Ciliary  motion  can  be  readily  studied  by  placing  a  scraping  from 
the  palate  of  a  frog  or  a  small  portion  of  a  gill  of  a  fresh-water  mussel 
under  the  microscope  in  a  drop  of  physiological  salt  solution.  The 
motion  of  the  cilia  is  at  first  so  rapid  that  it  is  impossible  to  make 
out  much,  except  that  a  stream  of  liquid,  recognized  by  the  solid 
particles  in  it,  is  seen  to  be  driven  by  them  in  a  constant  direction 
along  the  ciHated  edge.  When  the  motion  has  become  less  quick, 
which  it  soon  does  if  the  tissue  is  deprived  of  oxygen,  it  is  seen  to 
consist  in  a  swift  bending  of  the  cilia  in  the  direction  of  the  stream, 
followed  by  a  slower  recoil  to  the  original  position,  which  is  not  at 
right  angles  to  the  surface,  but  sloping  streamwards.  All  the  cilia 
on  a  tract  of  cells  do  not  move  at  the  same  time ;  the  motion  spreads 
from  cell  to  cell  in  a  regular  wave.  The  energy  of  ciliary  motion 
may  be  considerable,  although  far  inferior  to  that  of  muscular  con- 
traction. The  work  which  cilia  are  capable  of  performing  can  be 
calculated  by  remo\ing  the  membrane,  fixing  it  on  a  plate  of  glass, 
cilia  outwards,  putting  weights  on  the  glass  plate,  and  allowing  the 
ciUa,  like  an  immense  number  of  feet,  to  carry  it  up  an  inclined  plane. 
Bowditeh  found  in  this  way  that  the  cilia  on  a  square  centimetre  of 
mucous  membrane  did  nearly  7  gramme-millimetres  of  work  per 
minute  (equal  to  the  raising  of  7  grammes  to  a  height  of  a  milli- 
metre). 


734 


THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


Since  the  cilia  in  the  respiratory  tract  all  lash  upwards,  they 
must  play  an  important  part  in  carrying  up  foreign  particles  taken 

in  with  the  air,  and  the  mucus  in  which 
they  are  entangled,  as  well  as  patho- 
logical products.  Engelmann  found 
that  the  energy  of  ciliary  motion  in- 
creases as  the  temperature  is  raised 
up   to   about   40°  C,    afber   which    it 


Fig.  2)1.-  Ciliated  Cell  (M. 
Heidenhain).  From  a 
'  liver  duct '  of  the  garden 
snail  X  2,500. 


Fig.  242.— Ciliated  Cell  (Schneider). 
From  a  flatworm  (Planocera  folium). 
I,  space  between  two  adjoining 
ciliated  cells;  2,  basal  bodies;  4, 
inner  granule ;  5,  '  cilia  roots ' ; 
6,  boundary  layer. 


diminishes  quickly.  Over-heating  causes  cilia  to  come  to  rest,  but 
if  the  temperature  has  not  been  too  high,  and  has  not  acted  too 
long,  they  recover  on  cooling,  thus  exhibiting  the  phenomena  of 
heat  standstill  which  we  have  already  studied  in  the  heart. 

It  is  not  well  understood  in  what  way  the  contraction  of  the  cilia 
depends  upon  their  connection  with  the  body  of  the  ciliated  cell.  Very 
few  cases  occur  in  which  cilia  have  the  power  of  independent  motion 
when  severed  from  the  cell-body.  It  has  been  observed  in  certain  low 
forms  of  animals  that  cilia  which  have  been  broken  off  from  the  cell 
are  still  able  to  contract  when  a  small  portion  of  the  substance  of  the 
cell-body  at  the  point  where  the  ciHum  is  attached  to  the  cell,  the 
so-called  basal  piece,  or  basal  body  (Fig.  24^),  has  come  off  along  with 
them.  In  other  forms  isolated  cilia  can  contract  in  the  absence  of 
anything  corresponding  to  the  basal  piece.  It  cannot,  therefore,  be 
said  that  continuity  with  the  basal  piece  is  absolutely  necessary.  Nor 
is  it  known  wliat  significance  for  the  ciliary  movements  is  possessed 
by  the  long  fibrills,  called  the  '  roots  of  the  cilia,'  which  in  some  animals 


PHYSICAL  PROPERTIES  OF  MUSCLE  735 

run  down  through  the  cell  from  the  basal  bodies  (h'igs.  241,  242).  In 
some  worms  and  molluscs  ciliated  cells  are  supplied  with  nerve-fibres, 
but  this  has  not  been  demonstrated  for  the  higher  animals. 


Section  II. — Physical  Properties  and  Stimulation  of  Muscle. 

Since  most  of  our  knowledge  of  the  general  physiology  of  muscle 
has  been  gained  from  striped  muscle,  in  what  follows  we  always 
refer  to  ordinary  skeletal  muscle,  unless  it  is  otherwise  stated. 
The  sartorius  and  the  gastrocnemius  are  the  classical  objects  for 
experiments  on  striated  muscle.  For  smooth  muscle  the  adductor 
muscle  of  Anodon,  the  fresh-water  mussel,  a  ring  cut  from  the  middle 
portion  of  the  frog's  stomach,  the  rabbit's  ureter  and  uterus,  and 
the  cat's  bladder,  have  been  most  used. 

Physical  Properties  of  Muscle — Elasticity. — All  bodies  may  have  their 
shape  or  volume  altered  by  the  application  of  force.  Some  require  a 
large  force,  others  a  small  force,  to  produce  a  sensible  amount  of  dis- 
tortion. The  elasticity  of  a  body  is  the  property  in  virtue  of  which  it 
tends  to  recover  its  original  form  or  bulk  when  these  have  been  altered. 
Liquids  and  gases  have  only  elasticity  of  volume;  solids  have  also 
elasticity  of  form.  Most  solids  recover  perfectly,  or  almost  perfectly, 
from  a  slight  deformation.  The  limits  of  distortion  within  which  this 
occurs  are  called  the  limits  of  elasticity,  and  they  vary  greatly  for 
different  substances.  Living  muscle  has  very  wide  limits  of  elasticity; 
it  may  be  deformed — stretched,  for  example — to  a  very  considerable 
extent,  and  yet  recover  its  original  length  when  the  stretching  force 
ceases  to  act. 

The  extensibility  of  a  body  is  measured  by  the  ratio  of  the  increase 

of  length,  produced  by  unit  stretching  force  per  unit  of  area  of  the 

cross-section,  to  the  original  length  of  a  uniform  rod  of  the  substance. 

Is 
If  e  is  the  extensibility,  e=  :p=,  where  I  is  the  increase  of  length, 

L  the  original  length,  s  the  cross-section,  and  F  the  stretching  force. 
Suppose  we  wish  to  compare  the  extensibility  of  two  substances. 
Let  A  and  B  be  strips  or  rods  of  the  substances,  the  length  of  A  being 
500  mm.,  that  of  B  1,000  mm.;  the  cross-section  of  A,  100  sq.  ram.,  of 
B,  200  sq.  mm.     Let  the  elongation  produced  by  a  weight  of  i  kilo 

be  10  mm.  in  each,  then  the  extensibility  of  A  is  =  2 ;  and  that 

•^  500  X  I 

of  B  is =  2;  that  is,   the  substances  are  equally  extensible, 

1,000  XI  -i  J 

Young's  modulus  of  elasticity,  or  the  coefficient  of  elasticity,  is  the 
quotient  of  tlie  deforming  force  acting  on  unit  area  of  the  given  body 
by  the  deformation  produced  (within  the  limits  of  elasticity).     In  the 

above  example  it  is  -^f,  that  is,  -p,  the  reciprocal  of  the  extensi- 
bility e.  For  steel  the  coefficient  of  elasticity  is  very  large,  for  muscle 
small.  Or,  as  we  may  otherwise  express  it,  living  muscle  within  its 
limits  of  elasticity  is  very  extensible ;  a  small  force  per  unit  area  of 
cross-section  of  a  prism  of  it  will  produce  a  comparatively  great  elonga- 
tion. The  extensibilitv.  however,  diminishes  continually  with  the 
elongation,  so  that  equal  increments  of  stretching  force  produce  always 


736      THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

less  and  less  extension.  If,  for  instance,  the  sartorious  or  semi-mcm- 
branosus  of  a  frog  be  connected  with  a  lever  writing  on  a  blackened 
surface,  and  weights  increasing  by  equal  amounts  be  successively 
attached  to  it,  the  recording  surface  being  allowed  to  move  the  same 
distance  after  the  addition  of  each  weight,  a  series  of  vertical  lines, 
representing  the  amount  of  each  elongation,  will  be  traced.  When  the 
lower  ends  of  all  the  vertical  lines  are  joined,  a  smooth  curve  with  the 
concavity  upwards  is  obtained  (Fig.  243).  This  is  a  property  common 
to  living  and  dead  muscle  and  to  other  animal  structures,  such  as 
arteries.  Marey's  method,  in  which  the  weight  is  continuously  in- 
creased from  zero  and  then  continuously  decreased  to  zero  again  by 
the  flow  of  mercury  into  and  out  of  a  vessel  attached  to  the  muscle, 
gives  directly  the  curve  of  extensibility. 

The  elongation  oi  a  steel  rod  or  other 
inorganic    solid     is     proportional     within 
limits  to  the  extending  force  per  unit  of 
cross-section ;  and  a  curve  plotted  with  the 
weights  for  abscissae  and  the  amounts  of 
elongation  for  ordinates  would  be  a  straight 
line.     But  this  is  not  a  fundamental  dis- 
tinction between  animal  tissues,   and  the 
materials  of  unorganized  nature,  as  some 
writers  seem  to  suppose.     For  when  the 
slow    after-elongation    which    follows   the 
first  rapid  increase  in  length  in  tlie  loaded. 
Pig    243  —Curves   of   Extensi-    excised  muscle  is  waited  for,  tlie  curve  of 
bility.    M,  of  muscle ;  S,  of  on    extensibility    comes    out    a    straight    line 
ordinary  inorganic  solid.  (Wundt),  and  within  limits  this  is  also  the 

case  for  human  muscles  in  the  intact  body. 
And  although  a  steel  rod  much  more  quickly  reaches  its  maximum 
elongation  for  a  given  weight  when  loaded,  and  its  original  length  when 
the  weight  is  removed,  than  does  a  muscle,  time  is  required  in  both  cases, 
and  the  difference  is  one  of  degree  rather  than  of  kind.  When  muscle 
(striated  or  smooth)  is  not  stretched  beyond  the  limit  of  phj-siological 
relaxation,  the  amount  of  stretching  is  proportional  to  the  weight,  and 
the  same  is  true  of  all  the  simple  tissues  of  the  body  (Haycraft). 

Dead  muscle  is  less  extensible  than  living,  and  its  limits  of  elasticity 
are  much  narrower.  In  the  state  of  contraction  the  extensibility  is 
increased  in  excised  frog's  muscle.  When  fatigue  comes  on  after  many 
excitations,  the  after-elongation  becomes  more  pronounced,  but  the 
return  after  unloading  is  very  incomplete.  Bonders  and  Van  Mans- 
veldt  have  found  that  contraction  causes  little  difference  in  the  muscles 
of  a  living  man,  although  fatigue  increases  the  extensibility. 

The  great  extensibility  and  elasticity  of  muscle  must  play  a  con- 
siderable part  in  determining  the  calibre  of  the  vessels,  and  in  lessening 
the  shocks  and  strains  which  the  heart  and  the  vascular  system  in 
general  are  called  upon  to  bear,  and  must  contribute  much  to  the 
smoothness  with  which  the  movements  of  the  skeleton  arc  carried  out, 
and  immensely  reduce  the  risk  of  injury  to  the  bones  as  well  as  to  the 
muscles  themselves,  the  tendons  and  the  other  soft  tissues.  And  not 
only  is  smoothness  gained,  but  economy  also ;  for  a  portion  of  the 
energy  ot  a  sudden  contraction,  which,  if  the  muscles  were  less  ex- 
tensible and  elastic,  might  be  wasted  as  heat  in  the  jarring  of  bone 
against  bone  at  the  joints,  is  stored  up  in  the  stretched  muscle  and 
again  given  out  in  its  elastic  recoil.  The  skeletal  muscles,  too,  are 
even  at  rest  kept  slightly  on  the  stretch,  braced  up,  as  it  were,  and 


SriMULA  IION  OF  MUSCLE 


737 


ready  to  act  at  a  moment's  notice  witliout  taking  in  slack.  This  is 
shown  by  the  fuct  that  a  transverse  wound  in  a  muscle  '  gapes,'  the 
fibres  being  retracted,  in  virtue  of  their  elasticity,  towards  tiie  fixed 
points  of  origin  and  insertion.  Smooth  muscle,  as  we  meet  it  in  the 
hollow  viscera,  is  highly  distensible  and  elastic,  as  is  suited  to  organs 
whose  capacity  is  continually  varying  within  wide  limits  (Fig.  244). 

In  the  further  study  of  muscle  it  is  necessary  first  of  all  to  consider 
the  means  we  have  of  calling  forth  a  contraction — in  other  words,  the 
various  kinds  of  stimuli. 

Stimulation  of  Muscle. — A  muscle  may  be  excited  or  stimulated 
either  directly  or  through  its  motor  nerve.  It  is  usual  to  classify 
stimuli  as  electrical,  mechanical,  chemical,  or  thermal.  Electrical 
stinuili  are  by  far  the  most  commonly  employed,  and  will  be  dis- 
cussed in  detail.     A  prick,  a  cut,  or  a  blow  are  examples  of  mechani- 


Fig.  244. — Extensibility  of  Smooth  Muscle  (Griitznet).  The  upper  group  of  four 
ceils  (i  to  4)  is  from  a  hollow  organ,  whose  walls  are  contracted,  and  its  lumen 
almost  abolished;  the  under  group  represents  the  same  fibres  when  the  organ  is 
full.  The  fibres  are  longer  and  somewhat  darker.  They  are  also  displaced 
somewhat  along  each  other. 

cal  stimuli.  The  action  of  a  fairly  strong  solution  of  common  salt 
or  of  a  dilute  solution  of  a  mineral  acid  is  usually  described  as 
chemical  stimulation.  But  in  considering  the  excitation  of  nerve 
(p.  783)  we  shall  see  that  physical  changes  are  often  mixed  up  with 
so-called  chemical  stimulation.  The  contraction  caused  is  not  a 
single  brief  twitch,  as  is  the  case  with  a  not  too  severe  mechanical 
excitation,  but  a  sustained  contraction  or  a  tetanus.  Sudden  cooling 
or  heating  acts  as  a  stimulus  for  muscle,  but  thermal  stimulation  is 
somewhat  uncertain.  It  is  not  quite  settled  whether  the  contrac- 
tion which  can  be  obtained  from  a  muscle  when  it  is  subjected  to 
brief  local  heating — to  a  '  thermic  shock,'  as  some  writers  prefer 
to  say  {e.g.,  by  the  momentary  glow  of  a  platinum  wire  below  but 
not  touching  it) — is  an  ordinary  muscular  contraction,  or  a  physical, 
although  transient,  contracture  analogous  to  that  caused  by  certain 
drugs  (Waller).  Smooth,  like  striped,  muscle  is  susceptible  to 
electrical,  mechanical,  thermal,  and  chemical  stimulation.  In 
addition,  in  certain  situations  it  can  be  excited  by  light  (photic 
stimulation),  as  in  the  case  of  the  excised  iris  of  fish  and  amphibia. 
In  all  artificial  stimulation  there  is  an  element  of  sudden  or  abrupt 
change,  of  shock,  in  other  words;  but  we  cannot  tell  in  what  the 
'  natural  '  or  '  physiological  '  stimulus  to  muscular  contraction  in 

47 


738       THE  PHYSIOLOGY  OF  THE  COKTRACTILE  TISSUES 

the  intact  body  really  consists,  nor  how  it  differs  from  artificial 
stimuli.  All  we  know  is  that  there  must  be  a  wide  difference,  and 
that  our  methods  of  excitation  must  be  very  crude  and  inexact 
imitations  of  the  natural  ])roress. 

Direct  Excitability  of  Muscle. — The  famous  controversy  on  the 
existence  of  mdependent  '  muscular  irritability  '  has  long  been 
forgotten,  and  has  no  further  interest  except  for  the  antiquaries  of 
science,  if  such  exist.  The  direct  excitability  of  muscle  in  the  modern 
sense  is  not  quite  the  same  as  the  '  muscular  irritability,'  the  dis- 
cussion of  which  occupied  Haller  and  his  contemporaries.  What 
the  modern  physiologists  have  been  called  upon  to  decide  is  whether 
muscular  fibres  can  be  caused  to  contract  except  by  an  excitation 
that  reaches  them  through  their  nerves.  In  this  sense  there  can 
exist  no  doubt  that  muscle  is  directly  excitable,  and  some  of  the 
proofs  are  as  follows: 

(i)  The  ends  of  the  frog's  sartorius  contain  no  nerves,  yet  they 
respond  to  direct  stimulation.  (2)  Certain  chemical  stimuli — 
ammonia,  for  instance — excite  muscle  but  not  nerve.  (3)  When 
the  motor  nerves  of  a  limb  are  cut  they  degenerate,  and  after  a 
certain  time  stimulation  of  the  nerve-trunk  causes  no  muscular 
contraction,  while  the  muscles,  although  atrophied,  can  be  made 
to  contract  by  direct  stinmlation.  (4)  Finally,  there  is  the  cele- 
brated curara  experiment  of  Claude  Bernard,  which  is  described  in 
a  somewhat  modified  form  in  the  I^ractical  Exercises,  p.  811.  A 
ligature  is  tied  firmly  round  one  thigh  of  a  frog,  omitting  the  sciatic 
nerve;  then  curara  is  injected,  and  in  a  short  time  the  skeletal 
muscles  are  paralyzed.  That  the  seat  of  the  paralysis  is  not  the 
contractile  substance  of  the  muscles  itself  is  shown  by  their  \agorous 
response  to  direct  stimulation.  The  '  block  '  is  not  in  the  nerve- 
trunk,  nor  above  it  in  the  central  nervous  system,  for  the  ligated 
leg  is  often  drawn  up — -that  is,  its  muscles  are  contracted — although 
the  poison  has  circulated  freely  in  the  sacral  plexus  and  the  spinal 
cord.  Further,  if  the  nerve  of  the  ligated  leg  be  prepared  as  high 
up  above  the  ligature  as  possible,  where  the  curara  must  undoubtedly 
have  reached  it  (just  above  the  ligature  the  nerve  has  been  isolated 
and  the  circulation  in  it  more  or  less  interrupted),  stimulation 
of  it  will  cause  contraction  of  the  muscles  of  the  limb;  while  excita- 
tion of  the  other  sciatic  is  ineffective. 

It  can  be  also  shown,  by  means  of  the  negative  variation  or 
current  of  action  (p.  824),  that  a  nerve-trunk  on  which  curara  has 
acted  remains  excitable,  and  capable  of  conducting  the  nerve- 
impulse.  The  conclusion,  therefore,  is  that  the  curara  paralyzes 
neither  nerve-fibre  nor  the  contractile  substance  of  the  muscular 
fibre,  but  some  link  between  the  two.  If  the  assumption  be  made 
that  the  efferent  mcdullated  nerve-fibres  within  the  muscle,  since 


STIMJ'I.ATION  OF  MUSCLE 


739 


they  arc  anatomically  similar  to  those  in  the  nerve-trunk  till  near 
their  terminations,  are  similarly  affected  by  curara- — and  it  is  a 
justifiable  assumption — the  seat  of  the  curara  paralysis  must  either 
be  the  nerve-ending  or  some  mechanism,  physiological  if  not 
anatomical,  interposed  between  the  nerve-ending  and  the  con- 
tractile substance.  Now,  Langley  has  shown  that  the  contractions 
caused  by  the  local  application  of  dilute  nicotine  solution  to  points 
of  the  skeletal  muscles  of  the  frog,  both  in  normal  muscles  and  in 
muscles  whose  motor  nerves  and  nerve-endings  have  degenerated 
after  section  of  the  nerves,  are  prevented  by  curara       He  there- 


Fig.  245. — Frog's  Motor  Nerve-Ending  (Wilson).  A,  B,  C,  three  muscle-fibres.  The 
meduUated  nerve  a  loses  its  medullary  sheath  and  breaks  up  on  B  at  i.  It  gives 
off  at  2  a  large  non-medullated  branch,  which  also  breaks  up  on  B.  The  nerve- 
endings  send  ultraterminal  fibrillaj  to  A,  B,  and  C,  some  of  which  were  seen  to 
ead  in  small  knobs.  A  separate  non-medullated  nerve,  n.  is  shown,  which  forms 
a  small  plexus  on  B,  one  fibre  of  which  penetrates  to  a  lower  plane  than  the  other, 
and  ends  by  forming  a  knob  under  the  sarcolemma. 

fore  concludes  that,  since  nicotine  produces  its  effects  by  a 
direct  action  on  muscle,  and  not  by  an  action  on  nerve-endings 
or  on  any  special  structure  (such  as  the  protoplasmic  mass  or  '  sole  ' 
at  the  nerve-ending  in  many  animals)  interposed  between  the  nerve 
and  the  muscle,  no  such  special  structure  existing  in  the  frog 
(Fig.  245),  curara  must  also  act  directly  on  the  muscle.  But 
obviously  curara  does  not  paralyze  the  general  contractile  substance 
of  the  muscle,  else  the  curarized  muscle  would  not  contract  on  direct 
stimulation.  Langley  accordingly  assumes  that,  in  addition  to  the 
contractile  or  '  general  '  substance,  '  receptive  '  substances  exist 
in  the  fibre,  through  which  the  excitation  is  transferred  to  the  con- 
tractile substance  when  the  motor  nerve  is  stimulated.  He  pictures 
these  receptive  substances  as  '  side-chains  '  of  the  contractile  mole- 
cule, in  accordance  with  Ehrlich's  theory  of  immunity  (p.  31), 
and  distinguishes  those  in  the  neighbourhood  of  the  nerve-ending 


740       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

from  those  present  throughout  the  muscle  fibre.  Both  the  slow 
local  tonic  contraction  and  the  quick,  brief  conducted  contractions 
or  twitches  set  up  in  a  muscle  fibre  by  nicotine,  but  especially  the 
latter,  are  much  more  easily  elicited  in  that  part  of  it  which  lies 
under  the  nerve-ending  than  elsewhere.  Indeed,  the  position  of 
the  nerve-endings  in  the  superficial  fibres  of  a  muscle  can  be  ascer- 
tained by  observing  the  points  which  respond  most  readily  to  nico- 
tine. Nicotine  and  curara,  etc.,  are  supposed  to  combine  with  the 
receptive  substance,  which  is  then  in  both  cases  rendered  incapable 
of  being  affected  by  nerve  impulses.  In  the  case  of  nicotine  an 
',  additional  action  results  from  the  combination  with  the  receptive 
I  substance — viz.,  the  change  in  the  contractile  substance  which  leads 
to  contraction.  Curara  paralyzes  the  transmission  of  the  excitation 
from  the   motor  nerves  to  smooth   muscle — the   muscles  of  the 


Fig.  246. — Tonic  Contraction  of  Muscle  during  Passage  of  Constant  Current.  Two 
sartorius  muscles  of  frog  connected  by  pelvic  attachments.  Current  from  12 
small  Daniell  cells  in  series  passed  through  their  whole  length.  Current  closed 
at  Ml,  opened  at  b.     Time  trace,  two-second  intervals. 

bronchi,  for  instance — with  much  greater  difliculty  than  to  ordinary 
skeletal  muscle,  and  the  same  is  true  of  the  inhibitory  nerves  of 
the  heart. 

The  action  of  curara  gives  us  the  means  of  stimulating  muscle 
directly;  when  electrical  currents  are  sent  through  a  non-curarized 
muscle,  there  is  in  general  a  mixture  of  direct  and  indirect  stimula- 
tion, for  the  nerve-fibras  within  the  muscle  are  also  excited.  Induced 
currents  stimulate  nerve  more  readily  than  muscle.  Voltaic  currents 
may  excite  a  muscle  whose  nerves  have  degenerated,  while  induced 
currents  are  entirely  without  effect. 

For  direct  stimulation,  a  curarized  frog's  sartorius  or  semi-mem- 
branosus  is  generally  used  on  account  of  their  long  parallel  fibres.  For 
indirect  excitation,  a  muscle-nerve  preparation,  composed  of  a  frog's 
gastrocnemius  with  the  sciatic  nerve  attached  to  it,  is  commonly  em- 
ployed, as  it  is  easy  to  isolate  the  muscle  without  hurting  its  nerve. 


STIMULATION  OF  MUSCLE 


741 


Stimulation  by  the  Voltaic  Current. — While  the  current  continues  to 
pass  through  a  nerve  without  any  sudden  or  great  change  in  its  in- 
tensity, there  is  no  stimulation,  and  the  muscle  connected  with  the 
nerve  remains  at  rest.  The  same  is  true  of  striated  muscle  when  a 
weak  current  is  passed  directly  through  it.  But  in  muscle  the  con- 
stancy of  the  rule  is  more  and  more  frequently  broken  by  exceptional 
results  as  the  curreut  is  strengthened,  a  state  of  permanent  contrac- 
tion being  very  apt  to  show  itself  during  the  whole  time  of  flow  (Wundt) 
(Fig.  24b).  Above  a  certain  intensity  of  current  a  greater  or  less 
degree  of  permanent  contraction  is  invariably  produced.  This  is  some- 
times called  the  '  closing  tetanus.'  It  is,  however,  not  a  true  tetanus, 
but  a  tonic  contraction,  which  is  strongest  in  the  neighbourhood  of  the 
kathode,  and  does  not  spread  far  from  it.  A  similar  condition,  the 
so-called  galvanotonus,  is  normally  seen  in  human  muscles  when  they  or 
their  motor  nerves  are 
traversed  by  a  stream 
of  considerable  inten- 
sity. Under  certain  con- 
ditions, too — e.g.,  when 
a  strong  current  is 
allowed  to  flow  for  a 
comparatively  long  time 
through  a  muscle — the 
muscle  remains  contrac- 
ted after  the  opening  of 
the  current  (so-called 
'  opening  or  Ritter's  tet- 
anus ').  Smooth  muscle 
is  excited  to  contraction 
even  when  a  voltaic  cur- 
rent is  very  gradually 
passed  into  it  and  slow- 
ly increased,  and  again 
when  it  is  caused  very 
gradually  to  disappear. 
But  striped  muscle  is 
not  stimulated  under 
these  conditions. 

For  nerve,  and  with  these  qualifications  for  muscle,  too,  the  law 
holds  that  the  voltaic  current  stimulates  at  make  and  at  break,  but  not 
during  its  passage.  Or,  generalizing  this  a  little,  since  it  has  been 
shown  that  a  sudden  increase  or  decrease  in  the  strength  of  a  current 
already  flowing  also  acts  as  a  stimulus,  we  may  say  that  the  voltaic 
current  stimulates  only  when  its  intensity  is  suddenly  and  sufficiently 
increased  or  diminished,  but  not  while  it  remains  constant.* 

When  a  strong  current  is  closed  through  a  muscle  there  is  an  im- 
mediate sharp  contraction  (initial  contraction).  The  muscle  then 
promptly  relaxes,  but  incompletely.  When  the  current  is  opened, 
there  is  another  contraction  (Fig.  247).  The  force  of  the  initial  con- 
traction, as  measured  by  the  resistance  necessary  to  prevent  it,  is 
greater  than  that  of  the  tonic  contraction  which  follows  it. 

A  second  law  of  great  theoretical  importance  is  that  of  polar  stimula- 
tion. At  make  the  stimulation  occurs  only  at  the  kathode  ;  at  break  only 
at  the  anode.     This  is  true  both  for  muscle  and  nerve,  but  it  is  most 

*  This  law  of  Du  Bois-Reymond  has  been  questioned  by  Hoorweg  and  others. 
It  seenLs  to  need  modification,  but  the  subject  cannot  be  discussed  here. 


Fig.  247. — Tonic  Contraction  during  and  after  Flow 
of  Voltaic  Current.  Curve  from  frog's  gastroc- 
nemius. At  M  constant  current  closed,  at  B  broken. 
Contracture  continues  after  opening  of  current. 
Time  trace,  two-second  intervals. 


74=         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

directly  and  simply  demonstrated  on  muscle.  A  long  parallel-fibred 
curarized  muscle  is  supported  about  its  middle;  the  two  ends,  wliiLh 
hang  down,  are  connected  with  levers  writing  on  a  revolving  drum,  and 
a  current  is  sent  longitudinally  through  the  muscle.  It  is  not  difficult 
to  see  from  the  tracings  that  at  make  the  lever  attached  to  the  kathodic 
end  moves  first,  and  that  the  other  lever  only  moves  when  the  contrac- 
tion started  at  the  kathode  has  had  time  to  reach  it  in  its  progress 
along  the  muscle.  Similarly,  at  break  the  lever  connected  with  the 
anodic  end  moves  first.  The  law  of  polar  excitation  holds  both  for 
striated  and  for  smooth  muscle.  Not  only  is  there  no  excitation  of 
unstrip>ed  muscle  at  the  anode  on  closure  of  the  current,  but  a  previ- 
ously existing  contraction  disappears.  For  skeletal  muscle  the  make  is 
stronger  than  the  break  contraction.  It  has  not  been  proved  that  this 
is  the  case  for  smooth  muscle. 


Section  III. — Physical  and  Mech.wical  Phenomena  of  the 
Muscular  Contraction. 

When  a  muscle  contracts,  its  two  points  of  attachment,  or,  if  it 
be  isolated,  its  two  ends,  come  nearer  to  each  other;  and  in  exact 
proportion  to  this  shortening  is  the  increase  in  the  average  cross- 
section.  The  contraction  is  essentially  a  change  of  form,  not  a 
change  of  volume.  The  most  delicate  observations  fail  to  detect 
the  smallest  alteration  in  bulk  (Ewald).  Living  fibres  kept  con- 
tracted by  successive  stimuli  can  be  examined  under  the  microscope ; 
or  fibres  may  be  '  fixed  '  by  reagents  like  osmic  acid,  and  sometimes 
a  very  good  opportunity  of  stud\nng  the  microscopic  changes  in 
contraction  is  given  by  a  group  of  libres  in  which  the  '  fixing  ' 
reagent  has  caught  a  wave  of  contraction,  and,  so  to  speak,  pinned 
it  down.  It  is  then  seen  that  the  process  of  contraction  in  the  fibre 
is  a  miniature  of  that  in  the  anatomical  muscle.  The  individual 
fibres  shorten  and  thicken,  and  the  sum-total  of  this  shortening 
and  thickening  is  the  muscular  contraction  which  we  see  \nth  the 
naked  eve.  The  phenomena  of  the  muscular  contraction  may 
be  classified  thus:  (i)  Optical,  (2)  Mechanical,  (3)  Thermal, 
(4)  Chemical,  {5)  Sonorous,  (6)  Electrical.  (5)  will  be  treated  under 
'  Volimtan,'  Contraction  '  ;  (6)  in  Chapter  XV. 

(i)  Optical  Phenomena — Microscopic  Structure  of  Striped  Muscle. — 
The  structure  of  striped  muscle  has  long  been  the  enigma  of  histology-; 
and  the  labours  of  many  distingviished  men  have  not  sufficed  to  make 
it  clear.  On  the  contran,-,  as  investigations  have  multiplied,  new 
theories,  new  interpretations  of  what  is  to  be  seen,  have  multiplied  in 
proportion,  and  a  resolirte  brevity  has  become  the  chief  duty  of  a  writer 
on  elementar>-  physiology*  in  regard  to  the  whole  question. 

The  muscle-fibre,  the  unit  out  of  which  the  anatomical  muscle  is 
bviilt  up,  is  surrounded  by  a  structureless  membrane,  the  sarcolemma. 
The  length  and  breadth  of  a  fibre  var>-  greatly  in  different  situations. 
The  maximum  length  is  about  4  cm. ;  the  breadth  may  be  as  much 
as  70  ft  and  as  little  as  10  fi.  When  we  come  to  analyze  the  muscle- 
fibre  and  to  determine  out  of  what  units  it  is  built  up,  the  difficulty 
begins.     The  fibre  shows  alternate  dim  and  clear  transverse  stripes,  and 


OPTICAL   PHENOMENA  OF  MUSCULAR  CONTRACTION       743 


can  actually  be  split  up  into  discs  by  certain  reagents.     It  also  shows 
a  longitudinal  striation,  and  can  be  separated  into  fibrils.     Some  have 
supposed  that  the  discs  are  the  real  structural  units  which,  piled  end 
to  end,  make  up  the  fibre.     The  fibrils  they  consider  artificial.     This 
view  is  erroneous.     It  seems  certain  that  the  fibres  are  built  up  from 
fibrils  ranged  side  by  side,  and  that  the  discs  are  artificial.     The  con- 
tents of  the  muscle-fibre  appear  to  consist  of  two  functionally  different 
substances,  a  contractile  substance,  and  an  interstitial,  perhaps  nutri- 
tive,  non-contractile  material  of  more  fluid  nature.     The  contractile 
substance  is  arranged  as  longitudinal  fibrils  embedded  in  interfibrillar 
matter  (sarcoplasm).     In  a  muscle  impregnated  with  chloride  of  gold 
the  interfibrillar  matter  appears  as  a  network. 

Schafer  has  described  the  contractile  elements  of  the  muscle-fibre 
(Figs.   24S,  249)  as  fine  columns  (sarcostyles),  divided  into  segments 

(sarcomeres)     by    thin    transverse 
^______^_  discs  (Krause's  membranes),  occu- 

t  •^!S?'i"i'iIiimii!i!l!?^PIUfflBMniuu  I . ■ ' i;i: ■        pying  the  position  of  the  middle  of 

each  light  stripe.  Each  sarcomere 
contains  a  sarcous  element  (a.  por- 
tion of  the  dark  stripe)  with  a  clear 
substance  at  its  ends,  filling  up  the 


n 


Fig.  24S. — Living  .Muscle  of  Water- 
Beetle  (highly  magnified)  (Schafer). 
s,  sarcolemma  ;  a,  dim  stripe  ; 
b,  bright  stripe;  c,  row  of  dots  in 
bright  stripe,  which  appear  to  be 
the  enlarged  ends  of  rod-shaped 
particles,  d,  but  in  reality  represent 
expansions  of  the  interstitial  sub- 
stance (sarcoplasm). 


'■-'■[■'-K 


l"ig.  249. — Portion  of  Leg 
Muscle  of  Insect,  treated 
with  Dilute  Acetic  Acid 
(Schafer).  S,  sarco- 
lemma; D,  dot-like  en- 
largement of  sarcoplasm; 
K,  Krause's  membrane. 
The  sarcous  elements 
have  been  swollen  and 
dissolved  by  the  acid. 


space  between  the  sarcous  element  and  Krause's  membrane,  and  con- 
stituting a  portion  of  the  light  stripe.  The  sarcous  element  is  itself 
double,  and  if  the  fibre  be  stretched,  the  two  portions  separate  at  a 
line  which  runs  transversely  across  the  middle  of  the  dim  stripe  (Hensen's 
line) .  Schafer  considers  that  the  appearance  of  longitudinal  fibrillation 
in  the  sarcous  elements  is  due  to  the  presence  in  them  of  fine  longi- 
tudinal canals  or  pores. 

The  Krause's  membrane  of  the  individual  fibrils  is  scarcely  ever 
visible  in  an  intact  mammalian  fibre,  and  the  apparent  line  in  the  clear 
stripe  of  an  intact  fibre  is  an  optical  appearance  due  to  interference  of 
light.  Kiihne.  who  was  fortunate  enough  to  find  one  day  a  small 
nematode  worm  moving  in  the  interior  of  a  fibre,  saw  it  pass  along 
the  fibre  with  perfect  freedom,  ignoring  Krause's  membrane.  Possibly, 
however,  it  was  moving  in  the  sarcoplasm,  the  fibrils  being  simply 
pushed  aside. 


744        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

ChangesduringContraction— Theories  of  Contraction. — Incontractions, 
according  to  Scliafcr,  llie  clear  substance  between  Krause's  membrane 
and  the  sarcous  element  passes  into  the  canals,  wliich  arc  open  towards 
Krause's  membrane,  but  closed  towards  Hensen's  line.  The  sarcous 
element  therefore  swells  up,  and  the  sarcomere  is  shortened.  In  the 
extended  muscle  tlie  clear  substance  leaves  the  pores  of  the  sarcous 
element,  and  accumulates  in  the  space  between  it  and  Krause's  mem- 
brane. The  sarcomere  is  thus  lengthened  and  narrowed.  Vvliile  the 
existence  of  Schafer's  pores  is  not  admitted  by  all  ol  servers,  there  is  a 
pretty  general  agreement  that  the  sarcomere,  like  the  cytoplasm  of  an 
amoeboid  cell,  does  consist  of  two  substances,  one  of  which  (the  hyalo- 
plasm of  the  cell,  the  clear  material  of  the  sarcomere)  interpenetrates 
the  other  (spongioplasm  of  the  cell,  substance  of  the  sarcous  element); 
and  that  in  relaxation  the  clear  fluid  passes  from  the  sarcous  element 
to  the  ends  of  the  sarcomeres,  whereas  in  contraction  it  passes  in  the 
reverse  direction  into  the  sarcous  elements.  Whether  the  fluid  passes 
into  and  out  of  the  meshes  of  an  actual  network,  or  along  actual  physical 
pMDies  in  the  sarcous  element,  or  whether  it  is  transferred  by  some 
process  like  molecular  imbibition  (p.  426),  need  not  be  discussed  here, 
since  it  is  not  definitely  known.  The  fundamental  question  by  what 
process  the  transference  is  determined  when  the  muscle  is  excited  also 
remains  unsettled.  So  far  as  is  known  at  present,  it  is  probable  that 
the  mechanical  energy  of  the  contracting  muscle  must  be  derived  from 
the  transformation  of  chemical  energ\'  into  one  of  three  forms :  energy 
associated  with  osmotic  processes,  energy  associated  with  imbibition, 
and  energy  associated  with  changes  of  surface  tension.  It  is  not  diffi- 
cult to  see  that  a  sudden  increase  in  the  osmotic  concentration  in  the 
sarcous  element,  due  to  the  breaking  up  of  large  molecules  or  colloid 
aggregates  into  small  molecules,  or  the  liberation  of  electrolytes  from 
the  colloids,  might  lead  to  the  rapid  passage  of  water  into  it  from 
the  bright  bands.  A  sudden  change  of  permeability  of  the  sarcous 
elements  for  dissolved  substances  in  the  clear  fluid  would  have  a 
similar  efi^ect.  The  same  is  true  of  a  change  in  their  power  of  imbibi- 
tion. But,  according  to  Bernstein,  it  is  scarcely  to  be  supposed  that 
the  extraordinarily  rapid  movement  of  water  molecules  which  must 
occur  in  contraction  can  be  accounted  for  either  bj-  osmosis  or  by  im- 
bibition. A  more  plausible  theory  is  that  the  surface  tension — say 
between  the  substance  of  the  sarcous  element  and  the  clear  fluid — is 
altered.  That  the  shortening  of  the  muscle  in  fatigue  (p.  749)  and 
rigor  (p.  774),  as  well  as  its  shortening  in  normal  contraction,  is  due  in 
some  way  to  the  liberation  of  metabolic  products,  especially  lactic  acid, 
is  a  theory  of  some  standing,  and  fresh  evidence  in  its  favour  has  been 
recently  supplied.  Thus  it  has  been  pointed  otit  that  the  course  of 
heat  production  in  the  active  muscle,  and  its  relation  to  the  time  of 
the  mechanical  response,  and  the  development  and  time  relations  of 
the  electrical  change  which  precedes  that  response,  can  be  very  naturally 
explained  on  the  supposition  that  the  liberation  of  lactic  acid  on  or 
near  some  surface  in  the  contractile  substance  is  an  essential  factor  in 
the  contraction  (Mines,  etc.).  It  is  known  that  in  the  presence  of  acid 
on  the  surface  of  certain  colloid  structures  shortening  occurs  (Fischer 
and  Strietman). 

The  substance  of  the  sarcous  element  which  forms  the  dark  stripe 
is  doubly  refracting,  and  therefore  rotates  the  plane  of  polarization, 
but  the  clear  substance  of  the  light  stripe  is  singly  refracting.  When 
an  uncontracted  fibre  is  viewed  with  crossed  nicols.  the  dim  stripe 
accordimjly  appears  bright  in  the  otherwise  dark  field.  In  the  con- 
tracted fibre  the  doubly  refractive  material  remains  in  the  stripe  which 


MECHANICAL  PHEXOMEiWA  OF  MUSCULAR  CONTRACTION     745 


is  dim  in  ordinan,'  light.  Tliere  is  no  transference  of  it,  but,  according 
to  most  writers,  the  bands  which  are  dim  in  ordinary-  light  increase  in 
size  by  tlie  transference  of  liiiiiid  from  the  isotropous  band. 

Diffraction  Spectrum  of  Muscle. — When  a  beam  of  white  light  passes 
through  a  sirited  muscle,  it  is  broken  up  into  its  constituent  colours, 
and  a  series  of  diffraction  spectra  are  produced,  just  as  happens  when 
the  light  passes  through  a  diffraction  grating  (a  piece  of  glass  on  which 
are  ruled  a  number  of  fine  parallel  equidistant  lines).  The  nearer  the 
lines  are  to  each  other,  the  greater  is  the  displacement  of  a  ray  of  light 
of  any  given  wave-length.  It  has  accordingly  been  found  that  when  a 
muscular  fibre  contracts,  the  amount  of  displacement  of  the  diffraction 
spectra  increases.  At  the  same  time  the  whole  fibre  becomes  more 
transparent. 

(2)  Mechanical  Phenomena. — The  muscular  contraction  may  be 
graphically  recorded  by  connecting  a  muscle  with  a  lever  which  is 
moved  either  by  its  shortening  or  by  its  thickening.  The  lever  writes 
on  a  blackened  surface,  which  must 
travel  at  a  uniform  rate  if  the  form 
and  time-relations  of  the  muscle 
curve  are  to  be  studied,  but  may  be 
at  rest  if  only  the  height  of  the  con- 
traction is  to  be  recorded.  The  whole 
arrangement  for  taking  a  muscle- 
tracing  is  called  a  myograph  (Fig. 
287,  p.  812).  The  duration  of  a 
'  twitch '  or  single  contraction  (in- 
cluding the  relaxation)  of  a  frog's 
muscle  is  usually  given  as  about 
one-tenth  of  a  second,  but  it  may 
var\-  considerably  with  temperature, 
fatigue,  and  other  circumstances. 
It  is  measured  by  the  vibrations  of 
a  tuning-fork  written  immediately 
below  or  above  the  muscle  curve. 
When  the  muscle  is  only  slightly 
weighted,  it  but  ven.'  gradually 
reaches  its  original  length  after  con- 
traction, a  period  of  rapid  relaxation 
being  followed  by  a  period  of  '  resi- 
dual contraction,'  during  which  the 

descent  of  the  lever  towards  the  base-line  becomes  slower  and  slower, 
or  stops  altogether  some  distance  above  it.  The  duration  of  the  con- 
traction of  smooth  muscle  evoked  by  a  single  momentary  stimulus  is 
much  greater  than  that  of  stiiped  muscle  (two  to  seven  seconds  for  the 
rabbit's  ureter;  five  to  fifteen  seconds  for  the  cat's  nictitating  mem- 
brane ;  one  to  two  minutes  for  the  frog's  stomach). 

Latent  Period. — If  the  time  of  stimulation  is  marked  on  the  tracing, 
it  is  found  that  the  contraction  does  not  begin  simultaneously  with  it, 
but  only  after  a  certain  interval,  which  is  called  the  latent  period. 

This  can  be  measured  by  means  of  the  spring  myograph  (Fig.  251) 
or  of  the  pendulum  myograph,  a  pendulum  which  in  its  swing  carries 
a  smoked  plate  against  the  writing-point  of  a  le^"er  connected  with  a 
muscle.  The  carrier  of  the  recording  plate  opens,  at  a  definite  point 
in  its  passage,  a  key  in  the  priman,-  coil  of  an  induction  machine,  and 
so  causes  a  shock  to  be  sent  through  the  muscle  or  nerve,  which  is  con- 
nected with  the  secondary-.  The  precise  point  at  which  the  stimulus 
is  thrown  in  can  be  marked  on  the  tracing  by  carefully  bringing  the 


Fig.  250. — Living  Muscular  Fibre  (from 
Geotrupes  stercorarius).  i,  in  or- 
dinary; 2,  in  polarized  light.  (Van 
Gehuchten.)  In  li\ing  muscle  (at 
least  in  fibres  which  are  not  extended) 
in  contrast  to  dead  muscle  after  treat- 
ment with  reagents,  the  doubly  re- 
fracting or  anisotropous  substance  is 
present  in  the  greater  part  of  the  fibre ; 
and  with  crossed  nicols  the  position  of 
the  singly  refracting  or  isotropous 
material  is  indicated  only  by  narrow 
transverse  black  lines  or  rows  of  dark 
dots. 


745        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

plate  to  the  position  in  which  the  key  is  just  opened,  and  allowing 
the  lever  to  trace  lierc  a  vertical  line  (or,  rather,  an  arc  of -a  circle). 
The  portion  of  the  time-tracing  between  this  line  and  a  parallel  line 
drawn  through  the  point  at  which  the  contraction  begins  gives  the 
latent  period. 

Hehiiholtz  measured  the  length  of  the  latent  period  by  means  of  the 
principle  of  Pouillet,  that  the  deflection  of  a  magnet  by  a  current  of 
given  strength  and  of  very  short  duration  is  proportional  to  the  time 
during  which  the  current  acts  on  the  magnet.  He  arranged  that  at 
tlie  moment  of  stimulation  of  the  muscle  a  current  should  be  sent 
through  a  galvanometer,  and  should  be  broken  by  the  contraction  of 
the  muscle  the  moment  it  began.  In  this  way  he  obtained  the  value 
of  ,^0  second  for  the  latent  period  of  frog's  muscle.     The  tendency  of 


Fig.  251.— Spring  Myograph.  A,  B.  iron  uprights,  between  which  are  stretched  the 
guide-wires  on  which  the  travelling  plate  a  runs;  k,  pieces  of  cork  on  the  guides 
to  gradually  check  the  plate  at  the  end  of  its  excursion,  and  prevent  jarring; 
b,  spring,  the  release  of  which  shoots  the  plate  along;  h,  trigger-key,  which  is 
opened  by  the  pin  d  on  the  frame  of  the  plate. 

later  observations  has  been  to  make  the  latent  period  shorter.  Burdon 
Sanderson  found  that  tlie  change  of  form  licgins  in  unweighted  or  verv 
slightly  weighted  muscle  with  direct  stimulation  in  ,;/„„  second  after, 
and  the  electrical  change  (p.  824)  simultaneouslv  witli,  the  excitation! 
It  is  known  that  the  apparent  latent  period  depends  upon  the  resistance 
which  the  muscle  has  to  overcome  in  bcginninj,'  its  contraction. 

The  maximum  shortening,  or  '  height  of  the  lift,'  depends  upon  the 
length  of  the  muscle,  the  direction  of  the  fibres,  the  strength  of  the 
stimulus,  the  excitability  of  the  tissue,  and  the  load  it  has  to  raise. 

In  a  long  muscle,  other  things  being  equal,  the  absolute  shortening, 
and  therefore  the  maximum  height  of  the  curve,  will  be  greater  than 

in  a  short  muscle;  in  a  muscle  with  fibres  parallel  to  its  length the 

sartorius.  for  instance  —  it  will  be  greater  than  in  a  muscle  like  the 
gastrocnemius,  with  the  fibres  directed  at  various  angles  to  the  long 
axis.     For  stimuli  less  than  maximal,  the  absolute  contraction  increases 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION     7  i7 


with  the  strength  of  stimulation,  and  a  given  stimulus  will  cause  a 
greater  contraction  in  a  muscle  witli  a  given  excitability  than  in  a 
muscle  which  is  less  excitable.  Under  ordinary  experimental  condi- 
tions .vt  least,  weak  stimuli  cause  a  smaller  contraction  than  strong, 
not  only  because  each  stimulated  fibre  contracts  less,  but  because  a 
smaller  number  of  fibres  are  excited  (p.  155).  The  objects  used  for  the 
study  of  muscular  contraction  contain  many  fibres,  and  it  is  not  in 


Fig.  25.:. — Curve  of  a  Single  Muscular  Contraction  or  Twitch  taken  on  Smoked  Glass 
with  Spring  Myograph  and  photographed.  Vertical  line  A  nr.aiks  the  point  at 
which  the  muscle  was  stimulated;  time  tracing  shows  ,  Jn  of  a  second  (reduced). 

general  possible  to  distribute  the  stimulus  equally  to  all.  This  is  true 
fbr  smooth  muscle  a3  well  as  for  striped.  Finally,  increase  of  the  load 
per  imit  of  cross-section  of  the  muscle  diminishes  above  a  certain  limit 
the  '  lieight  of  the  lift.' 

Influences  which  affect  the  Time-Relations  of  the  Muscular  Contrac- 
tion.— Many  circumstances  attect  the  form  of  the  muscle  curve  and  its 
time-relations. 

[a)  Influence  of  the  Load — Isotonic  and  Isometric  Contraction. — The 
first  effect  of  contraction  is  to  suddenly  stretch  the  muscle,  and  the 
more  the  muscle  is  loaded  the  greater  will  this 
elongation  be.  So  that  at  the  beginning  of  the 
actual  shortening  part  of  the  energy  of  contraction 
is  already  expended  without  visible  effect,  and  has 
to  be  recovered  from  the  elastic  reaction  during 
the  ascent  of  the  lever. 

The  contraction  of  a  muscle  loaded  by  a  weight 
which  is  not  increased  or  diminished  during  the 
contraction  is  said  to  be  isotonic,  for  here  the 
tension  of  the  muscle  is  the  same  throughout,  and 
its  length  alters.  When  the  muscle  is  attached  very 
near  the  fulcrum  of  the  lever,  so  that  it  acts  upon 
a  short  arm,  while  the  long  arm  carrying  the 
writing-point  is  prevented  from  moving  much  by 
a  spring,  the  muscle  can  nnly  shorten  itself  very 
slightly;  but  the  changes  of  tension  in  it  will  be 
related  to  those  in  the  spring,  and  therefore  to  the 
curve  traced  by  the  writing-point.  Such  a  curve 
is  called  isometric,  since  the  length  of  the  muscle 
remains  almost  unaltered.  In  the  body  muscles 
usually  contract  under  conditions  more  nearly 
allied  to  those  of  the  isometric  than  to  those  of 
the  isotonic  contraction. 

The  work  done  by  a  muscle  in  raising  a  weight  is  equal  to  the  product 
of  the  weight  by  the  height  to  which  it  is  raised.  Beginning  with  no 
load  at  all,  it  is  found  that  the  weight  can  be  increased  up  to  a  certain 
limit  without  diminishing  the  height  of  the  contraction;  perhaps  the 
height  may  even  increase.  Up  to  this  limit,  then,  the  work  evidently 
increases  with  the  load.     If  the  weight  is  made  still  greater,  the  con- 


Fig.  253.  —  Contrac- 
tions ol  Smooth  Mus- 
cle: Cat's  Bladder 
(C.  C.  Stewart). 
Stimulated  with  pro- 
gressively stronger 
induction  shocks. 
The  lowest  line  is  the 
time  trace  (lo-second 
intervals).  Immedi- 
ately below  the  mus. 
cular  contractions  are 
marked  the  points  at 
which  the  stimuli 
were  thrown  in. 


748        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

traction  becomes  less  and  less,  but  up  to  another  limit  the  increase  of 
weight  more  than  compensates  for  the  diminution  of  '  lift.'  and  the 
work  still  increases.     Beyond  this,  further  increase  of  weight  can  no 


Fig.  254. — Influence  of  Load  on  the  Form  of  the  Muscle  Curve,  i,  curve  taken  with 
unloaded  lever;  2,  3,  4,  weight  successively  increased;  5,  abscissa  line:  time  trace, 
■j^  second  (reduced). 

longer  make  up  for  the  lessening  of  the  lift,  and  the  work  falls  oflf  till 
ultimately  the  muscle  is  unable  to  raise  the  weight  at  all. 

The  '  absolute  contractile  force  '  of  an  active  muscle  may  be  measured 
by  determining  the  weight  which,  brought  to  bear  upon  the  muscle  at 


Fig.  255 — Influence  of  Temperature  on  the  Striated  Muscle  Curve.  2,  air  tempera- 
ture; I.  25°— 3o'C.;  3.  7°— io°C.;  4.  ice  in  contact  with  muscle.  The  fifth  curve 
was  taken  at  a  little  above  air  temperature. 


the  instant  of  contraction,  is  just  able  to  prevent  shortening  without 
stretching  the  muscle.  It,  of  course,  depends,  among  other  things,  on 
the  cross-section  of  the  muscle.  During  the  contraction  the  absolute 
force  diminishes  continually,  so  that  a  smaller  and  smaller  weight  is 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION   749 


sufficient  to  stop  any  further  contraction  the  more  the  muscle  has 
already  shortened  before  it  is  apjiHcd.  At  the  maximum  of  the  con- 
traction the  absohite  force  is  zero.  Hence  a  muscle  works  under  the 
most  favourable  conditions  when  the  weight  decreases  as  it  is  raised, 
and  this  is  the  case  with  many  of  the  muscles  of  the  body.  During 
flexure  of  the  forearm  on  the  elbow,  with  the  upper  arm  horizontal,  a 
weight  in  the  hand  is  felt  less  and  less  as  it  is  raised,  since  its  moment, 
which  is  proportional  to  its  distance  from  a  vertical  line  drawn  through 
the  lower  end  of  the  humerus,  continually  diminishes. 

(b)  Influence  of  Temperature  on  the  Muscular  Contraction. — Increase 
of  temperature  of  the  muscle  up  to  a  certain  limit  diminishes  the  latent 
period  and  the  length  of  the  curve,  and  increases 
the  height  of  the  contraction,  but  beyond  this  limit 
the  contractions  are  lessened  in  height  (Fig.  255). 
Marked  diminution  of  temperature  causes,  in 
general,  an  increase  in  the  latent  period  and  length, 
and  a  decrease  in  the  height  of  the  contraction.  In 
the  heart  the  effect  of  cold  in  strengthening  the 
beat  is  often  very  marked.  Temperature  affects 
the  contraction  curve  of  smooth  muscle  much  in  the 
same  way  as  that  of  striated  muscle  (Fig.  256). 

(c)  Influence  of  Previous  Stimulation — Fatigue. 
—U  a  muscle  is  stimulated  by  a  series  of  equal 
shocks  thrown  in  at  regular  intervals,  and  the 
contractions  recorded,  it  is  seen  that   at   first 
each    curve    overtops    its    prede- 
cessor by  a  small  amount.*     This 
phenomenon,  which    is    regularly 
V.    observed  in  fresh  skeletal  muscle 


Fig.  256. — Influence  of  Temperature  on  the  Smooth  Muscle  Curve:  Cat's  Bladder 
(C.  C.  Stewart).  Contractions  at  different  temperatures  with  the  same  strength 
of  stimulus.     The  temperatures  (Centigrade)  are  marked  on  the  curves. 

(Fig.  260),  although  it  was  at  one  time  supposed  to  be  peculiarly  a 

property  of  the  muscle  of  the  heart  (Fig.  2bi),  is  called  the  staircase,' 

and  seems  to  indicate  that  within  limits  the  muscle  is  benefited  by 

contraction  and  its  excitability  increased  for  a  new  stimulus.     Soon, 

however,  in  an  isolated  preparation,  the  contractions  begin  to  decline 

in  height,  till  the  muscle  is  at  length  utterly  exhausted,  and  reacts 

no  longer  to  even  the  strongest  stimulation  (Figs.  258,  259,  288). 

A    conspicuous    feature    of   the    contraction-curves   of   fatigued 

muscle  is  the  progressive  lengthening,  which  is  much  more  mark«cd 

in  the  descending  than  in  the  ascending  p?riods;  in  other  words, 

*  Guthrie  has  recently  described  an  interesting  series  of  phenomena  illus- 
trating the  influence  of  previous  stimulation  on  the  irritabihty  of  muscle. 
Under  given  conditions,  for  example,  strong  stimulation  increases  the  response 

of  skeletal  musclei  to  subsequent  single  stimuli,  it  may  be,  by  hundreds  per 

cent. 


750       THE  PHYSIOLOGY  Ol-   THL  CONTRACTILE   TISSUES 


relaxation  becomes  more  and  more  difficult  and  imperfect  (Fig.  288. 
p.  814).  In  smooth  muscle  (cat's  bladder  or  ring  from  frog's  stomach) 
fatigue  can  be  very  easily  demon- 
strated in  the  same  way,  and  the 
curves  present  similar  features,  with 
the  exception  that,  instead  of  be- 
coming longer  in  fatigue,  the  suc- 
cessive contractions  become  shorter. 
It  is  by  no  means  so  easy  to 
fatigue  a  muscle  still  in  connection 
with  the  circulation  as  an  isolated 
muscle.  But  even  the  latter,  if  left 
to  itself,  will  to  some  extent  re- 
cover, and  be  again  able  to  con- 
tract, although  exhaustion  is  now 
more  readily  induced  than  at  first. 


Fig.  258. — Fatigue  Curve  of  Muscle-. 
Frog's  Gastrocnemius.  The  arrange- 
ment with  which  the  curve  figured 
was  obtained  was  a  so-called  auto- 
matic muscle  interruptor  (Fig.  257). 
A  wire  on  the  lever  is  made  to  close 
and  open  the  primary  circuit  of  an 
inductorium.  the  muscle  or  nerve 
being  connected  with  the  secondary. 
Every  time  the  needle  touches  the 
mercury  the  muscle  is  stimulited 
automatically. 


fr 


'B^ 


Fig.  25-. — Automatic  Muscle  Interruptor. 
K,  battery;  P,  primary;  S,  secondary  coil; 
A,  axis  of  lever;  N.  needle;  Hg,  mercury 
cup. 


In  man,  muscular  fatigue  can  be  studied  by  means  of  an  arrange- 
ment called  an  ergograph  (Fig.  2()2).     A  record  of  successive  con- 


259. — fatigue  curse  taken  on  a  Slowly-moving  Drum  (reduced  to  Half):  Frogs 
Gastrocnemius.  Excited  through  the  sciatic  nerve  by  maximal  shocks  once  lu 
six  seconds. 


Fig.  259.— Fatigue  Cur 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION  751 

tractions,  say,  of  one  of  the  flexor  muscles  of  a  finger,  in  raising  a 
weight  (isotonic  method)  or  in  cU'forming  a  spring  (isometric  method) 
is  taken  on  a  drum.     When  the  contractions  are  repeated  every 
second,  or  every  half-second,  distinct  evidence  vi  fatigue  is  seen  on 
the  tracing  after  a  longer  or  shorter 
period,  according  to  the  conditions.* 
What   is   the  cause  of  muscular 
fatigue  ?     An   exact   answer  is  not 
possible  in  the  present  state  of  our 
knowledge,  but  we  may  fairly  con- 
clude that  in  an  isolated  preparation 
it   is  twofold  :    (i)  Waste  products, 
among  which  some  are   so   directly 
related  to  the  onset  of  fatigue  as  to 
deserve  the  name  of  '  fatigue  sub- 
stances,'  are  formed  by  the  acti\c 
muscle  faster  than  they  can  be  re- 
moved, oxidized  or  otherwise  decom- 
posed.  (2)  The  material  necessary  for 
contraction  is  used  up  more  quickly 
than  it  can  be  reproduced  or  brought 
to  the  place  where  it  is  required.    That  the  accumulation  of  fatigue 
products  has  something  to  do  with  the  exhaustion  is  shown  by  the 
fact  that  the  muscles  of  a  frog,  exhausted  in  spite  of  the  continuance 
of  the  circulation,  can  be  restored  by  bleeding  the  animal,  or  washing 
out  the  vessels  with  physiological  salt  solution,  while  injection  of  a 
watery  extract   of  exhausted  muscle  into  the   bloodvessels  of  a 


Fig.  260. — '  Staircase  '  in  Skeletal 
Muscle:  Frog.  Stimulation  by  an 
automatic  arrangement. 


Fig.  261. — 'Staircase'  in  Cardiac  Muscle.  Contractions  recorded  on  a  much  more 
quickly  moving  drum  than  in  Fig.  260.  The  contractions  were  caused  by  stimu- 
lating a  heart  reduced  to  standstill  by  the  tirst  Stannius'  ligature  (p.  199).  The 
contractions  gradually  increase  in  height. 

curarized  muscle  renders  it  less  excitable  (Ranke).  This  observer 
supposed  that  it  was  specially  the  removal  of  the  acid  products  of 
contraction  which  restored  the  muscle.  Such  acid  products  as 
carbon  dioxide  and  lactic  acid,  or  the  lactates  which  it  may  form 
with  bases  in  the  blood,  lymph  or  tissues,  when  they  act  on  muscle 

*  Recent  observations  (by  Ryan  and  Agnew)  with  improved  methods  have 
emphasized  the  necessity  for  care  in  the  interpretation  of  ergographic  records. 
This  caution  is  timely,  inasmuch  as  in  modern  war  the  question  of  the  rela- 
tion of  fatigue  to  industrial  practice  acquires  tirst-class  importance. 


75^        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

in  more  than  a  certain  concentration,  produce  the  same  effects  on 
its  power  of  contraction  as  are  produced  by  fatigue,  and  there  is 
some  reason  to  suppose  that  lactic  acid  is  tlie  most  influential  of  the 
fatigue  substances.  In  smaller  concentration,  on  the  contrary,  they 
increase  the  excitability  of  the  muscle,  and,  according  to  Lee,  the 
phenomenon  of  the  '  staircase  '  is  due  to  the  augmenting  action  of 
thise,  and  perhaps  otlier  f:  tigue  substances,  before  they  have  accu- 
mulated sufficiently  to  cause  fatigue. 

The  lack  of  oxygen  holds  a  conspicuous  place  among  the  con- 
ditions which  permit  an  excessive  accumulation  of  fatigue  substances, 
and  may  contribute  also  to  the  failure  of  the  processes  normally 
going  on  in  the  muscle  which  replenish  the  store  of  materials 
needed  for  contraction.  An  isolated  muscle  is  necessarily  an 
asphyxiated  muscle,  and  the  favourable  action  of  an  atmosphere 
of  oxygen  on  restoration  of  its  contractile  power  after  exhaustion 


Fig.  2f>2. — Ergograph  (Mosso's,  modified  by  Lombard). 

(Fig.  123,  p.  269)  shows  that  asphj-xia  is  itself  an  important  factor 
in  the  onset  of  fatigue.  Injection  of  arterial  blood,  or  even  of 
an  oxidizing  agent  like  potassium  permanganate,  into  the  vessels 
of  an  exhausted  muscle  causes  restoration  (Kronecker).  The 
depletion  of  the  available  store  of  carbo-hydrate  in  the  form  of 
glycogen  (and  dextrose)  seems  to  be  another  factor  in  fatigue, 
although  not  the  chief  direct  cause  of  the  phenomena  associated 
with  that  condition. 

Seat  of  Exhaustion  in  Fatigue. — When  a  fatigued  muscle  responds 
no  longer  to  indirect  stimulation,  it  can  still  be  directl}^  excited. 
The  seat  of  exhaustion  must  therefore  be  either  the  nerve-trunk 
or  the  nerve-endings.  It  is  not  the  nerv-e-trunk  which  is  first 
fatigued,  for  this  still  shows  the  negative  variation  (p.  824)  on  being 
excited.     And  if  the  two  sciatic  nerves  of  a  frog  or  rabbit  be  stimu- 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     75i 

latocl  continuously  with  interrupted  currents  of  equal  strength, 
while  the  excitation  is  prevented  from  reaching  the  muscles  of  one 
limb  till  those  of  the  other  cease  to  contract,  it  will  be  found  that 
when  the  '  block  '  is  removed  the  corresponding  muscles  contract 
vigorously  on  stimulation  of  their  nerve.  The  passage  of  a  constant 
current  tlirough  a  portion  of  the  nerve  or  the  ai)plication  of  ether 
between  the  point  of  stimulation  and  the  muscles  may  be  used  to 
prevent  the  excitation  from  passing  down  (p.  813)-  Or  a  dose  of 
curara  just  sufficient  to  paralyze  the  motor  innervation  may  be 
given  to  a  rabbit,  and  the  animal  kept  alive  by  artificial  respiration. 
The  sciatic  is  now  stimulated  for  many  hours.  As  soon  as  the 
influence  of  the  curara  begins  to  wear  off,  the  muscles  of  the  leg 
contract. 

The  possible  seats  of  fatigue  caused  by  voluntary  muscular  con- 
traction are  (i)  the  nmscle;  (2)  the  nerve-endings  (or  the  receptive 
substances  in  the  muscles,  p.  739);  (3)  the  nerve-trunk;  and  (4)  the 
path  of  the  voluntary  motor  impulses  in  the  central  nervous 
system,  which  includes  the  pyramidal  cells  in  the  motor  region  of 
the  cerebral  cortex  (p.  875),  the  fibres  of  the  pyramidal  tract,  and 
the  motor  cells  in  the  anterior  horn  of  the  spinal  cord. 

The  two  weak  links  in  this  chain  appear  to  be  the  motor  nerve- 
endings  and  the  muscles.  The  nerve-fibres,  whether  peripheral 
or  central,  are  certainly  the  strongest  link.  Ergographic  experi- 
ments have  hitherto  yielded  results  too  discordant  to  justify  any 
very  definite  statement  as  to  the  point  at  which  the  chain  snaps  in 
complete  fatigue,  if,  indeed,  it  al  vays  necessarily  breaks  at  the  same 
point.  The  muscles  and  motor  endings  appear  to  be  always  affected. 
The  position  of  the  nerve  centres,  including  the  synapses  (p.  852), 
is  in  doubt.  That  the  synapses  easily  lose  their  power  of  con- 
ducting nerve  impulses  under  the  influence  of  repeated  excitations 
is  indicated  by  the  experiments  of  Sherrington  on  fatigue  of  reflex 
mechanisms  in  which  two  or  more  afferent  paths  can  cause  discharge 
along  a  common  efferent  path  (p.  902).  When  excitation  of  one 
of  the  afferent  paths  has  ceased  to  be  effective,  the  reflex  contrac- 
tions can  still  be  obtained  on  exciting  the  other.  In  this  case  the 
motor  neuron  from  cell-body  to  nerve-ending  and  the  muscle  are 
eliminated  as  the  seats  of  the  fatigue  block.  Whether  the  tem- 
porary loss  of  conduction  in  this  case  is  comparable  to  the  fatigue 
of  muscle,  or  is  a  perfectly  different  phenomenon  ('  pseudo- fatigue  ' 
of  Lee),  scarcely  bears  on  our  present  question.  For  if  '  pseudo- 
fatigue  '  of  afferent  synapses  can  cause  a  reflex  to  miss  fire,  this  at 
least  shows  that  the  conductivity  of  the  synapse  is  very  easily  affected 
by  repeated  excitation,  just  as  it  is  known  to  be  very  easily  affected 
by  anaemia.  The  fact  that  a  muscle,  ct)mpletely  fatigued  by  direct 
electrical  stimulation,  can  still  be  voluntarily  contracted,  has  been 
supposed  to  indicate  that  the  voluntary  excitation  is  more  effective 


754        THE  PHYSIOLOGY  01-   TJIE  CONTRACTILE  TISSUES 

than  any  artificial  stimulus.  But  tlu-  alternative  explanation  that 
the  electrical  stimuli  cannot  be  applied  to  a  muscle  in  situ,  so  as  to 
cause  uniform  excitation,  and  therefore  uniform  fatigue,  of  all  the 
fibres  of  the  muscle,  is  more  probable  (Hough). 

It  has  been  shown  that  the  injection  of  the  blood  of  an  animal 
exhausted  by  running  or  other  muscular  effort  into  the  circulation 
of  a  normal  animal  produces  in  the  latter  all  the  symptoms  of  fatigue. 
Here  the  fatigue-producing  substances  will  have  the  opportunity 
of  acting  on  both  the  central  and  the  peripheral  mechanisms.  There 
are  reasons  for  believing  that  the  fatigue  process  is  fundamentally 
the  same  in  different  tissues.     The  fatigue  substances  produced  in 


Fig.  2  )3. — Influenrf  of  >STitaI  Fatigue  on  Muscular  Contraction,  i,  series  of  con- 
tractions of  Uexors  of  middle  finger  before,  and  2,  series  of  contractions  imme- 
diately after,  a  period  of  three  and  a  half  hours'  hard  mental  work.  In  both 
cases  the  muscles  were  stimulated  directly  every  two  seconds  by  an  electrical 
current,  and  caused  to  raise  a  certain  weight  till  temporary  exhaustion  occurred. 
In  the  first  series  fifty-three  contractions  were  found  possible,  in  the  second  only 
twelve  (Maggiora). 

muscle,  and  not  immediately  eliminated  or  transformed  during 
active  muscular  exertion,  may  therefore  very  well  be  a  factor  in 
inducing  fatigue  of  the  central  nervous  mechanisms  in  addition  to 
the  formation  of  fatigue  products,  and  the  using  up  of  necessary 
material  in  these  mechanisms  themselves.  Conversely,  active 
and  long-continued  mental  exertion  may  occasion  muscular  fatigue 
(Fig.  2(.3).    The  sensation  of  fatigue  is  alluded  to  in  Chapter  XVIII. 

{d)  The  Influence  of  Drugs  on  the  Contraction  of  Muscle. — The  total 
wor*K,  which  a  muscle  can  perform,  its  excitability  and  the  absolute 
force  of  the  contraction,  may  all  be  altered  either  in  the  plus  or  the 
minus  sense  by  drugs.  But  in  connection  with  our  present  subject 
those  drugs  wliich  conspicuously  alter  the  form  and  time-relations  of 
the  muscle-curve  have  most  interest.     Of  these  veratrine  is  especially 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     755 


importiuit.  W  licii  a  small  i|uantity  of  this  subs'.aiice  is  injected  below 
tlie  skin  oi  a  frog,  spasms  of  the  voluntary  muscles,  well  marked  in  the 
limbs,  come  on  in  a  few  minutes.  These  are  attended  with  great 
stiffness  ojj  movement,  for  while  the  animal  can  contract  the  extensor 
muscles  of  its  legs  so  as  to  make  a  spring,  they  relax  very  slowly,  and 
some  time  elapses  before  it  can  spring  again.  If  it  be  killed  before  the 
reflexes  are  completely  gone,  the  peculiar  alterations  in  the  form  of  the 
muscle-curve  caused  by  veratrine  will  be  most  marked.     The  poisoned 

1 


F^ig.  264- — Veratrine  Curve  compared  with  Normal:  Frog's  Gastrocnemius.  The 
tuning-fork  marks  hundredths  of  a  second.  Between  i  and  2  a  portion  of  the 
tracing  corresponding  to  one  and  a  half  seconds  has  been  cut  out,  and  between 
2  and  3  a  portion  corresponding  to  one  second.  The  veratrine  curve  does  not 
show  a  peak.     At  3  it  has  not  yet  fallen  to  the  base-line. 

muscle,  stimulated  directly  or  through  its  nerve,  contracts  as  rapidly 
as  a  normal  muscle,  while  the  height  of  the  curve  is  about  the  same, 
but  the  relaxation  is  enormously  prolonged  (Fig.  204).  This  effect 
seems  to  be  to  a  considerable  degree  dependent  on  temperature,  and 
it  may  temporarily  disappear  when  the  muscle  is  made  to  contract 
se^■eral  times  without  pause.  Barium  salts,  and.  in  a  less  degree,  those 
.  of  strontium  and  calcium,  have  an  action  on  muscle  similar  to  that  of 
veratrine.  Sometimes  the  curve  shows  a  peak  (Fig.  265).  due  to  a 
rapid  descent  of  the  lever  for  a  certain  distance.  This  is  followed  by 
a  slow  relaxation.  The 
peak  appears  to  be  analo- 
gous to  the  initial  con- 
traction when  a  strong 
voltaic  current  is  passed 
through  a  muscle,  and 
the  rest  of  the  curve  to 
the  tonic  contraction. 

[e)  The  individuality  of 
the  muscle  itself  has  an 
influence  on  the  muscle- 
curve.  Not  only  do  the 
muscles  of  different  animals  vary  in  the  rapidity  of  contraction,  but 
there  are  also  differences  between  the  skeletal  muscles  of  the  same  animal. 

In  the  rabbit  there  are  two  kinds  of  striped  muscle,  the  red  and  the 
pale  (the  semitendinosus  is  a  red.  and  the  adductor  magnus  a  pale 
muscle),  and  the  contraction  of  the  former  is  markedly  slower  than 
that  of  the  latter.  In  many  fishes  and  birds,  and  in  some  insects,  a 
similar  difference  of  colour  and  structure  is  present. 

Even  where  there  is  no  distinct  histological  difference,  there  may  be 
great  variations  in  the  length  of  contraction.  In  the  frog,  for  instance, 
the  hyoglossus  muscle  contracts  much  more  slowly  than  the  gastroc- 


Fig.  265. — Veratrine  Curve:  Frog's  Gastrocnemius. 
The  curve  shows  a  peak,  the  lever  falling  a  little 
before  the  sustained  contraction  begins. 


?5f>       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

nemius.  The  \va\e  of  contraction,  which  in  frogs'  striped  muscle  lasts 
only  about  0-07  second  at  any  point,  may  last  a  second  in  the  forceps 
muscle  of  the  crayfish .  though  only  half  as  long  in  the  muscles  of  the  tail. 
In  the  muscles  of  the  tortoise  the  contraction  is  also  very  slow.  The 
muscles  of  the  arm  of  man  contract  more  quickly  than  those  of  the  leg. 
Summation  of  Stimuli  and  Superposition  of  Contractions. — Hitherto 
we  have  considered  a  single  muscular  contraction  as  arising  from  a 
single  stimulus,  and  we  have  assumed  that  the  muscle  has  completed 
its  curve  and  come  back  to  its  original  length  before  the  next  stimulus 
was  thrown  in.  We  have  now  to  inquire  what  happens  when  a  second 
stimulus  acts  upon  the  muscle  during  the  contraction  caused  by  a  fi.rst 
stimulus,  or  during  the  latent  period  before  the  contraction  has  actually 
begun;  and  what  happens  when  a  whole  series  of  rapidly-succeeding 
stimuli  are  thrown  into  the  muscle. 

First  let  us  take  two  stimuli  separated  by  a  smaller  interval  than 
the  latent  period  (p.  745)-  If  they  are  both  maximal — i.e.,  if  each  by 
itself  would  produce  the  greatest  amount  of  contraction  of  which  the 
muscle  is  capable  when  excited  by  a  single  stimulus — the  second  has 
no  effect  whatever ;  the  contraction  is  precisely  the  same  as  if  it  had 

ne^'er  acted.  But  if  they  are  less 
than  maximal,  the  contraction, 
although  it  is  a  single  contraction, 
is  greater  than  would  have  been 
due  to  the  first  stimulus  alone ;  in 
other  words,  the  stimuli  have  been 
summed  or  added  to  each  other 
during  the  latent  period,  so  as  to 
produce  a  single  result. 

Next  let  us  consider  the  case  of 
two  stimuli  separated  by  a  greater 
_  .  .        .  _  interval  than  the  latent  period,  so 

Fig.  2fi6 .-Superposition  of  Contractions,  that  the  second  falls  into  the 
I  IS  the  curve  when  only  one  stimulus  j^^j^^j^  during  the  contraction  pro- 
IS  thrown  m;  2,  when  a  second  stimulus      ,        j  1     ^.u    ^     j.     -ri  ij.  -u 

acts  at  the  time  when  curv-er  has  nearly     ^uced  bv  the  first^    The  result  here 
reached  its  maximum  height.  '^  very  different :  tracesof  two  con- 

tractions appear  upon  the  muscle- 
curve,  the  second  curve  being  that  which  the  second  stimulus  would  have 
caused  alone,  but  rising  from  the  point  which  the  first  had  reached  at  the 
moment  of  the  second  shock  (Fig.  266).  Although  the  first  curve  is 
cut  short  in  this  manner,  the  total  heiglit  of  the  contraction  is  greater 
than  it  would  have  been  had  only  the  first  stimulus  acted ;  and  this  is 
true  even  when  both  stimuli  are  maximal.  Under  favourable  circum- 
stances, when  the  second  curve  rises  from  the  apex  of  the  first,  the  total 
height  may  be  twice  as  great  as  that  of  the  contraction  which  one 
stimulus  would  have  caused  (p.  816).  It  is  worthy  of  note  that  striated 
muscle  has  no  power  of  summation  of  subminimalstimuli  each  of  which 
is  just  too  weak  to  cause  contraction.  No  matter  how  rapidly  they  are 
thrown  in,  the  muscle  remains  at  rest.  It  is  otherwise  with  smooth 
muscle.  Stimuli  which  are  singly  ineffective  cause  contraction  when 
repeated. 

Tetanus. — Not  only  may  we  have  superposition  or  fusion  of  two 
contractions,  but  of  an  indefinite  number;  and  a  series  of  rapidly 
following  stinuili  causes  complete  tetanus  of  the  muscle,  which 
remains  contracted  during  the  stimulation,  or  till  it  is  exhausted 
(Fig.  267). 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    757 

The  meaning  of  a  complete  tetanus  is  readily  grasped  if,  beginning 
with  a  series  of  shocks  of  such  rapidity  that  the  muscle  can  just 
completely  relax  in  the  intervals  between  successive  stimuli,  we 
gradually  increase  the  frequency  (p.  8i6).  As  this  is  done,  the 
ripples  on  the  curve  become  smaller  and  smaller,  and  at  last  fade 
out  altogether.  The  maximum  height  of  the  contraction  is  greater 
than  that  produced  by  the  strongest  single  stimulus;  and  even  after 
complete  fusion  has  been  attained,  a  further  increase  of  the  fre- 
quency of  stimulation  may  cause  the  curve  still  to  rise. 


Fig.  267. — Analysis  of  Electrical  Tetanus  (reduced  to  f ).  Four  curves  showing  the 
effect  of  increasing  frequency  of  stimulation  of  the  frog's  gastrocnemius  through 
its  nerve.  In  the  lowest  curve  the  frequency  is  such  that  the  muscle  relaxes 
almost  completely  betweeH  the  successive  contractions.  In  the  uppermost 
curve,  with  a  frequency  more  than  three  times  greater,  the  contractions  are 
almost  completely  fused.  In  all  the  curves  the  fusion  becomes  more  nearly 
complete  as  stimulation  goes  on,  owing  to  the  slower  relaxation  of  the  fatigued 
muscle. 

It  is  evident  from  what  has  been  said  that  the  frequency  of 
stimulation  necessary  for  complete  tetanus  will  depend  upon  the 
rapidity  with  which  the  muscle  relaxes;  and  everything  which 
diminishes  this  rapidity  will  lessen  the  necessary  frequency  of 
stimulation.  A  fatigued  muscle  may  be  tetanized  by  a  smaller 
number  of  stimuli  per  second  than  a  fresh  muscle,  and  a  cooled  by 
a  smaller  number  than  a  heated  muscle.  The  striped  muscles  of 
insects,  which  can  contract  a  million  times  in  an  hour,  require 
300  stimuli  per  second  for  complete  tetanus,  those  of  birds  100, 
of  man  40,  the  torpid  muscles  of  the  tortoise  only  3.  The  pale 
muscles  of  the  rabbit  need  20  to  40  excitations  a  second,  the  red 


758       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

muscles  only  lo  to  20;  the  tail  muscles  of  the  crayfish  40,  but  the 
muscles  of  the  claw  only  6  in  winter  and  20  in  summer.  The 
gastrocnemius  of  the  frog  requires  30  stimuli  a  second,  the  hyo- 
glossus  muscle  only  half  that  number  (Richet).  The  frequency  of 
stimulation  necessar\'  for  complete  tetanus  of  unstrip^d  muscle 
is  much  less  than  for  striped  muscle.  Smooth  tetanus  of  a  band  of 
muscle  from  the  frog's  stomach  was  obtained  \sith  strong  opening 
induction  shocks  at  the  rate  of  i  in  5  seconds. 

Tlitrc  appears  also  to  be  an  upper  limit  bevond  which  a  series  of 
stimuli  becomes  too  rapid  to  produce  complete  tetanus,  and  at  which  an 
interrupted  current  acts  like  a  constant  current,  causing  a  single  twitch 
at  its  commencement  or  at  its  end,  but  no  contraction  during  its  pas- 
sage. This  limit  docs  not  depend  upon  the  frequency  of  stimulation 
alone ;  the  intensity  of  the  individual  excitations,  the  temperature  of 
the  muscle,  and  probably  other  factors,  affect  it.  For  Bernstein  found 
that  with  moderate  strength  of  stimulus  tetanus  failed  at  about  230 
per  second,  and  was  replaced  by  an  initial  contraction ;  with  strong 
stimuli  at  more  than  1,700  per  second,  tetanus  could  still  be  obtained. 
Kronecker  and  Stirling  saw  tetanus  even  with  4,000  shocks  a  second. 
Kries  in  a  cooled  muscle  found  tetanus  replaced  by  the  simple  initial 
twitch  at  100  stimuli  per  second,  although  in  a  muscle  at  38^  C.  stimu- 
lation of  ten  times  this  frequency  still  caused  tetanus.  Einthoven, 
exciting  the  nerve  of  a  frog's  nerve-muscle  preparation  with  extremely 
frequent  oscillatory  condenser  discharges,  observed  tetanus  up  to  even 
a  million  vibrations  a  second,  if  the  current  intensity  was  at  the  same 
time  very  greatlv  increased  (to  more  than  16,000  times  the  intensity 
needed  with  a  constant  current).  These  results  are  not  really  so  dis- 
cordant as  they  appear ;  for  it  is  known  that  with  electrical  stimulation 
the  number  of  excitations  is  not  necessarily  the  same  as  the  nominal 
number  of  shocks.  By  applying  a  telephone  to  a  muscle  excited  through 
its  motor  nerve,  it  has  been  shown  that  the  pitch  of  the  note  produced 
by  the  tetanized  muscle  corresponds  exactly  to  the  rate  of  excitation 
up  to  a  certain  frequency.  This  frequency  is  about  200  per  second  for 
frog's  and  about  1,000  per  second  for  mammalian  muscle  under  the 
best  conditions.  If  the  rate  of  excitation  is  still  further  increased,  there 
is  no  corresponding  increase  in  the  pitch.  Therefore,  some  of  the 
stimuli  are  now  producing  no  effect—'  falling  flat,'  so  to  speak  (Weden- 
sky).  A  physical  reason  for  this  is  the  overlappmg  of  the  make  and 
break  shocks  (Erlanger  and  Garrey) ;  and  a  physiological  reason,  the 
alterations  of  conductivity  and  excitability,  which  even  very  brief 
currents  leave  behind  them  (Sewall),  and  which  we  shall  have  to  discuss 
in  another  chapter. 

It  is  only  while  the  actual  shortening  is  taking  place  that  a  tetanized 
muscle  can  do  external  work.  But,  although  during  the  maintenance 
of  the  contraction  no  work  is  done,  energy  is  nevertheless  being  ex- 
pended for  the  metabolism  of  a  muscle  during  tetanus  is  greater  than 
during  rest,  and,  among  other  changes,  lactic  acid  is  produced.  There 
are  great  differences  in  the  case  with  which  different  muscles  can  be 
exhausted  by  tetanus.  For  example,  the  muscles  which  close  the 
forceps  of  the  cravfish  or  lobster  have,  as  everyone  knows,  the  power 
of  most  obstinate  contraction.  Richet  tetanized  one  for  over  seventy 
minutes,  and  another  for  an  hour  and  a  half,  before  exhaustion  came 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION   759 

on,  while  a  tetanus  of  a  single  minute  exhausted  the  ^inu^c^es  of  ti.e 
crayfish's  tail.  The  gastrocnemius  of  a  summer  frog  kept  up  for  twelve 
minutes,  and  a  tortoise  muscle  for  forty  minutes. 

Continuous  stimulation  is  not  always  necessary  for  the  production 
of  continuous  contraction ;  in  some  conditions  a  single  sti.nulus  is  suffi- 
cient. A  blow  with  a  hard  instrument  may  cause  a  dying  or  exhausted, 
and  in  thin  persons  even  a  fairly  normal,  muscle  to  pass  into  long- 
continued  contraction.  This  so-called  '  idio-muscular  '  contraction 
seems  to  depend,  in  part  at  least,  on  the  great  intensity  of  the  stimulus. 
It  can  sometimes  be  obtained  in  the  frog's  gastrocnemius,  partici  larly 
in  spring  after  the  winter  fast.  It  is  not  a  tetanus  and  is  not  propa- 
gated along  the  muscular  fibres,  as  an  electrical  tetanus  is,  but  remains 
localized  at  the  spot  wlicre  it  arises.  Similar  non-tetanic  contr.  ctions 
have  already  been  mentioned,  such  as  the  tonic  contraction  during  the 
passage  of  a  strong  voltaic  current  and  the  sust;uncd  veratrinc  contrac- 
tion. Amnaonia  causes  also  a  long  but  non-tetanic  contraction,  and  this, 
too,  does  not  spread  when  the  substance  has  acted  only  on  a  portion 
of  the  muscle.  The  contraction  force  of  all  these  tonic  contractions, 
as  measured  by  the  rv?sistance  necessary  to  overcome  or  prevent  them, 
is  less  than  the  contrc'.clion  force  in  electrical  tetanus  (Schenck). 

The  rate  at  which  the  wave  of  muscular  contraction  travels  may  be 
measured  by  stimulating  the  muscle  at  one  end,  and  recording,  by 
means  of  levers,  the  movements  of  two  points  of  its  surface  as  far 
apart  from  each  other  as  possible.  Time  is  marked  on  the  tracing  by 
means  of  a  tuning-fork,  and  the  distance  between  the  points  at  which 
the  two  curves  begin  to  rise  from  the  base-line  divided  by  the  time  gives 
the  velocity  of  the  wave.  Another  method  is  founded  upon  the  measure- 
ment of  the  rate  at  which  the  negative  variation  (p.  824)  passes  over 
the  muscle,  this  being  the  same  as  the  velocity  of  the  contraction-wave. 
In  frog's  muscle  it  is  about  three  metres  a  second,  or  six  miles  an  hour. 
Rise  of  temperature  increases,  fall  of  temperature  lessens  it.  When  a 
muscle  is  excited  through  its  nerve,  the  contraction  springs  up  first  of 
all  about  the  middle  of  each  muscular  fibre  where  the  nerve-fibre  enters 
it,  and  then  sweeps  out  in  both  directions  towards  the  ends.  But  so 
long  is  the  wave,  that  all  parts  of  the  fibre  are  at  the  same  time  involved 
in  some  phase  or  other  of  the  contraction. 

The  wave  of  contraction  in  unstriped  muscle  lasts  a  relatively  long 
time  at  any  given  point,  and  in  tubes  like  the  intestines  and  ureters, 
the  walls  of  which  are  largely  composed  of  smooth  muscle  arranged  in 
rings,  the  wave  shows  itself  as  a  gradually-advancing  constriction 
travelling  from  end  to  end  of  the  organ.  There  is  no  evidence  that 
the  contraction  of  smooth  muscular  fibres  is  discontinuous — that  is, 
;omposed  of  summated  contractions  like  a  tetanus ;  it  appears  to  be  a 
d;reatly-prolonged  simple  contraction.  An  artificial  stimulus,  mechani- 
cal or  electrical,  causes,  after  a  long  latent  period,  a  ver^'  definitely- 
localized  contraction  in  a  rabbit's  ureter,  which  slowly  spreads  in  a 
peristaltic  wave  in  one  or  both  directions  along  the  muscular  tube. 
Here,  as  in  the  cardiac  muscle,  the  excitation  passes  from  fibre  to  fibre, 
while  in  striped  skeletal  muscle  only  the  fibres  excited  directly  or 
through  their  nerves  contract.  That  the  rh^'thmical  contraction  of 
the  heart  is  not  a  tetanus  has  already  been  seen.  It  is  a  simple  con- 
traction, intermediate  in  its  duration  and  other  characters  between  the 
twitch  of  voluntary  muscle  and  the  contraction  of  smooth  muscle.  The 
contraction  both  of  unstriped  and  of  cardiac  muscle  is  lengthened  and 
made  stronger  by  distension  of  the  viscera  in  whose  walls  they  occur, 
just  as  a  skeletal  muscle  contracts  more  powerfully  against  resistance. 


76o        THE  PJIYSIOLCGY  OF  THE  CONTRACTILE  TISSUES 

Voluntary  Contraction. — There  is  evidence  that  the  voluntary 
contraction  is  a  tetanus.  One  of  the  strongest  buttresses  of  the 
theory  of  natural  tetanus  has  been  the  muscle-sound,  a  low  rumbling 
note  which  can  be  heard  by  listening  witli  a  stethoscope  over  the 
contracting  biceps,  or,  when  all  is  still,  by  stopping  the  ears  with  the 
fingers  and  strongly  contracting  the  masseter  and  the  other  muscles 
concerned  in  closing  the  jaws.*  Discovered  about  ninety  years 
ago,  first  by  Wollaston  and  then  by  Erman,  half  a  century  passed 
away  before  it  was  investigated  more  fully  by  Helmholtz.  The 
latt(^r  observer,  confirming  the  results  of  his  predecessors,  put  down 
the  pitch  of  the  sound  at  36  to  40  vibrations  per  second.  He  found, 
however,  that  little  vibrating  reeds  with  a  rate  of  oscillation  of  about 
19  5  per  second  were  more  affected  when  attached  to  muscle  thrown 
into  voluntary  contraction,  than  those  that  vibrated  at  a  smaller 
or  a  greater  rate.  He  therefore  concluded  that  the  fundamental 
tone  of  the  muscle  corresponded  to  this  frequency,  although,  since 
such  a  low  note  is  not  easily  appreciated,  the  sound  actually  heard 
was  really  its  octave  or  first  harmonic  (p.  310). 

The  objection  has  been  brought  forward  that  the  resonance  tone  of 
the  ear  also  corresponds  to  a  vibration  frequency  of  36  to  40  a  second. 
In  other  words,  this  is  the  natural  rate  of  swing  of  the  elastic  struc- 
tures in  the  middle  ear,  the  rate  they  will  most  easily  fall  into  if  set 
moving  by  an  irregular  mixture  of  faint,  low-pitched  tones  and  noises, 
and  not  compelled  to  vibrate  at  some  other  rate  by  a  distinct  sound 
of  definite  pitch.  Now,  tliis  resonance  tone  might  be  elicited  by  a 
quivering  muscle  if,  among  many  diverse  rates  of  oscillation  of  different 
portions  of  its  substance,  the  rate  of  36  to  40  a  second  anywhere  ap>- 
peared,  and  the  note  corresponding  to  the  real  rate  of  vibration  of  the 
muscle  as  a  whole  might  be  overpowered.  Or,  even  if  there  were  no 
regular  rate  of  vibration  of  the  whole  muscle,  but,  instead,  a  series  of 
irregular  tremors  or  pulls  due  to  irregularities  in  the  contraction,  con- 
nected with  a  want  of  co-ordination  of  all  the  fibres  (Haycraft),  the  ear 
might  from  time  to  time  pick  out  of  the  turmoil  of  feeble  aerial  waves 
those  corresponding  to  its  resonance  tone,  just  as  a  tuning-fork  or  a 
piano-string  attuned  to  a  particular  note  would  catch  it  up  amid  a 
thousand  other  sounds  and  strengthen  it. 

But  while  this  renders  it  highly  probable  that  the  resonance  of  the 
ear  contributes  to  the  production  of  the  muscle-sound,  and  shows  that 
we  cannot  from  the  pitch  of  the  musclc-.sounci  alone  deduce  the  rate 
at  which  the  muscle-substance  is  vibrating,  it  does  not  invalidate 
Helmholtz's  objective  observjitions  with  the  oscillating  reeds. 

And  several  observers  (Schafer,  Horsley,  v.  Kries)  have  noticed 
periodic  oscillations,  at  the  rate  of  10  or  12  per  second,  in  the 
curves  taken  from  muscles  (Fig.  268),  contracted  voluntarily 
against  a  small  resistance.  When  the  resistance  is  greater,  the 
rate  may  be  as  much  as  18  or  20  a  second,  and  in  quick  and  rapidly 

*  In  order  that  a  muscular  sound  may  be  produced  there  must  be  a  certain 
abruptness  in  the  contraction.  Thus,  the  slowly-tontracting  smooth  muscles 
do  not  produce  a  sound,  nor  the  slowly-contracting  heart-muscle  of  cold- 
blooded animals. 


MECHANICAL  PHENOMENA   01'  MUSCULAR  CONTRACTION     761 

repeated  movements  of  the  fingers  even  40  a  second.  In  habitual 
movements,  such  as  those  employed  by  a  man  in  his  trade,  the 
tremors  are  much  less  coarse  than  in  unaccustomed  movements. 
For  this  reason  the  tremors  of  the  left  hand  are  greater  than  those 
of  the  right  in  executing  a  movement  usually  made  with  the  latter 
(Eshner).  In  disease  these  tremors  are  often  increased — e.g.,  in 
the  clonic  convulsions  of  epilepsy — but  the  frequency  is  the  same. 


;1 


^M^W*i« 


Fig.  268.- 


-Vibrations  of  Contracted  Arm  Muscles  (Griffiths).     The  arm  was  stretched 
out,  holding  a  weight  of  about  6  kilos. 


Similar  vibrations,  and  at  about  the  same  rate,  are  seen  in  curves 
traced  by  muscles  excited  through  stimulation  of  the  motor  areas 
of  the  surface  of  the  brain.  Since  this  rate  remains  the  same  whether 
the  motor  cortex,  the  corona  radiata,  or  the  spinal  cord  is  excited, 
and,  unlike  the  rate  of  response  to  excitation  of  peripheral  nerves, 
is  independent  of  the  frequency  of  stimulation  (so  long  as  the  rate 
of  stimulation  is  greater  than  10  or  12  a  second),  it  has  been  supposed 
to  represent  the 
rhythm  with  which 
impulses  are  dis- 
charged from  the 
motor  cells  of  the  cord 
(Fig.  269).  It  is  prob- 
able that  the  cortical 
centres  discharge  at 
about  the  same  rate, 
for  not  only  is  it  im- 
possible to  articulate 
more  rapidly  than 
eleven  syllables  per 
second,  but  it  is  impossible  to  reproduce  the  act  of  articulation  in 
thought  at  a  greater  rate  than  this  (Richet).  But  while  this  rate 
of  10  or  12  a  second  does  seem  to  represent  a  fundamental  rhythm 
of  the  central  discharge,  there  are  facts  which  indicate  that  upon 
this  relatively  slow  rhythm  a  quicker  rhythm  is  superposed.  In 
other  words,  each  of  these  discharges  is  itself  discontinuous,  and 
made  up  of  a  number  of  separate  impulses. 


Fig.  269. — Contractions  caused  by  Stimulation  of  the 
Spinal  Cord. 


762    •   THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Thus,  according  to  Piper,  the  total  number  ot  simple  discharges, 
each  associated  with  an  electrical  change  in  the  muscle,  as  recorded  by 
the  string  galvanometer,  is  47  to  50  a  second.  The  rhythm  of  strych- 
nine tetanus  in  the  frog  is  about  8  to  12  per  second.  By  means  of  the 
capillary  electrometer  (p.  729)  large  electrical  oscillations  at  this  rate 
can  be  demonstrated,  each  of  which  represents  a  short  tetanic  spasm, 
as  is  shown  by  the  fact  that  a  number  of  smaller  electrical  oscillations 
are  superposed  upon  the  large  ones  (Sanderson).  The  electrical  changes 
suggest  that  each  discharge  causes  a  simple  contraction  much  more 
prolonged  than  the  twitch  of  a  directly  stimulated  muscle.  This 
removes  the  difficulty  of  understanding  how  such  a  small  number  as 
10  contractions  per  second  could  be  smoothly  fused,  and  indicates  that 
even  the  stiortest  possible  voluntary^  movement,  which  can  be  executed 
in  ^  to  T^fj  of  a  second,  is  not  caused  by  a  single  impulse,  but  is  a 
tetanus.  For  these  brief  mo\ements  the  frequency  of  oscillation,  as 
shown  by  the  action  currents,  is  the  same  as  for  sustained  contractions. 
The  electrical  changes  in  the  voluntarily-  contracted  muscle  seem  to 
differ  in  amplitude  or  abruptness  from  those  produced  in  experimental 
tetanus.  For  secondarj'  tetanus  (p.  833)  is  not  caused  by  muscle  in 
volimtary  contraction.  But  this  is  also  the  case  with  the  ftthcr  pro- 
longed contractions  caused  by  continuous  artificial  stimulation — e.g., 
Ritter's  tetanus  (p.  74T)  and  the  contraction  produced  by  sodium 
chloride  or  ammonia.  We  need  not  hesitate  to  conclude,  then,  that 
the  voluntary  contraction  is  discontinuous,  in  the  sense  that  it  is  not 
a  perfectly  smooth  and  uniform  tonic  contraction,  although  we  still 
lack  a  decisive  proof  that  it  is  maintained  by  a  strictly  intermittent 
outflow  of  nervous  energy,  and  not  by^  a  continuous  outflow  causing  a 
sustained  contraction,  which,  it  may^  be,  remits  and  is  reinforced  at 
intervals.  The  apparent  discrepancies  as  to  the  rate  of  discharge  in 
the  results  obtained  by^  dilierent  observers,  and  by  different  methods, 
far  from  exciting  distrust  of  them  all,  really  lend  support  to  the  idea 
of  a  fundamental  and  fairly  constant  rhythm  in  the  outflow  as  soon 
as  it  is  recognized  that  the  higher  rates  are  approximately-  multiples 
of  the  lower.  Thus,  the  number  deduced  by  Helmholtz  from  the  ex- 
periment of  the  springs  is  twice  the  lowest  rate  calculated  from  graphic 
records  of  the  contraction.  The  rates  corresponding  to  the  muscle- 
sound  and  to  the  frequency  of  the  electrical  oscillations  are  about  four 
times  this  number.  Now,  in  a  vibrating  elastic  body  like  a  contracting 
muscle,  a  simple  mathematical  relation  of  this  sort  might  be  expected 
to  appear  when  determinations  of  the  rate  of  oscillation  and  of  accom- 
panying periodic  changes  are  made  by  methods  varying  in  principle  and 
in  delicacy.  For  instance,  an  arrangement  suited  to  record  and  to 
count  coarse  vibrations  could  not  be  expected  to  give  the  same  result 
as  an  arrangement  suited  to  record  and  count  fine  vibrations.  But  if 
both  the  coarse  and  the  fine  vibrations  were  related  to  a  fundamental 
rhythm,  a  simple  proportion  might  be  expected  to  exist  between  tlic 
two  sets  of  results. 

(3)  Thermal  Phenomena  and  Transformation  of  Energy  in  the 
Muscular  Contraction. — When  a  muscle  contracts,  its  temperature 
rises;  the  production  of  heat  in  it  is  increased.  This  is  most  dis- 
tinct when  the  muscle  is  tetanized,  but  has  also  been  proved  for 
single  contractions.  The  change  of  temperatuie  can  be  detected 
by  a  delicate  mercury  or  air  thermometer;  and,  indeed,  a  ther- 
mometer thrust  among  the  thigh-muscles  of  a  dog  may  rise  as  much 


THERMAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     7(>i 


as  1°  to  2°  C.  wlu-n  the  muscles  are  thrown  into  tetanus.  In  the 
isolated  muscles  of  cold-blooded  animals  the  increase  of  tempera- 
ture is  much  less;  and  tliermo-electrical  methods,  which  are  the 
most  delicate  at  present  known,  have  generally  been  used  for  its 
detection  and  measurement. 

They  de^>end  upon  the  fundamental  fact  of  thermo-electricity,  that 
in  a  circuit  composed  of  two  metals  a  current  is  set  up  if  the  junctions 
of  the  metals  are  at  different  tempera- 
tures 

Where  no  very  fine  differences  of 
temperature  are  to  be  measured,  a  single 
thermo-j unction  of  (ierman  silver  and 
iron,  or  copper  and  iron,  is  inserted  into 
a  muscle  or  between  two  muscles.  But 
the  electromotive  force,  and  therefore 
the  strength  of  the  thermo-electric  cur- 
rent, is  proportional  for  any  given  pair 
of  metals  to  the  number  of  junctions, 
and  for  plicate  measurements  it  may 
be  necessary  to  use  several  connected 
together  in  series.  A  thermopile  of 
antimony  -  bismuth  junctions  gives  a 
stronger  current  for  a  given  difference  of 
temperature  than  the  same  number  of 
German  silver-iron  couples,  but  from  its 
brittle  nature  is  otherwise  less  convenient . 

The  direction  of  the  current  in  the  cir- 
cuit is  such  that  it  passes  through  the 
heated  junction  from  bismuth  to  anti- 
mony and  from  copper  or  German  silver 
to  iron.  Knowing  this  direction,  we  are 
aware  of  the  changes  of  temperature 
which  take  place  from  the  movements 
of  the  mirror  of  the  gah'anometer  with 
which  the  pile  is  connected.  In  the 
thermopiles  emploj-ed  in  the  recent  ex- 
tensive investigations  of  Hill  the  alloy 
constantan  is  coupled  with  iron,  the 
electromotive  force  of  this  combination 
being  exceptionally  great. 

The  muscle  which  is  to  be  excited  is 
brought  into  close  contact  with  one 
junction  or  set  of  junctions,  the  other 
set  being  kept  at  constant  temperature. 
The  image  will  now  come  to  rest  on  the 
scale;  and  excitation  of  the  muscle  will 
cause  a  movement  indicating  an  increase 
of  temperature  in  it,  the  amount  of  which 
can  be  calculated  from  the  deflection.  In 
one  form  (Fig.  270)  the  thermopile  con- 
stitutes a  hollow  cone,  in  which  a  muscle  can  be  arranged  so  as  to  eliminate 
largely  the  errors  due  to  differences  of  temperature  of  the  muscle,  or  to 
the  "slip"  of  the  contracting  muscle  over  the  junctions. 

In  this  way  Helmholtz  observed  a  rise  of  temperature  of  0-14°  to 
0  18°  C.  in  excised  frogs'  muscles  when  tetanized  for  a  couple  of  minutes . 


5 

Fig.  270.  —  Conical  Thermopile 
containing  Gastrocnemius  Mus- 
cle Reversed.  C,  copper  leads 
to  galvanometer;  S,  stimulating 
wire.  The  straight  lines  indicate 
iron,  the  crossed  lines  constan- 
tan, the  external  junctions  em- 
bedded in  the  ebonite  frame 
being  at  a,  the  internal  junc- 
tions, b,  in  contact  with  the 
muscle. 


764        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


Heidenhain,  with  a  very  delicate  pile,  found  a  rise  of  0001°  to 
0-005°  C.  f(jr  a  single  contraction  of  a  frog's  muscle.  On  the  assump- 
tion that  the  pile  had  time  to  take  on  the  temperature  of  the 
muscle  before  there  was  any  appreciable  loss  of  heat,  this  would 
be  equal  to  the  production  by  every  gramme  of  muscle  of  a  thou- 
sandth to  five-thousandths  of  a  gramme-calorie  (p.  676)  of  heat. 
From  Pick's  observations  we  may  take  about  three-thousandths 
of  a  gramme-calorie  as  the  maximum  production  of  a  gramme  of 
frog's  muscle  in  a  single  contraction. 

Hill  has  shown  that  in  the  case  of  the  single  contraction  or  twitch 
the  evolution  of  heat  may  be  so  rapid  as  to  be  practically  instan- 
taneous, indicating  that  it  depends  upon  some  sudden  '  explosive  ' 
chemical  reaction;  or,  on  the  other  hand,  under  certain  conditions 

it  may  last  as  long  as  two 
seconds — that  is,  from  four 
to  ten  times  as  long  as  the 
contraction  itselff  In  the 
absence  of  oxygen,  when 
the  muscle  is  left,  for  in- 
stance, in  an  atmosphere  of 
hydrogen,  the  heat  produc- 
tion becomes  markedly  pro- 
longed. When  abundant 
oxygen  is  supplied,  the  dura- 
tion of  the  discharge  of  heat 
is  decreased.  In  a  tetanus 
the  evolution  of  heat  lags 
behind  the  excitation,  and 
the  discharge  associated 
with  each  stimulus  is  not 
complete  till  0-5  to  2*5 
seconds  after  the  stimulus.  In  a  prolonged  complete  tetanus 
the  heat  production  corresponding  to  the  first  tenth  of  a  second 
of  excitation  is  far  greater  than  that  corresponding  to  the  second 
tenth  of  a  second,  and  so  on.  until  eventually  a  uniform  dis- 
charge of  heat,  at  a  rate  much  smaller  than  the  initial  rate,  is 
reached.  When  frogs'  muscles  are  rapidly  stimulated  indirectly 
(through  the  nerves)  till  fatigue  has  occurred,  the  maximum  value 
of  the  heat  evolved  approximates  to  09  gramme  -  calorie  per 
gramme  of  muscle,  about  70  or  80  per  cent,  being  liberated  in  the 
first  two  minutes  (Peters). 

A  fact  of  great  significance  in  regard  to  the  relation  of  the  reaction 
upon  which  the  heat  production  depends  and  the  mechanical 
conditions  in  the  active  muscle  is  that  the  production  of  heat  is 
determined  by  the  length  of  muscular  fibres  existing  at  the  time 
when  the  heat  is  being  evolved.  From  this  it  has  been  assumed 
that  the  production  of  heat  in  active  muscle  is  a  surface  effect,  and 


Fig.  271. — A,  a  single  copper-iron  thermo- 
ckciric  couple;  B.two  pairs,  one  inserted  into 
the  tissue  b,  the  other  dipping  into  water  in  a 
beaker  a.  The  temperature  of  the  water 
maj'  be  adjusted  so  that  the  galvanometer 
shows  no  deflection.  The  temperature  of  the 
tissue  is  then  the  same  as  that  of  the  water. 


THERMAL  PHENOMENA  OF  MUSCULAR  CONTRACTION        765 

not  an  effect  taking  place  uniformly  throughout  the  muscle  substance 
and  related  accordingly  to  the  volume  or  mass  of  the  muscular 
substance  (Blix).  Much  evidence  has  been  accumulated  in  favour 
of  this  hypothesis.  For  example,  a  muscle  contracting  isometrically 
(p.  747)  produces  more  heat  the  greater  is  the  initial  tension  (the 
more  it  is  stretched  at  the  begining  of  the  excitation) — that  is, 
the  greater  its  length  during  contraction  (Heidenhain).  When  a 
muscle  is  allowed  to  shorten  in  a  tetanus,  the  heat  production  as 
compared  with  that  of  an  isometric  contraction  of  the  same  dura- 
tion, and  evoked  by  the  same  strength  of  stimulus,  is  diminished 
by  as  much  as  40  per  cent. 

Relation  between  the  Development  of  Mechanical  Energy  and 
Heat  Production  in  Active  Muscle. — There  is  no  simple  relation 
between  the  external  work  done  in  a  muscle  twitch  and  the  heat 
set  free.  The  efficiency  of  the  muscular  machine,  as  estimated 
by  the  proportion  of  the  work  done  to  the  total  energy  degraded, 
varies  with  a  number  of  factors — e.g.,  the  load,  the  number  of  fibres 
excited,  and  the  intensity  of  the  excitation  of  each  fibre,  the  two 
latter  factors  depending  upon  the  strength  of  the  stimulus. 

The  greater  the  resistance,  so  long  as  the  muscle  can  overcome 
it  so  as  to  do  its  utmost  amount  of  external  work,*  the  larger  is 
the  proportion  of  energy  which  appears  as  work,  the  smaller  the 
proportion  which  appears  as  heat.  For  every  muscle,  under  given 
conditions,  there  is  a  certain  load  which  can  be  raised  more  advan- 
tageously than  any  other;  but  even  in  the  most  favourable  case, 
an  excised  frog's  muscle  never  does  work  equal  to  more  than  J  of 
the  heat  given  off.  Generally  the  ratio  is  much  less,  and  may  sink 
as  low  as  ^.  In  the  intact  mammahan  body  the  muscles  work 
somewhat  more  economically  than  the  excised  frog's  muscles  at 
their  best;  for  both  experiment  and  calculation  show  (p.  687) 
that  in  a  normal  man  under  the  most  favourable  conditions  as 
much  as  J  of  the  energy  is  converted  into  work.  According  to 
Zuntz  and  Katzenstein,  35  per  cent,  of  the  total  energy  appeared 
as  muscular  work  in  cUmbing  a  mountain,  and  in  bicycling  onlv 
25  per  cent.  Movements  which  have  been  much  practised  are 
more  economically  performed  than  unaccustomed  ones,  and  this 
explains  the  superior  efficiency  of  the  muscles  concerned  in  climbing, 
for  no  movements  can  possibly  be  more  familiar  than  those  con- 
cerned in  locomotion.  So  far  as  this  indication  goes,  it  would  seem 
that  in  the  treatment  of  obesity  unfamiliar,  and  therefore  physio- 
logically expensive,  forms  of  exercise  should  be  recommended,  in 
so  far,  of  course,  as  they  do  not  injuriously  react  upon  the  general 
condition,  especially  upon  the  circulation. 

•  This  statement,  based  on  experiments  with  excised  frog's  muscles,  is  not, 
of  course,  inconsistent  with  the  fact  mentioned  on  p.  687,  that  in  the  intact 
body  the  fraction  of  the  energy  transformed  into  heat  is  greater  in  hard  than 
in  moderate  work. 


766       THE  PHYSIOLOGY  01-   THE  CONTRACTILE  TISSUES 

When  a  muscle,  excited  by  maximal  stimuli,  is  made  to  lift  con- 
tinuously increasing  weights,  both  the  woik  done  and  the  heat  given 
out  increase  up  to  a  certain  limit.  The  muscle,  as  it  were,  burns  the 
candle  at  both  ends.  The  heat-production  reaches  its  maximum  some- 
what sooner  than  the  work. 

It  is  certain  that  when  work  is  done  by  a  muscle  an  equivalent 
amount  is  subtracted  from  its  sum-total  of  energy,  and  under  proper 
conditions  this  can  be  actually  demonstrated  by  the  deficiency  in  the 
heat-production.  This  is  done  by  means  of  a  contrivance  called  a 
work-adder.  It  consists  of  a  wheel,  the  rotition  of  which  raises  a 
weight  attached  to  a  cord  wound  round  its  axle.  The  muscle  acts  on 
the  periphery  of  the  wheel,  and  by  rotating  it  raises  the  weight  a  little 
at  each  contraction.  At  the  end  of  the  contraction  the  wheel  is  pre- 
vented from  moving  back  by  a  catch.  The  work  done  in  a  series  of 
contractions  is  calculated  from  the  total  height  to  which  the  weight 
has  been  raised.  Suppose  a  frog's  gastrocnemius  is  made  to  contract 
a  certain  number  of  times  while  attached  to  the  work-adder,  and  that 
simultaneously  the  heat-production  is  measured  by  means  of  a  thermo- 
pile. Let  H  represent  the  heat  actually  produced,  and  h  the  heat 
equivalent  of  the  work  done.  Now  let  the  muscle  be  disconnected  from 
the  adder  and  made  to  raise  the  same  weight,  directly  attached  to  it, 
by  a  series  of  contractions  elicited  in  precisely  the  same  way  as  the 
previous  ones,  except  that  the  weight  is  allowed  to  fall  with  the  muscle 
when  it  relaxes  after  each  contraction.  Here  heat  corresponding  to  the 
external  work  disappears  from  the  muscle  during  the  contraction  just 
as  in  the  first  experiment,  but  this  heat  is  returned  to  the  muscle  during 
the  relaxation,  since  on  the  whole  no  external  work  is  done.  The  heat 
produced  in  the  second  experiment  is  found,  as  a  matter  of  fact, 
allowing  for  unavoidable  errors,  to  be  equal  to  H  +  h. 

According  to  Hill,  the  true  '  efficiency  '  of  the  muscle  is  not  the 
fdtio  W/H,  where  W  is  the  external  work  and  H  the  total  heat  liberated, 
but  T/H  where  T  is  the  maximum  increase  of  tension  set  up  during  the 
twitch  when  the  muscle  is  contracting  isometrically.  This  fraction  TjH 
IS  constant  whatever  be  the  initial  tension,  the  number  of  fibres  excited, 
or  the  strength  of  excitation  of  each  fibre.  For  the  theory  of  the 
muscular  contraction  the  tension  auring  an  isometric  muscle  twitch, 
which  represents  the  potential  energj^  suddenly  developed  in  conse- 
quence of  the  excitation,  is  accordingly  much  more  important  than  the 
height  of  the  contraction,  which  is  related  to  the  work  actually  done. 
The  essential  thing  in  muscular  contraction  may  be  the  abrupt  develop- 
ment of  this  tension  thiough  a  chemical  reaction  which  liberates  certain 
substances  at  some  membrane  or  surface  in  the  muscle.  The  potential 
energy  once  in  being  may  or  may  not  be  transformed  into  work,  and  if 
so  transformed  the  change  may  be  accomplished  economically  or  waste- 
fully,  according  to  the  conditions  of  the  contraction.  The  ratio  T/H 
decreases  in  fatigue,  and  with  the  time  during  which  the  muscle  has 
been  deprived  of  its  blood-supply.  Hill  has  calculated  the  absolute 
value  of  the  heat-production  in  tetanus  of  a  sartorius  or  semimem- 
branosus muscle  of  the  frog.  This  quantity,  reckoned  per  centimetre 
of  length  of  the  muscle,  per  gramme  weight  of  the  tension  developed 
and  per  second  of  maintenance  of  the  tension,  is  relatively  constant  at 
about  0-000015  gramme-calorie.  Including  the  recovery  processes  of 
oxidation  following  the  contraction  the  total  heat-production  would 
amount  to  about  0-000025  calorie.  The  potential  energy  possessed  by 
a  muscle  of  a  length  of  a  centimetre  when  maintaining  a  tension  of  a 
gramme  is  about  ()'00ooo4  calorie.  So  that  to  maintain  this  state  of 
potential  energy  six  or  seven  times  as  much  energy  must  be  liberated 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     767 

per  second.  The  maintenance  of  prolonged  tension  is,  therefore,  from 
the  point  of  view  of  the  mechanical  result,  an  exceedingly  wasteful 
process,  with  a  very  low  efficiency  in  comparison  with  the  high  efficiency 
in  a  rapid  twitch.  This  enables  U5  to  see  how  important  a  part  in  heat- 
production,  and  therefore  in  temperature  regulation,  the  tonusof  muscle 
and  the  prolonged  contractions  of  shivering  may  possess  (p.  695). 

We  are  as  yet  in  the  dark  as  to  the  precise  relation  of  the  energy 
which  appears  as  heat  and  of  that  which  is  converted  into  work. 
The  ultimate  source  of  both  is,  of  course,  the  oxidation  (and 
cleavage)  of  the  food  substances.  It  was  at  one  time  a  favourite 
theory  that  in  a  muscle,  as  in  a  heat-engine,  the  chemical  energy 
is  first  converted  iaito  heat,  and  part  of  the  heat  then  transformed 
into  work.  There  is  no  evidence  that  this  is  the  case.  It  is, 
indeed,  impossible  that  such  differences  of  temperature  can  exist 
as  would  be  compatible  with  the  known  efficiency  of  the  muscular 
machine.  Hypotheses  based  on  the  assumption  that  the  chemical 
energy  is  immediately  changed  into  work,  perhaps  through  the  pro- 
duction of  surface  effects,  have  met  with  increasing  favour,  but 
data  are  as  yet  too  few  for  the  formulation  of  any  really  satisfactory 
theory.  The  close  relation  between  the  heat-production  and  the 
formation  of  lactic  acid  in  contraction  which  have  been  shown  to 
exist,  is  a  suggestive  fact  whose  full  significance  will  only  be  revealed 
by  further  investigation.  The  restitution  processes  by  which  the 
original  state  of  the  muscle  is  restored  after  contraction  are,  of 
course,  intimately  related  to  those  concerned  in  the  actual  shorten- 
ing; but  unless  we  know  how,  and  in  consequence  of  what  chemical 
or  physical  changes,  the  equilibrium  of  the  resting  muscle  has  been 
disturbed,  we  cannot  know  how,  or  in  consequence  of  what  chemical 
or  ph\'sical  changes,  it  is  restored. 

Section  TV. — Chemical  Phenomena  of  the  Muscular 
Contraction. 

The  composition  of  dead  mammalian  muscle  of  the  striped  variety  may 
be  stated,  in  round  numbers,  as  follows,  but  there  are  con-siderable 
variations,  even  within  the  same  species: 

Water         --------    73  per  cent. 

Proteins     --------     20        ,, 

Fats,  lecithin,  and  cholesterin    -         -         -         -       2         ,, 

Nitrogenous  extractives,  creatin  (about  04  per>| 
cent.),  carnosin,  phospho-carnic  acid,  inosinic 
acid,  purin  bodies,  such  as  uric  acid,  hypoxan- 
thin,  xanthin,  etc.  ------ 

Carbo-hvdrates  (glycogen,  dextrose,  maltose) 

Non-nitrogenous  organic  substances  (lactic  acid, 
inosit)     -         -         -         -         -         -         -         -J 

Pigment  (myohsematin  or  myochrome,  a  haemoglobin  not  precisely- 
identical  with  that  of  blood). 

Inorganic  substances  less  than  i  per  cent,  (chlorides,  carbonates, 
phosphates,  and  sulphates  of  potassium,  sodium,  iron,  calcium, 
magnesium).     Potassium  is  absent  from  the  nuclei  (Frontispiece). 


758        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Of  the  nilropcnniis  extractives,  crcatin  (p.  597)  and  carnosiii  are 
present  in  greatest  quantity,  muscle  containing  0-2  to  0-4  per  cent,  of 
krcatin.  Carnosin  (C9H14N4O3)  is  a  substance  with  basic  properties, 
and  can  be  split  up  into  histidin  and  /3-aniino-propionic  acid,  an 
aniino-acid  not  identical  with  alanin  (or  "-amino-propionic  acid),  but 
having  the  NH2  coui)led  to  the  fi  instead  of  the  a  carbon  atom  (p.  56O*. 

There  is  more  water  in  the  muscles  of  young  than  of  old  anim.  Is 
(v.  Bibra),  and  more  in  tetanized  than  in  rested  muscle  (Ranke).  The 
fats  are  variable  in  amount,  and  belong  to  a  small  extent  to  the  actual 
muscle-fibres.  For  even  when  the  visible  fat  is  separated  with  the 
utmost  care,  nearly  i  per  cent,  of  fat  still  remains  (Steil). 

The  glycogen  content  varies  extremely  in  different  muscles  and  in 
the  same  muscle  under  different  nutritive  and  functional  conditions. 
Thus,  in  one  and  the  same  dog  the  biceps  brachii- contained  o'ly  and 
the  quadriceps  femoris  0-53  per  cent.  In  dogs  on  a  diet  rich  in  carbo- 
hydrate and  protein  the  percentage  in  the  whole  skeletal  musculature 
ranged  from  0*7  to  3*7,  and  in  the  heart  from  o-i  to  1*2.  The  average 
for  human  muscles  has  been  given  as  0-4  per  cent.  In  lean  horse-flesh 
Pfliiger  found  0-35  per  cent,  of  glycogen,  but  no  sugar.  The  total 
nitrogen  was  3*21  per  cent,  of  the  moist  tissue.  The  lactic  acid  of 
muscle  and  other  tissues  is  the  d-lactic  acid,  which  rotates  the  plane  of 
polarization  to  the  right.  By  the  action  of  certain  bacteria  on  cane- 
sugar  /-lactic  acid  is  obtained,  which  is  left  rotatoiy.  The  optically 
inactive  fermentation  lactic  acid  is  obtained  by  the  fermentation  of 
lactose. 

Smooth  muscle  is  somewhat  richer  in  water  than  the  striated  variety 
from  the  same  species,  because  skeletal  muscle  is  richer  in  fat.  Glycogen 
is  either  absent  or  present  only  in  traces  in  the  smooth  muscle  (of  the 
stomach  and  bladder).  Lactic  acid,  creatin,  and  creatinin  are  also 
found  in  much  smaller  amount  than  in  striped  muscle  (Mendel  and  Saiki). 
As  in  striated  muscle,  hypoxanthin  is  the  conspicuous  purin  base 
occurring  in  the  free  form — i.e.,  obtainable  in  muscle  extracts.  The 
most  remarkable  difference  in  the  quantitative  relations  of  the  inorganic 
constituents  is  that  in  striated  muscle  potassium  preponderates  over 
sodium  and  magnesium  over  calcium,  whereas  in  the  smooth  variety 
this  relation  is  reversed. 

It  would  be  natural  to  expect  that  the  proteins,  which  bulk  so 
largely  among  the  solids  of  the  dead  muscle,  and  which  are  so  obvi- 
ously important  in  the  living  muscle,  should  be  affected  by  contrac- 
tion. But  up  to  the  present  time  no  quantitative  difference  in  the 
proteins  of  resting  and  exhausted  muscle  has  ever  been-  made  out. 
The  quantity  of  creatin  (and  creatinin)  is  said  by  some  authorities 
to  be  increased.  The  following  chemical  changes  have  been  defi- 
nitely established.     In  an  active  muscle — 

(a)  More  carbon  dioxide  is  produced,  (b)  More  oxygen  is  consumed, 
(c)  Lactic  acid  is  formed,  {d)  Glycogen  is  used  up.  (c)  The  substances 
soluble  in  water  diminish  in  amount;  those  soluble  in  alcohol  increase. 

Production  of  Carbon  Dioxide  and  Consumption  of  Oxygen  during 
Contraction. — This  subject  has  already  been  dealt  with  in  jiart  in 
connection  with  tissue  respiration  (p.  266).  The  fact  that  nmscular 
exercise  increases  the  carbon  dioxide  output  and  the  oxygen  absorp- 
tion at  the  pulmonary  surface,  shows  that  oxidation  processes 
involving  ultimately  the  combustion  of  carbon-containing  substances 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    7^9 

axe  associated  with  the  activity  of  the  muscular  tissue,  but  does 
not  of  itself  prove  that  the  final  steps  of  the  oxidation  occur  in  the 
nuiscles  themselves.  This  has  been  demonstrated,  however,  by 
observations  on  isolated  muscles.  When  well  supplied  with 
oxygen,  these,  in  addition  to  the  stock  of  carbon  dioxide  in  solution, 
in  the  form  of  carbonates  and  in  other  combinations,  which  they 
possess  at  the  moment  of  isolation,  continue  to  produce  carbon 
dioxide,  and  this  production  is  markedly  increased  by  stimulation. 
The  best  evidence  is  to  the  effect  that  only  preformed  carbon  dioxide 
is  given  off  by  isolated  muscles  in  the  absence  of  oxygen.  They 
can  go  on  contracting  indeed,  as  previously  stated,  in  an  atmosphere 
of  hydrogen  or  nitrogen,  and  may  seem  to  be  producing  carbon 
dioxide,  but  the  increased  output  appears  to  be  due  simply  to  an 
accelerated  decomposition  of  already  existing  carbonates,  or  perhaps 
other  combinations  in  which  carbonic  acid  is  loosely  held,  brouglit 
about  by  lactic  acid,  which  in  the  absence  of  oxygen,  is  not  trans- 
formed as  it  is  under  normal  conditions,  and  accumulates  in  the 
muscular  substance,  uniting  with  bases,  and  thus  displacing 
carbonic  acid. 

Formation  of  Lactic  Acid — Reaction  of  Muscle. — To  litmus-paper 
fresh  muscle  is  amphicroic — that  is,  it  turns  red  litmus  blue  and  blue 
litmus  red.  This  is  due,  partly  at  least,  to  the  phosphates.  Mono- 
phosphate (tribasic  phosphoric  acid,  H3PO4,  in  which  one  hydrogen 
atom  is  replaced,  say,  by  sodium  or  potassium)  reddens  blue  litmus, 
while  diphosphate  (where  two  hydrogen  atoms  are  replaced)  turns  red 
litmus  blue.  Litmoid  (lacmoid)  differs  from  litmus  in  not  being  affected 
by  monophosphates.  Diphosphates  turn  red  litmoid  blue,  and  so  does 
fresh  muscle,  which  has  no  effect  on  blue  litra.oid.  A  cross-section 
of  fresh  muscle  is  about  neutral  (sometimes  faintly  acid)  to  turmeric 
paper,  which  is  turned  yellow  by  monophosphates.  A  muscle  which 
has  entered  into  rigor  or  has  been  fat\gued  by  prolonged  stimulation  is 
distinctly  acid  to  blue  litmus  and  to  brown  turmeric,  reddening  the 
former  and  turning  the  latter  yellow,  but  does  not  affect  blue  litmoid. 

Perfectly  fresh  resting  muscle  excised  with  avoidance  of  all  un- 
necessary manipulation  contains  very  little  lactic  acid  (as  little  as 
0-02  per  cent,  expressed  as  zinc  lactate).  Mechanical  injury, 
heating,  and  chemical  irritation  cause  a  marked  increase  in  the 
amount.  Under  anaerobic  conditions — in  an  atmosphere  of 
hydrogen,  for  instance — lactic  acid  is  spontaneously  developed  in 
the  resting  muscle  so  long  as  irritability  persists,  but  not  longer. 
In  air,  which  for  even  small  excised  muscles  corresponds  to  a  partial 
asphyxia,  there  is  a  small  increase  in  the  lactic  acid,  but  its  pro- 
duction is  very  slow  in  comparison  with  that  in  the  hydrogen 
atmosphere.  In  pure  oxygen  not  only  is  there  no  accumulation 
of  lactic  acid  for  a  long  time  after  excision,  but  a  portion  of  the 
amount  originally  present  in  the  resting  excised  muscle  disappears. 
The  same  is  true  of  the  lactic  acid  formed  in  a  muscle  fatigued  by 
stimulation  when  it  is  afterwards  placed  in  an  atmosphere  of  pure 

49 


770        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

oxv^t-'ii.  There  is  no  doubt  that  the  pro(kiction  of  lactic  acid  in 
functional  activity  and  its  transformation  into  other  substances 
are  processes  that  go  on  also  in  the  muscles  of  the  intact  body. 
The  formation  of  the  acid  in  the  excised  nuiscle,  far  from  being  a 
sign  of  death,  is  an  index  of  the  '  survival  '  of  a  process  by  which 
it  is  normally  formed,  as  the  accumulation  of  it  is  an  index  of  the 
crippling,  in  the  absence  of  oxygen,  of  a  mechanism  by  which  it  is 
normally  transformed. 

The  lactic  acid  which  accumulates  in  the  excised  muscle  in  rigor 
and  activity  docs  not  remain  free,  since  blue  litmoid  paper  is  not 
reddened  as  it  would  be  by  free  lactic  acid.  It  causes  a  repartition 
of  the  bases  at  the  expense  of  the  sodium  carbonate  and  disodium 
phosphate,  the  latter  being  changed  into  monophosphate,  which, 
in  part  at  least,  accounts  for  the  acid  reaction  to  turmeric  (Koh- 
mann).  It  is  of  great  interest  that  this  oxidative  transformation 
of  lactic  acid  only  occurs  in  muscle  whose  structure  is  so  far  pre- 
served that  its  irritability  is  not  lost.  In  minced  or  triturated 
muscle  it  does  not  take  place. 

The  relations  between  the  heat  production,  the  formation  of 
carbon  dioxide,  and  the  production  of  lactic  acid  indicate  that 
liberation  of  lactic  acid  from  some  precursor  is  an  essential  stage 
in  the  sudden,  '  explosive  '  reaction  or  series  of  reactions  which 
precedes  and  induces  the  mechanical  response  to  stimulation.  This 
stage  takes  place  whether  oxygen  be  present  or  absent,  and  it  seems 
to  be  accompanied  by  a  considerable  liberation  of  energy,  at  the 
expense  of  which  alone  the  anaerobically  contracting  muscle  works. 
It  is  most  probable  that  the  liberation  of  lactic  acid  follows  the  same 
course  in  the  muscle  abundantly  supplied  with  oxygen,  although  it 
has  not  been  shown  that  oxidative  processes,  resulting  in  the  forma- 
tion of  carbon  dioxide,  do  not  contribute  also  at  this  stage  to  the 
energy  which  is  transformed  into  the  mechanical  effect.  But  while 
in  the  absence  of  oxygen  the  reaction  stops  at  the  formation  of 
lactic  acid,  when  oxygen  is  available  the  cycle  is  completed  by 
restitution  processes  which  lead  to  the  disappearance  of  the  lactic 
acid  either  by  restoration  to  its  original  position  in  the  precursor 
from  which  it  is  derived,  or  perhaps  in  the  case  of  a  portion  of  the 
"lactic  acid  to  its  combustion  to  carbon  dioxide  and  water.  For 
these  restitution  processes  oxygen  is  essential,  and  it  is  to  be 
supposed  that  the  energy  required  for  the  rebuilding  of  the  lactic 
acid  precursor,  or,  to  speak  more  generally,  for  the  restoration  of 
the  muscle  to  its  original  state  in  readiness  for  a  fresh  contraction, 
is  derived  largely  from  oxidations  in  which  carbon  dioxide  makes 
its  appearance. 

The  Precursor  of  Lactic  Acid. — What  material  is  the  lactic  acid 
formed  from  ?  There  are  reasons  for  thinking  that  lactic  acid  is  an 
interniediate  substance  which  in  metabolism  serves  as  a  link  between 


CHEMICAL  PHENOMENA  Of  MUHCULAU  CONTRACTION     771 

the  products  of  protein  decomposition  and  carbo-hydrates,  and 
between  carbo-hydrates  and  fat.  From  what  we  know  of  the 
production  of  lactic  acid  both  outside  the  body  and  in  the  intestine 
from  carbo-hydrates,  it  might  seem  a  most  plausible  suggestion 
that  in  the  active  muscle  it  comes  from  glycogen. 

Glycogen  is  the  one  solid  constituent  of  muscle  which  has  been 
definitely  proved  to  diminish  during  activity.  It  accumulates  in 
a  resting  muscle,  especially  in  a  muscle  whose  motor  nerve  has  been 
cut;  but  rapidly  disappears  from  the  muscles  of  an  animal  made 
to  do  work  while  food  is  withheld;  or  from  the  muscles  of  an  animal 
poisoned  by  strychnine, which  causes  violent  muscular  contractions. 
But  the  best  evidence  points  the  other  way — e.g.,  in  rigor  mortis 
lactic  acid  is  produced  just  as  in  muscular  contraction.  Nay, 
more,  the  amount  of  lactic  acid  (as  much  as  0-5  per  cent,  expressed 
as  zinc  lactate)  produced  in  full  heat  rigor  (at  40°  to  45°  C.)  is  con- 
stant for  similar  excised  muscles.  This  *  acid-maximum  '  is  the 
same  when  fresh  muscle  is  at  once  put  into  rigor;  or  when  fatigue 
is  first  induced,  with  formation  of  lactic  acid,  before  rigor;  or, 
finally,  when  the  lactic  acid  of  the  fatigued  muscle  is  caused  to 
disappear  under  the  influence  of  oxygen,  and  heat  rigor  is  then 
brought  about  in  the  muscle  (Fletcher  and  Hopkins).  Yet  in  rigor 
mortis  the  quantity  of  glycogen  is  unaltered  (Boehm).  Further, 
under  certain  conditions  an  excised  muscle  is  capable  of  producing 
a  quantity  of  lactic  acid  much  greater  than  could  be  derived  from 
the  glycogen  contained  in  it. 

An  indirect  argument  against  the  view  that  the  lactic  acid  pre- 
cursor is  glycogen  has  been  based  by  Hill  on  the  results  of  his  studies 
on  the  heat  production  of  surviving  muscle.  From  the  amount 
of  heat  evolved,  he  calculates  that  the  precursor  of  lactic  acid 
must  have  a  heat  value  10  per  cent,  greater  than  that  of  lactic  acid. 
Now,  the  heat  of  combustion  of  dextrose  is  only  about  3  per  cent, 
more  than  that  of  lactic  acid.  He  concludes  that  the  precursor 
which  yields  lactic  acid  is  a  body  of  greater  energy  than  dextrose. 
This,  of  course,  does  not  preclude  the  possibility  that  the  complex, 
whatever  it  is,  from  which  lactic  acid  is  liberated,  contains  a  carbo- 
hydrate group.  But  it  would  not  be  profitable  to  pursue  these 
speculations  at  present.  The  facts  just  mentioned  suggest  that  it 
is  the  same  precursor  which  yields  the  lactic  acid  developed  with 
the  onset  of  rigor.  Further  evidence  of  the  close  relations  between 
the  chemical  changes  occurring  in  contraction  and  those  occurring 
in  rigor  will  be  developed  in  considering  the  latter  phenomenon. 

The  Substances  metabolized  in  Muscular  Contraction. — If  the 
liberation  of  lactic  acid  were  assumed  to  be  the  immediate  cause  of 
the  mechanical  changes  in  muscular  contraction,  if  the  nature  of 
the  body  which  yields  lactic  acid  were  known,  and  if  it  were  proved, 
which  is  far  from  being  the  case,  that  the  whole  of  the  energy  con- 


772        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


cerned  in  initiating  and  carrying  out  the  mechanical  effect  is  derived 
from  the  decomposition  of  this  precursor,  the  question  would  still 
confront  us,  What  are  the  materials  at  the  expense  of  the  energy 
of  which  the  muscle  is  restored  to  its  original  condition  ready  for 
another  contraction  ?  If  the  lactic  acid  is  used  over  and  over 
again,  it  is  indeed  the  metabolism  of  these  substances  which  will 
be  chiefly  represented  in  the  waste  products  given  off  by  the  muscle ; 
the  lactic  acid  complex  will  merely  represent  a  chemical  machine 
through  which  the  energy  of  these  other  substances  is  transformed 
into  mechanical  energy,  and  they  will  constitute  the  ultimate  source 
of  energy  of  the  muscular  contraction.  In  this  sense  the  muscular 
glycogen,  whether  it  yields  lactic  acid  or  not,  is  almost  certainly 
one  source  of  energy  for  the  active  muscle,  being  converted  into 
dextrose,  of  course,  before  utilization.  Dextrins  and  maltose,  the 
intermediate  products  of  this  decomposition,  have  been  detected 
in  muscle,  more  maltose,  indeed,  than  dextrose  being  present 
(Osborne),  since  the  dextrose  is  rapidly  oxidized.  Glycogen  cannot 
be  the  only  source  of  muscular  energy,  for  its  amount  is  too  small. 

For  example,  the  heart  of  an  average  man,  which  weighs  280  grammes, 
contains  about  60  grammes  of  solids,  and  among  these  certainly  not 
more  than  i  gramme  of  glycogen.  In  twenty-four  hours  it  produces 
120  calories  of  heat  (pp.  138,  688),  equivalent  to  the  complete  com- 
bustion of  a  little  less  than  30  grammes  of  glycogen.  To  supply  this 
amount,  the  whole  store  of  glycogen  in  the  heart  would  ha\'e  to  be  used 
and  replaced  every  fifty  minutes.  But  the  accumulation  of  glycogen 
is  immensely  slower  in  the  muscles  of  a  rabbit  made  glycogen-free  by 
strychnine,  and  therefore  we  have  to  look  around  for  some  other  source 
of  energy  to  supplement  the  glycogen.  We  have  already  brought 
forward  evidence  (p,  610)  that,  under  ordinary  circumstances,  not  a 
great  deal,  at  any  rate,  of  the  energy  of  muscular  contraction  comes 
from  the  proteins.  Of  carbo-hydrates,  the  only  one  except  the  glycogen 
of  the  heart  muscle  which  is  at  all  adecjuate  to  the  task  of  supplying  so 
much  energy  is  the  dextrose  of  the  blood.  The  quantity  of  blood 
passing  through  the  coronary  circulation  has  been  estimated  at  30  c.c. 
per  TOO  grammes  of  cardiac  muscle  per  minute  (Bohr  and  Henriques), 
which  would  be  equivalent  for  an  average  man  to  about  120  litres  in 
twenty-four  hours.  This  quantity  of  blood  will  contain  at  least 
120  grammes  of  dextrose,  and  about  32  grammes  will  suffice  to  supply 
all  the  heat  produced  by  the  heart.  There  is  no  reason  to  suppose  that 
this  dextrose  must  first  be  changed  into  muscular  glycogen,  which  only 
represents  a  certain  amount  of  reserve  carbo-hydrate.  Of  proteins  a 
little  less  than  30  grammes  would  be  needed,  of  fat  a  little  more  than 
12  grammes.  We  see,  therefore,  how  intense  must  be  the  metabohsm 
that  goes  on  in  an  actively  contracting  muscle.  On  any  probable 
assumption  as  to  the  source  of  muscular  energy,  a  quantity  of  material 
equal  to  half  of  its  solids  must  be  used  up  by  the  heart  in  twenty-four 
hours.  Or,  to  put  it  in  another  way,  the  heart  requires  not  less  than 
two-fifths  of  its  weight  of  ordinary  solid  food  in  a  day.  The  body  as  a 
whole  requires  ^  to  -^  of  its  weight. 

The  general  conclusions  to  which  physiologists  have  been  led 
as  to  the  relative  importance  of  the  different  food  substances  for 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    773 

muscular  work  have  been  previously  given  (p.  612),  and  need  not 
be  repeated  here.  It  may  be  added  that  the  various  food  substances 
yield  muscular  energy  in  isodynamic  relation.  In  other  words,  a 
given  amount  of  muscular  work  requires  the  expenditure  of  approxi- 
mately the  same  quantity  of  chemical  energy,  whether  it  comes 
almost  entirely  from  protein,  or  chiefly  from  carbo-hydrates,  or 
chiefly  from  fat.  Some  observers  have  stated  that  the  taking  of 
even  a  comparatively  small  quantity  of  sugar  vastly  increases  the 
capacity  for  muscular  work  as  measured  by  the  ergograph  (p.  750). 
But  although  it  is  not  to  be  doubted  that  sugar  is  under  normal 
circumstances  one  of  the  most  important  substances  used  up  in 
muscular  contraction,  the  claim  that  sugar  is,  par  excellence,  the 
food  for  muscular  exertion  has  not  yet  been  made  out. 

Physico- Chemical  Conditions  of  Muscular  Contraction. — For  excised 
fresh  muscle  A  (p.  427)  has  been  estimated  at  o-68°  C.  But  this  is 
probably  higher  than  in  the  living  body,  for  after  excision  waste  products, 
with  their  relatively  smaJ  and  numerous  molecules,  are  still  for  a  time 
produced,  and  are  no  longer  removed  by  the  blood.  In  salt  solutions 
isotonic  with  the  muscle  substance — e.g.,  for  the  frog's  gastrocnemius 
at  room-temperature  a  0*75  per  cent,  solution  of  sodium  chloride — the 
resting  muscle  neither  gains  nor  loses  water  for  some  hours.  The  active 
muscle  behaves  quite  differently.  When  a  muscle  immersed  in  isotonic 
salt  solution  is  tetanized,  water  enters  it,  leading  to  an  increase  in 
weight  and  a  diminution  in  specifig  gravity  (Ranke,  Loeb,  Barlow). 
The  same  occurs  even  when  blood  is  circulated  through  active  muscles, 
the  blood  becoming  poorer  in  water  (Ranke).  This  may  be  explained 
by  the  increase  of  osmotic  pressure  in  the  muscle  substance  which  must 
accompany  the  decomposition  of  large  molecules  into  small.  As  fatigue 
progresses,  a  movement  of  water  in  the  reverse  direction  occurs,  and 
the  muscle  rapidly  loses  water.  Exposure  of  the  fatigued  muscle  for  a 
sufficient  time  to  an  atmosphere  of  oxygen  restores  the  osmotic  proper- 
ties of  the  resting  muscle.  Striking  differences  have  also  been  demon- 
strated in  the  behaviour  of  resting  and  fatigued  muscle  to  hypotonic 
solutions  or  water.  Hales  observed  long  ago  that,  on  injecting  large 
quantities  of  water  into  the  bloodvessels  of  a  dog,  so  as  to  replace  the 
blood,  marked  swelling  of  the  muscles  occurred.  This  physiological  fact 
is  well  known  to  the  pork-butchers  in  China,  who  have  given  it  a 
practical,  if  not  a  very  praiseworthy,  application  in  sophisticating  their 
product  by  increasing  its  weight  (MacGowan). 

So  long  as  the  muscular  fibres  are  uninjured  they  are  permeable  or 
impermeable  for  exactly  the  same  compounds  as  other  animal  and 
vegetable  cells.  All  substances  easily  soluble  in  media  like  ether  or 
oli\e  oil  readily  penetrate  them  (Overton).  To  most  salts  they  are 
relatively  impermeable,  as  is  shown  by  the  fibres  retaining  their  original 
v^olume  in  isotonic  solutions  of  them.  In  particular,  they  cannot  easily 
take  up  or  retain  the  .salts  of  the  blood-plasma,  otherwise  the  observed 
qualitative  differences — e.g.,  the  preponderance  of  potassium  in  the 
muscle  and  sodium  in  the  plasma — could  not  be  maintained.  There  are 
facts  which  indicate  that  temporary  changes  in  the  permeability  to  ions, 
not  only  of  muscular  fibres,  but  also  of  nerve  fibres  and  other  excitable 
structures,  are  concerned  in  their  stimulation.  Potassium  salts  after  a 
time  seem  to  produce  an  effect  upon  frog's  muscle,  which  alters  its 
permeability   so   that  it  takes   up   water   from  hypertonic  solutions. 


774        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Calcium  salts  have  the  opposite  effect  (Loeb).  Sodium  (and  in  a  minor 
degree  lithium)  salts  have  a  peculiar  relation  to  the  contraction  of 
skeletal  muscle,  for  which  they  appear  to  be  indispensable.  Yet  sodium 
cliloride  produces  a  paralyzing  action  on  the  frog's  motor  nerve-endings, 
so  that  after  perfusion  with  a  solution  of  that  salt  stimulation  of  the 
motor  nerve  causes  no  contraction,  or  with  a  slighter  degree  of  jiaralysis 
contraction  only  after  a  long  interval.  The  eilect  can  be  counteracted 
by  solutions  containing  calcium  salts  (Locke,  Gushing). 

Rigor  Mortis. — When  a  muscle  is  dying,  its  excitability,  after 
perhaps  a  temporary  rise  at  the  beginning,  diminishes  more  and 
more  until  it  ultimately  responds  to  no  stimulus,  however  strong. 
The  loss  of  excitability  is  not  in  itself  a  sure  mark  of  death,  for, 
as  we  have  seen,  an  inexcitable  muscle  may  be  partially  or  com- 
pletely restored;  but  it  is  followed,  or,  where  the  death  of  the  muscle 
takes  place  very  rapidly,  perhaps  accompanied,  by  a  more  decisive 
event,  the  appearance  of  rigor.  The  muscle,  which  was  before  soft 
and  at  the  same  time  elastic  to  the  touch,  becomes  firm;  but  its 
elasticity  is  gone.  The  fibres  are  no  longer  translucent,  but  opaque 
and  turbid.  If  shortening  of  the  muscle  has  not  been  opposed,  it 
may  be  somewhat  contracted,  although  the  absolute  force  of  this 
contraction  is  small  compared  with  that  of  a  living  muscle,  and  a 
slight  resistance  is  enough  to  prevent  it.  The  reaction  is  now 
distinctly  acid  to  litmus.  This  is  rigor  mortis,  the  death-stiffening 
of  muscle. 

An  insight  into  the  real  meaning  of  this  singular  and  sometimes 
sudden  change  was  first  given  by  the  experiments  of  Kiihne.  He 
took  living  frog's  muscle,  freed  from  blood,  froze  it,  and  minced  it 
in  the  frozen  state.  The  pieces  were  then  rubbed  up  in  a  mortar 
with  snow  containing  i  per  cent,  of  common  salt,  and  a  thick  neutral 
or  alkaline  liquid,  the  '  muscle- plasma,'  was  obtained  by  filtration. 
This  clotted  into  a  jelly  when  the  temperature  was  allowed  to  rise, 
but  at  0°  C.  remained  fluid.  The  clotting  was  accompanied  by  a 
change  of  reaction,  the  liquid  becoming  acid.  An  equally  good, 
or  better,  method  is  to  use  pressure  for  the  extraction  of  the  plasma 
from  the  frozen  fragments  of  muscle.  A  low  temperature  is  essential, 
otherwise  the  plasma  will  coagulate  rapidly  within  the  injured 
muscle.  A  similar  plasma  can  be  expressed  from  the  skeletal 
muscles  of  warm-blooded  animals  (Halliburton),  and  with  greater 
difficulty  from  the  heart. 

When  the  muscle,  after  exhaustion  with  water,  is  covered  with  a 
solution  of  a  neutral  salt,  a  5  per  cent,  solution  of  magnesium  sulphate 
or  10  per  cent,  solution  of  ammonium  chloride  being  the  best,  certain 
proteins  are  extracted  which  clot  or  are  precipitated  much  in  the  same 
way  as  the  muscle-plasma  obtained  by  cold  and  pressure;  and  the 
process  is  hastened  by  keeping  them  at  a  temperature  of  40°  C. 

In  the  extracts  of  mammalian  muscle  three  chief  proteins  are  present: 
paramyosinogen  (v.  Fiirth's  myosin),  coagulating  by  heat  at  47°  to 
50°  C;  myosinogen  (v.  Fiirth's  myogen),  coagulating  at  55°  to  60°  C, 
usually  about  56°);  and  serum-albumin,  coagulating  about  73°.     The 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    775 

serum-albumin  belongs  to  the  blood  and  lymph,  and  is  not  a  constituent 
of  the  muscle-fibre.     The  most  recent  work  on  the  subject  is  that  of 
Botazzi,  who  obtained  muscle  juice  without  the  addition  of  water  or 
salt  solutions,  by  rubbing  muscles  up  with  sand,  ;ind  then  subjecting  the 
triturated  material  to  a  pressure  of  many  atmospheres.     >le  iinds  that, 
leaving  out  of  account  the  serum-albumin,  muscle  juice  contains  only 
one  protein  in  solution,  and  this  corresponds  upon  the  whole  in  its 
properties  to  myosinogen.     A  second  protein,  and  only  these  two  have 
been  proved  to  exist  in  muscle  juice,  is  not  in  solution,  but  in  tiie  form 
of  very  line  granules  re\'caled  by  the  ultramicroscope.     This  corresponds 
in  a  general  way  to  paramyosinogen.     Botazzi  supposes  tliat  it  repre- 
sents the  substance  of  the  muscular  fibrils.     The  granules  show  a  ten- 
dency even  at  the  ordinary  temperature  to  agglutinate  and  to  be  pre- 
cipitated.    The  process  is  hastened  by  dilution  with  water,  removal  of 
the  salts  by  dialysis,  addition  of  acids,  and  the  agglutination  and  pre- 
cipitation are  accomplished  very  rapidly  at  45°  to  55°  C,  giving  rise 
to   '  heat  coagulation.'     The  protein  in  solution   (myosinogen)   is  in- 
soluble in  distilled  water  when  thoroughly  freed  from  salts,  and  is  pre- 
cipitated by  dialysis,  but  not  so  easily  as  paramyosinogen.     The  total 
proteins  in  the  juice  obtained  by  pressure  varied  from  5*3  to  9*5  per 
cent.,  a  great  deal  of  the  muscle  protein  being,  of  course,  left  in  the 
residue.     The  granules  (paramyosinogen)  constituted  from  a  third  to 
two-thirds  of  the  protein  in  dilferent  experiments,  and  the  true  pro- 
portion must  have  been  considerably  higher,  since  on  account  of  their 
small  size  the  loss  in  separating  them  by  filtration  was  great.     The 
'  myosin  '  precipitate,  which  rapidly  forms  in  muscle-plasma  at  body 
temperature,  is  sometimes  called  the  muscle-clot,  and  the  liquid  which 
is  left  the  muscle-serum,  but  it  would  probably  be  better  to  avoid  these 
terms,  as  they  sugge.st  an  analogy  with  the  coagulation  of  blood-plasma, 
which  is  apt  to  be  misleading.     A  similar  precipitate  or  clot  seems  to 
be  formed  in  the  interior  of  the  muscular  fibres  in  natural  rigor  and  in 
the  rapid  rigor  produced  by  heating  a  muscle  to  a  little  above  the  body- 
temperature.     But  in  natural  rigor  the  whole  of  the  paramyosinogen 
and  myosinogen  do  not  undergo  the  change,  since  a  certain  amount  of 
these  substances  can  asa  rule  be  extracted  from  dead  muscle  by  saline 
solutions.     Thus,  in  rabbit's  muscles,  before  the  onset  of  rigor  mortis, 
87'3  per  cent,  of  the  total  protein  was  found  to  be  soluble  in  10  per  cent, 
ammonium  choride  solution,  and  only  12-7  per  cent,  coagulated;  while 
after  rigor  had  occurred,  71 -5  per  cent,  was  coagulated,  and  only  28-5  per 
cent,  remained  soluble  (Saxl).     It  is  not  known  whether  in  the  living 
muscle  paramyosinogen  and  myosinogen  exist  as  such.     It  has,  indeed, 
been  stated  that,  if  a  tracing  is  taken  from  a  muscle  which  is  gradually 
heated,  it  first  shortens  at  the  temperature  of  coagulation  of  para- 
myosinogen, and  then  again  at  that  of  myosinogen,  and  that  in  frog's 
muscle  there  is  an  additional  shortening  at  40°,  the  temperature  at 
which  in  extracts  an  additional  heat  precipitate  occurs.     The  conclusion 
has  been  drawn  that  these  substances  must  be  present  as  such  in  the 
living  fibres,  and  that  the  successive  shortenings  are  mechanical  phe- 
nomena due  to  their  heat  coagulation.     Similar  shortenings  have  been 
described  in  nerve  and  liver  tissue  at  about  the  temperatures  at  which 
the  proteins  in  extracts  of  these  tissues  are  coagulated  by  heat.     But 
Meigs  has  shown  that  the  supposed  correspondence  is  far  from  being 
exact,  and  that  muscles  whose  proteins  have  been  already  coagulated  in 
a  mixture  of  alcohol  and  salt  solution  still  show  the  typical  shortening 
on   being  heated.     The   heat  shortening  is,   therefore,   dependent  on 
some  other  process  than  aggregation  of  the  particles  of  coagulable 
protein. 


776         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Certain  analogies  between  rigor  and  muscular  contraction  were 
early  pointed  out.  In  both  there  is  (i)  shortening;  (2)  heat-pro- 
duction; (3)  formation  of  lactic  acid;  (4)  discharge  of  carbon 
dioxide;  (5)  electrical  changes.  As  regards  the  production  of  lactic 
acid,  there  is  reason  to  believe  that  the  process  is  fundamentally 
the  same  as  in  contraction,  and  the  study  of  rigor,  especially  of 
certain  of  the  artilicially  induced  forms — e.g.,  heat  rigor — in  relation 
to  the  liberation  of  lactic  acid,  carbon  dioxide,  and  heat,  has  thrown 
light  upon  the  changes  normally  occurring  in  muscle.  Another 
analogy  might  be  forced  into  the  list  by  anyone  who  was  deter- 
mined to  see  only  rigor  in  contraction:  the  rigor  passes  off  as  the 
contraction  passes  off,  although  the  '  resolution  '  of  a  rigid  muscle 
takes  days,  the  relaxation  of  an  active  muscle  a  fraction  of  a  second. 
The  disappearance  of  rigor  is  not  dependent  on  putrefaction;  it 
takes  place  when  growth  of  bacteria  is  prevented  (Hermann). 
Possibly  it  is  connected  with  autolytic  processes  due  to  intracellular 
ferments  (p.  599). 

Why  does  coagulation  of  m\'osin  occvir  at  the  death  of  the  muscle  ? 
To  this  question  no  clear  answer  can  be  given.  Some  have  looked 
on  the  process  as  analogous  to  the  clotting  of  blood  when  it  is  shed, 
and  it  has  even  been  suggested  that  just  as  a  fibrin  ferment  is 
developed  when  the  leucocytes  and  blood-plates  begin  to  die,  a 
myosin  ferment,  which  aids  coagulation,  is  developed  in  dead  or 
dying  muscle.  But  no  proof  has  been  given  of  the  existence  of  such 
a  ferment.  And  it  is  easy  to  make  too  much  of  the  apparent 
analogy  between  the  clotting  of  muscle  and  the  clotting  of  blood, 
for  there  are  differences  as  well  as  resemblances.  For  instance,  the 
addition  of  potassium  oxalate  does  not  prevent  coagulation  of 
muscle  extracts,  as  it  does  of  blood  and  blood-plasma.  If  the 
development  of  lactic  acid  in  the  muscle  is  not  the  primary  cause 
of  the  coagulation  which  constitutes  the  essential  feature  of  rigor 
mortis,  it  seems  to  be  closely  related  to  it.  For  when  excised 
muscles  are  abundantly  supplied  with  oxygen,  no  lactic  acid 
accumulates  in  them,  and  the  final  loss  of  excitability  of  the  muscle 
is  not  followed  by  rigor.  In  any  case,  direct  precipitation  of 
hitherto  unclotted  muscle  proteins  may  be  induced  by  the  acid,  or 
the  acid  salts  formed  in  its  presence.  Deficiency  of  oxygen  is 
associated  with  the  occurrence  of  rigor  mortis,  as  it  is  with  the 
accumulation  of  lactic  acid,  and  a  developing  rigor  can  be  abolished 
by  oxygen,  and  its  onset  long  or  indefinitely  delayed.  When  strict 
aseptic  technique  is  observed  an  excised  sartorius  muscle  of  the 
frog  may  remain  irritable  in  sterile  Ringer's  solution,  even  without 
oxygenation,  for  as  long  as  three  weeks  (Mines). 

Various  influences  affect  the  onset  of  rigor.  Fatigue  hastens 
it;  heat  has  a  similar  effect;  the  contact  of  caffeine,  chloroform, 
and  other  drugs  causes  most  pronounced  and  immediate  rigor. 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    777 

Blood  applied  lo  the  cross-section  of  a  muscle  first  stimulates  the 
fibres  with  which  it  is  in  contact,  and  then  renders  them  rigid. 
But  it  is  to  be  remembered  that  normally  the  blood  does  not  come 
into  direct  contact  even  with  the  sarcolemma,  much  less  with  its 
consents. 

The  effect  of  heat  is  of  special  interest.  A  skeletal  muscle  of 
a  frog,  like  the  gastrocnemius,  if  dipped  into  physiological  saline 
solution  at  40°  or  41°  C.  goes  into  rigor  at  once;  the  frog's  heart 
requires  a  temperature  3°  or  4°  higher;  the  distended  bulbus  aortae 
can  withstand  even  a  temperature  of  48°  for  a  short  time.  An 
excised  mammalian  muscle  passes  into  immediate  rigor  at  45°  to 
50°.  In  heat  rigor  the  reaction  of  the  muscle  becomes  strongly 
acid  owing  to  the  formation  of  lactic  acid,  and  the  evolution  of 
carbon  dioxide  is  also  increased. 

The  total  discharge  of  carbon  dioxide  in  heat  rigor  induced  at  40° 
amount.s  to  35  to  40  c.c.  per  100  grammes  of  muscle.  An  additional 
15  to  20  per  cent,  is  obtained  on  heating  to  75°  C.  to  completely  coagu- 
late the  proteins,  and  a  further  15  to  20  per  cent,  on  heating  to  about 
100°  C.  When  a  muscle  is  scalded  by  being  suddenly  immersed  in 
boiling  salt  solution,  lactic  acid  is  not  formed,  but  carbon  dioxide  to  the 
amount  of  60  to  70  per  cent,  is  discharged.  An  excised  muscle  kept  in 
oxygen  for  many  hours,  during  which  it  has  discharged  several  times 
as  much  caibon  dioxide  as  is  ever  liberated  by  heating,  still  yields  the 
normal  discharge  on  heating  whether  to  40°  C.  or  to  100°  C.  On  the 
other  hand,  previous  survival  in  an  anaerobic  atmosphere  (of  nitrogen) 
reduces  greatly  or  abolishes  the  yield  of  carbon  dioxide  at  40°  C, 
although  not  that  at  100°  C,  the  sum  of  the  carbon  dioxide  given  off  to 
the  atmosphere  of  nitrogen  and  that  given  off  on  heating  to  100°  C. 
being  about  equal  to  the  total  amount  which  would  have  been  dis- 
charged by  a  freshly-excised  muscle  on  heating  first  to  40°  C.  and  then 
to  100°  C.  If  acid  is  added  to  a  fresh  muscle  at  about  0°  C.  even  more 
carbon  dioxide  is  liberated  than  in  heat  rigor,  while  the  yield  of  lactic 
acid  is,  even  after  many  hours,  very  little  increased  above  the  normal 
amount  for  fresh  resting  muscle.  When  the  acidified  muscle  after  the 
discharge  of  the  carbon  dioxide  is  now  heated  to  40°  C,  the  yield  of 
lactic  acid  is  increased,  but  only  traces  of  carbon  dioxide  are  given  off. 

From  these  and  similar  observations,  Fletcher  concludes  that  the 
carbon  dioxide  discharged  during  heat  rigor  at  40°  C.  is  pre-existent 
carbon  dioxide  set  free  from  carbonates  or  other  compounds  by 
the  lactic  acid  known  to  be  produced  in  heat  rigor.  The  carbon 
dioxide  discharged  at  75°  and  100°  C  he  regards  as  held  by 
muscle  colloids  or  in  combination  with  amino-acid  groups.  These 
results  tend  to  discredit  the  '  inogen  '  theory  (p.  270),  with  its 
assumption  that  '  intramolecular  oxygen  '  is  stored  away  in  the 
muscle,  which  was  largely  based  upon  erroneous  observations  on 
the  discharge  of  carbon  dioxide  from  heated  muscles.  According 
to  this  theory,  carbon  dioxide  and  lactic  acid  were  supposed  to  arise 
from  a  common  precursor  into  which  oxygen  had  been  previously 
introduced. 


778        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

The  production  of  heat  in  heat  rigor  is  also  of  great  interest. 
Hill  has  shown  that  it  amounts  to  from  oO  to  i-o  gramme  calorie 
per  gramme  of  muscle.  Of  this  no  more  than  005  calorie  can  be 
due  to  the  heat  of  neutralization  of  lactic  acid  by  the  sodium 
bicarbonate  in  the  muscle,  with  which  it  reacts  as  soon  as  it  is 
liberated.  The  rest  of  the  heat  is  associated  with  the  chemical 
reaction  by  which  lactic  acid  is  formed  from  its  precursor,  a  reaction 
which,  there  is  every  reason  to  believe,  is  the  same  as  that  which 
occurs  in  muscular  contraction.  The  heat  production  can  only 
be  due  in  very  slight  degree  to  the  physical  alteration  (clotting  or 
precipitation)  of  the  muscle  proteins. 

The  so-called  rigor  caused  by  water,  which  is  not  a  true  rigor, 
causes  no  increase  in  the  carbon  dioxide  given  off.  Chloroform, 
on  the  other  hand,  produces  a  marked  increase  in  the  carbon 
dioxide  production,  and  this  is  evidently  related  to  its  action  in 
hastening  the  onset  of  rigor.  Rigor  mortis  is  to  some  extent  in- 
fluenced by  the  nervous  system,  for  section  of  its  nerves  retards 
the  onset  of  rigor  in  the  muscles  of  a  limb.  Ante-mortem  stimula- 
tion of  the  peripheral  ends  of  the  vagi,  even  with  currents  too  weak 
to  cause  a  perceptible  effect  upon  the  heart-beats,  prolongs  the 
period  of  spontaneous  contraction  and  the  irritability  of  the  ven- 
tricles after  death,  and  retards  the  onset  of  rigor  (Joseph  and 
Meltzer).  Cold  rigor  is  obtained  when  frog's  muscles  are  cooled 
to  —15°  C.  The  muscles  remain  perfectly  translucent.  They 
do  not  recover  their  irritability  on  thawing,  but  if  cooled  only  to 
—  7°  C.  they  recover  (Folin). 

In  a  human  body  rigor  generally  appears  not  earlier  than  an 
hour,  and  not  later  than  four  or  five  hours,  after  death.  In  ex- 
ceptional cases,  however,  it  may  come  on  at  once,  and  the  annals 
of  war  and  crime  contain  instances  where  a  man  has  been  found 
after  death  still  holding  with  a  firm  grip  the  weapon  with  which 
he  had  fought,  or  which  had  been  thrust  into  his  hand  by  his 
murderer  (so-called  cataleptic  rigor).  It  is  related  that  after 
one  of  the  battles  of  the  American  Revolutionary  War  some  of  the 
dead  were  found  with  one  eye  open  and  the  other  closed  as  in  the 
act  of  taking  aim.  A  high  temperatuie  favours  a  rapid  onset;  a 
body  wrapped  up  in  bed  will,  other  things  being  equal,  become  rigid 
sooner  than  a  body  lying  stripped  in  a  field.  Muscular  exhaustion, 
as  we  have  said,  is  another  favouring  condition:  hunted  animals 
and  the  victims  of  wasting  diseases  go  quickly  into  rigor.  It  is 
a  rule,  but  not  an  invariable  one,  that  rigor,  when  it  comes  on 
quickly,  is  short,  and  lasts  longer  when  it  comes  on  late.  All  the 
muscles  of  the  body  do  not  stiffen  at  the  same  time;  the  order 
is  usually  from  above  downwards,  beginning  at  the  jaws  and  neck, 
then  reaching  the  arms,  and  finally  the  legs.  After  two  or  three 
days  the  rigor  disappears  in  the  same  order.     The  position  of  the 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION   779 

limbs  in  rigor  is  the  same  as  at  death;  the  m.uscles  stiffen  without 
any  marked  contraction.  This  can  be  strikingly  shown  on  a  newly- 
killed  animal  by  cutting  the  tendons  of  the  extensors  of  one  foot 
and  the  flexors  of  the  other ;  when  natural  rigor  comes  on,  the  feet 
remain  just  as  they  were.  If  heat  rigor,  however,  is  caused,  the 
one  foot  becomes  rigid  in  flexion  and  the  other  in  extension;  and 
the  contraction-force  is  considerable,  although  not  so  great  as  that 
of  an  electrical  tetanus  in  a  living  muscle. 

The  Possibility  of  Recovery  of  Muscles  after  Rigor. — Wlien  the  circu- 
lation in  the  hind  legs  of  rabbits  is  interrupted  by  compression  or 
ligation  of  the  abdominal  aorta  (Stenson's  experiment),  the  muscles  lose 
their  excitability,  but  speedily  recover,  if  they  have  not  been  deprived 
of  arterial  blood  for  too  long  a  time,  when  the  blood  is  again  allowed  to 
reach  them.  A  longer  interruption  of  the  circulation  leads  not  only 
to  total  inability  to  respond  to  stimulation,  but  also  to  rigor,  and  most 
observers  are  agreed  that,  as  regards  the  skeletal  muscles  at  least,  this 
is  the  irrevocable  end  of  excitability.  Brown-Sequard,  indeed,  stated 
that  after  the  full  development  of  rigor  in  the  rabbit's  muscles  (Stenson's 
experiment),  and  also  in  the  hand  of  an  executed  criminal  through 
which  an  artificial  circulation  was  established,  recovery  ensued.  But 
probably  the  rigor  was  incomplete  or  did  not  involve  all  the  fibres.  In 
heart  muscle  the  conditions  appear  to  be  somewhat  different,  and  Heubel 
has  alleged  that  rhythmical  contractions  of  the  frog's  heart  can  be 
restored  by  filling  its  cavity  with  blood,  after  rigor  has  been  caused  by 
heat  and  in  other  ways,  and  we  have  already  seen  that  the  same  is  true 
of  the  mammalian  heart  alter  the  onset  of  rigor.  Excised  frog's 
muscles  which  have  undergone  rigor  mortis  become  less  stiff  when 
exposed  to  an  atmosphere  of  oxygen. 


CHAPTER  XIV 
NERVE 

The  voluntary  movements  are  originated  by  efferent  or  outgoing 
impulses  from  the  brain,  which  reach  the  muscles  along  their 
motor  nerves.  The  involuntary  movements  and  the  secretions 
are  in  many  cases  able  to  go  on  in  the  absence  of  central  connec- 
tions, but  are  normalh'  under  central  control.  Afferent  impulses 
are  continually  ascending  to  the  cord  and  brain  from  the  skin, 
joints,  bones,  muscles,  and  organs  of  special  sense  like  the  eye  and 
the  ear.  Everj^vhere  the  connection  between  the  nervous  centres 
and  the  peripheral  organs,  and  between  different  parts  of  the 
central  nervous  system,  is  made  by  nerve-fibres.  Those  which 
run  outside  the  brain  and  cord  are  called  peripheral  nerve-fibres 
to  distinguish  them  from  the  intracentral  fibres  of  the  central 
nervous  system  itself. 

In  this  chapter  we  propose  to  consider  certain  of  the  general 
properties  of  nerve-fibres.  Most  of  our  knowledge  of  these  proper- 
ties has  been  derived  from  experiments  on  the  peripheral,  and 
particularly  the  peripheral  motor  nerves ;  but  there  is  every  reason 
to  believe  that  the  main  results  are  true  of  all  nerve-fibres,  afferent 
and  efferent,  peripheral  and  central. 

What  we  call  nerve-fibres  were  known  and  named,  and  many  im- 
portant facts  in  their  physiology  discovered,  long  before  their  true 
morphological  significance  was  recognized.  The  researches  of  recent 
years  have  shown  that  every  nerve-fibre  is,  as  regards  its  essential  con- 
stituent the  axis-cylinder,  a  process  of  a  nerve-cell.  The  nerve-cells, 
each  of  which,  including  all  its  processes,  may  be  conveniently  termed 
a  neuron,  are  the  essential  elements  of  the  nervous  system.  The  cell- 
bodies  of  most  of  the  neurons  are  situated  in,  or  in  close  relation  to,  the 
spinal  cord  and  the  brain,  and  therefore  the  detailed  description  of 
them  will  be  reserved  till  we  come  to  treat  of  the  central  nervous  system 
(see  p.  850  and  Figs.  328  to  340).  It  is  enough  to  say  here  that  in 
general  a  nerve-cell  gives  off  two  kinds  of  processes:  (i)  one  or  more 
dendrites  or  protoplasmic  processes,  which  repeatedly  bifurcate  like  the 
branches  of  a  tree  into  thinner  and  thinner  twigs,  and  extend  only  for 
a  relatively  short  distance  from  the  cell-body;  {2)  an  axis-cylinder 
process  or  axon,  which  as  a  rule  runs  for  a  considerable  distance  without 
altering  its  calibre,  and  either  gives  off  no  branches  (as  in  the  peripheral 
nerves)  or  only  a  comparatively  small  number  of  lateral  twigs  (col« 

780 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE      781 

laterals).  Ultimately  the  axis-cylinder  process  and  its  collaterals,  if  it 
has  any,  end  by  breaking  up  into  a  brush,  a  plexus  or  a  feltwork  or 
baskctwork  of  hbrils.  The  axons  of  different  nerve-cells  vary  greatly 
in  length.  Some  terminate  within  the  grey  matter  of  the  brain  or  spinal 
cord  not  far  from  their  origin;  others  run  in  the  white  tracts  of  the 
central  nervous  system  or  in  the  peripheral  nerves  for  half  the  height 
of  a  man.  All  except  the  shortest  axis-cylinder  processes  become 
clothed  at  a  little  distance  from  the  cell-body  with  a  protective  covering, 
which  continues  to  invest  them  (and  their  collaterals)  throughout  the 
rest  of  their  course,  disappearing  only  when  they  begin  to  break  up  at 
their  terminations.  An  axis-cylinder  process  (spoken  of  simply  as  the 
axis-cylinder,  when  considered  apart  from  the  nerve-cell)  constitutes, 
with  its  covering,  a  nerve-fibre. 

The  axis-cylinder  is  the  essential  conducting  part  of  the  fibre,  for  it  is 
present  in  every  nerve-fibre,  running  from  end  to  end  of  it  without  break, 
and  towards  the  periphery  it  is  alone  present.  It  is  made  up  of  fine 
longitudinal  fibrils  embedded  in  interstitial  substance  (Fig.  329,  p.  851). 
Such  a  fibrillar  structure  is  best  shown  after  treatment  of  the  nerve- 
fibres  with  certain  reagents,  although  it  is  certain  that  it  exists  pre- 
formed in  the  living  fibres. 

Section  I. — The  Nerve-Impulse  or  Propagated  Disturbance: 
ITS  Initiation  and  Conduction. 

So  far  as  we  know,  the  only  function  of  nerve-fibres  is  to  conduct 
impulses  from  nerve-centres  to  peripheral  organs,  or  from  peripheral 
organs  to  nerve-centres,  or  from  one  nerve-centre  to  another. 
In  the  normal  body  these  impulses  never,  or  only  very  rarely, 
originate  in  the  course  of  the  nerve-fibres;  they  are  set  up  either 
at  their  peripheral  or  at  their  central  endings.  By  artificial  stimu- 
lation, however,  a  nerve-impulse  may  be  started  at  any  part  of  a 
fibre,  just  as  a  telegram  may  be  dispatched  by  tapping  any  part  of 
a  telegraph  wire,  although  it  is  usually  sent  from  one  fixed  station 
to  another. 

Nature  of  the  Nerve- Impulse. — What  the  nerve-impulse  actually 
consists  in  we  do  not  know.  All  we  know  is  that  a  change  or  dis 
turbance  of  some  kind,  of  which  the  most  evident  token  is  an 
electrical  change,  passes  over  the  nerve  with  a  measurable  velocity, 
and  gives  tidings  of  itself,  if  it  is  travelling  along  efferent  fibres — 
that  is,  out  from  the  central  nervous  system — by  the  contraction 
or  inhibition  of  muscle  or  by  secretion;  if  it  is  travelling  along 
afferent  fibres — that  is,  up  to  the  central  nervous  system — by  sensa- 
tion, or  by  reflex  muscular  or  glandular  effects. 

Whether  the  wave  which  passes  along  the  nerve  is  a  wave  of 
chemical  change  (such,  to  take  a  very  crude  example,  as  runs 
along  a  train  of  gunpowder  when  it  is  fired  at  one  end),  or  a  wave 
of  mechanical  change,  a  peculiar  and  most  delicate  molecular 
shiver,  if  we  may  so  phrase  it,  or  a  shear  in  a  definite  direction  along 
the  colloidal  substance  of  the  axis-cyhnder  (Sutherland),  there  is 
no    absolutely    definite    experimental    evidence    to    decide.     An 


782  NERVE 

electrical  change  accompanies  the  nervc-inipulse  travelling  at  the 
same  rate,  and  although  this  is  to  be  distinguished  from  the  impulse 
itself,  there  is  little  doubt  that  the  latter  is  essentially  connected 
with  a  disturbance  of  the  electrical  equilibrium  of  the  nerve- 
substance. 

An  attempt  has  been  made  to  settle  the  question  by  determining  the 
temperature  coeflicient  of  the  velocity  of  conduction  of  the  impulse  — 
i.e.,  the  quantity  which  measures  the  change  of  velocity  for  a  given 
change  of  temperature.  For  most  physical  processes  the  quotient 
velocity  at  T«+ 1 o°     ,         ™     .  .         ,  ^         ■        i.  j. 

— r    rj^ — Yt .  where  T«  is  any  given  temperature,  is  not  greater 

than  i'2,  while  for  frog's  sciatic  nerve  the  temperature  coefficient  for 
the  most  part  lies  between  2  and  3  (Snyder).  The  mean  value  of  a 
large  number  of  observations  is  i'79,  with  T«=  8°  to  9°  C.  (Lucas).  For 
the  pedal  nerve  of  the  giant  slug  the  mean  value  of  the  temperature 
coefficient  is  1-78  (Maxwell).  In  other  words,  while  for  the  majority  of 
physical  processes  an  increase  of  10°  C.  increases  the  velocity  of  the 
process  by  at  most  one-fifth,  the  same  increase  of  temperature  increases 
the  velocity  of  conduction  of  the  nerve-impulse  by  four-fifths,  or  even 
more.  While  it  is  true  that  it  may  not  be  entirely  safe  to  apply  such  a 
criterion  to  a  biological  process  which  need  not  be  either  entirely  chemical 
or  entirely  physical,  and  very  likely  is  a  complex  one,  the  suggestion, 
so  far  as  it  goes,  is  undoubtedly  in  favour  of  the  chemical  hypothesis. 
That  chemical  changes  go  on  in  living  nerve  we  need  not  hesitate  to 
assume;  and,  indeed,  if  the  circulation  through  a  limb  of  a  warm- 
blooded animal  be  stopped  for  a  short  time,  the  nerves  lose  their 
excitability.  Even  the  nerves  of  cold-blooded  animals  gradually 
become  inexcitable  and  incapable  of  conduction  when  placed  in  an 
oxygen-free  medium,  as  the  oxygen  already  contained  in  the  tissue  is 
exhausted.  The  excitability  and  conductivity  of  the  nerve  are  restored 
by  oxygen.  It  is  clear,  then,  that  even  a  resting  nerve  requires  oxygen, 
and  it  can  be  shown  that  the  loss  of  function  is  acceleiated  by  stimulation 
in  the  absence  of  oxygen.  But  the  metabolism  is  very  slight  compared 
with  that  in  muscle  or  gland.  Until  recently  even  in  active  nerve  no 
measurable  production  of  carbon  dioxide  had  ever  been  observed,  nor, 
in  fact,  had  any  chemical  difference  between  the  excited  and  the  resting 
state  ever  been  unequivocally  made  out.  However,  it  has  been 
announced  that  by  the  aid  of  an  extremely  delicate  method  of  estimating 
small  quantities  of  carbon  dioxide,  a  measurable  production  of  carbon 
dioxide  can  be  detected  even  in  resting  frogs'  nerves,  and  that  this  pro- 
duction is  increased  two  to  three  times  on  stimulation  (Tashiro).  This 
result  is  somewhat  puzzling  in  view  of  the  fact  that  neither  in  cold- 
blooded nor  in  mammalian  nerves  is  there  any  sensible  rise  of  temper- 
ture  during  stimulation.  With  the  apparatus  shown  in  Fig.  272  (an 
electrical  resistance  thermometer  or  bolometer  whose  use  depends  upon 
the  fact  that  the  electrical  resistance  of  a  metallic  conductor  varies 
with  its  temperature)  an  increase  even  of  0-0003°  C.  in  the  temperature 
of  the  sciatic  nerves  of  dogs  could  not  be  detected  during  tetanization. 
Rolleston  failed  to  find  evidence  of  a  rise  of  even  0-0002°  C.  in  frog's 
nerves  during  stimulation.  And  according  to  the  latest  investigation 
with  a  more  suitable  and  much  more  sensitive  thermo-electric  arrange- 
ment, the  passage  of  a  single  nerve  impulse  along  a  frog's  nerve  cannot 
be  associated  witli  an  increase  of  temperature  in  the  nerve  of  even  the 
hundredth  million  of  a  degree  (A.  V.  Hill).  The  difficulty  of  inducing 
fatigue  in  nerves  under  ordinary  conditions  has  been  considered  a  strong 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE 


783 


support  of  the  physical  nature  of  the  conduction  process.  Neverthe- 
less, it  is  possible  to  show  by  special  methods  that  nerve  can  be  tempor- 
arily fatigued,  although  it  recovers  very  rapidly.  When  a  mcduUated 
nerve  is  stimulated,  a  brief  period  ensues  during  which  it  refuses  to 
resp)ond  to  a  second  stimulus.  This  refractory  period  is  normally  very 
short — not  more  than  0-002  second  for  the  frog's  sciatic.  But  it  can 
be  greatly  piolongcd  by  cold,  asphy.xia,  or  anaesthesia,  especially  by 
the  alkaloid  yohimbine  (Tait  and  Gunn),  and  when  tiie  refractory  period 
is  thus  prolonged,  fatigue  phenomena  are  readily  induced  by  stimulation. 
And  while  the  nerves  of  warm-blooded  animals  at  body  temperature 
and  those  of  cold-blooded  animals  at  about  32°  C.  can  hardly  be  shown 
to  undergo  fatigue  when  tetanized  in  atmospheric  air,  fatigue  phe- 
nomena are  easily  elicited  wlien  the  temperature  is  lowered  even 
although  air  is  supplied  (Thorner). 

Stimulation  of  Nerve. — With  some  differences,  the  same  stimuli 
are  eftcctivo  for  nerve  as  for  muscle  (p.  737) ;  but  chemical  stimula- 
tion is  not  in  general  so  easily  obtained.     The   so-called  thermal 


Fig.  272.  —  Electrical  -  Resistance 
Thermometer  (Natural  Size)  as 
used  for  investigating  heat-pro^ 
duction  in  mammalian  nerves  in 
situ.  A,  a  piece  of  hard  rubber  in 
the  hook-shaped  part  of  which  the 
fine  platinum  wire  P  is  fixed,  and 
covered  with  insulating  varnish; 
c,  c,  thick  copper  wires  connected 
with  P,  fastened  in  grooves,  and 
covered  with  paraffin.  Above  they 
end  in  contact  with  the  small 
binding  posts,  Bj,  B,.  B  is  a  hard 
rubber  sliding  piece,  with  a  slot  s. 
When  B  is  in  position  the  screw,  a, 
projects  througli  the  slot.  By  a  nut 
on  this  screw  B  is  fixed  on  A  when 
the  nerve  has  been  arranged  in  the 
groove. 


B  B 


B 


ikak 


stimulation  is  not  a  real  stimulation  due  to  the  sudden  change  of 
temperature.  The  irregular  contractions  of  the  muscle  caused  by 
the  local  application  of  heat  to  the  nerve  are  dependent  on  desicca- 
tion of  the  nerve. 

Chemical  Stimulation. — When  hyper-  or  hypotonic  solutions  arc  em- 
ployed, the  withdrawal  or  entrance  of  water  may  be  an  important  factor. 

For  salts  which  penetrate  the  fibres  with  equal  difficulty  this  factor 
can  be  eliminated  by  applying  them  as  isotonic  solutions.  There  is 
evidence  that  chemical  stimulation  proper,  as  distinguished  from  the 
stimulation  produced  by  changes  in  the  water  content  of  the  fibres  by 
osmosis,  is  connected  with  the  electrical  charges  on  the  dissociated  ions 
of  the  salts  (p.  428).  Electrical  stimulation,  indeed,  may  only  be  a 
variety  of  chemical  stimulation  (Loeb.  Mathews,  etc.). 

Mechanical  Stimulation  may  be  applied  to  a  nerve  by  allowing  a  small 
weight  to  fall  on  it  from  a  definite  height  or  by  permitting  mercury  to  ,i  rop 
upon  it  from  a  vessel  with  a  fine  outflow  tube.  A  regular  tetanus  may 
thus  be  obtained.  Tigerstedt  found  that  the  smallest  amount  of  .vork 
spent  on  a  frog's  nerve  which  would  suffice  to  excite  it  was  a  little  less 


784  KERVE 

than  a  gramme-millimetre — that  is,  the  work  done  by  a  gramme  falling 
through  a  distance  of  a  millimetre,  or  (taking  an  erg  as  equivalent  to 
ii/ro  gramme-centimetre)  about  100  ergs.  No  doubt  a  great  part  of 
this  is  wasted,  as  a  much  smaller  quantity  of  work  done  by  a  beam  of 
light  on  the  retina  or  by  an  electrical  current  on  an  isolated  nerve,  both 
of  which  may  be  supposed  to  act  more  directly  on  the  excitable  con- 
stituents, suffices  to  cause  stimulation.  Thus,  the  work  done  by  the 
minimal,  natural  or  specific,  stimulus  for  the  retina  in  the  form  of  green 

hght  may  be  as  little  as  — g  erg  (S.  P.  Langley),  or  only  one-ten-thousand- 

millioneth  part  of  the  minimum  work  necessary  for  mechanical  stimula- 
tion. Again,  with  electrical  stimulation  (closure  of  a  voltaic  cuirent, 
or  condenser  discharges)  it  has  been  shown  that  an  amount  of  work 

equal  to  —^  erg  may  be  enough  to  cause  excitation  of  a  frog's  nerve. 

This  is  ten  thousand  times  as  great  as  the  minimal  luminous  stimulus, 
but  a  million  times  less  than  the  minimal  mechanical  stimulus. 

The  laws  of  electrical  stimulation  for  nerve  are  essentially  the  same 
as  those  we  have  already  discussed  for  muscle  (p.  741).  The  voltaic 
current  stimulates  a  nerve,  as  it  does  a  muscle,  at  closure  and  opening. 
During  the  flow  of  the  current,  so  long  as  its  intensity-  remains  constant, 
there  is  as  a  rule  no  excitation,  or  at  least  none  which  is  propagated 
along  the  nerve,  so  that  the  muscles  supplied  by  it  remain  uncontracted. 
But  under  certain  conditions — for  example,  when  the  nerve  is  more 
excitable  than  usual  (as  is  the  case  with  nerves  taken  from  frogs  which 
have  been  long  kept  in  the  cold) — a  closing  tetanus  may  be  seen  while 
the  current  continues  to  pass  through  the  nerve,  and  an  opening  tetanus 
after  it  has  ceased  to  flow^  just  as  when  the  current  is  led  directly 
through  the  muscle.  Sensory-  nerve-fibres,  too,  are  stimulated  by  a 
voltaic  current  during  the  whole  time  of  flow.  Induction  shocks  are 
relatively  more  powerful  stimuli  for  nerve  than  the  make  or  break  of  a 
voltaic  current.  The  opposite,  as  we  have  seen,  is  true  of  muscle;  and, 
upon  the  whole,  we  may  say  that  muscle  is  more  sluggish  in  its  response 
to  stimuli,  and  is  excited  less  easily-  by  very  brief  currents,  than  nerve 
is.  An  apparent  illustration  of  this  difference  is  the  fact  that  the 
nervous  excitation  has  no  measurable  latent  period,  while  muscular 
excitation  has.  But  it  is  quite  possible  that,  if  the  conditions  of  experi- 
ment were  as  favourable  in  nerve  as  in  muscle,  a  sensible  latent  period 
might  be  found  here  too. 

In  nerve  as  in  muscle,  strength  of  stimulus  and  intensity  of  response 
correspond  within  a  fairh-  wide  range,  when  we  take  the  height  of  the 
muscular  contraction  or  the  amount  of  the  negative  variation  (p.  S24) 
as  the  measure  of  the  nervous  excitation.  Summation  of  stimuli,  super- 
position of  contractions,  and  complete  tetanus,  are  caused  by  stimulating 
the  muscle  through  its  nerve,  just  as  by  stimulating  the  muscle  itself 
(P-  736). 

Excitability  of  Nerve.^ — It  has  usually  been  stated  that  the  ex- 
citability of  frog's  nerve,  as  measured  by  the  muscular  response  to 
stimulation,  is  increased  by  rise  of  temperature,  and  diminished  by 
fall  of  temperature.  It  has,  however,  been  shown  that  this  increase 
of  excitabilit}-  is  only  apparent,  and  due  to  the  strengthening  of 
the  current  by  diminution  of  the  resistance,  since  the  resistance 
of  all  animal  tissues,  like  that  of  electrolytic  conductors  in  general, 
diminishes  as  the  temperature  rises  (Golch).     When  precautions 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     785 

are  taken  to  keep  the  current  intensity  the  same  at  the  various 
temperatures  compared,  it  is  found  that  coohng  of  a  (frog's)  nerve, 
even  to  5°  C,  increases  the  excitabihty  for  currents  of  long  duration 
(several  hundredths  of  a  second).  It  has,  indeed,  been  shown  both 
for  muscle  and  for  nerve  that  the  cooler  tissue  requires  a  smaller 
current  strength  for  its  excitation  when  the  current  is  of  long  dura- 
tion. With  brief  currents  this  effect  is  masked,  either  partially  or 
completely,  by  the  greater  increase  of  current  strength  needed  in  the 
case  of  the  cooler  tissue  to  compensate  fora  given  decrease  in  duration 
(p.  789)  (Lucas  and  Mines).  This  is  the  reason  that  for  induction 
shocks  or  voltaic  currents  of  short  duration,  the  excitabihty  of  the 
nerve  seems  to  be  increased  by  a  rise  of  temperature  (up  to  about 
30°  C.  in  the  case  of  frog's  nerve),  and  diminished  by  cooling. 

Drjnng  of  a  nerve  at  first  increases  its  excitability;  and  the  same 
is  true  of  separation  of  a  nerve  from  its  centre.  In  the  latter  case 
the  increase  of  irritability  begins  at  the  proximal  end  of  the  nerve, 
and  travels  towards  the  periphery.  As  time  goes  on,  the  excita- 
bility diminishes,  and  ultimately  disappears  in  the  same  order 
(Ritter-Valli  Law).  At  a  certain  stage  it  may  be  found  that  a 
given  stimulus  causes  a  smaller  and  smaller  contraction  the  farther 
down  the  nerve — that  is,  the  nearer  to  the  muscle — it  is  applied. 
On  this  was  based  the  now  abandoned  '  avalanche  theory,'  according 
to  which  the  impulse  continually  unlocked  new  energy  as  it  passed 
along  the  nerve,  and  so  gathered  strength  in  its  course  like  an 
avalanche.  It  is  now  known  that  no  material  change  takes  place 
in  the  intensity  of  the  excitation  while  it  is  being  propagated  along 
a  normal  uninjured  nerve.  For  instance,  experiments  on  the 
phrenic  nerve,  in  its  natural  position,  and  with  all  its  connections 
intact,  have  shown  that  with  a  given  strength  of  stimulus  the 
amount  of  contraction  of  the  diaphragm  is  the  same  whether  the 
nerve  be  excited  in  the  upper,  middle,  or  lower  portion  of  its  course. 
In  the  above  experiment  on  the  isolated,  and  therefore  injured, 
nerve,  the  contraction  varies  in  height  with  the  distance  of  the 
point  of  stimulation  from  the  muscle,  not  because  the  excitation 
grows  as  it  travels,  but  because  it  is  already  greater  at  the  moment 
when  it  sets  out  from  a  point  near  the  central  end  of  the  nerve 
than  at  the  moment  when  it  sets  out  from  a  point  near  the  muscle. 

Electrotonus. — Although  the  constant  current  does  not,  unless 
it  is  very  strong  or  the  nerve  very  irritable,  cause  stimulation  during 
its  passage,  it  modifies  profoundly  the  excitabihty  and  conductivity 
of  the  nerve.  In  the  neighbourhood  of  the  kathode  the  excitabihty 
is  increased  (condition  of  kat electrotonus),  while  around  the  anode 
it  is  diminished  (anelectrotonus).  Immediately  after  the  opening 
of  the  current  these  relations  are  for  a  brief  time  reversed,  the 
excitability  of  the  post-kathodic  area  (area  which  was  at  the  kathode 
during  the  flow)  being  diminished,  and  that  of  the  post-anodic 

50 


786 


NERVE 


increased.  In  the  intrapolar  area  there  is  one  point  the  excita- 
blHty  of  whicli  is  not  altered.  This  inchfferent  point,  as  it  is  called, 
shifts  its  position  when  the  intensity  of  the  current  is  varied,  moving 
towards  the  katliodc  when  the  current  is  increased,  towards  the 
anode  when  it  is  diniinislied. 

It  is  only  under  certain  definite  condition.s  tliat  these  phenomena,  first 
described  by  Pfliigcr,  appear  in  their  purity  and  uncomplicated  by  other 
changes.  The  nerve  should  be  quite  fresh,  the  current  a  weak  or  at 
most  a  modciatcly  strong  one,  and  the  stretch  of  nerve  employed 
should  be  as  far  as  possible  from  the  cross  section,  and  from  the  cross 
sections  of  branches.  The  middle  region  of  the  frog's  sciatic  nerve  is 
the  best.  Wlien  all  these  conditions  are  fulfilled,  the  whole  stretch 
of  nerve  in  katelcctrotonus — i.e.,  the  part  on  both  sides  of  the  kathode 
and  at  the  kathode  itself  shows  an  increased  stimulation  clfect,  the 
more  pronounced  the  nearer  to  the  kathode  the  point  of  stimulation. 
This  condition,  however,  only  lasts  an  instant.  Then  the  excitability 
begins  to  sink  sharply  fir^t  at  the  kathode,  then  on  both  sides  of  it,  till 

it  ultimately  becomes  decidedly  less  than 
the  initial  excitability-  This  secondary 
depression  of  excitability,  always  most 
marked  at  the  very  kathode,  is  just  as  con- 


Fig.  273.—  Katelcctrotonus.  Weak 
tetanus  of  muscle  (the  right-hand 
elevation),  greatly  intensified  in 
katelcctrotonus  of  the  motor  nerve 
(the  left-hand  elevation). 


Fig.  274.—  .Xnclectrotonus.  Strong 
tetanus  of  muscle  (left-hand  t  le- 
vatinii),  lessened  in  strength  by 
aiielectrotonic  condition  of  the  mo- 
tor nerve  (right-hand  elevation). 


stant  a  phenomenon  as  the  preliminary  increase.  The  stronger  the  cur- 
rent the  more  profound  is  the  depression,  the  more  (pjickly  it  is  de- 
veloped, and  the  greater  is  the  distance  to  which  it  spreads  along  the 
nerve.  With  a  certain  strength  of  current  the  depression  ajipears  so 
rapidly  that  the  preliminary  increase  of  excitability  ma}'  be  completely 
missed.  When  the  current  is  opened  the  excitability  cjuickly  increases 
again,  but  with  strong  currents  it  may  remain  depressed  for  a  while.  At 
the  anode  changes  in  the  reverse  direction  may  be  observed,  although 
they  are  less  pronounced  than  at  the  kathode.  Thus  at  the  anode 
during  the  passage  of  the  current  the  initial  depression  of  the  excitability 
tends  to  give  place  to  an  increase  (Werigo). 

These  statements  have  been  made  on  the  strength  of  experiments  in 
which  the  height  of  the  muscular  contraction  was  taken  as  the  index  of 
the  excitability  of  the  nerve  at  any  given  point.  It  is  difficult,  however, 
to  disentangle  the  effects  of  alterations  in  the  excitability  from  the 
effects  of  alterations  of  conductivity — i.e..  of  the  power  of  a  portion  of 
the  nerve  to  conduct  an  impulse  set  up  elsewhere.  Whether  these  two 
properties  arc  distinct  or  not  is  a  question  which  will  be  considered  a 
little  later  on.     But  it  is  perfectly  clear  that  in  deducing  conclusions 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE      787 


as  to  the  effect  produced  on  a  nerve  by  excitation  at  a  given  point  from 
tlie  resultant  effect  on  tlie  muscle  to  which  the  nerve  is  attached  (or 
on  a  galvanometer  or  electrometer  if  we  arc  following  the  effect  by 
means  of  the  electrical  changes),  we  must  know  whether  the  change 
set   up  in  the  nerve  at  the 

f)oint  of  excitation  can  pass 
reely  along  the  nerve  to  the 
muscle  or  to  the  point  at 
which  it  is  led  ofE  to  the 
galvanometer.  Now,  changes 
of  conductivity  are  certainly 
produced  in  a  nerve  by  the 
constant  current,  which  even 
outlast  its  flow.  For  all 
currents  above  a  certain 
strength  the  conductivity  at 
the  kathode  and  in  its  neigh- 
bourhood is  eventually  dim- 
inished, and  with  currents 
still  only  moderately  strong 
the  block  deepens  into  im- 
passability.  The  conduc- 
tivity at  the  anode  is,  during 
this  stage,  higher  than  at  the 
kathode,  so  that  at  the  time 
of  full  kathodic  block  tire 
nerve  -  impulse  still  passes 
through  the  region  around 
the  positive  pole.  With  still 
stronger  currents  the  con- 
ductivity here,  too,  dimin- 
ishes, until  the  anode  as  well 
as  the  whole  intrapolar  re- 
gion is  blocked.  After  the 
opening  of  the  current,  the 
relation  between  kathodic 
and  anodic  conductivity  is 
reversed,  for  now  the  post- 
kathodic  region  conducts  the 
nerve-impulse  relatively  bet- 
ter than  the  post-anodic.  It 
will  be  seen  that  these 
changes  of  conductivity  up- 
on the  whole  run  parallel  to 
the  (secondary)  changes  of 
excitability,  depression  of 
excitability  corresponding  to 
depression  of  conductivity, 
and  vice  versa.  With  the 
relatively  strong  currents  re- 
quired to  produce  decided 
effects  on  the  conductivity, 

any  preliminary  change  in  the  same  sense  as  the  (so-called  primary) 
effects  on  the  excitability  (increase  at  kathode,  decrease  at  anode) 
might  be  expected  to  be  fleeting,  and  therefore  less  eas}-  to  detect. 

The  above  facts  serve  to  explain  the  manner  in  which  the  effects  of 
stimulation  of  a  nerve  with  the  constant  current  vary  with  the  strength 


Fig.  275. — Diagram  of  Changes  of  Excitability 
and  Conductivity  produced  in  a  Nerve  by  a 
Voltaic  Current.  E,  changes  of  excitability 
during  the  flow  of  the  current,  according  to 
Pfliiger.  These  are  seen  most  typically  with 
the  weaker  currents.  In  particular  the  in- 
creased excitability  at  and  around  the  kathode 
when  the  current  is  strong  very  quickly  gives 
place  to  depression.  The  ordinates  drawn 
from  the  abscissa  axis  to  cut  the  curve  repre- 
sent the  amount  of  the  change.  C(i),  changes 
of  conductivity  found  shortly  after  the  closure 
and  during  the  flow  of  a  moderately  strong 
current.  Conductivity  greatly  reduced  around 
kathode;  little  affected  at  anode.  C(2), 
changes  of  conductivity  during  flow  of  a  very 
strong  current.  Conductivity  reduced  both  in 
anodic  and  kathodic  regions,  but  less  in  the 
former.  C,  changes  of  conductivity  just  after 
opening  a  moderately  strong  current.  Con- 
ductivity greatly  reduced  in  region  which  was 
formerly  anodic;  little  affected  in  region  for- 
merly kathodic. 


788 


NERVE 


and  direction  of  the  stream.  These  effects,  so  far  as  the  contraction  of 
tlie  muscles  supplied  by  the  nerve  is  concerned,  have  been  formulated 
in  what  lias  been  somewhat  loosely  termed  the  law  of  contraction.  In 
this  formula  the  direction  of  the  current  in  the  nerve  is  commonly  dis- 
tinguished by  a  thoroughly  bad  but  now  ingrained  phraseology,  as 
ascending  when  the  anode  is  next  the  muscle,  and  descending  when  the 
kathode  is  next  the  muscle. 


Current. 

Ascending. 

Descending. 

M. 

B. 

c 
c 

M. 

B. 

Weak      - 
Medium - 
Strong    - 

c 
c 

c 
c 
c 

c 

Here  M  means  '  make, 
traction  follows.' 


B,  '  break,'  of  the  current;  C  means  '  con- 


The  explanation  generally  given  is  as  follows:  Wherever  there  is  an 
increase  of  excitability  sufficiently  rapid  and  sufficiently  large,  stimula- 
tion is  supposed  to  take  place;  where  there  is  a  fall  of  excitability, 
stimulation  does  not  occur.  Accordingly,  at  closure  the  kathode  stimu- 
lates— the  anode  does  not;  while  at  opening,  the  anode,  at  which  the 
depressed  excitability  jumps  up  to  normal  or  more,  is  the  stimulating 
pole;  the  kathode,  at  which  it  declines  to  normal  or  under  it,  is  inactive. 

With  a  tveak  current,  (i)  contraction  only  occurs  at  make,  and  (2)  the 
diiection  of  the  current  is  indifferent.  The  explanation  of  the  first  fact 
is  that  the  make  is  a  stronger  stimulus  than  the  break,  and  when  the 
current  is  weak  enough  the  break  is  less  than  a  minimal  stimulus.  No 
sensible  change  of  conductivity  is  caused  by  weak  currents,  which 
suffices  to  explain  (2). 

With  a  '  medium  '  current,  contraction  occurs  at  make  and  break  with 
both  directions.  Here  the  break  excitation  is  effective  as  well  as  the 
make.  With  anode  next  the  muscle  (ascending  current),  there  is,  of 
course,  nothing  to  prevent  the  opening  excitation,  which  starts  at  the 
anode,  from  passing  down  the  nerve  and  causing  contraction ;  and  since 
there  is  no  block  around  the  anode  or  in  the  intra  polar  region  with 
'  medium  '  currents,  there  is  nothing  to  keep  the  closing  (kathodic) 
excitation  from  reaching  the  muscle  too.  With  the  kathode  next  the 
muscle  (descending  current),  the  closing  excitation,  which  starts  from 
the  kathode,  has  no  reigon  of  diminished  conductivity  to  pass  through, 
nor  has  the  opening  (anodic)  excitation,  for  the  kathodic  block,  caused  by 
moderately  strong  currents,  is  removed  as  soon  as  the  current  is  broken. 

With  '  strong  '  currents  there  are  only  two  cases  of  contraction  out 
of  the  four,  just  as  with  '  weak,'  but  for  very  different  reasons.  There 
is  a  break-contraction  with  ascending,  and  a  make-contraction  with 
descending  current.  With  ascending  current  the  anode  is  next  the 
muscle,  and  the  break-excitation  starting  there  has  nothing  to  hinder 
its  course.  The  make-excitation,  although  as  strong  or  stronger,  has  to 
pass  through  the  whole  intrapolar  region  and  over  the  anode,  and  here 
the  conductivity  is  depressed  and  the  nerve-impulse  blocked.  With 
descending  current  the  kathode  is  next  the  muscle,  and  there  is  no 
hindrance  to  the  passage  of  the  make-excitation.  The  break-excitation, 
however,  has  to  traverse  the  whole  intrapolar  region,  and  this  does  not 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     789 


at  once,  after  a  strong  current,  become  passable.     The  break-excitation, 

accordingly,  rannot  get  through  to  the  muscle. 

A  formula  similar  to  the  law  of  contraction  has  been  shown  to  hold 
for  the  inhibitory  fibres  of  the  vagus  (Bonders),  '  inhibition  '  being 
substituted  for  '  contraction.'  There  is  also  some  evidence  that  a 
similar  law  obtains  for  sensory  nerves. 

It  is  not  difficult  to  see  that  with  currents  of  brief  duration  the  break 
follows  so  quickly  on  the  make  that  interference  of  theii  opposed  effects 
may  occur.  This  is  the  reason — or,  at  least,  one  reason — why,  r  bove 
a  certain  frequency,  a  muscle  or  nerve  ceases  to  respond  to  all  of  a 
series  of  rapidly  recurring  electrical  stimuli  (p.  7.58).  It  is  aUo  the 
reason  why,  with  single  very  brief  stimuli,  a  greater  current  intensity 
must  be  emploved  in  order  to  cause  excitation  than  when  the  duration 
of  the  stimulating  current  is  greater  (Woodworth,  Lucas). 

The  Law  of  Contraction  for  Nerves  '  in  Situ.' — When  a  nerve  is  stimu- 
lated without  previous  isolation — in  the  human  body,  for  instance, 
through  electrodes  laid  on  the  skin — the  current  wiU  not  enter  and 
leave  it  through  definite  small  portions 
of  its  sheath,  nor  will  it  be  possible  to 
make  the  lines  of  flow  nearly  parallel  to 
each  other  and  to  the  long  axis  of  the 
nerve,  as  is  the  case  in  a  slender  strip  of 
tissue  when  there  is  a  considerable  dis- 
tance between  the  electrodes. 

On  the  contrary-,  when,  as  is  usual  in 
electro-therapeutical  treatment,  a  single 
electrode — say,  the  positive — is  placed 
over  the  position  of  the  nerve,  and  the 
other  at  a  distance  on  some  convenient 
part  of  the  body,  the  current  will  enter 
the  ner\-e  by  a  broad  fan  of  stream-lines 
cutting  it  more  or  less  obliquely,  and  pass 
out  again  into  the  surrounding  tissues; 
so  that  both  an  anode  (surface  of  en- 
trance) and  a  kathode  (still  larger  surface 
of  exit)  will  correspond  to  the  single 
positive  pole.  Similarly,  the  single  nega- 
tive electrode  will  correspond  to  an 
anodic  surface  where  the  now  narrowdng 


Fig.  276- — Diagram  of  Lines  of 
Flow  of  a  Current  passing 
through  a  Nerve.  A,  an  isolated 
nerve;  B,  a  nerve  t>ts:<M.  Secon- 
dary anodes  (  +  )  are  formed 
where  the  current  re-enters  the 
nerve  below  the  negative  elec- 
trode after  passing  through  the 
tissues  in  which  it  is  embedded 
and  secondary  kathodes  {  -  ) 
where  the  current  passes  out  of 
the  nerve  into  the  surrounding 
tissues  below  the  positive  elec- 
trode. 


sheaf  of  lines  of  flow  enters  the  nerve,  and 
a  smaller  kathodic  surface,  where  they  emerge.     Even  if  the  two  elec- 
trodes were  on  the  course  of  the  nerve,  the  stream-lines  would  still  cut 
it  in  such  a  way  that  each  electrode  would  correspond  both  to  anode  and 
kathode  (Fig.  276). 

It  is  impossible  under  these  circumstances  to  take  account  of  the 
direction  of  a  current  in  a  nerve,  or  to  connect  direction  with  any  specific 
effect.  When  we  place  one  of  the  electrodes  over  the  nerve  and  the 
other  at  a  distance,  the  law  of  contraction  only  appears  in  a  disguised 
form;  for  since  a  kathode  and  an  anode  exist  at  each  pole,  there  is,  with 
a  current  of  sufficient  strength  ('  strong  current  '),  excitation  at  each, 
both  at  make  and  break.  The  negative  make  contraction  is,  however, 
stronger  than  the  positive,  for  the  excitation  corresponding  to  the  latter 
arises  at  the  secondary  kathodic  surface,  where  the  sheaf  of  current-lines 
spreading  from  the  positive  electrode  passes  out  of  the  nerve.  Now. 
this  is  much  larger  than  the  primary  kathodic  surface,  through  which 
the  narrow  wedge  of  stream-lines  passes  to  reach  the  negative  electrode, 
and  the  current  density  at  the  latter  is  accordingly  much  greater.     The 


790  NERVE 

positive  break-contraction  is,  for  a  similar  reason,  stronger  than  the 
negative. 

With  a  '  weak  '  current,  the  only  contraction  is  a  closing  one  at  the 
kathode;  with  a  '  medium  '  current  there  are  both  opening  and  closing 
contractions  at  the  positive  pole,  and  a  closing  but  no  opening  con- 
traction at  the  negative  (Practical  Exercises,  p.  846). 

Conductivity  of  Nerve. — The  disturbance  which  is  called  the 
nerve-impulse,  once  set  up,  is  propagated  along  the  fibres.  Are 
the  changes  in  the  nervous  substance  involved  in  the  initiation  of 
the  disturbance  at  a  given  point  identical  with  those  involved  in 
its  transmission  from  one  point  to  the  next,  or  are  they  different  ? 
This  is  a  question  which  has  been  much  discussed,  and  many 
attempts  have  been  made  to  prove  that  the  two  processes  can  be 
dissociated  by  acting  on  nerves  with  substances  like  carbon  dioxide, 
ether,  and  alcohol,  which  gradually  suspend  their  functions,  by 
cutting  nerves  off  from  the  circulation  and  allowing  them  to  die 
gradually,  by  depriving  them  of  oxygen  and  in  other  ways.  Many  of 
the  results  obtained  from  such  experiments  seem  at  first  sight  to 
be  favourable  to  the  view  that  the  local  change  is  different  from  the 
propagated  disturbance.  Nevertheless,  careful  examination  of  the 
results  on  which  such  statements  are  based  indicates  that  none  of 
them  supplies  a  crucial  test  of  the  question  at  issue.  For  example, 
when  a  stretch  of  frog's  sciatic  nerve  is  treated  with  ether  or  another 
of  the  narcotics  which  act  on  nerve,  and  the  strength  of  stimulus 
determined  which  is  necessary  to  elicit  a  contraction  when  applied 
to  an  untreated  portion  more  remote  from  the  muscle  than  the 
narcotized  area,  this  strength  is  found,  for  some  time  after  the 
application  of  the  narcotic,  to  be  just  the  same  as  it  was  previous 
to  the  application.  '  The  conductivity  '  of  the  narcotized  stretch 
appears  to  be  unaltered.  On  the  other  hand,  the  stimulus,  when 
applied  within  the  narcotized  region,  must  be  strengthened,  and 
the  narcotic  appears  to  have  diminished  the  '  excitability  '  of  the 
nerve.  When  the  narcotic  has  acted  for  a  longer  time,  the  reverse 
effect  appears.  No  stinnilus,  however  strong,  applied  to  the  central 
non-narcotized  stretch  will  cause  a  contraction,  the  '  conductivity  ' 
having  been  apparently  totally  abolished  by  the  narcotic,  whereas 
a  strong  stimulus  applied  in  the  narcotized  region  will  still  cause 
a  contraction,  showing  that  '  excitability  '  still  remains.  As  to 
the  facts  there  is  general  agreement;  it  is  their  interpretation 
which  is  in  doubt.  Now,  it  has  been  shown  that  in  passing  along 
a  narcotized  nerve  the  propagated  disturbance  diminishes  in  pro- 
portion to  the  length  of  nerve  which  it  has  to  traverse.  Accordingly 
in  the  second  stage  of  narcosis  the  failure  of  the  stimulus  applied 
to  the  upper  part  of  the  nerve  to  elicit  a  contraction  is  explained 
most  naturally  as  due  to  the  extinction  of  the  distiu-bance,  which 
must  pass  through  the  whole  narcotized  region,  whereas  the  dis- 
turbance set  up  by  stimulation  in  that  region  succeeds  in  reaching 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     7<Jl 

the  muscle,  sinr(>  it  has  a  sliorter  strelcli  of  narcotized  nerve  to 
traverse.  This  expiM'inient,  then,  in  reahty  affords  no  proof  that 
excitability  and  conchictivity  can  vary  independently.  Facts  are 
also  known,  to  which  allusion  need  not  be  made  here,  but  which 
greatly  modify  the  ordinary  interpretation  of  the  experimental 
results  obtained  in  the  first  stage  of  narcosis,  and  upon  the  whole 
it  may  be  said  that  these  direct  methods  of  determining  the  question 
have  failed  to  yield  a  satisfactory  answer.  Indirect  evidence 
exists,  however,  that  the  local  process  initiated  by  stimulation  is 
not  quite  the  same  as  the  process  involved  in  the  propagation  of 
the  disturbance  (Lucas).  Thus,  a  brief  current  too  weak  to  set  up  a 
propagated  disturbance,  nevertheless  causes  some  change  at  the  point 
of  stimulation,  since  a  second  current,  also  too  weak  to  be  effective 
by  itself,  will,  when  thrown  in  a  short  time  after  the  first,  cause 
a  disturbance  which  is  propagated  along  the  nerve.  There  is  good 
reason  to  believe  that  the  change  produced  by  the  first  current  is 
not  the  same  in  kind  as  that  produced  by  the  second,  only  weaker, 
but  that  it  is  inherently  different  in  quality.  Above  all,  it  is  a 
local  change  incapable  of  being  itself  propagated,  but  constituting 
the  necessary  prelude  to  the  starting  of  the  propa.gated  disturbance. 
Lucas  has  called  this  preliminary  local  effect  the  '  local  excitatory 
process.' 

There  are  many  facts  which  indicate  that  the  capacity  of  different 
functional  or  anatomical  groups  of  nerve-fibres  for  responding  to  stimu- 
lation and  for  conducting  the  nerve-impulse  can  be  differently  affected 
by  one  and  the  same  influence.  For  example,  pressure  abolishes  the 
conductivity  of  sensory  fibres  sooner  than  that  of  motor  fibres. 

Cocaine  locally  applied  to  a  nerve  diminishes  or  abolishes  its  con- 
ductivity, according  to  the  dose.  It  exercises  a  selective  action  as 
regards  nerve-fibres  of  different  kinds,  picking  out  and  paralyzing 
sensory  fibres  before  motor;  vagus  fibres  conducting  upwards  before 
those  conducting  downwards,  vaso-constrictors  before  vaso-dilators, 
and  broncho-constrictors  before  broncho-dilators  (Dixon). 

The  conduction  or  propagation  of  a  definite  disturbance  or  impulse  is 
a  phenomenon  not  confined  to  nervous  tissue.  It  is  also  characteristic- 
ally seen  in  muscle,  although  there  the  mechanical  effect  which  con- 
stitutes the  normal  respon.?e  to  the  arrival  of  the  propagated  disturbance 
obtrudes  itself  and  tends  to  divert  attention  from  the  latter.  It  is 
unlikely  that  the  conduction  process  m  muscle  should  be  essentially 
different  from  that  in  nerve,  and  in  muscle,  as  in  nerve,  there  is 
evidence  that  it  is  associated  with  only  a  small,  perhaps  not  even  a 
detectable,  liberation  of  heat.  The  main  heat-production  in  muscle 
is  essentially  a  feature  not  of  conduction,  but  of  contraction.  Con- 
duction in  muscle  can  be  completely  dissociated  from  the  contraction 
process  in  various  ways.  For  example,  if  a  portion  of  a  muscle  is 
immersed  for  a  time  in  distilled  water,  so-called  water  rigor  ensues,  and 
the  altered  muscle  has  lost  the  power  of  contraction.  It  will  never- 
theless conduct  the  impulse  which  on  reaching  the  unaltered  part  of  the 
muscle  causes  it  to  contract  normally. 

Double  Conduction. — When  a  nerve  (or  muscle)  is  stimulated 
artificially,  the  excitation  runs  along  it  in  both  directions  from  the 


792  NERVE 

point  of  stiimilation;  so  that  nervc-libres  which  in  the  intact  body 
are  afferent  can  conduct  impulses  towards  the  periphery  and 
efferent  fibres  can  conduct  impulses  away  from  the  periphery.  In 
the  normal  state,  however,  double  conduction  must  seldom  occur, 
for  efferent  fibres  are  connected  centrally,  and  afferent  fibres 
peripherally,  with  the  structures  in  whicli  their  natural  stimuli 
arise.  In  general,  too,  an  impulse,  if  it  did  pass  centrifugally  along 
an  afferent  fibre,  would  not  give  any  token  of  its  existence,  for  the 
peripheral  organ  would  not  be  able  to  respond  to  it;  and  there  is  no 
ground  for  assuming  that  the  central  mechanisms  connected  with 
afferent  fibres  are  better  fitted  to  answer  such  foreign  and  un- 
accustomed calls  as  impulses  reaching  them  along  normally  efferent 
nerves.  There  is  good  evidence  that  muscular  excitation  is  no' 
carried  over  to  the  motor  nerve- fibres;  in  other  words,  the  v.ave 
of  action  flows  from  the  nerve  to  the  muscle,  but  cannot  be  got 
to  flow  backwards.  Excitation  of  the  central  end  of  an  efferent 
(anterior)  spinal  root  is  not  transferred  to  the  corresponding  afferent 
(posterior)  root,  the  connection  between  the  efferent  and  afferent 
neurons  presenting  the  character  of  a  physiological  '  valve,'  which 
permits  impulses  to  pass  only  in  one  direction.  We  have  seen  that 
vaso-dilator  impulses  possibly  pass  out  to  the  limbs  over  fibres 
which,  morphologically  speaking,  are  afferent  fibres  (p.  i8i).  And 
we  shall  see  that  a  nutritive  influence  is  exerted  over  the  afferent 
fibres  of  the  spinal  nerves  by  the  ganglion  cells  of  the  posterior  root 
ganglia  (p.  796),  an  influence  which  must  spread  along  these  fibres 
in  the  opposite  direction  to  that  of  the  normal  excitation. 

The  best  proofs  of  double  conduction  in  nerves,  with  artificial  stimu- 
lation, are:  (i)  The  propagation  of  the  negative  variation  or  action 
current  in  both  directions.  This  holds  for  sensory  as  well  as  for  motor 
fibres,  as  du  Bois-Reymond  showed  on  the  posterior  roots  of  the  spinal 
nerves  of  the  frog  and  the  optic  nerves  of  fishes.  (2)  Stimulation  of  the 
posterior  free  end  of  the  electrical  nerve  of  Malaptcrurus  (p.  841)  causes 
discharge  of  the  electric  organ,  although  the  nerve-impulse  travels  nor- 
mally in  the  opposite  direction.  (3)  If  the  lower  end  of  the  frog's 
sartorius  is  split  into  two,  gentle  stimulation  of  one  of  the  tongues  causes 
contraction  of  individual  fibres  in  the  other.  This  is  supposed  to  be  due 
to  conduction  of  the  nerve-impulse  up  a  twig  of  a  nerve-fibre  distributed 
to  the  one  tongue,  and  down  another  twig  of  the  same  fibre  going  to  the 
other  tongue.  A  similar  experiment  can  be  done  on  the  gracilis  of  the 
frog.  This  muscle  is  divided  by  a  tendinous  inscri]Hion  into  two  parts, 
each  supplied  by  a  branch  of  a  nerve  which  divides  after  entering  the 
muscle.  Stimulation  of  either  twig  is  followed  by  contraction  of  both 
parts  of  the  muscle  (Kiihne). 

Bert's  much-quoted  experiment  on  the  rat  is  valueless  as  a  proof  of 
double  conduction.  lie  caused  union  of  the  point  of  the  tail  with  the 
tissues  of  the  back,  then  divided  the  tail  at  the  root,  and  found  that 
stimulation  of  what  was  now  the  distal  end  caused  pain.  From  this  he 
concluded  that  the  sensory  fibres  of  the  '  transposed  '  tail  conducted 
in  the  direction  from  root  to  tip.  But  the  conclusion  is  not  warranted, 
for  sensation  disappeared  in  the  tail  after  the  section,  and  did  not 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     70S 

return  till  some  months  later,  when  the  nerve-fibres,  after  degenerating, 
woulil  i-.avc  been  replaced  by  new  sensory  fibres  growing  down  from 
the  (I  rl  nerves  (Ranvier).  For  a  similar  reason  the  so-called  union 
of  the  riphcral  end  of  the  cut  hypoglossal  nerve  (motor)  with  the 
central  end  of  the  cut  lingual  (sensory)  proves  nothing  as  to  double 
conduction,  nor  as  to  the  possibility  of  motor  nerves  taking  on  a  sensory 
funrtion.  For  while  sensation  is  after  a  time  restored  in  the  affected 
portion  of  the  tongue,  this  is  due  to  the  growth  of  sensory  fibres  from  the 
central  stump  of  the  lingual  down  through  the  degenerated  hypoglossal, 
and  not  to  the  conduction  upwards  of  sensory  impulses  by  the  motor 
fibres  of  the  latter. 

Every  fibre  of  a  nerve  is  physiologically  isolated  from  the  rest, 
so  that  an  impulse  set  up  in  a  fibre  runs  its  course  within  it,  and 
does  not  pass  laterally  into  others  (law  of  isolated  conduction).  In 
connection  with  this  physiological  fact  there  is  the  anatomical  fact 
that  nerve-fibres  do  not  normally  branch  in  the  trunk  of  a  peripheral 
nerve.  (But  see  p.  802.)  It  has,  however,  been  shown  that  bifurca- 
tion of  nerve-fibres  may  occur  in  the  spinal  cord  (Sherrington). 
The  axis-C3dinder  of  a  peripheral  nerve-fibre  only  begins  to  branch 
where  complete  isolation  of  function  is  no  longer  required,  as  within 
a  muscle.  The  expteriment  of  Kiihne  on  double  conduction,  men- 
tioned above,  shows  that  an  excitation  set  up  in  one  twig  or  one 
fibril  of  an  axis-cyhnder  which  has  branched  can  spread  to  the  rest. 

Velocity  of  the  Nerve- Impulse. — We  have  said  that  the  nerve- 
impulse  travels  with  a  measurable  velocity.  It  is  now  time  to 
describe  how  this  has  been  ascertained  (p,  818).  For  motor  fibres 
the  simplest  method  is  to  stimulate  a  nerve  successively  at  two 
points,  one  near  its  muscle,  the  other  as  far  away  from  it  as  possible, 
and  to  record  the  contractions  on  a  rapidly-moving  surface  (pendu- 
lum or  spring  myograph)  (p.  746).  The  apparent  latent  period  of 
the  curve  corresponding  to  the  nearer  point  will  be  less  than  that 
of  the  curve  corresponding  to  the  point  which  is  more  remote,  by 
the  time  which  the  impulse  takes  to  pass  between  the  two  points. 
The  distance  between  these  points  being  measured,  the  velocity  is 
known.  Helmholtz  found  the  velocity  for  frog's  nerves  at  the 
ordinary  temperature  of  the  air  to  be  a  little  under,  and  for  human 
nerves,  cooled  so  as  to  approximate  to  the  ordinary  temperature, 
a  little  over  30  metres  per  second.  For  observations  on  man  the 
contraction  curves  of  the  flexors  of  one  of  the  fingers  or  of  the 
thumb  may  be  recorded,  first  with  stimulation  of  the  brachial  plexus 
at  the  axilla,  and  then  with  stimulation  of  the  median  or  ulnar 
nerve  at  the  elbow.  Probably  at  the  same  temperature  there  is 
little  difference  in  the  rate  of  transmission  in  the  nerves  of  warm- 
blooded and  cold-blooded  animals,  but  temperature  has  a  con- 
siderable influence  (p.  782). 

By  cooling  a  frog's  nerve  Helmholtz  reduced  the  rate  to  y^y  of  its  value 
at  the  ordinary  temperature.  In  the  human  arm  he  found  a  variation 
from  30  to  90  metres  per  second,  according  to  the  temperature,  50  metres 


794  N/ii?  VE 

being  about  the  normal  rate.  This  is  greater  than  the  speed  of  the 
fastest  train  in  the  world.  According  to  Piper's  recent  measiireiiients 
the  velocity  in  human  mediillated  nerve  is  even  greater  than  Helmiioltz 
concluded,  about  120  metres  a  second  under  ordinary  condition.?.  The 
rate  is  independent  of  the  intensity  of  the  excitation.  The  velocity 
with  which  the  negative  variation  is  propagated  (p.  824)  is  the  same  as 
that  of  the  nerve-impulse. 

In  sensory  nerves  there  is  no  reason  to  believe  that  the  velocity  of  the 
nerve-impulse  difters  from  that  in  motor  nerves,  but  experiments  on 
man  really  free  from  objection  are  as  yet  wanting. 

The  usual  method  is  to  stimulate  the  skin  first  at  a  point  distant  from 
the  brain,  and  then  at  a  much  nearer  point.  The  person  experimented 
on,  as  soon  as  he  feels  the  stimulation,  makes  a  signal,  say,  by  closing 
or  opening  with  the  hand  a  current  connected  with  an  electric  time- 
marker,  writing  on  a  moving  surface.  There  is,  of  course,  a  measurable 
interval  between  the  excitation  and  the  signal,  and  this  being  in  general 
longer  the  more  remote  the  point  of  stimulation  is  from  the  brain,  it  is 
assumed  that  the  excess  represents  the  time  taken  by  the  nerve-impulse 
to  pass  over  a  length  of  sensory  nerve  equal  to  the  difference  in  the 
length  of  the  path.  But  there  is  this  difficulty,  that  the  propagation 
of  the  impulse  from  the  point  of  stimulation  to  the  brain  is  only  one 
link  in  the  chain  of  events  of  which  the  signal  marks  the  end.  The 
impulse  has  first  to  be  transformed  into  a  sensation,  and  then  the  will 
has  to  be  called  into  action,  and  an  impulse  sent  down  the  motor  nerves 
to  the  hand.  And  while  the  time  taken  by  the  excitation  in  travelling 
up  and  down  the  peripheral  nerve-fibres  is  probably  fairly  constant,  the 
time  spent  in  the  intermediate  psychical  processes  is  very  variable. 


Section  II. — Chemistry,  Degeneration,  and  Regeneration  of 

Nerve. 

Chemistry  of  Nerve. — Our  knowledge  of  this  subject  is  still  scanty; 
and  most  of  what  we  do  know  has  been  obtained  from  analyses, 
not  of  the  peripheral  nerves,  but  of  the  white  matter  of  the  central 
nervous  system 

Proteins  are  present,  especially  in  the  axis-cylinder.  The  proteins  of 
nervous  tissue  include  two  globulins,  one  coagulated  by  heat  at  47°  C, 
the  other  at  70°  to  75°  C,  and  a  nuclco-protein  coagulating  at  56**  to 
60°  C. 

Very  important  constituents  are  certain  substances  soluble  in  organic 
solvents,  like  benzol  and  ether,  and  comprising  cholesterin,  certain 
phosphatides  {kephalin  and  lecithin),  and  certain  cerebri )is  or  cerebrosides. 
The  cerebrins  are  glucosides  containing  nitrogen,  but  no  phosphorus, 
and  they  yield  a  reducing  sugar  (galactose)  on  hydrolysis.  In  the 
nervous  tissue  there  is  also  present,  according  to  some  authorities,  a 
compound  called  protagon.  Others  consider  it  a  mere  mixture  of  phos- 
phatides and  cerebrosides.  The  lipoids  of  nerve-fibres  belong  largely  to 
the  medullary  sheath,  but  they  are  not  confined  to  it,  since  non-medul- 
lated  nerves  also  yield  a  considerable  quantity  of  lipoids  (ii"5  per  cent, 
of  the  solids  as  against  46'6  per  cent,  for  medullatcd  nerves).  Non- 
medullated  nerves  (splenic  nerves  of  the  ox)  are  distinguished  from 
meduUated  nerves  (human  sciatic)  by  the  high  proportion  of  their  total 
lipoids  constituted  by  the  phosphatides  (kephalin  and  lecithin)  and 
cholesterin.     Thus,  in  non-meduUated  fibres  47  per  cent,  of  the  lipoid 


CHEMISTRY  OF  NERVE  795 

extract  consisted  of  cholcstcrin,  and  23*7  per  cent,  of  kephalin;  while 
in  the  mcdulhited  fibres  cholcstcrin  made  up  only  25  per  cent,  of  the 
extract,  and  kephalin  12*4  per  cent.  On  the  other  hand,  the  cere- 
brosides  arc  present,  both  relatively  and  absolutely,  in  much  larger 
quantity  in  medullated  than  in  non-medullatcd  nerves.  In  both 
varieties  of  fibres  kephalin,  and  not  lecithin,  is  the  chief  phosphorus- 
containing  body  (Falk).  The  medullary  sheath  further  contains  a 
kind  of  network  of  a  peculiar  resistant  substance,  neurokeratin.  The 
netcr ilem ma  consists  oi  substances  insoluble  in  dilute  sodium  hydroxide. 
Gelatin  is  obtained  from  the  connective  tissue  which  binds  the  nerve- 
fibres  together.  There  may  also  be  ordinary  fat  in  the  meshes  of  the 
epineurium  connecting  the  bundles.  Small  quantities  of  xanthin, 
hypoxanthin,  and  other  extractives,  can  also  be  obtained  from  nerve. 
According  to  Halliburton's  analyses,  the  water  in  sciatic  nerves  amounts 
to  65'i  per  cent.,  and  the  solids  to  34*9  per  cent.  The  proteins  make  up 
29  per  cent,  of  the  solids. 

For  an  analysis  of  the  white  matter  of  the  brain,  see  Chapter  XVI. 

Nerve-cells  contain  no  potassium,  according  to  Macallum;  and  this 
is  true  both  of  the  dendrites  and  the  axons.  In  medullated  nerves,  how- 
ever, potassium  compounds  are  present  external  to  the  axons,  chiefly  at 
the  nodes  of  Ranvier  (Frontispiece)  and  in  the  neurokeratin  framework 
of  the  sheath. 

The  only  chemical  difference  between  living  and  dead  nervous  tissue 
which  has  been  made  out  with  any  degree  of  certainty  is  that  the  former 
is  neutral  or  faintly  alkaline,  and  the  latter  acid,  in  reaction  to  such 
indicators  as  litmus.  This  is  especially  true  of  the  grey  matter  of  the 
central  nervous  system,  although  the  white  matter  also  is  often  found 
acid.  The  change  of  reaction  is  due  to  the  accumulation  of  lactic  acid. 
Such  a  change  has  not  hitherto  been  clearly  demonstrated  in  peripheral 
nerves,  either  after  death  or  after  prolonged  stimulation.  The  (non- 
medullated)  splenic  nerves  of  the  dog,  even  after  stimulation  for  six 
hours,  never  became  acid  (Halliburton  and  Brodie). 

Degeneration  of  Nerve. — Nerve-fibres  are  '  bound  in  the  bundle 
of  life  '  with  the  nerve-cells  from  which  their  axis-cylinders  arise; 
the  connection  between  cell  and  axon  once  severed,  the  nerve- 
fibre  dies  inevitably.  This  is  an  illustration  of  a  general  law  that 
no  portion  of  a  cell  can  live  once  it  is  separated  from  the  nucleus. 
We  shall  see  later  on  that  changes  also  occur  in  the  nerve-cell  whose 
axon  has  been  divided  from  it,  although  they  are  of  a  different 
nature  (rather  a  slow  atrophy  than  an  acute  degeneration),  and 
do  not  necessarily  lead  to  the  destruction  of  the  cell.  We  must 
regard  the  neuron  not  only  as  a  morphological  unit,  a  single  cell 
from  nucleus  to  remotest  end-brush,  but  also  as  a  functional  and 
nutritive  unit,  the  fortune  of  any  portion  of  which  is  not  in- 
different to  the  rest.  Thus,  when  a  man's  arm  is  amputated  the 
arm  fares  worse  than  the  man,  for  the  arm  dies.  But  the  man  is 
not  unaffected.  He  lives,  but  he  suffers  much  temporary  disturb- 
ance and  some  permanent  loss.  What  is  left  of  him  is  not  quite 
the  same  as  it  was.  The  acute  changes  that  occur  in  severed  nerve- 
fibres  are  most  conveniently  studied  in  the  peripheral  nerves, 
although  essentially  similar  phenomena  take  place  also  in  the  fibres 
of  the  central  nervous  system. 


796 


NERVE 


A  spinal  nerve  is  composed  of  efferent  fibres  whose  cells  of  origin 
are  in  the  grey  matter  of  the  anterior  horn,  and  afferent  fibres 
whose  cells  of  origin  are  in  the  posterior  root  ganglion.  When  such 
a  nerve  is  cut  below  the  junction  of  its  roots,  muscular  paralysis 
and  impairment  of  sensation  at  once  follow  in  the  region  supplied 
by  the  nerve;  but  for  a  time  the  nerve  remains  excitable  to  direct 

stimulation.       The    excitability 
gradually  diminishes,  and  in   a 
few   days    is    completely    gone. 
If  portions  of  the  nerve   distal 
to    the   lesion   are  examined  at 
different  periods  after  section,  a 
remarkable  process  of  degenera- 
tion  (commonly    spoken    of  as 
Wallerian  degeneration)  is  seen 
to  be  going  on.     In  the  medul- 
lated   fibres  this  begins  on  the 
second    or    third    day    with    a 
swelling    of    the    axis-cylinder, 
which  breaks  up  into  detached 
pieces  (fragmentation),  and  as- 
sumes   a   granular   appearance. 
The  medullary  sheath  also  under- 
goes fragmentation  at  the  lines 
of  Lantermann,  and  a  little  later 
separates  into  clumps  and  drop- 
lets of  myelin.    The  nuclei  under 
the  neurilemma  increase  in  size, 
proliferate  by  mitosis,  and  in- 
sinuate themselves  between  the 
fragments     of     the     medullary 
sheath  and  axis-cylinder,  which 
ultimately  disappear,  leaving  the 
nerve- fibre  represented  onl^^  by  a 
kind  of   mummy  of  connective 
tissue,  in  which  the  neurilemma 
with   its    abnormally  numerous 
nuclei    can   still   be   recognized. 
The  fragmentation  of  the  myelin 
sheath  is  not  dependent  upon  the  proliferation  of  the  nuclei,  since  it 
occurs  also  in  nerves  removed  from  the  body  and  kept  under  con- 
ditions in  which  the  nuclei  do  not  proliferate  (Feiss  and  Cramer). 
The  protoplasm  around  the  nuclei  of  the  neurilemma  also  increases  in 
amount,  and  undergoes  other  changes,  which  will  be  more  particularly 
referred  to  in  describing  the  regeneration  of  nerve.    The  degenerative 
process  begins  near  the  cut  end,  and  extends  gradually  to  the  peri- 


Fig-  277. — Degeneration  of  Nerve-Fibres 
after  Section  (Bari<er,  after  Thoma). 
I,  normal  fibre;  II,  degenerating  fibre; 
III,  further  stage  of  degeneration; 
S.  neurilemma;  m,  medullary  sheath; 
A,  axis-cylinder;  L,  Lantcrmann's  line 
or  cleft;  R,  node;  mt,  drops  of  myelin; 
a,  remains  of  axis-cylinder ;  w,  prolifera- 
ting cells  of  neurilemma. 


DEGENERATION  OF  NERVE 


797 


phory,  and  more  rapidly  in  warm-  than  in  cold-blooded  animals.  At 
any  rate,  that  is  the  interpretation  generally  given  to  the  fact  that  at 
a  given  period  after  section  the  changes — especially  the  breaking- 
up  of  the  myelin — are  more  pronounced  near  the  proximal  end  of 
the  peripheral  stump.  In  a  mammal  degeneration  is  far  advanced 
in  a  fortnight,  although  the  last  renmants  of  the  myelin  may  not 
be  absorbed  for  months.  In  the  degenerated  nerve  (cat's  sciatic) 
the  percentage  of  phosphorus  undergoes  a  diminution  from  about 
the  third  day.  About  the  eighth  day  the  loss  of  phosphorus — i.e., 
of  the  phosphatides  (lecithin,  kephalin) — is  markedly  accelerated, 
coinciding  with  the  appearance  of  a  strong  ]\Iarchi*  staining  re- 
action. By  the  twenty-ninth  day  the  degenerated  nerve  is  prac- 
tically devoid  of  phosphorus.  A  progressive  increase  in  the  water 
and  a  diminution  in  the  total 
solids  also  culminate  about  the 
same  time  (Mott  and  Halli- 
burton). In  the  portion  of  the 
nerve-fibre  still  connected  with 
the  nerve-cell  the  degeneration 
only  extends  as  far  back  as  the 
next  node  of  Ranvier,  and  seems 
to  be  due  to  the  direct  effect  of 
the  injury.  In  non-medullated 
fibres,  such  as  the  fibres  arising 
from  the  cells  of  the  superior 
cervical  ganglion  (Tuckett),  the 
degeneration  is  confined  to  the 
axis-cylinders.  It  begins  in 
about  twenty-four  hoiirs  after  section,  and  the  loss  of  excitability 
and  conducti\'ity  is  complete  by  the  fortieth  hour. 

It  follows  from  what  has  been  said  as  to  the  position  of  the  cells 
of  origin  of  the  root  fibres  of  the  spinal  nerves  that  section  of 
the  anterior  root  causes  degeneration  on  the  peripheral,  but  not  on 
the  central  side  of  the  lesion,  f  Only  the  anterior  root  fibres  in  the 
mixed  nerve  degenerate.  Section  of  the  posterior  root  above  the 
ganglion  causes  degeneration  of  the  central  stump,  but  not  of 
the  portion  still  connected  with  the  ganglion,  nor  of  the  posterior 
root  fibres  below  the  ganglion  or  in  the  mixed  nerve.  Section  of 
the  posterior  root  below  the  ganglion  causes  degeneration  of  the 
fibres  of  the  root  below  the  section  and  in  the  mixed  nerve,  but  not 
above  it. 

*  The  chief  constituents  of  Marchi's  solution  are  potassium  bichromate  and 
osmic  acid.  It  stains  meduUated  nerve-fibres  black  in  the  earlier  stages  of 
degeneration. 

t  A  few  fibres  in  the  peripheral  stump  of  the  anterior  root  do  not  degenerate, 
and  a  few  fibres  in  the  central  stump  do.  These  are  the  '  recurrent  fibres,' 
whose  course  is  described  on  p.  892. 


Fig.  278. — Degeneration  of  Spinal  Nerves 
and  their  Roots  after  Section.  The 
shading  shows  the  degenerated  portions. 


798  NERVE 

Regeneration  of  Nerve. — Degeneration  of  nerve  is  followed,  if 
its  divided  ends  are  not  kept  artiticially  apart,  by  a  process  of  re- 
generation, already  distinct  under  favourable  conditions  in  from 
three  to  four  weeks  after  the  section,  and  indeed  in  some  cases 
commencing  as  early  as  the  second  week.  This  consists  in  the 
outgrowth  of  new  axis-cylinders,  in  the  form  of  fine  fibres,  from 
the  ends  of  the  divided  axis-cylinders  of  the  central  stump  of  the 
nerve.  These  push  their  way  into  and  along  the  degenerated 
fibres,  ultimately  acquire  a  medullary  sheath,  and  develop  into 
complete  nerve-fibres,  restoring  first  sensation,  and  later  on  volun- 
tary motion,  to  the  paralyzed  part.  The  process  needs  several 
months  for  its  completion,  even  in  warm-blooded  animals.  It 
takes  place  under  the  influence  of  ths  nucleated  portion  of  the 
neuron  (the  cell-body),  and  is  never  completed  if  the  peripheral 
and  central  portions  of  the  nerve  are  permanently  separated  by  a 
substance  through  which  the  new  axis-cylinders  cannot  grow  or 
]m  a  gap  too  wide  for  them  to  bridge  over.  When  the  cut  ends  of 
me  nerve  are  carefully  sutured  together,  the  conditions  for  com- 
plete and  speedy  regeneration  are  rendered  more  favourable — a 
fact  which  finds  its  application  in  the  surgical  treatment  of  injured 
nerves.  The  cycle  of  chemical  changes  described  in  the  degenerating 
nerve  is  retraced  in  the  reverse  order.  In  the  cat's  sciatic  the 
first  sign  of  the  return  of  the  phosphorus  was  seen  with  the  beginning 
of  the  normal  myelin  reaction  about  the  sixtieth  day  after  section. 
At  the  one-hundredth  day  the  phosphorus  content  was  almost  as 
great  as  that  of  the  normal  nerve  (a  little  under  i  per  cent,  of  the 
solids  for  the  regenerated,  as  compared  with  a  little  over  i  per  cent, 
for  the  normal  nerve). 

It  is  not  as  yet  well  understood  how  the  regenerating  fibres  are 
directed  in  their  growth,  so  that  they  join  their  centres  to  the  appro- 
priate end-organs  without  mistake.  That  they  have  a  high  capacity 
for  finding  their  way  is  indicated  by  the  results  of  cross-suturing 
such  nerves  as  the  median  and  ulnar^ — i.e.,  of  uniting  the  central  end 
of  the  one  with  the  peripheral  end  of  the  other.  Howell  and  Huber 
found  that  after  this  operation  in  the  dog,  both  co-ordinated  volun- 
tary motion  and  sensation  returned  in  large  measure  in  the  parts 
supplied  by  the  nerves.  Here  the  motor  fibres  of  the  median  nerve 
must,  of  course,  have  made  connection  with  muscles  previously 
supplied  by  the  ulnar,  being  guided  to  them  along  the  nerve-sheaths 
of  the  latter.  Doubtless  the  old  nerve-sheaths  serve  to  some 
extent  as  mechanical  guides  by  offering  to  the  new  axons  a  path  of 
least  resistance.  And  when  a  nerve-trunk  containing  motor  and 
sensory  fibres  is  simply  crushed  so  as  to  destroy  all  physiological 
continuity,  but  is  not  cut,  no  distortion  of  the  motor  and  sensory 
'  patterns  '  of  the  nerve — in  other  words,  no  '  straying  '  of  the  fibres 
from  their  old  paths — can  be  detected  on  regeneration.     When  the 


REGENERATION  OF  NERVE 


799 


nerve  is  cut  and  then  sutured,  a  certain  amount  of  distortion  of  the 
pattern  is  inevitable.  The  mechanical  apposition  of  central  and 
peripheral  stumps  is,  of  course,  much  more  nearly  perfect  in  the 
crushed  nerve  than  in  the  cut  nerve,  however  exact  the  suturing 
may  be  (Osborne  and 
Kilvington).  Yet,  even 
after  crusiiing  or  liga- 
tion of  nerves,  or  after 
section  and  suturing, 
the  regenerating  fibres 
do  not  pass  straight 
through  the  scar  tissue 
from  the  central  to  the 
peripheral  stump,  but 
cross  and  mingle,  ap- 
parently in  the  most 
inextricable  confusion 
(Feiss)  (Fig.  279).  This 
is  due  to  the  prolifera- 
tion of  cells  in  the  scar 
which  run  in  all  direc- 
tions, and  show  no 
signs  of  following  the 
parallel  arrangement  of  the  nerve-sheaths  in  the  central  or  the 
distal  segment.  These  being  formed  before  the  regenerating 
nerve-fibres,  the  latter  must  necessarily  grow  also  in  all  direc- 
tions   in    the    scar. 


Fig.  279. — Regenerating  Fibres  crossing  in  the  Scar 
after  Ligation  of  a  Dog's  Sciatic  Nerve  165  Days 
previously.  Weigert-Pal  stain.  Drawn  under  oil- 
immersion  (Feiss). 


^nl^foglileal 


# 


Nturomu.'^ 


This,  however,  is  a 
local    phenomenon. 
Beyond  the  scar  the 
arrangement  of  the 
regenerating  axis- 
cylinders     recovers 
its   regularity,    and 
the  amount  of  dis- 
tortion of  the  nerve 
pattern,  as  indicated 
by   histological   ex- 
amination   and 
functional  tests,    is 
by     no     means     so 
great   as   the   com- 
plete effacement  of  the  pattern  in  the  scar  might  appear  to  promise. 
That  the  degenerated  peripheral  stump  directs  the  growth  of 
the  axons  from  the  central  stump  in  some  other  than  a  merely 
mechanical  way  is  evident  from  the  experiments  of  Langley  on 


EP- 


Fig.  280. — Semidiagrammatic  Representation  of  Longi- 
tudinal Section  through  Neuroma  or  Scar  produced  by 
ligating  the  Sciatic  Nerve  with  Catgut,  and  crushing  it 
with  a  haemostat  just  above  its  Division  into  the  Ex- 
ternal and  Internal  Popliteal  Nerves.  Weigert-Pal 
preparation  (Feiss). 


8oo  NERVE 

regeneration  of  the  cervical  sympathetic  in  the  cat  after  section 
below  the  superior  cervical  ganglion.  The  nerve  contains  fibres 
of  various  functions  which  reach  it  from  the  upper  thoracic  nerves. 
The  anterior  roots  of  the  first  and  third  thoracic  nerves  supply  the 
cervical  sympathetic  mainly  with  fibres  which  end  in  the  ganglion 
around  cells  that  give  off  dilator  fibres  for  the  pupil.  The  fibres 
connected  with  the  cells  in  the  ganglion  which  send  vaso-motor 
fibres  to  the  vessels  of  the  ear  are  for  the  most  part  contained  in 
the  anterior  roots  of  the  second  and  fifth  thoracic  nerves;  and  the 
fibres  connected  with  the  cells  that  give  origin  to  the  pilo-motor 
fibres  for  the  hairs  of  the  face  and  neck  in  the  anterior  roots  of  the 
fourth  to  the  seventh.  Stimulation  of  any  one  of  the  upper  thoracic 
roots  accordingly  causes  a  specific  effect,  which,  according  to 
Langley,  is  in  general  the  same  after  regeneration  as  before  section 
of  the  cervical  sympathetic.  We  must  assume,  therefore,  that  each 
regenerating  fibre  seeks  out  either  the  ganglion  cell  with  which  it 
was  originally  connected,  or  one  belonging  to  the  same  class.  No 
mere  mechanical  guidance  of  the  growing  axons  by  the  old  neuri- 
lemmas will  suffice  to  explam  this  selective  growth.  It  is  necessary 
to  postulate,  in  addition,  an  attraction  of  a  chemical  or  physico- 
chemical  nature  (chemiotaxis),  dependent  upon  a  specific  relation 
between  the  new  axons  and  the  scaffolding  of  the  peripheral  stump 
or  the  ganglion  cells.  But  it  is  not  possible  at  present  to  form  any 
very  precise  conception  of  the  properties  on  which  the  chemiotactic 
phenomena  depend.  And  the  specificity  is  not  an  absolute  one. 
Under  certain  conditions  these  pre-ganglionic  nerve-fibres  (that  is 
to  say,  nerve-fibres  running  from  the  spinal  cord  to  end  around  the 
sympathetic  ganglion  cells)  can  form  connections  with  nerve-cells 
of  a  different  class — e.g.,  pupillo-dilators  with  cells  whose  axons 
end  in  the  erector  muscles  of  the  hairs.  Further,  after  section  of 
the  sympathetic  above  the  superior  cervical  ganghon,  the  post- 
ganglionic nerve-fibres  {i.e.,  the  fibres  coming  off  from  the  cells  of 
the  ganghon)  may  also,  if  the  opportunity  be  favourable  during 
regeneration,  exchange  their  old  end-organs  for  new  ones;  pilo- 
motor fibres,  for  instance,  finding  their  way  into  the  iris  and  becoming 
pupillo-dilators.  After  excision  of  the  superior  cervical  ganglion, 
the  cervical  sympathetic  does  not  recover  its  function.  Accordingly 
the  pre-ganglionic  fibres  cannot  form  direct  functional  connection 
with  the  post-ganglionic  fibres,  but  can  become  connected  with 
them  only  indirectly  through  the  ganglion  cells.  Nor  can  efferent 
post-ganglionic  fibres  achieve  regenerative  union  with  a  cerebro- 
spinal (somatic)  motor  nerve,  although  they  can  themselves  re- 
generate, as  has  been  shown,  e.g.,  in  the  case  of  the  vaso-constrictors 
of  the  limbs.  On  the  other  hand,  union  easily  takes  place  between 
pre-ganglionic  fibres  and  efferent  somatic  fibres,  and  vice  versa. 
For  example,  the  cervical  sympathetic  can  unite  with  the  phrenic 


RnGENERATinN  OF  NEUVE  Soi 

norve,  and  cause  contraction  of  the  diaphragm,  or  with  the  iccunent 
laryngeal  nerve,  and  cause  movement  of  the  vocal  cords,  or  with 
the  spinal  accessory,  and  cause  contraction  of  the  sterno- mastoid 
muscle.  Conversely,  the  j^hrenic  nerve,  when  united  wit  h  the  cer- 
vical sympathetic,  can,  when  stimulated,  produce  the  usual  effects 
observed  on  exciting  the  latter  nerve  (I.angley  and  Anderson). 

Central  and  Autogenetic  Theories  of  Regeneration. — Although 
the  establishment  of  connection  with  tlie  central  end  of  the 
cut  nerve  is  necessary  for  complete  regeneration,  it  must  not 
be  supposed  that  no  share  wliatever  is  taken  in  the  process  by 
the  peripheral  stump.  Even  while  it  remains  completely  isolated 
from  the  central  nervous  system,  changes  occur  which  are  often 
described  as  the  third  or  final  stage  of  degeneration,  but  which  are 
more  correctly  interpreted  as  forming  a  stage  in  the  regenerative 
cycle.  Spindle-shaped  cells  or  fibres  with  elongated  nuclei  make 
their  appearance,  produced  by  the  proliferation  of  the  nuclei  of  the 
primitive  sheath  already  described,  and  the  increase  of  the  proto- 
plasm in  which  these  nuclei  are  embedded.  These  so-called  axial 
strand  fibres  or  this  fibrillated  protoplasm  may  appear  long  before 
the  remains  of  the  degenerated  axis-cylinder  and  myehn  sheath 
have  been  completely  removed.  It  is  generally  acknowledged  that 
in  the  adult  they  do  not  develop  beyond  this,  so  long  as  the  peri- 
pheral portion  of  the  nerve  remains  completely  isolated,  but  neither 
do  thty  disappear  even  after  a  very  long  interval.  When  strict 
precautions  against  union  with  other  nerve-trunks  were  taken,  the 
radial  nerve  of  an  adult  cat  was  found  in  this  resting-stage  nearly 
a  year  and  a  half  after  division,  and  the  same  was  true  after  two 
years  and  a  half  in  a  nerve  divided  in  a  human  being.  The  fibres 
are  incapable  of  being  excited  or  of  conducting  nerve  impulses. 
The  precise  relation  between  these  axial  strand  fibres  of  the  peri- 
pheral stump  and  the  myelinated  fibres  found  there  after  regenera- 
tion has  been  much  debated.  All  are  agreed  that  nerve- fibrils 
sprout  from  the  central  stump,  and  the  weight  of  evidence  is  in 
favour  of  the  long-accepted  view  that  it  is  by  the  growth  of  these 
fibrils  along  the  peripheral  stump  that  the  new  axons  are  formed, 
and  that  all  the  changes  in  the  distal  portion  of  the  nerve,  however 
important  for  directing  and  perhaps  sustaining  the  growth  of  the 
central  fibrils,  are  subsidiary  to  this.  But  some  maintain  that  the 
outgrowing  central  fibrils  meet  and  unite  with  corresponding  fibrils 
sprouting  from  the  peripheral  stump,  and  that  the  new  axis- 
cylinders  arise  from  the  fibrils  of  the  axial  strand.  It  is  said  that 
very  shortly  after  being  brought  into  connection  with  the  central 
portion  of  the  same  or  of  another  nerve  by  careful  suturing  the 
spindle  cells  begin  to  lengthen,  and  form  non-medullated  fibres, 
like  those  of  the  sympathetic.  Four  weeks  after  union  the  afferent 
fibres,  although  still  non-medullated,  are  capable  of  being  stimulated 

51 


8o2  NERVE 

meclianically  and  iltrtrically,  and  of  conducting  ini])iilscs  towards 
t'v  centre,  in  about  eight  weeks  they  become  nirdullated,  but  at 
fust  are  of  small  calibre  (Head  and  I  lam).  Bethe,  the  most  strenuous 
defender  of  the  inherent  regenerative  power  of  the  isolated  peri- 
pheral stump  (autogenetic  theory),  has  even  stated  that  complete 
regeneration  occurs  in  young  animals  in  nerves  entirely  separated 
from  their  centres.  There  is  no  doubt  that  this  result  is  due  to 
st)me  error  of  technique  or  of  interpretation.  The  controversy 
turns  largely  upon  the  precautions  judged  necessary  to  prevent  the 
ingrowth  of  central  fibres.  And  while  it  is  comparatively  easy  to 
make  sure,  by  removing  a  large  part  of  it,  that  the  central  end  of 
the  nerve  under  observation  shall  remain  completely  unconnected 
with  the  peripheral  end,  it  is  often  a  matter  of  the  greatest  difftculty 
to  prevent  tlic  union  of  the  distal  stump  with  central  fibres  from 
other  sources — e.g.,  from  the  nerves  cut  in  the  wound.  Many  of  the 
results  which  seemed  to  favour  the  autogenetic  theory  were  cer- 
tainly due  to  this  cause. 

The  most  conclusive  evidence  in  favour  of  central  and  against 
autogenetic  regeneration,  because  the  most  direct  and  uncompli- 
catecl.  has  been  afforded  by  the  demonstration  that  the  development 
of  axis-cylinders  occurs  in  vitro  in  a  suitable  plasmatic  medium,  in 
the  absence  of  any  other  elements  than  the  nerve-cells  from  which 
they  arise  (Harrison).  This  observer,  working  with  the  medullary 
plates  of  tadpoles,  in  which  the  nerve-cells  originate  in  the  embryo, 
showed  further  that  peripheral  nerves  do  not  develop  when  the 
nerve-centres  are  removed,  and  that  the  sheath-cells  of  Schwann  are 
not  essential  to  the  growth  of  axis-cylinders,  since  in  their  absence 
the  latter  continue  to  grow  and  reach  their  normal  length.  It  has 
also  been  proved  that  nerve-fibres  grow  out  from  pieces  of  the  cere- 
bellum and  spinal  ganglia  (Fig.  281)  of  young  mammals  when  cul- 
tivated on  clotted  plasma  outside  of  the  body  (Fig.  337,  p.  857). 
Many  fibres  sprouting  out  from  the  spinal  ganglia  attain  a  length  of 
more  than  half  a  millimetre  in  forty-eight  hours,  and  their  growlh 
need  not  be  accompanied  by  either  neuroglia  or  connective  tissue. 
When  portions  of  normal  peripheral  ner\-e  are  incubated  in  plasma 
no  growth  of  axis  cvlinders  is  ever  observed,  nor  does  the  \\'allerian 
degeneration  occurring  in  peripheral  nerves  incubated  in  Ringer's 
solution  take  place  (F'g.  282).  On  the  other  hand,  if  nerves  in  which 
Wallerian  degeneration  has  been  produced  by  section  are  placed  in 
plasma  on  the  fifth  day  after  section  or  later,  growth  of  the  elements 
of  the  sheath  of  Schwann  may  be  seen,  again  unaccompanied  by  any 
growth  of  axis  cylinders  (Ingebrigtsen). 

A  fact  of  great  physiological  interest,  and  also  of  practical  impor- 
tance, in  connection  with  the  anastomosis  of  nerves  for  tlic  relief  of 
certain  forms  of  paralysis,  is  the  bifurcation  of  axons  in  regeneration, 
wluMi  the  conditions  arc  such  that  the  axons  of  the  central  stump  are 
oticrcd  more  than  one  path  along  which  to  regenerate.  If.  for  instance, 
a  limb  nerve-trunk  containing  motor  fibres  is  cut,  and  its  central  end 


REGEWEHATfOS  OF  NERVE 


803 


Sutured  both  to  its  own  ilistal  end  and  to  the  distal  end  of  an  adjacent 
ner\e-tnink,  the  sum  of  the  nerve-fibres  in  the  two  distal  trunks  after 
regeneration  has  occurred  is  greater  than  the  numlK-r  of  fibres  in  the 
central  stump  ^Kilvington).     That  this  is  due  to  splitting  of  axons  is 


Fig.   281.— Two-day-old  Culture  of  Spinal  Ganglia  of  a  Guinea  Pig  Six  Days  Old 

(Ingebrigtseu).  ^ 


Fig.  282. — Microphotograph  of  Nerve  Fibres  from  the  Sciatic  Nerve  of  a  Rabbit, 
incubated  in  Plasma  for  Twelve  Days.  Hardened  in  formalin  and  stained 
with  hematoxylin.     No  trace  of  Wallerian  degeneration  (Ingebrigtsen). 

shown  by  the  fact  that  an  axon  reflex  (p.  913)  can  be  elicited  on  dividing 
one  of  the  distal  trunks  and  stimulating  its  central  end  after  complete 
separation  of  the  proximal  or  parent  stem  from  the  central  nervous 
system.  Even  when  the  second  path  offered  to  the  regenerating  motor 
axon  is  a  sensory  path,  bifurcation  of  the  axon  occurs,  one  branch 


So4  NERVE 

passing  down  along  tlic  previous  motor  path  to  its  proper  muscular 
termination,  and  the  other  passing  down  the  sensory  jjath.  Although 
there  is  no  evidence  that  etierent  fibres  can  unite  with  alferent  fibres,  a 
degenerated  atterent  path  can  therefore  serve  as  a  cheniiotactic  scaffold- 
ing or  guide  for  the  growth  of  regenerating  motor  axons,  though  not 
such  an  efficient  one  as  a  degenerated  motor  path.  Sensory  fibres, 
however,  cannot  regenerate  along  motor  paths  or  make  functional  union 
with  the  receptive  substance  of  skeletal  muscle. 

Regeneration  of  the  fibres  of  the  central  nervous  system  either  does  not 
in  general  occur,  or  is  exceedingly  difficult  to  realize.  This  lends  support 
to  the  doctrine  of  the  importance  of  the  neurilemma  in  regeneration, 
since  its  elements  are  scantily  developed  in  the  fibres  of  the  brain  and 
cord  (p.  Sflo).  Kegeneration  of  the  fibres  which  proceed  from  the  cells  of 
the  spinal  ganglia  along  the  posterior  roots  into  the  cord  may  take  place 
after  the  roots  have  been  cut,  so  that  the  normal  reflexes  through  the  res- 
piratory, cardiac,  and  vaso-motor  centres  may  be  once  more  obtained. 

Degeneration  of  Muscle. — Experimental  section  or,  in  man, 
traumatic  division  or  compression  of  a  nerve  leads  not  only  to  its 
degeneration,  but  ultimately,  if  regeneration  of  the  nerve  does  not 
take  place,  to  degeneration  of  the  muscles  supplied  by  it  as  well. 
The  muscle- fibres  dwindle  to  a  quarter  of  their  normal  diameter; 
the  stripes  disappear;  the  longitudinal  fibrillation  fades  out;  and  at 
length  only  hyaline  moulds  of  the  fibres  are  left,  filled,  and  separated 
by  fatty  granules  and  globules  and  surrounded  by  engorged  capil- 
laries. Amidst  the  general  decay,  the  muscular  fibres  of  the 
tciminal  '  spindles  '  with  which  the  afferent  nerves  of  muscles  are 
coimected  alone  remain  unchanged  (Sherrington).  Certain  dis- 
eases of  the  cord  which  interfere  with  the  cells  of  the  anterior  horn 
cause  degeneration  of  motor  nerves,  and  ultimately  of  muscles. 
The  motor  nerve-endings  degenerate  sooner  than  the  sensory. 
Both  may,  under  suitable  conditions,  regenerate  (Huber). 

Reaction  of  Degeneration. — Muscles  whose  motor  nerves  have  been 
separated  from  their  trophic  centres  show,  when  a  certain  stage  in 
degeneration  has  been  reached,  a  peculiar  behaviour  to  electrical 
stimulation,  called  the  '  reaction  of  degeneration.'  To  the  constant 
current  the  muscles  are  more  excitable,  and  the  contraction  slower  and 
more  prolonged  than  normal.  When  a  current,  either  constant  or 
induced,  is  passed  through  a  normal  muscle,  the  muscular  fibres  may  be 
stinuilated  either  directly,  or  indirectly  through  the  intramuscular 
nerves.  Under  ordinary  conditions  the  nerves  respond  more  readily 
than  the  muscular  fibres,  especially  to  momentary  stimuli  like  induction 
shocks,  and  therefore  the  so-called  direct  stimulation  of  uncurarized 
muscle  is  as  a  rule  an  indirect  stimulation.  When  the  muscle  is 
curarized  and  the  nerves  thus  eliminated,  the  excitability  to  induced 
currents  is  found  to  be  diminished.  The  same  is  the  case  in  a  muscle 
which  exhibits  the  reaction  of  degeneration  after  section  of  its  motor 
nerve,  only  the  loss  of  excitability  to  induced  currents  is  greater,  and 
may  even  be  complete.  The  common  statement  that  the  closing  anodic 
contraction  is  stronger  than  the  closing  kathodic — the  opposite  ot  the 
ordinary  law — is  subject  to  so  many  exceptions  that  it  has  no  diagnostic 
value.  The  nerves  are  inexcitable  either  to  constant  or  induced 
currents.  The  reaction  of  degeneration  is  only  obtained  from  paralyzed 
muscles  when  the  paralyzing  lesion  is  situated  in  the  cells  of  the  arterior 


TROPHIC  NERVES  805 

horn  from  which  the  motor  nerves  take  origin,  or  below  that  level. 
Accordingly,  it  is  sometimes  of  use  in  localizing  the  position  of  a  lesion. 
For  instance,  a  group  of  muscles  might  be  paralyzed  by  a  lesion  in  the 
grey  matter  of  the  brain  or  in  the  nerve-fibres  connecting  this  with  the 
grey  matter  of  the  anterior  horn  of  the  cord,  or  in  the  grey  matter  of 
the  anterior  horn  itself,  or  in  the  peripheral  nerve-fibres  leading  from 
this  to  the  muscles.  In  the  first  two  cases  the  reaction  of  degeneration 
would  be  absent,  although  the  muscles,  if  the  lesion  was  of  long  standing, 
would  be  atrophied  to  some  extent;  in  the  last  two  there  would  be  acute 
atrophy  of  the  muscles,  and  the  reaction  of  degeneration  would  be 
obtained. 

Trophic  Nerves. — There  is  no  question  that  nerves  exert  a  very 
important  inlluence  upon  the  nutrition  of  the  parts  supplied  by 
them,  in  influencing  the  specific  function  of  those  parts.  So  that 
in  this  sense  all  nerves  arc  trophic  nerves.  The  fact  that  the  proper 
nutrition  of  nerve-fibres  and  striated  muscular  fibres  is  dependent 
on  their  connection  with  nerve-cells  has  been  by  some  writers 
generalized  into  the  doctrine  that  all  tissues  are  provided  with 
'  trophic  '  nerves,  which,  apart  from  any  influence  of  functional 
activity,  regulate  the  nutrition  of  the  organs  they  supply.  But  the 
evidence  for  this  view,  when  weighed  in  the  balance,  is  found 
wanting;  and  it  may  be  said  that  up  to  the  present  no  unequivocal 
proof,  experimental  or  clinical,  has  ever  been  given  of  the  existence  of 
specific  trophic  fibres,  anatomically  distinct  from  other  efferent  or 
aff'erent  nerves. 

It  is  true  that  in  various  diseases  and  injuries  of  the  nervous  .system 
nutritive  changes  in  the  skin,  and  sometimes  in  the  bones  and  joints, 
are  apt  to  appear.  But  it  is  very  difficult  in  such  cases  to  disentangle 
the  effects  produced  by  accidental  injuries  acting  on  structures  whose 
normal  sensibility  is  lost  or  lessened,  or  whose  circulation  is  deranged, 
from  true  trophic  changes.  The  most  that  can  be  said  is  that  there  is 
some  evidence  that  the  power  of  the  skin  to  resist  injur)^  and  the 
capacity  of  recovering  from  it,  are  diminished  by  interference  with  its 
nerve-supply,  so  that  a  large  sore  may  result  from  a  trifling  lesion,  and 
healing  may  be  slow  and  difficult.  Experimentally  it  has  been  found 
that  division  of  the  trigeminus  nerve  within  the  skull  is  sometimes 
followed  by  cloudiness  of  the  cornea,  going  on  to  ulceration,  and  ulti- 
mately inflammation  and  destruction  of  the  eyeball.  Ulcers  also  form 
on  the  lips  and  on  the  mucous  membrane  of  the  mouth  and  gums;  and 
the  nasal  mucous  membrane  on  the  side  corresponding  to  the  divided 
nerve  becomes  inflamed.  But  in  this  case  the  sensibility  of  the  eye  is 
lost,  and  reflex  closure  of  the  eyelids  ceases  to  prevent  the  entrance  of 
foreign  bodies.  The  animal  is  no  longer  aware  of  the  contact  of  particle.s 
of  dust  or  bits  of  straw  or  accumulated  secretion  with  the  conjunctiva, 
and  makes  no  effort  to  remove  them.  The  lips,  being  also  without 
sensation,  are  hurt  by  the  teeth,  particularly-  as  the  muscles  of  mastica- 
tion on  the  side  of  the  divided  nerve  are  paralyzed,  and  decomposed 
food,  collecting  in  the  mouth,  and  inhaled  dust  in  the  nose,  will  tend 
still  further  to  irritate  the  mucous  membranes.  There  is  thus  no  more 
need  to  assume  the  loss  of  unknown  trophic  influences  in  order  to 
explain  the  occurrence  of  the  ulcerative  changes  than  there  is  to 
explain  the  production  of  ordinary^  bed-sores,  bunions  or  corns  on  parts 
peculiarly  liable  to  pressure.     And,  as  a  matter  of  fact,  if  the  eye  be 


8o6  NERVE 

artificially  protected,  after  section  of  the  trigeminal  nerve,  the 
ophtlialmia  either  does  not  occur  or  is  much  delayed. 

In  man,  too,  a  case  has  been  recorded  in  which  both  the  fifth  and 
the  third  nerves  were  paralyzed.  The  eye  was  still  shielded  by  the 
contraction  of  the  orbicularis  oculi  supplied  by  the  seventh  nerve,  as 
well  as  by  the  drooping  of  the  upper  eyelid  that  accompanies  paralysis 
of  the  third.  It  remained  perfectly  sound  for  many  months,  till  at 
length  the  tumour  at  the  base  of  the  brain  which  had  affected  the  other 
nerves  involved  the  seventh  too.  The  eye  was  now  no  longer  com- 
pletely closed;  inflammation  came  on,  and  vision  was  soon  permanently 
lost  (Shaw).  In  another  case  a  patient  lived  for  seven  years  with 
complete  paralysis  of  the  fifth  nerve,  yet  the  eye  remained  free  from 
disease  and  sight  was  unimpaired  (Gowers). 

The  so-called  '  trophic  '  effects  following  division  of  both  vagi  we 
have  already  discussed  (p.  286)  so  far  as  they  are  concerned  with  the 
respiratory  system.  The  degenerative  changes  sometimes  seen  in  the 
heart  are  perhaps  due  to  its  being  overworked  in  the  absence  of  nervous 
restraint  on  its  functional  activity.  The  nutritive  alterations  in 
muscles  and  salivary  glands  after  section  of  motor  and  secretory  nerves 
seem  to  depend  in  part  on  functional  and  vaso-motor  changes.  In  the 
paralyzed  muscles  nutrition  is  not  only  interfered  with  in  consequence 
of  their  inactivity,  as  would  be  the  case  even  if  the  paralysis  wers  due 
to  a  lesion  above  the  level  of  the  anterior  cornual  cells,  but  the  already 
poorly  nourished  fibres  are  continually  pressed  upon  by  the  capillaries, 
which  are  dilated  owing  to  the  division  of  the  vaso-motor  nerves.  The 
degeneration  may  also  be  in  part  ascribed  to  the  loss  of  a  reflex  tonic 
influence  exerted  on  the  muscles  by  the  spinal  cord,  through  the 
ordinary  motor  nerves  (p.  917).  When  all  allowance  has  been  made  for 
these  factors,  the  rapid  and  characteristic  degeneration  of  the  striated 
muscles,  after  their  connection  with  the  central  nervous  system  is 
severed,  is  still  inexplicable,  except  on  the  assumption  that  their 
nutrition  is  specially  related  to  the  integrity  of  their  efferent  nerves. 
In  other  words,  it  is  necessary  to  suppose,  not,  indeed,  that  distinct 
trophic  nerves  exist  for  the  muscles,  but  that  an  influence  or  impulses, 
which  can  be  termed  trophic  or  nutritive,  do  normally  pass  out  to  them 
from  the  spinal  cord  along  their  motor  nerves. 

Section  of  the  cervical  sympathetic  in  young  rabbits  and  dogs  increases 
the  growth  of  the  ear  and  of  the  hair  on  the  same  side.  But  it  is 
impossible  to  separate  these  consequences  from  the  vaso-motor  paral- 
ysis; and  the  same  is  true  of  the  hypertrophy  following  section  of  the 
vaso-motor  nerves  of  the  cock's  comb  and  of  the  nerves  of  the  bones. 
After  section  of  the  superior  laryngeal  the  vocal  cord  on  the  side  of  the 
section  is  at  once  rendered  motionless,  and  remains  so,  but  the  muscles, 
notwithstanding  their  inaction,  do  not  degenerate.  And  Mott  and 
Sherrington  have  found  that,  although  section  of  the  posterior  roots  in 
monkeys  is  followed  after  a  time  (three  weeks  to  three  months)  by 
ulceration  over  certain  portions  of  the  foot,  no  corresponding  lesions 
occur  in  the  hand.  They  believe,  therefore,  that  the  lesions  are  not  due 
to  the  withdrawal  of  a  reflex  trophic  tone,  but  are  accidental  injuries 
in  positions  specially  exposed  to  mechanical  or  microbic  insults. 

One  of  the  best  examples  of  interference  with  the  proper  nutrition  of 
a  part  produced  by  a  lesion  in  the  nerves  supplying  it  is  an  eruption 
(herpes  zoster),  limited  to  the  skin  supplied  by  the  nerve-fibres  coming 
from  one  or  more  spinal  ganglia,  and  depending  on  an  (infectious) 
inflammatory  change  in  the  ganglia.  It  has  been  suggested  that  the 
Vehicles  are  formed  either  because  the  pa.ssage  of  afferent  impulses 
normally  concerned  in  the  nutrition  of  the  skin  is  interfered  with  or 


ci..issrrh'.\ Tin\'  nr  ni:rvi:s 


807 


because  the  skin  is  boiul)ar(lcd  by  antidromic  (p.  t8i)  impulses  dis- 
charged irom  tlie  inflamed  gmglia.  But  an  alternative  liypothcsis  is 
that  a  toxine  spreads  out  along  the  nerves  from  the  ganglia,  just  as 
in  traumatic  tetanus  the  toxine  is  known  tf)  pass  in  the  opposite  direc- 
tion along  the  nerves  from  the  scat  of  injury  to  the  central  nervous 
system. 

Classification  of  Nerves. — Omitting  the  group  of '  trophic  '  nerves, 
and  tlie  even  more  problematical '  thermogenic  '  fibres  (which  some 
have  supposed  to  preside  over  the  production  of  heat,  and  therefore 
to'  assist  in  the  regulation  of  the  temperature  of  the  body,  but  of 
whose  existence  as  distinct  and  specific  nerve-fibres  with  no  other 
function  there  is  not  the  slightest  proof),  peripheral  nerves  may  be 
classified  as  follows: 


Centripetal  , 
or    afferent  ^ 
fibres. 


I.  Nerves  of  special  sensation  .  „' 


f  Smell. 
I  Tas 


aste. 


2.   Nerves  of  general  sensation 


3.*  Possibly  nerves  other  than 
those  included  under  i 


and    2,     concerned 
reflex  changes  in 


in 


I  Hearing. 
I  Sight. 
Touch  (light  touch). 
Pressure      (perhaps      in- 
cludmg  the   nerves   of 
muscular  sense). 
Warmth— Cold. 
^  Pain. 

'  Calibre  of  small  arteries 
(pressor,  depressor). 
Action  of  heart. 
Respiratory  movements. 
Visceral  movements. 
Glandular  secretion. 
Ordinary      skeletal 
muscles. 
'  Skeletal  muscles 
Visceral 

Motor  nerves  for     Vascular      , ,       (  Vaso-constrictor 

I  Cardio-augmentor. 
Erector  muscles  of  hairs  (pilo-motor 
fibres). 
f  Visceral  muscles 

2.  Inhibitory  nerves  for  -  f  Vaso-dilator. 
[  Vascular       ,,        -.'  Cardio-inhibi- 

3.  Secretory  nerves  [      tory. 

*  It  is  not  known  whether  the  afferent  portion  of  a  reflex  arc  is  always  com- 
posed of  fibres  included,  in  the  first  two  categories,  although  undoubtedly  in 
some  cases  it  is. 


Centrifugal 

or    efferent 

fibres. 


PRACTICAL  EXERCISES  ON  CHAPTERS  XIII.  AND  XIV. 

I,  Difference  of  Make  and  Break  Shocks  from  an  Induction  Machine. 

— Connect  a  Daniell  or  other  cell  B  (p.  724)  with  the  two  upper  binding- 
screws  of  the  primary  coil  P,  and  interpose  a  spring  kej^  K  in  the  circuit. 
Connect  a  pair  of  electrodes  with  the  binding-screw's  of  the  secondary 
cod  (Fig.  283). 


8o8 


Ml'SCLE  AND  NIIRVE 


Electrode  s  cnn  he  very  simply  made  by  pushing  copper  wires  through 
two  glass  tubes,  filling  the  ends  of  the  tubes  with  sealing-wax  and 
binding  thcni  together  with  waxed  thread.  The  projecting  points  may 
be  filed,  and  the  nerve  laid  directly  on  them,  or  they  may  be  tipped  with 
small  pieces  of  platinum  wire  soldered  on. 

(a)  Push  the  secondary  away  from  the  primary,  until  no  shock  can 
be  felt  on  the  tongue  when  the  current  from  the  battery  is  made  or 
broken  with  the  key.  Then  bring  the  secondary  gradually  up  towards 
the  primary,  testing  at  every  new  position  whether  the  shock  is  per- 
cejitible.  It  will  be  felt  first  at  break.  If  the  secondary  is  pushed  still 
further  up,  a  shock  will  be  felt  both  at  make  and  at  l)reak.  From  this 
we  learn  that  for  sensory  nerves  the  break  shock  is  stronger  than  the 
make.  The  same  can  easily  be  demonstrated  for  motor  nerves  and 
foi  muscle. 

(b)  Smoke  a  drum  and  arrange  a  myograph,  as  shown  in  Fig.  287. 
But  omit  the  brass  piece  F,  and  do  not  connect  the  primary  through 
the  drum,  as  there  sliown,  but  connect  it  as  in  Fig.  283.  Pith  a  frog 
(brain  and  cord),  and  make  a  muscle-nerve  preparation. 

To  make  a  Muscle-Nerve  Preparation. — Hold  the  frog  by  the  hind  legs 
back  upwards;  the  front  part  of  the  body  will  hang  down,  making  an 
angle  with  the  posterior 
portion.  With  strong 
scissors  divide  the  back- 
bone anterior  to  this 
angle,  and  cut  away  all 
the  front  portion  of  the 
body,  which  \vill  fall 
down  of  its  own  weight. 
Make  a  circular  incision 
at  the  level  of  the  tendo 
Achillis,  and  another  at 
the  lower  end  of  tiie 
femur,  through  the  skin. 
The  sciatic  nerve  must 
now  be  dis.sected  out,  as 
follows :  Remove  the 
skin  from  the  thigh ,  and, 
holding  the  leg  in  the 
left  hand,  slit  up  the  fascia  which  connects  the  external  and  internal 
groups  of  muscles  on  the  back  of  the  thigh.  Complete  the  separa- 
tion with  the  two  thumbs.  Cut  through  the  iliac  bone,  taking 
care  that  the  blade  of  the  scissors  is  well  pressed  against  the  bone, 
otherwise  there  is  danger  of  severing  the  sciatic  plexus.  Now  divide 
in  the  middle  line  the  part  of  the  spinal  column  which  remains  above 
the  urostyle.  A  piece  of  bone  is  thus  obtained  by  means  of  which  the 
nerve  can  be  manipulated  without  injury.  Seize  this  piece  of  bone  with 
the  forceps,  and  carefully  free  the  sciatic  plexus  and  nerve  from  their 
attachments  right  down  to  the  gastrocnemius  muscle,  taking  care  not 
to  drag  upon  the  nerve.  The  muscles  of  the  thigh  will  contract,  as  the 
branches  going  to  them  are  cut.  This  is  an  instance  of  mechanical 
stimulation.  Now  pass  a  thread  under  the  tendo  Achillis,  tie  it,  and 
divide  the  tendon  below  it.  Strip  up  the  tube  of  skin  that  covers  the 
gastrocnemius,  as  if  the  finger  of  a  glove  were  being  taken  ofif.  Tear 
through  the  loo.se  connective  tissue  between  the  muscle  and  the  bones 
of  the  leg,  and  divide  the  latter  with  scissors  just  below  the  knee.  Cut 
across  the  thigh  at  its  middle. 

Fix  the  preparation  on  the  cork  plate  of  the  myograph  by  a  pin  passed 


Fig.  283. — Arrangement  of  Coil  for  Single  Shocks. 


PRACTICAL  Kxr.ncisES 


809 


through  the  cartilaginous  lower  end  of  the  fcniur,  and  attach  the 
thread  to  the  upright  arm  of  the  lever  by  one  of  the  holes  in  it.  Hang 
not  far  from  the  axis  by  means  of  a  hook  a  small  leaden  weight  (5  to 
10  grammes)  on  the  arm  of  the  lever  which  carries  the  writing-point, 
and  move  the  myograph  plate  or  the  muscle-nerve  preparation  until 
this  arm  is  just  horizontal.  Fasten  the  electrodes  from  the  secondary 
coil  on  the  cork  plate  with  an  indiarubbcr  band ;  lay  the  nerve  on  them ; 
and  cover  both  muscle  and  nerve  with  an  arch  of  blotting-paper 
moistened  with  physiological  salt  .solution,  taking  care  that  the  blotting- 
paper  does  not  touch  the  thread.  Or  put  the  preparation  in  a  moist 
chamber*  (Fig.  322,  p.  843).     Muscle  troughs  of  various  kinds  may  also 


Fig.  284. — Lucas's  Muscle  Trough.  A,  trough  made  of  hard  rubbsr;  B,  a  hard  rubber 
boss  with  a  hole  drilled  in  it  to  receive  the  pin  which  fastens  the  gastrocnemius 
preparation;  H,  H,  electrodes  cased  in  hard  rubber  except  at  the  ends,  which 
in  the  trough  carry  platinum  wires;  C,  a  brass  plate  mounted  on  one  side  of  the 
trough,  carrying  a  lever  with  a  vertical  arm  F  ending  in  a  hook,  which  is  attached 
by  a  loop  of  thread  to  the  tendon  of  the  preparation;  G,  the  writing  arm  of  the 
lever;  K,  M,  holes  in  G  for  loading  the  muscle.  C  can  be  slid  horizontally  by 
means  of  the  slots  in  it,  and  clamped  by  the  screw  E.  I,  tube  for  running  off 
the  solution. 

be  used,  which  permit  immersion  of  a  muscle  (or  nerve)  in  Ringer's 
solution.  A  convenient  form  is  shown  in  Fig.  284,  but  a  trough  suffi- 
cient for  the  purposes  of  the  student  can  be  easily  impi"ovised  in  any 
laboratory.  Adjust  the  v.'riting-point  to  the  drum.  Begin  with  such 
a  distance  between  the  coils  that  a  break  contraction  is  just  obtained 
on  opening  the  key  in  the  primary  circuit,  but  no  make  contraction. 
The  lever  will  trace  a  vertical  line  on  the  stationary  drum.  Read  off 
on  the  scale  of  the  induction  machine  the  distance  between  the  coils, 
and  mark  this  on  the  drum.  Now  allow  the  drum  to  move  a  little,  still 
keeping  the  writing-point  in  contact  with  it ;  then  push  up  the  secondary 
coil  I  centimetre  nearer  the  primary,  and  close  the  key.     If  there  is  a 

*  Porter's  moist  chamber  is  found  in  many  laboratories,  and  is  very  con- 
venient. It  consists  of  a  porcelain  plate  around  which  runs  a  groove.  A  bell- 
shaped  glass  cover,  which  can  be  lifted  off  at  will,  rests  in  the  groove.  The 
femur  of  the  muscle-nerve  preparation  is  fixed  in  a  small  clamp,  composed 
of  a  split  screw  on  which  moves  a  nut.  By  means  of  the  nut  the  clamp  is 
tightened  on  the  femur.  The  gastrocnemius  hangs  vertically  down,  the  thread 
on  the  tendo  Achillis  passing  through  a  hole  in  the  porcelain  plate  to  a  lever 
separately  supported  on  the  same  stand  as  the  moist  chamber.  A  piece  of 
wet  blotting-paper  fixed  inside  the  cover  keeps  the  air  in  the  chamber  saturated. 


8io  MUSCLE  AND  NERVE 

contraction,  let  the  drum  move  a  little  before  opening  the  key  again, 
so  that  the  lines  corresponding  to  make  and  break  may  be  separated 
from  each  other.  If  there  is  still  no  contraction  at  make,  go  on  moving 
the  secondary  up,  a  centimetre  (or  less)  at  a  time,  till  a  make  con- 
traction appears.  When  the  coils  are  still  further  approximated,  the 
make  may  become  equal  in  height  to  the  break  contraction,  both  being 
maximal — i.e.,  as  great  as  the  muscle  can  give  with  any  single  shock 
(Fig.  2  85)- 

{c)  Attach   a  thin   insulated   copper  wire  to  each  terminal  of  the 
secondary'.     Loop  the  bared  end  of  one  of  the  wires  through  the  tendo 


Fig.  285. —  Contractions  caused  by  Make  and  Break  Shocks  from  an  Induction 
Machine.  M,  make,  B,  break,  contractions.  The  numbers  give  the  distance 
between  the  primary  and  secondary  coils  in  centimetres. 

Achillis,  and  coil  the  other  round  the  pin  in  the  femur,  so  that  the  shocks 
will  pass  through  the  whole  length  of  the  muscle.  Repeat  the  experi- 
ment of  (b),  with  direct  stimulation  of  the  muscle. 

2.  Stimulation  of  Nerve  and  Muscle  by  the  Voltaic  Current. — (a)  Con- 
nect a  Daniell  cell  through  a  kev  with  a  pair  of  electrodes  on  which  the 
nerve  of  a  muscle-nerve  preparation  lies.  Observe  that  the  muscle  con- 
tracts when  the  current  is  closed  or  broken,  but  not  during  its  passage. 


286.  Simple  Rheocord  arranged  to  send  a  Twig  of  a  Current  through  a  .Muscle 
or  Nerve.  B,  battery;  R,  rheocord  wire  (German  silver);  S,  slider  formed  of 
a  short  piece  of  thick  indiarubber  tubing  filled  .vith  mercury;  K,  spring  key; 
NV,  W,  wires  connected  with  electrodes. 


Connect  the  cell  with  a  simple  rheocord,  as  shown  in  Fig.  280,  so  that 
a  twig  of  the  current  of  any  desired  strength  may  be  sent  through  the 
nerve.  As  the  strength  of  the  current  is  decreased  by  moving  the 
slider  S,  it  will  be  found  that  it  first  becomes  impossible  to  obtain  a 
contraction  at  break.  The  current  must  be  still  further  reduced  before 
the  make  contraction  disappears,  for  the  closing  of  a  galvanic  stream 
is  a  stronger  stimulus  than  the  breaking  of  it.     The  break  or  make  con- 


PRACTICAL  EXEIiCISES  8ii 

traction  obtained  by  stimulating  a  ncive  with  an  induction  macliinc 
must  not  be  confused  with  the  break  or  make  contraction  caused  by  the 
voltaic  current.  In  the  case  of  the  induction  machine,  the  break  or 
make  applies  merely  to  what  is  done  in  the  primary  circuit,  not  to  what 
happens  to  the  current  actually  passing  through  the  nerve.  The 
current  induced  in  the  secondary  at  make  of  the  primary  circuit  is,  of 
course,  both  made  and  broken  in  the  nerve — made  when  it  begins  to 
flow,  broken  when  the  flow  is  over;  the  shock  induced  at  break  of  the 
primary  is  also  made  and  broken  in  the  nerve.  And  although  make  and 
break  of  the  actual  stimulating  current  come  very  close  together,  the 
real  make,  here,  too,  is  a  stronger  stimulus  than  the  real  break. 

(6)  Repeat  {a)  with  the  muscle  directly  connected  to  the  cell  by  thin 
copper  wires,  or,  better,  unpolarizable  electrodes  (p.  73 1)- 

3.  Ciliary  Motion. — Cut  away  the  lower  jaw  of  the  same  frog,  and 
place  a  small  piece  of  cork  moistened  with  physiological  salt  solution 
(o'75  per  cent.)  on  the  ciliated  surface  of  the  mucous  membrane  covering 
the  roof  of  the  mouth.  It  will  be  moved  by  the  cilia  down  towards  the 
gullet.  Lay  a  small  rule,  divided  into  millimetres,  over  the  mucous 
membrane,  and  measure  with  a  stop-watch  the  time  the  piece  of  cork 
takes  to  travel  over  10  millimetres.  Then  pour  salt  solution  heated  to 
30°  C.  on  the  ciliary  surface,  rapidly  swab  with  blotting-paper,  and 
repeat  the  observation.  The  piece  of  cork  will  now  be  moved  more 
quickly  than  before,  unless  the  salt  solution  has  been  so  hot  as  to  injure 
the  cilia. 

4.  Direct  Excitability  of  Muscle — Action  of  Curara. — Pith  the  brain 
of  a  frog,  and  prevent  bleeding  by  inserting  a  piece  of  match.  Expose 
the  sciatic  nerve  in  the  thigh  on  one  side.  Carefully  separate  it,  for  a 
length  of  half  an  inch,  from  the  tissues  in  which  it  lies.  Pass  a  strong 
thread  under  the  nerve,  and  tie  it  tightly  round  the  limb,  excluding 
the  nerve.  Now  inject  into  the  dorsal  or  ventral  lymph-sac  a  few  drops 
of  a  I  per  cent,  curara  solution.  As  soon  as  paralysis  is  complete,  make 
two  muscle-nerve  preparations,  isolating  the  sciatic  nerves  right  up  to 
the  vertebral  column.  Lay  their  upper  ends  on  electrodes  and  stimu- 
late; the  muscle  of  the  ligatured  limb  will  contract.  This  proves  that 
the  nerve-trunks  are  not  paralyzed  by  curara,  since  the  poison  has  been 
circulating  in  them  above  the  ligature.  The  muscle  of  the  leg  which 
was  not  ligatured  will  contract  if  it  be  stimulated  directly,  although 
stimulation  of  its  nerve  has  no  effect.  The  ordinary  contractile  sub- 
stance of  the  muscular  fibres,  accordingly,  is  not  paralj-zed.  The  seat 
of  paralysis  must  therefore  be  some  structure  or  substance  physiologic- 
ally intermediate  between  the  nerve-trunk  and  the  general  contractile 
substance  of  the  muscular  fibres  (p.  738). 

3.  Graphic  Record  of  a  Single  Muscular  Contraction  or  Twitch. — Pith 
a  frog  (brain  and  cord),  make  a  muscle-nerve  preparation,  and  arrange 
it  on  the  myograph  plate,  as  in  i  {b).  Lay  the  nerve  on  electrodes 
connected  with  the  secondary  coil  of  an  induction  machine  arranged 
for  single  shocks.  Introduce  a  short-circuiting  key  (Fig.  240,  p.  732) 
between  the  electrodes  and  the  secondary  coil,  and  a  spring  key  in  the 
primary  circuit.  Close  the  short-circuiting  key,  and  then  press  down 
the  spring  key  with  the  finger.  Let  the  drum  off  (fast  speed) ;  the 
writing-point  will  trace  a  horizontal  abscissa  line.  Open  the  short- 
circuiting  key,  and  then  remove  the  finger  from  the  spring  key.  The 
nerve  receives  an  opening  shock,  and  the  muscle  traces  a  curve.  Now 
adjust  the  writing-point  of  an  electrical  tuning-fork  (Fig.  2S7),  vibrating, 
say,  100  times  a  second,  to  the  drum,  and  take  a  time-tracing  below  the 
muscle-curve.  Stop  the  drum,  or  take  off  the  writing-point,  the 
moment  the  time-tracing  has  completed  one  circumference  of  the  drum, 


8l3 


MUSCLE  AND  NLIiVE 


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write  on  it  a  brief  description  of  the  experiment,  with  the  time-vahie  of 


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each  vibration  of  the  fork,  the  date,  and  the  name  of  the  maker  of  the 
tracing,  and  then  varnish  it.  An  exactly  similar  tracing  can  be  obtained 
by  directly  stimulating  the  muscle  (curarized  or  not). 


PRACTICAL  EXERCISES  813 

o.  Influence  of  Temperature  on  the  Muscle-Curve. — Pith  a  frog  (brain 
and  cord),  make  a  muscle-nerve  j)rcparalion,  and  arrange  it  on  a 
myograph.  Lay  the  nerve  on  electrodes  connected  through  a  short- 
circuiting  key  with  the  secondary  coil  of  an  induction  machine,  or 
connect  the  muscle  directly  with  the  key  by  thin  copper  wires.  Take 
a  Diiniell  cell,  connect  one  pole  through  a  simple  key  with  one  of  the 
upper  binding-screws  of  the  primary  coil,  and  the  other  pole  with  the 
metal  of  the  drum.  A  wire,  insulated  from  the  drum,  but  clamped  on 
the  vertical  part  of  its  su})port,  and  with  its  bare  end  projecting  so  as 
to  make  contact  with  a  strip  of  brass  fastened  on  the  spindle,  is  con- 
nected with  the  other  upper  terminal  of  the  primary  (Fig.  28/).  At 
each  revolution  of  tlie  drum  the  primary  circuit  is  made  and  broken 
once  as  the  strip  of  brass  brushes  the  projecting  end  of  the  wire.  The 
object  of  this  ■arrangement  is  to  ensure  that  when  the  writing-point  of 
the  myograph  le\-er  has  been  once  adjusted  to  the  drum,  successive 
stimuli  will  cause  contractions,  the  curves  of  which  all  rise  from  the 
same  point.  Close  the  key  in  the  primary,  set  the  drum  off  (fast  speed), 
open  the  short-circuiting  key,  and  as  soon  as  the  muscle  has  contracted 
once,  close  it  again.  Now  stop  the  drum,  mark  with  a  pencil  the 
position  of  the  feet  of  the  stand  carrying  the  myograph  plate,  take  the 
writing-point  off  the  drum,  and  surround  the  muscle  with  pounded  ice 
or  snow.  After  a  couple  of  minutes  brush  away  any  ice  which  could 
hinder  the  movement  of  the  muscle,  rapidly  replace  the  stand  in  exactly 
its  original  position,  with  the  writing-point  on  the  drum,  and  take 
another  tracing.  Again  take  off  the  writing-point,  and  remove  all 
unmelted  ice  or  snow.  With  a  fine-pointed  pipette  irrigate  the  muscle 
with  physiological  salt  sohation  at  30°  C,  and  quickly  take  another 
tracing.  Then  put  on  a  time-tracing  with  the  electrical  tuning-fork. 
Fig.  255,  p.  748,  shows  a  series  of  curves  obtained  in  this  way. 

7.  Influence  of  Load  on  the  Muscle- Curve. — Arrange  everything  as 
in  6.  Take  a  tracing  first  with  the  lever  alone,  then  with  a  weight  oi 
10  grammes,  then  with  50,  100,  200,  and  500  grammes  (Fig.  254,  p.  748). 

8.  Influence  of  Fatigue  on  the  Muscle- Curve. — Arrange  as  in  7,  but 
leave  on  the  same  weight  (say  10  grammes)  all  the  time.  Place  the 
nerve  on.  the  electrodes.  Leave  the  short-circuiting  key  open.  The 
nerve  will  be  stimulated  at  each  revolution  of  the  drum,  and  the  writing- 
point  will  trace  a  series  of  curves,  which  become  lower,  and  especially 
longer,  as  the  preparation  is  fatigued.  Two  or  four  curves  can  be 
taken  at  the  same  time,  if  both  ends  of  one  or  of  two  brass  slips  be 
arranged  so  as  to  make  contact  with  the  projecting  wire  at  an  interval 
of  a  semicircumference  or  quadrant  of  the  drum  (Fig.  287).  (For 
specimen  curve,  see  Fig.  288,  p.  814.) 

9.  Seat  of  Exhaustion  in  Fatigue  of  the  Muscle-Nerve  Preparation  for 
Indirect  Stimulation. — When  the  nerve  of  a  muscle-nerve  preparation 
has  been  stimulated  until  contraction  no  longer  occurs,  the  muscle  can, 
under  ordinary  conditions,  be  made  to  contract  by  direct  stimulation. 
The  seat  of  exhaustion  is,  therefore,  not  the  general  contractile  sub- 
stance of  the  muscular  fibres  themselves.  To  determine  whether  it  is 
the  nerve-fibres  or  some  structure  or  substance  intermediate  between 
them  and  the  ordinary  contractile  substance  of  the  muscle,  perform 
the  following  experiments : 

(a)  Pith  a  frog;  make  two  muscle-nerve  preparations;  arrange  them 
both  on  a  mj-ograph  plate,  which  has  two  levers  connected  with  it. 
Attach  each  of  the  muscles  to  a  lever  in  the  usual  wa}',  and  lay  botli 
nerves  side  by  side  on  the  same  pair  of  electrodes.  Cover  with  moist 
blotting-paper.  The  electrodes  are  connected  with  the  secondary  of  an 
induction  machine  arranged  for  tetanus.     With  a  camel's  hair  brush 


Si4 


MUSCLE  ASD  NERVE 


moisten  one  of  the  nerves  between  the  electrodes  and  the  muscle  with  a 
mixture  ot  eiju.il  jxirts  of  ether  and  akohol,  diluted  with  twice  its  volume 
of  water,  to  abolish  the  conductivity.  Or  put  the  mixtinc  in  a  small 
bottle,  in  which  dips  a  piece  of  filter-paper.  The  projecting  end  of  the 
filter-paper  is  pointed,  and  the  nerve  is  laid  on  the  point.  As  soon  as 
it  is  possible  to  stimulate  the  nerves  without  obtaining  contraction  in 
this  muscle,  proceed  to  tetanize  both  nerves  till  the  contracting  muscle 
is  exhausted.  If  the  other  muscle  begins  to  twitch  during  the  stimu- 
lation, more  of  the  ether  mixture  must  be  painted  on  the  nerve.  As 
soon  as  th«  stimulation  ceases  to  cause  contraction  in  the  non-etherized 
preparation,  wash  off  the  mixture  from  the  other  nerve  with  physio- 
logical salt  solution,  and  soon  contraction  may  be  seen  to  take  place  in 


l"ig.  288. — Fatigue  Curve  of  Skeletal  Muscle:  Gastrocnemius  of  Frog.  Indirei  t 
stimulation;  taken  with  arrangement  shown  in  Fig.  287  (p.  S12).  Time-tracing. 
J  J^  of  a  second. 

the  muscle  of  this  preparation.  This  shows  that  the  nerve-trunk  is  still 
excitable.  Now,  both  nerves  have  been  equally  stimulated,  and  there- 
fore the  exhaustion  in  the  non-etherized  preparation  was  not  due  to 
fatigue  of  the  nerve-fibres,  but  of  something  between  them  and  the 
contractile  substance  of  the  muscle. 

10.  Influence  of  Veratrine  on  Muscular  Contraction.  —  Arrange  a 
drum  as  in  Fig.  287.  Pith  a  frog  (brain  only),  expose  the  sciatic  nerve 
in  one  thigh,  and  isolate  it  for  ^  inch  from  the  surrounding  tissues. 
Pass  under  it  a  strong  thread,  and  ligature  everything  except  the  nerve. 
Now  inject  into  the  dorsal  or  ventral  lymph-sac  a  few  drops  of  o-i  per 
cent,  solution  of  sulphate  of  veratrine.  In  a  few  minutes  make  two 
muscle-nerve  preparations  from  the  posterior  limbs.  First  put  the 
preparation  from  the  unligatured  limb  on  the  myograph  plate.     Lay 


pr.mth  .11.  i-.xr.RcisES  815 

tlie  nerve  on  electrodes  connected  Ihrougli  a  sliort-circuiting  key  with 
the  secondary  of  an  induclion  machine  arranged  as  in  Fig.  287.  Put 
the  writing-point  on  tiie  drum  and  set  it  oil  (fast  speed).  Open  the 
short-circuiting  key  till  tlic  nerve  has  been  once  stimulated,  then  close 
it  again.  Tiie  curve  obtained  differs  from  a  normal  curve,  in  that 
the  period  of  descent  (relaxation)  is  exceedingly  prolonged.  Now 
connect  the  preparation  from  the  ligatured  limb  with  the  lever,  and 
take  a  tracing  of  a  single  contniction.  Put  on  a  time-tracing  with  the 
electrical  tuning-fork  (see  Figs.  264,  265,  p.    735). 

II.  Measurement  of  the  Latent  Period  of  Muscular  Contraction. — 
(i)  For  this  the  drum  must  traxel  at  a  faster  speed  than  usual.  It 
is  most  con\cnient  to  use  a  drum  rotated  very  rapidly  by  a  cord 
attached  to  a  falling  weight  or  by  the  recoil  of  a  stretched  rubber  band 
or  spring.  The  arrangement  for  automatic  stimulation  described  in 
Experiment  b  (p.  813)  may  be  employed.  Or  an  electro-magnetic  signal 
may  be  connected  in  the  primary  circuit  of  the  induction  coil  so  that 
when  the  primary  is  closed  or  opened  the  writing-point  of  the  signal 
moves.  Arrange  the  writing-point  of  the  signal  on  the  drum  in  the 
same  vertical  line  as  the  writing-point  of  the  muscle  lever,  and  in  the 
same  line  place  the  writing-point  of  a  vibrating  electric  tuning-fork. 
The  coil  is  adjusted  for  single  opening  shocks  as  in  Experiment  5 
(p.  811).  Pith  a  frog,  and  make  a  muscle-nerve  preparation.  Arrange 
it  on  the  myograph  plate.  The  muscle,  or  the  nerve  very  near  the 
muscle,  is  to  be  excited  by  a  single  opening  shock  while  the  drum  is 
moving.  When  the  curve  has  been  traced,  the  latent  period  is  got  by 
drawing  a  vertical  line  through  the  point  at  which  the  curve  just  begins 
to  rise  from  the  abscissa  line,  and  another  through  the  signal  mark. 
The  number  of  vibrations  of  the  tuning-fork  included  between  these 
two  verticals  gives  the  latent  period. 

Or  (2)  use  the  spring  myograph  (Fig.  231,  p.  746),  raising  it  on  blocks 
of  wood.  Smoke  the  glass  plate  over  a  paraffin  f!ame,  or  cover  it  with 
paper,  and  smoke  the  paper.  Connect  the  knock-over  kev  of  the  myo- 
graph with  the  primary  circuit  of  an  induction  coil.  Arrange  a  muscle- 
ner\'e  preparation  on  the  myograph  plate.  Place  electrodes  below  the 
nerve  as  near  the  muscle  as  possible,  and  connect  by  a  short-circuiting 
key  with  the  secondary.  Bring  the  writing-point  in  contact  with  the 
smoked  surface  of  the  spring  myograph,  so  as  to  get  the  proper  pressure. 
See  that  the  writing-point  of  the  tuning-fork  is  in  the  right  position  for 
tracing  time.  Then  push  up  the  plate  so  as  to  compress  the  spring, 
till  the  rod  connected  with  the  frame  which  carries  the  plate  is  held  by 
the  catch. 

With  the  short-circuiting  key  closed,  press  the  release  and  allow  an 
abscissa  line  to  be  traced.  Again  shove  back  the  frame  till  it  is  caught. 
Push  home  the  rod  by  means  of  which  the  prongs  of  the  tuning-fork  are 
separated,  and  rotate  it  through  90°.  Close  the  knock-over  key,  open 
the  short-circuiting  key,  shoot  the  plate  again,  and  a  muscle-curve  and 
time-tracing  will  be  recorded.  Again  close  the  short-circuiting  key, 
withdraw  the  writing-point  of  the  tuning-fork,  push  back  the  plate, 
close  the  trigger  key,  then  open  the  short-circuiting  key,  and.  holding 
the  travelling  frame  with  the  hand,  allow  it  just  to  open  the  knock- 
over  and  stimulate  the  nerve.  The  writing-point  now  records  a  vertical 
line  (or,  rather,  an  arc  of  a  circle),  which  marks  on  the  tracing  the 
moment  of  stimulation.  The  latent  period  is  obtained  by  drawing  a 
parallel  line  (or  arc)  through  the  point  of  the  muscle-curve  where  it  just 
begins  to  diverge  from  the  abscissa  line.  The  value  of  the  portion  of  the 
time-tracing  between  these  two  lines  can  be  readily  determined,  and 
is  the  latent  period. 


8i6  AJLSCLH  AND  Mih'VE 

12.  Summation  of  Stimuli. — Arrange  two  knock-over  keys  on  tho 
spring  nivograph  at  sucli  a  distance  from  each  other  that  the  plate 
travels  fn;ni  one  to  the  other  in  a  time  less  than  the  latent  period. 
Connect  each  key  with  the  primary  circuit  of  a  separate  induction  coil 
having  a  couple  of  Daniells  in  it.  Join  two  of  the  binding-screws  of 
the  secondaries  together;  connect  the  other  two  through  a  short- 
circuiting  key  with  electrodes,  on  which  the  nerve  of  a  muscle-nerve 
preparation  is  arranged.  Push  up  the  secondaries  till  the  break  shocks 
obtained  on  opening  the  two  knock-over  keys  are  maximal.  Then 
shoot  the  plate  as  described  in  ii,  first  with  one  trigger  key  closed,  and 
then  with  both.  The  curves  obtained  should  be  of  the  same  height  in 
the  two  cases,  as  a  second  maximal  stimulus  falling  within  the  latent 
period  is  ignored  by  the  nerve  or  muscle.  Repeat  the  experiment  with 
submaximal  stimuli — i.e.,  with  such  a  distance  of  the  coils  that  opening 
of  either  trigger  key  does  not  cause  as  strong  a  contraction  as  is  caused 
when  the  coils  are  closer.  The  cur\e  will  now  be  higher  when  the  two 
shocks  are  thrown  in  successively  than  when  the  nerve  is  only  once 
stimulated.  This  shows  that  (submaximal)  stimuli  can  be  summed  in 
the  nerve.     The  same  could  be  demonstrated  for  muscle  (p.  756). 

13.  Superposition  of  Contractions. — Smoke  a  drum  arranged  for  auto- 
matic stimulation  as  in  Fig.  287.  Adjust  the  brass  points  with  a 
distance  of.  say,  i  centimetre  between  them,  so  that  a  second  stimulus 
may  be  thrown  into  the  nerve  at  an  interval  greater  than  the  latent 
period  of  muscle.  Put  two  Daniells  in  the  primary  circuit.  Lay  the 
nerve  of  a  muscle-nerve  preparation  on  electrodes  connected  through  a 
short-circuiting  key  with  the  secondary.  Allow  the  drum  to  revolve 
(fast  speed) ;  open  the  short-circuiting  key  till  both  brass  points  have 
passed  the  projecting  wire,  then  close  it.  Now  bend  back  the  second 
brass  point,  and  take  a  tracing  in  which  the  first  curve  is  allowed  to 
complete  itself.  This  will  not  rise  as  high  as  the  second  curve  obtained 
when  the  two  stimuli  were  thrown  in.  Repeat  the  experiment  with 
varying  intervals  between  the  brass  points — that  is,  between  the  two 
successive  stimuli.  Put  on  a  time-tracing  with  the  electrical  tuning- 
fork.      (For  specimen  curve,  see  Fig.  260,  p.  756.) 

14.  Composition  of  Tetanus. — {a)  Adjust  a  muscle-nerve  preparation 
on  a  myograph  plate,  the  nerve  being  laid  on  electrodes  connected 
through  a  short-circuiting  key  with  the  secondary  of  an  induction 
machine,  the  primary  circuit  of  which  contains  a  Daniell  cell  and  is 
arranged  for  an  interrupted  current  (Fig.  93,  p.  200).  The  lever  should 
be  shorter  than  that  used  for  the  previous  experiments,  or  the  thread 
should  be  tied  in  a  hole  farther  from  the  axis  of  rotation,  so  as  to  give 
less  magnification  of  the  contraction.  Set  the  Neef's  hammer  going, 
let  the  drum  revolve  (slow  speed),  and  open  the  key  in  the  secondary. 
The  writing-point  at  once  rises,  and  traces  a  horizontal  or  perhaps 
slightly-ascending  line.  Close  the  short-circuiting  key,  and  the  lever 
sinks  down  again  to  the  abscissa  line.  If  it  does  not  quite  return,  it 
should  be  loaded  with  a  small  weight.  This  is  an  example  of  complete 
tetanus. 

{b)  Connect  the  spring  shown  in  Fig.  289  with  one  of  the  upper 
terminals  of  the  primarj-  coil,  and  the  mercury  cup  with  the  other. 
Fasten  the  end  of  the  spring  in  one  of  the  notches  in  the  upright  piece 
of  wood  by  means  of  a  wedge,  so  that  its  whole  length  can  be  made  to 
vibrate.  Let  the  drum  off,  set  the  spring  vibrating  by  depressing  it 
with  the  finger,  then  open  the  key  in  the  secondary.  The  muscle  is 
thrown  into  incomplete  tetanus,  and  the  writing-point  traces  a  wavy 
curve  at  a  higher  level  than  the  abscissa  line.  Close  the  short-circuiting 
key,  and  the  lever  falls  to  the  horizontal.     Repeat  the  experiment  with 


PRACrtCAL  EXERCISES 


817 


the  spring  fastened,  so  that  only  }.  \,  J.  i  of  its  length  is  free  to  vibraic. 

The  rate  of  interruption  of  tlie  primary  circuit  increases  in  proi^ortion 

to  the  shortening  of 
tlie  spring,  and  the 
tetanus  becomes  more 
and  more  complete, 
till  ultimately  the 
writing- point  marks 
an  unbroken  straight 
line.  Put  on  a  time- 
tracing  by  means  of 
an  electro  -  magnetic 
marker  connected 
with  a  metronome 
beating  seconds  or 
half-seconds  (Fig.  88, 
p.  195).  (For  speci- 
men curves,  see  Fig. 
267,  p.  757-) 

15.   Contraction    of 

Smooth  Muscles — 

Spontaneous 


Fig.  289  —Arrangement  for  Tetanus.  A,  upright  with 
notches,  in  which  the  spring  S  is  fastened  (shown  in 
section);  C,  horizontal  board  to  which  A  is  attached, 
and  in  a  groove  in  which  the  mercury-cup  E  slides. 
The  primary  coil  P  is  connected  with  E,  and  through 
a  simple  key,.K,  with  the  battery  B,  the  other  pole 
of  which  is  connected  with  the  end  of  the  spring. 
The  wires  from  the  secondary  coil,  P',  go  to  a  short- 
circuiting  key,  K',  from  which  the  wires  F  go  off  to 
the  electrodes. 


Rhythmical  Contrac- 
tions. —  Immerse  in 
oxygenated  Ringer's 
solution  a  ring  of 
CESophagus  obtained 
inunediately  after  death  from  a  cat,  or,  still  better,  from  a  chicken.  Or 
a  segment  of  rabbit's  intestine  may  be  employed  as  described  on  p.  45O. 
Use  the  arrangement 
described  on  p. -}56.  In 
the  case  of  the  ca  t's  oeso- 
phagus the  ring  should 
be  taken  from  the  lower 
half  of  the  oesophagus, 
since  the  upper  portion 
contains  purely  striated 
muscle.  Obtain  tracings 
of  the  rhythmical  con- 
tractions on  a  slowly- 
moving  drum  (Fig.  290). 
(2)  Fix  one  end  of 
a  piece  of  cat's  oeso- 
phagus, 2  to  5  centi- 
metres long, to  a  muscle- 
cla  rap  in  a  moist 
chamber,  and  the  other 
end  to  a  lever  writing 
on  a  drum.  Connect 
thin  copper  wires  from 
the  secondary  coil  of  an 
inductorium  with  the 
two  ends  of  the  piece 
of  oesophagus.  Take 
tracings  to  show  [a]  the  curve  of  a  single  contraction  caused  by  a  single 
make  or  break  shock,  with  estimation  of  the  latent  period,  as  in  Experi- 
ment II,  p.  815;  (6)  summation,  as  in  Experiment  12,  p.  8r6;  {c)  genesis 

52 


Fig.  290. 


-Rhythmical  Contractions  of  CEsophagus  of 
Chicken  (Botazzi). 


Sid 


MUSCLE  AND  NERVE 


of  tetanus,  as  in  Experiment  14,  p.  816;  {d)  the  relations  between 
strength  of  r-timuhis  and  amount  of  contraction.  For  this  hist  experi- 
ment the  (Iriun  should  be  stationary  while  the  contraction  is  being 
recorded,  and  should  be  allowed  to  move  a  little  between  successive 
contractions.  Begin  with  the  secondary  at  such  a  distance  from  the 
primary  that  a  contraction  is  just  caused  by  a  break  shock.  Then 
gradually  increase  the  strength  of  the  stimulus  (always  using  the  break) 
till  miximum  contraction  is  obtained.  The  gradual  increase  in  the 
response  is  very  clearly  seen  with  the  oesophageal  preparation  (Waller). 

For  further  exjx'rimcnts  on  the  contraction  of  smooth  muscle,  see 
pp.  66  and  457. 

16.  Velocity  of  the  Nerve-Impulse. — Use  the  spring  myograph 
(Fig.  251.  p.  74f))  or  a  very  rapidly  rotating  drum.  IMake  a  muscle- 
nerve  preparation  from  a  large  frog  (preferably  a  bull-frog),  so  that  the 
sciatic  nerve  may  be  as  long  as  possible.  Connect  the  knock-over  key 
with  the  primary  circuit  of  an  induction  machine,  which  should  contain 


Fig.  291.  .■\rrangcmont  for  Measurinp;  th*^  \Vlocity  of  the  Nerve-Impulse.  A.  travel 
ling  plate  of  spring  myograph;  M,  mubcle  lying  on  a  myograph  plate;  N,  nerve 
lying  on  two  pairs  of  electrodes,  E  and  E';  C,  Pohl's  (  oinimitator  without  cross- 
wires;  K,  knock-over  key  of  si)ring  myograph  (only  the  binding-screws  shown); 
K',  simple  key  in  primary  circuit;  B,  battery;  P,  primary  coil;  S.  secondary  coil. 

a  single  Danicll  cell.  Arrange  two  pairs  of  fine  electrodes  under  the 
nerve  on  the  myograph  plate,  one  near  the  muscle,  the  other  at  the 
central  end.  Connect  the  electrodes  with  a  Fold's  commutator  (with- 
out cross-wires),  the  side-cups  of  which  are  joined  to  the  terminals  of 
the  secondary  coil,  as  shown  in  Fig.  291.  By  tilting  the  bridge  of  the 
commutator  the  nerve  may  be  stimulated  at  either  point.  Great  care 
mu.st  be  taken  to  keep  the  nerve  in  a  moist  atmosphere  by  means  of  wet 
blotting-paper  or  a  moist  chamber;  but  at  the  same  time  it  must  not 
lie  in  a  pool  of  salt  solution,  as  twigs  of  the  stimidating  current  would 
in  this  case  spread  down  the  nerve;  and  we  could  never  be  sure  that 
the  apparent  was  always  the  real  point  of  stimulation.  The  writing- 
points  of  the  lever  and  tuning-fork  having  been  adjusted  to  the  smoked 
plate,  as  in  11  (p.  815),  the  bridge  of  the  Ptjhl's  commutator  is  arranged 
for  stimulation  o[  the  distal  point  of  the  nerve,  the  plate  is  shot  with 
the  short-circuiting  key  in  the  secondary  closed,  and  an  abscissa  line 
and  time-curve  traced.  Then  the  writing-point  of  the  fork  is  removed 
and  the  plate  again  shot  with  the  key  in  the  secondary  open,  and  a 


PRACTICAL  EXERCISES  8i9 

mupclc-curvc  is  obtained.  The  commutator  is  now  arranged  for  stimu- 
lation of  the  central  end  of  the  nerve,  and  another  mu.scle-curve  taken. 
Vertical  lines  are  drawn  through  the  points  where  the  two  curves  just 
begin  to  separate  out  from  the  abscissa  line.  The  interval  between 
these  lines  corresponds  to  the  time  taken  by  the  nerve-impulse  to  travel 
along  the  nerve  from  the  central  to  the  distal  pair  of  electrodes.  Its 
value  in  time  is  given  by  the  tracing  of  the  tuning-fork.  The  length  of 
the  nerve  between  the  two  pairs  of  electrodes  is  now  carefully  measured 
with  a  scale  divided  in  millimetres,  and  the  velocity  calculated  (p.  793). 
17.  Chemistry  of  Muscle. — Mince  up  some  muscle  from  the  hind-legs 
of  a  dog  or  rabbit  (used  in  some  of  the  other  experiments),  of  which 
the  bloodvessels  have  been  washed  out  by  injecting  0*9  per  cent,  salt 
solution  through  a  cannula  tied  into  the  abdominal  aorta  until  the 
washings  arc  no  longer  tinged  with  blood.  To  some  of  the  minced 
muicle  add  twentv  times  its  bulk  of  distilled  water,  to  another  portion 
ten  times  its  bulk  of  a  5  per  cent,  solution  of  magnesium  sulphate. 
Let  stand,  with  frequent  stirring,  for  twenty-four  hours.  Then  strain 
through  several  folds  of  linen,  press  out  the  residue,  and  filter  through 
paper,  (i)  With  the  filtrate  of  the  watery  extract  make  the  following 
observations : 

(a)  Reactio)!. — To  litmus-paper  acid. 

(b)  Determine  the  temperatures  at  which  coagulation  of  the  various 
proteins  in  the  extract  takes  place,  according  to  the  method  described 
on  p.  9.*  Put  some  of  the  watery  extract  in  the  test-tube,  and  heat 
the  bath,  stirring  the  water  in  the  beakers  occasionally  with  a  feather. 
Note  at  what  temperature  a  coagulum  first  forms.  It  will  be  about 
47°  C.  Filter  this  off,  and  again  heat;  another  coagulum  will  form  at 
56*  to  58°.  Filter,  and  heat  the  filtrate;  a  third  slight  coagulum  may- 
be formed  at  60°  to  65°  C,  but  this  represents  merely  a  residue  of  the 
myosinogen  which  was  left  in  solution  at  the  previous  heating.  A 
fourth  precipitate  (of  serum-albumin)  will  come  down  at  70°  to  73°. 
Saturate  some  of  the  water\'  extract  with  magnesium  sulphate;  a  large 
precipitate  will  be  formed,  showing  the  presence  of  a  considerable 
amount  of  globulin.  Filter  off  the  precipitate  and  heat  the  filtrate; 
coagulation  will  again  occur  at  very  much  the  same  temperatures  as 
before,  although  the  total  amount  of  precipitate  will  be  less.  Note  in 
particular  that  there  is  still  some  precipitate  at  47°  to  50°.  Paramyo- 
sinogen possesses  some  of  the  characters  of  both  globulins  and  albumins, 
for  it  is  partially  but  not  entirely  precipitated  by  saturation  with 
magnesium  sulphate,  and  is  not  precipitated  b}-  sodium  chloride. 

(2)  (a)  Test  the  reaction  of  the  magnesium  sulphate  extract.  It 
will  usually  be  faintly  acid  to  litmus. 

{b)  Heat  some  of  it.  Precipitates  will  be  obtained  at  the  same  tem- 
peratures as  in  (i)  {b).  but  those  at  47"  to  50°  and  56°  to  58°  will  be 
more  abundant.  Of  the  two,  that  at  47°  to  50°  will  usually  be  the 
larger  when  time  is  given  for  it  to  come  down  and  the  heating  is  gradual. 

{c)  Dilute  some  of  the  magnesium  sulphate  extract  with  three  times, 
another  portion  with  four  times,  and  another  with  five  times,  its  volume 
of  water  in  a  test-tube,  and  put  in  a  bath  at  40°  C.     Coagulation  or 

*  It  should  be  remembered  that  the  temperature  of  heat-coagulation  of 
any  substance  is  by  no  means  an  absolute  constant.  It  depends  on  the 
reaction,  the  proportion  and  kind  of  neutral  salts  present,  perhaps  on  the 
strength  of  the  protein  solution  and  the  manner  of  heating.  A  solution  oi 
egg-albumin,  e.g.,  can  be  coagulated  at  a  temperature  much  below  70°  when 
it  is  heated  for  a  week.  Small  differences  in  the  temperature  of  heat-coagula- 
tion, unless  supported  by  well-marked  chemical  reactions,  are  not  enough 
to  characterize  protein  substances  as  chemical  individuals. 


820  MUSCLE  AND  NERVE 

precipitation  will  occur  in  one  or  all  of  these  test-tubes.  To  another 
test-tube  of  the  extract  diluted  in  the  proportion  which  has  given  the 
best  '  muscle-clot  '  add  a  few  drops  of  a  dilute  solution  of  potassium 
oxalate,  and  place  in  a  bath  at  40°.  Coagulation  occurs  as  before. 
Filter  off  the  clot  from  all  the  test-tubes.  The  filtrate  is  the  '  muscle- 
serum,'  and  yields  a  precipitate  of  serum-albumin  at  70*  to  73°  C. 

(3)  Myosiyiogen,  like  other  globulins,  is  insoluble  in  distilled  water, 
but  soluble  in  weak  saline  solutions.  Saturation  with  neutral  salts  like 
sodium  chloride  and  magnesium  sulphate  precipitates  mycsinogen,  but 
not  albumin,  from  its  solutions;  .saturation  with  ammonium  sulphate 
precipitates  both.  Verify  the  following  reactions  of  myosinogen,  using 
the  original  magnesium  sulphate  extract  of  the  muscle: 

(a)  Dropped  into  water,  it  is  precipitated  in  flakes,  which  can  be 
redissolved  by  a  weak  solution  of  a  neutral  salt  (say  5  per  cent,  mag- 
nesium sulphate). 

(6)  When  a  solution  of  myosinogen  is  dialyzed,  it  is  after  a  time  pre- 
cipitated on  the  inside  of  the  dialyzer  as  the  salts  pass  out. 

[c)  If  a  piece  of  rock-salt  is  suspended  in  a  solution,  the  myosin 
gradually  gathers  upon  it,  diffusion  of  the  salt  out  through  the  precipi- 
tated myosin  always  keeping  a  saturated  layer  around  it. 

{d)  Saturate  a  solution  containing  myosinogen  with  crystals  of 
magnesium  sulphate,  stirring  or  shaking  at  frequent  intervals.  The 
myosinogen  is  precipitated. 

{e)  Without  adding  any  salt,  simply  shake  a  myosinogen  solution 
vigorously;  a  certain  amount  of  the  myosinogen  will  be  precipitated 
and  the  solution  will  become  turbid.  This  reaction  can  also  be  ob- 
tained with  solutions  of  other  proteins,  such  as  albumins  (Ramsden). 

Extracts  qualitatively  similar  to  those  obtained  from  the  muscles 
of  a  freshly-killed  animal  can  be  got  from  muscles  that  have  entered 
into  rigor,  but  the  quantity  of  the  various  proteins  going  into  solution 
is  less. 

18.  Reaction  of  Muscle  in  Rest,  Activity,  and  Rigor  Mortis. ^(a)  Take 
a  frog's  muscle,  cut  it  across,  and  press  a  piece  of  red  litmus-paper  on 
the  cut  end;  it  is  turned  blue.  Yellow  turmeric  paper  is  not  affected. 
{b)  Immerse  another  muscle  in  physiological  salt  solution  (0*75  per 
cent,  for  frog's  tissues)  at  40°  to  42°  C.  It  becomes  rigid.  The  reaction 
becomes  acid  to  litmus-paper,  and  also  turns  brown  turmeric  paper 
yellow. 

(c)  Plunge  another  muscle  into  boiling  physiological  salt  solution. 
It  becomes  harder  than  in  (6). 

(d)  Stimulate  another  muscle  with  an  interrupted  current  from  an 
induction  machine  (Fig.  93,  p.  200),  till  it  no  longer  contracts.  The 
reaction  is  now  acid  to  litmus-paper.  Brown  turmeric  paper  may  also 
be  turned  yellow. 

{e)  To  demonstrate  the  formation  of  lactic  acid  in  muscle  in  heat 
rigor  or  fatigue,  perform  the  following  experiment :  Pith  a  frog,  and 
afterwards  leave  it  for  half  an  hour  at  rest,  so  that  the  lactic  acid  pro- 
duced in  the  movements  connected  with  the  pithing  operation  may 
disappear  from  the  muscles.  See  that  the  circulation  in  the  hind-limbs 
is  not  interfered  with  by  pressure  or  flexion.  Then  remove  both  hind- 
limbs.  Carefully,  but  rapidly,  remove  the  muscles  of  one  from  the 
bones  with  as  little  manipulation  as  possible.  Immediately  place  them 
in  a  small  mortar  cooled  in  ice,  and  containing  some  sand  and  20  or 
30  c.c.  of  ice-cold  95  per  cent,  alcohol,  and  quickly  grind  them  up. 
Produce  heat  rigor  (p.  777)  of  the  muscles  of  the  other  hind-limb,  or 
fatigue  them  with  induction-shocks,  and  then  grind  them  up  imder 
alcohol   in   the   same   way.     Filter  the   alcoholic   extracts,   and   then 


PRACTICAL  EXERCISES  821 

evaporate  them  to  dryness  on  the  water-bath.  Rub  up  the  residues 
with  a  few  c.c.  of  hot  water.  Add  to  each  aqueous  extract  a  small 
quantity  (say  a  decigramme)  of  finely  powdered  charcoal.  Then  heat 
each  extract  to  boiling  in  a  test-tube,  and  filter.  Evaporate  the 
filtrates  to  dryness,  and  apply 

Hopkins's  Reaction  for  Lactic  Acid. — The  reagents  required  are  (i)  a 
very  tiilute  alcoholic  solution  of  tliiophene  (C4H4S)  (10  to  20  drops  in 
100  c.c);  (2)  a  saturated  solution  of  copper  sulphate;  and  (3)  ordinary 
strong  sulphuric  acid. 

Have  ready  a  glass  beaker  containing  water  briskly  boiling.  Place 
about  5  c.c.  of  strong  sulphuric  acid  in  a  test-tube,  with  i  drop  of  the 
copper  sulphate  solution.*  Add  to  the  mixture  a  few  drops  of  the 
solution  to  be  tested,  and  shake  well.f 

(In  the  case  of  the  muscle  extracts  the  dry  residues  arc  dissolved  in 
the  5  c.c.  of  strong  sulphuric  acid,  the  acid  transferred  to  test-tubes, 
and  the  test  proceeded  with  by  the  addition  of  the  copper  sulphate 
solution,  etc.) 

Now  place  the  test-tube  in  the  boiling  water  for  one  to  two  minutes. 
Then  cool  it  well  under  the  cold-water  tap.  and  add  2  or  3  drops  of 
the  thiophene  solution  from  a  pipette.  Replace  the  tube  in  the  boiling 
water,  and  immediately  observe  the  colour.  If  lactic  acid  is  present, 
the  liquid  rapidly  takes  on  a  bright  cherry-red  colour,  which  is  only 
permanent  if  the  test-tube  be  cooled  immediately  after  its  appearance. 
The  tube  should  always  be  cooled  as  described,  before  addition  of  the 
thiophene,  as  the  gradual  appearance  of  the  colour  on  re-warming 
makes  the  test  more  delicate. 

(The  extract  of  the  resting  limb  generally  gives  a  negative,  that  of 
the  other  a  strongly  positive,  reaction.) 

*  The  copper  sulphate  is  added  to  hasten  the  oxidation  that  follows. 

•{•  For  practice  use  a  i  per  cent,  alcoholic  solution  of  lactic  acid.  The  test 
cannot  be  applied  directly  to  material  which  chars  with  the  strong  sulphuric 
acid  used.  In  this  case  preliminar}^  extraction  of  the  lactic  acid  is  necessary. 
Alcohol  should  be  used  as  the  solvent,  or  if  ether  is  employed  it  must  first  be 
well  washetl  to  remo\'e  aldehvde-yielding  products,  since  the  colour-change  is 
due  to  an  aldehyde  reaction  with  thiophene. 


CHAPTER  XV 
ELECTRO-PHYSIOLOGY 

A  LITTLE  more  than  a  hundred  years  ago  the  foundation  both  of  electro- 
physiology'  and  of  the  vast  science  of  voltaic  electricity  was  laid  by  a 
chance  observation  of  a  professor  of  anatomy  in  an  Italian  garden.  It 
is  indeed  true  that  long  before  this  electrical  fishes  were  not  only 
popularly  known,  but  the  shock  of  the  torpedo  had  been  to  a  certain 
extent  scientifically  studied.  But  it  was  with  the  disco\  cry  of  Galvani 
of  Bologna  that  the  epoch  of  fruitful  work  in  electro-physiology  began. 
Engaged  in  experiments  on  the  effect  of  static  and  atmospheric  elec- 
tricity in  stimulating  animal  tissues,  he  happened  one  day  to  notice 
that  some  frogs'  legs,  suspended  by  copper  hooks  on  an  iron  railing, 
twitched  whenever  the  wind  brought  them  into  contact  with  one  of 
the  bars  (p.  842).  He  concluded  that  electrical  charges  were  developed 
in  the  animal  tissues  themselves,  and  discharged  when  the  circuit  was 
completed.  Volta,  professor  of  physics  at  Pavia,  fixing  his  attention  on 
the  fact  that  in  Galvani's  experiment  the  metallic  part  of  the  circuit 
was  composed  of  two  metals,  maintained  that  the  contact  of  these  was 
the  real  origin  of  the  current,  and  that  the  tissues  served  merely  as 
moist  conductors  to  complete  the  circuit ;  and  after  a  controversy  lasting 
for  more  than  a  decade,  he  finally  clinched  liis  argument  by  constructing 
the  voltaic  pile,  a  series  of  copper  and  zinc  discs,  every  two  pairs  of 
which  were  separated  by  a  disc  of  wet  cloth,  or  paper  moistened  with  salt 
solution.  The  pile  yielded  a  continuous  current  of  electricity.  '  So,' 
said  Volta,  '  it  is  clear  that  the  tissue  in  Galvani's  experiment  only  acts 
the  part  of  the  cloth.'  Galvani,  however,  had  shown  in  the  meantime 
that  contraction  without  metals  could  be  obtained  by  dropping  the  nerve 
of  a  preparation  on  to  the  muscle  (p.  842) ;  and  it  soon  began  to  be  recog- 
nized that  both  Galvani  and  Volta  were  in  part  right,  that  the  tissues 
produce  electricity,  and  that  the  contact  of  different  metals  does  so 
too.  Although  it  is  curious  to  note  how  completely  the  growth  of 
that  science  of  which  Volta's  discovery  was  the  germ  has  overshadowed 
the  parent  tree  planted  by  the  hand  of  Galvani,  yet  animal  electricity 
has  been  deeply  studied  by  a  large  number  of  observ-ers,  and  many 
interesting  and  important  facts  have  been  brought  to  light. 

Since  it  is  in  muscle  and  nerve  that  the  phenomena  of  electro- 
physiology  are  seen  in  their  simplest  expression,  and  have  been 
chiefly  studied,  we  shall  develop  the  fundamental  laws  with  reference 
to  muscle  and  nerve  alone,  and  afterwards  apply  them  to  other 
excitable  tissues. 

I.  All  points  of  an  uninjured  resting  muscle  or  nerve  are  approxi- 
mately at  the  same  potential  {or  i so- electric).     In  other  words,  if  any 

822 


DEMARCATION  CURRENT 


823 


two  points  are  connected  with  a  galvanometer  by  means  of  un- 
polarizable  clcctrodos,  little  or  no  current  is  indicated.  (Although 
it  is  scarcely  possible  to  isolate  a  muscle  without  its  showing  some 
current,  the  more  carefully  the  isolation  is  performed,  the  feebler 
is  the  current;  and  between  two  points  of  the  inactive,  uninjured 
ventricle  of  the  frog's  heart  no  electrical  difference  has  been  found. 
Frogs'  nerves  kept  ten  to  twenty  hours  after  excision  in  physiological 
salt  solution  to  which  a  little  calcium  salt  and  frog's  blood  have 
been  added,  are  absolutely  iso-electric.) 

2.  Any  uninjured  point  of  a  resting  muscle  or  nerve  is  at  a  different 
potential  from  any  injured  point.  The  difference  of  potential  is  such 
that  a  current  will  pass  through  the  galvanometer  from  uninjured  to 
injured  point  and  through  the  tissue  from  injured  to  uninjured  point 
(current  of  rest,  or  demarcation  current,  or  injury  response)  (Fig.  292). 

3.  Any  unexcjted  point  of  a  muscle  or  nerve  is  at  a  different  potential 
from  any  excited  point,  and  any  less  excited  point  is  at  a  different 


Fig.  292. — A,  uninjured,  B,  injured, 
portion  of  nerve;  G,  galvanometer. 
The  large  arrows  show  direction  of 
demarcation  current  or  current  of 
rest,  the  small  arrows  direction  of 
negative  variation  or  action  current. 


Fig.  293.  —  Diagram  of  Currents  of 
Rest  in  a  Regular  Muscle,  or  Muscle 
Cylinder.  E,  equator.  The  dotted 
lines  join  points  at  the  same  po- 
tential, between  which  there  is  no 
current. 


potential  from  any  more  excited  point.  The  difference  of  potential 
is  such  that  a  current  will  pass  through  the  galvanometer  to  the 
excited  from  the  unexcited  or  less  excited  point  (action  current, 
01  negative  variation,  or  excitatory  electrical  response). 

It  has  been  customary  in  physiological  writings  to  speak  of  the 
electrical  change  in  injured  or  active  tissue  as  a  negative  one,  because 
when  the  tissue  is  led  off  to  a  galvanometer  the  current  passes  from 
the  galvanometer  to  the  injured  or  excited  portion  of  the  tissue. 
It  may  be  called  with  greater  precision  ' galvanometrically  negative.' 
It  is  in  this  sense  that  we  shall  employ  the  term. 

The  best  object  for  experiments  on  the  demarcation  current  is  a 
straight-fibred  muscle  like  the  frog's  sartorius.  If  this  muscle  be  taken, 
and  the  ends  cut  off  perpendicularly  to  the  surface,  a  muscle-prism  or 
muscle-cylinder  is  obtained  (Fig.  2qi).  The  strongest  current  is  got 
when  one  electrode  is  placed  on  the  middle  of  either  cross-section,  and 
the  other  on  the  '  equator  ' — that  is,  on  a  line  passing  roimd  the  longi- 
tudinal surface  midway  between  the  ends.  The  direction  of  this 
current  is  from  the  cross-section  towards  the  equator  in  the  muscle. 
If  the  electrodes  are  placed  on  symmetrical  points  on  each  side  of  the 
equator,  there  is  no  current. 


824  ELFXTRO-PHYSIOLOGY 

Current  of  Action,  or  Negative  Variation. — When  a  muscle  or 
nerve  is  excited,  an  electrical  change  sweeps  over  it  in  the  form  of 
a  wave.  Suppose  two  points,  A  and  B  (Fig.  294),  on  the  longi- 
tudinal surface  of  a  muscle  to  be  connected  with  a  capillary  electro- 
meter (p.  729),  the  movements  of  the  mercury  being  photographed 
on  a  travelling  surface — for  example,  a  pendulum  carrying  a  sensitive 
plate.  Let  the  muscle  be  excited  at  the  end,  so  that  the  wave  of 
excitation  will  be  propagated  in  the  direction  of  the  arrow.  The 
wave  will  reach  A  first,  and  while  it  has  not  yet  reached  B,  A  wall 


Fig.  29 1 . — iJiagram  to  illustrate  Propagation  of  the  Electrical  Change  along  aa 
Active  Muscle  or  Nerve.  Suppose  AB  to  be  a  horizontal  bar  representing  the 
muscle  or  nerve.  Let  C  be  a  curved  piece  of  wood  representing  the  curve  of  the 
electrical  change  at  any  point.  Let  W,  W  be  two  glass  cylinders  connected  by 
a  flexible  tube,  the  whole  being  filled  with  water.  Suppose  the  rims  of  the 
cylinders  originally  to  touch  AB  at  the  points  A  and  B,  and  let  them  be  movable 
only  in  the  vertical  direction.  The  level  of  the  water  being  the  same  in  both, 
there  is  no  tendency  for  it  to  flow  from  one  to  the  other.  This  represents  the  resting 
state  of  the  tissue  when  A  and  B  are  symmetrical  points.  Now  let  C  be  moved 
along  the  bar  at  a  uniform  rate.  The  cylinder  W,  being  free  to  move  down,  but 
not  horizontally,  will  be  displaced  by  C,  and,  if  it  is  kept  always  in  contact  with 
its  curved  margin,  will,  after  describing  the  curve  of  the  electrical  variation, 
come  again  to  rest  in  its  old  position  at  A.  B  will  do  the  same  when  C  reaches 
it.  But  since  C  reaches  A  before  B,  the  level  of  the  water  in  B  will  at  first  be 
higher  than  that  in  A,  and  water  will  flow  from  B  to  A  as  the  current  Hows 
through  the  galvanometer.  This  will  correspond  to  the  time  during  which  the 
point  of  the  tissue  represented  by  A  would  be  gaivanometrically  negative  t.)  a 
point  represented  by  B.  Later  on,  when  C  has  reached  the  position  shown  by 
the  dotted  lines,  the  level  of  the  water  in  .•K  will  be  higher  than  that  in  B,  and  a 
flow  will  take  place  in  the  opposite  direction  to  the  first  flow.  This  corresponds 
to  a  second  phase  of  the  electrical  variation. 

become  negative  to  B.  If  there  is  a  resting  difference  of  potential 
between  A  and  B,  this  will  be  altered,  the  new  and  transitory  differ- 
ence adding  its«-lf  algebraically  to  the  old.  When  the  wave  reaches 
B,  it  may  already  have  passed  over  A  altogether,  and  B  now  be- 
coming negative  to  A,  there  will  be  a  movement  of  the  meniscus 
of  the  electrometer  in  the   opposite  direction.      This  is  called  the 


NEGATIVE  VARIATION  825 

dipliasic  current  of  action.  If  the  wave  has  not  passed  over  A  before 
it  reaches  B,  as  would  in  general  be  the  case  in  an  actual  experiment, 
there  will  be  first  a  period  during  which  A  is  relatively  negative  to 
B  (first  pliase) ;  this  will  end  as  soon  as  B  has  become  iso-electric 
with  A,  and  will  be  succeeded  by  a  period  during  which  B  is  rela- 
tively negative  to  A  (second  phase).  Since  the  wave  takes  time  to 
reach  its  maximum,  it  is  evident  that  a  well-marked  first  phase  will 
be  favoured  when  the  interval  between  its  arrival  at  A  and  at  B  is 
long,  for  in  this  case  A  will  have  a  chance  of  becoming  strongly 
negative  while  B  is  still  normal.  Similarly,  if  A  has  again  become 
normal,  or  nearly  normal,  before  the  maximum  negative  change  has 
passed  over  B,  a  strong  second  phase  will  be  favoured.  The  heart- 
muscle,  accordingly,  where  the  wave  of  contraction,  and  its  accom- 
panying electrical  change,  move  with  comparative  slowness,  is 
better  suited  for  showing  a  well-marked  diphasic  variation  than 
skeletal  muscle,  and  still  better  suited  than  nerve.     In  the  gastroc- 


Fig.  205. — Photuf^raphic  Electrometer  Curves  from  Sartorius  Muscle  (Sanderson). 
The  darkly-shaded  curv'e  represents  the  diphasic  variation  of  the  uninjured 
muscle;  the  lightly-shaded  curve  the  monophasic  variation  of  the  muscle  after 
injury  of  one  end.  The  toothed  curve  at  the  top  is  the  time-tracing  registered  by 
photographing  the  prong  of  a  tuning-fork  vibrating  five  hundred  times  a  second. 

nemius  muscle  of  the  frog,  when  excited  through  its  nerve,  the  elec- 
trical response  begins  about  y^Vo  second,  and  the  change  of  form  of 
the  muscle  about  yxfvo  second,  after  the  stimulation.  It  is  believed 
that  in  a  muscle  directly  excited  the  electrical  change  begins  in  less 
than  jjy^jj  second,  and  the  mechanical  change  in  iu\x>  second  (Burdon 
Sanderson,  Figs.  295-300). 

When  one  electrode  is  placed  on  an  injured  part,  the  wave  of  action 
and  of  electrical  change  chminishesas  it  reaches  the  injured  tissue; 
and  if  the  tissue  is  killed  at  this  part,  it  diminishes  to  zero;  so  that 
here  the  second  phase  may  be  greatly  weakened  or  may  disappear 
altogether,  and  we  then  have  what  is  called  a  monophasic  variation. 

In  this  case  the  current  of  action  can  be  demonstrated,  even  for  a 
single  excitation,  but  .still  better  for  a  tetanus,  with  an  ordinary  galvan- 
ometer, which  in  general  is  not  quick  enough  to  analyze  a  diphasic 
variation  with  equal  phases,  and  gives,  therefore,  only  their  algebraic 
sum — that  is,  zero.  When  the  muscle  or  nerve  is  tetanized,  the  action 
current  appears,  while  stimulation  is  kept  up,  as  a  permanent  deflection 
representing  the  '  sum  '  of  the  separate  eftects.  It  is  in  the  opposite 
direction  to  the  current  ot  rest,  since  the  injured  tissue,  being  less 


Pz6 


ELECTRO-PHYSIOLOGY 


affected  by  the  excitation,  and  therefore  undcrg.oing  a  smaller  negative 
change  than  the  uninjured,  becomes  relatively  to  the  latter  less  nega- 
tive. Appearing  as  a  diminution  or  reversal  of  the  current  of  rest,  it  was 
called  the  negative  variation.  The  term  negative  is  not  used  here  in 
its  electrical,  but  in  its  algebraic,  sense,  and  merely  as  indicating  the 
direction  of  the  current  with  reference  to  that  of  the  demarcation 
current.  It  is  in  this  sense  that  '  negative  variation  '  and  the  converse 
term,  '  positive  variation,'  are  used  (pp.  838,  8jc))  in  speaking  of  the 
electrical  changes  produced  in  glands  and  in  the  retina  by  stimulation. 


jn^j-yryr^j^ 


Fig.  2q6. — 'Spike'  (Diphasic  Variation)  of  Uninjured 
Gastrocnemius    (Sanderson). 

A  photographed  on  slow,  B  on  fast-moving,  plate. 


Fig.  297. — Variation  of  In- 
jured Gastrocnemius  (San- 
derson). A  'spike'  fol- 
lowed by  a  '  hump.' 


Fig.  298. — Variation  of  Injured  Gas- 
trocnemius (Sanderson).  The  plate 
was  moving  ten  times  faster  than  in 
Fig.  297. 


Fig.  299. — Variation  of  Uninjured 
Muscle  excited  Eighty-Four  Times 
a  Second  (Sanderson). 


pjg  300. — Curve  of  an  Injured  Muscle  excited  Sixty  Times  a  Second  (Sanderson). 


NEGATIVE  VARIATION  827 

When  the  current  of  rest  is  compensated  by  a  branch  of  an  external 
current  just  sufficient  to  balance  it  and  bring  the  galvanometer  image 
back  to  zero  (Fig.  234,  p.  727),  the  action  current  appears  alone  in  un- 
diminished strength.  This  shows  that  the  latter  is  not  due  to  a  change 
of  electrical  resistance  during  excitation,  since  such  a  change  would 
equally  alYect  current  of  rest  and  compensating  current,  and  they  would 
still  balance  each  other.  The  action  current  is  really  due  to  a  change 
of  potential,  which  can  be  measured  by  determining  what  electro- 
motive force  is  just  required  to  balance  it,  and  which  may  actually 
exceed  that  of  the  current  of  rest.  Thus,  Sanderson  and  Gotch  obtained 
an  average  of  0-08  of  a  Daniell  cell  (the  electromotive  force  of  the 
Daniell  would  be  about  a  volt)  as  the  electromotive  force  of  the  action 
current  due  to  a  single  indirect  excitation  of  a  vigorous  frog's  gastroc- 
nemius, and  about  0-04  Daniell  as  that  of  the  current  of  rest.  The 
electromotive  force  of  the  current  of  rest  in  the  rabbit's  nerve  was 
found  by  du  Bois-Reymond  to  be  0-026;  Gotch  and  Horsley  found  the 
average  for  the  cat  o-oi,  and  for  the  monkey  only  0*005. 

That  the  fusion  of  the  successive  variations  of  a  tetanized  muscle, 
as  seen  with  an  ordinary  galvanometer,  is  only  apparent  has  been 
shown  by  means  of  the  capillary  electrometer  or  the  string  galvanometer. 
Even  with  a  frequency  of  stimulation  far  beyond  what  is  necessary  for 
complete  tetanus,  each  stimulus  is  answered  by  a  movement  of  the 
meniscus  (Figs.  299,  300).  In  nerve,  also,  each  of  two  successive 
stimuli  causes  its  appropriate  electrical  change  when  they  are  separated 
by  an  interval  longer  than  a  certain  small  fraction  of  a  second.  The 
precise  interval  at  which  the  second  stimulus  ceases  to  be  effective 
depends  on  the  temperature  of  the  nerve,  being  markedly  increased  by 
cold  (Gotch  and  Burch) . 

The  rate  of  propagation  of  the  electrical  change  in  muscle  is  the 
same  as  that  of  the  mechanical  change,  and  in  nerve  the  same  as  that 
of  the  nervous  impulse.  The  velocity  of  propagation  of  the  diphasic 
variation  along  a  fresh  sartorius  at  14°  C.  was  in  one  experiment 
2-8  metres,  in  another  at  18°  C,  3*5  metres  (Sanderson).  (See  p.  759.) 
Lucas  has  pointed  out  that  in  strict  accuracy  what  is  observed  is  merely 
that  the  time  interval  separating  contraction  at  one  point  of  the  muscle 
from  contraction  at  another  is  equal  to  the  time  interval  separating 
the  electrical  changes  which  occur  at  the  same  points.  The  facts 
observed  do  not  formally  prove  that  either  the  contraction  or  the  elec- 
trical disturbance  is  propagated  at  all.  So  far  as  they  go,  some  other 
perfectly  distinct  change  may  be  propagated,  which  at  all  points  of  the 
fibre  at  which  it  arrives  sets  up  both  the  contraction  and  the  electrical 
change.  Such  direct  evidence,  however,  as  we  possess  goes  to  show 
that  it  is  the  electrical  disturbance  which  is  the  propagated  one,  and 
that  this  evokes  the  contractile  disturbance. 

There  is  ample  evidence  that  the  excitatory  electrical  response 
is  a  normal  physiological  phenomenon.  In  human  skeletal  muscles 
the  current  of  action  has  been  demonstrated  by  connecting  a  gal- 
vanometer with  ring  electrodes  passing  round  the  forearm,  and 
throwing  the  muscles  into  contraction.  A  diphasic  variation  is  thus 
obtained;  and  the  electrical  change  travels  with  a  velocity  of  as 
much  as  twelve  metres  per  second,  which  is  greater  than  the  velocity 
in  frogs'  muscles.  Electromotive  changes  are  likewise  associated 
with  the  beat  of  the  heart.  Action  currents  have  also  been  detected 
in  the  phrenic  nerves  of  living  animals  accompanying  the  respiratory 


828 


ELECTRO-PHYSIOLOG  Y 


discharge  (Reid  and  Macdonald),  in  the  vagi  accompanvnng  the 
movements  of  the  lungs,  in  the  oesophagus  during  swallowing,  in 
the  cutaneous  sensory  nerves  in  response  to  the  '  adequate  '  stimulus 
of  pressure  (Steinach),  in  the  retina  in  response  to  the  adequate 
stimulus  of  light,  in  glands  during  secretion,  in  the  central  nervous 
s^'stem  during  the  passage  of  impulses  along  its  conducting  paths. 
Some  of  these  will  be  further  considered  a  little  later  on. 

As  to  the  interpretation  of  the  facts  we  have  been  describing, 
and  which  are  summed  up  in  the  three  propositions  on  p.  S2i,  two 
chief  doctrines  long  divided  the  physiological  world:  (i)  the  theory  of 
du  Bois-Revmond,  the  pioneer  of  electro-physiolog}-,  and  (2)  the  theory 
of  Hermann.  It  was  believed  by  du  Bois-Reymond  that  the  current 
of  rest  seen  in  injured  tissues  is  of  deep  physiological  import,  and  that 
the  electrical  difference  which  gives 
rise  to  it  is  not  developed  by  the 
lesion  as  such,  but  only  unmasked 
when  the  electrical  balance  is  upset 
by  injury.  He  looked  upon  the 
muscle  or  nerve  as  built  up  of  elec- 
tromotive particles,  with  definite 
positive  and  negative  surfaces  ar- 
ranged in  a  regular  manner  in  a  sort 
of  ground-substance  which  is  elec- 
trically indifferent.  The  '  negative 
variation'  he  supposed  to  depend  en 
an  actual  diminution  of  previously 
existing  electromotive  forces;  and 
from  this  conception  arose  its  his- 
toric name.  Hermann  and  his  school 
assumed  that  the  uninjured  muscle 
or  nerve  is  '  streamless,'  not  because 
equal  and  opposite  electromotive 
forces  exactly  balance  each  other  in 
the  substance  of  the  tissue,  but  be- 
cause electromotive  forces  are  absent 
until  they  are  called  into  existence 
(by  chemical  changes)  at  the  boun- 
dary, or  plane  of  demarcation,  be- 
tween sound  and  injured  tissue.  For  this  reason  du  Bois-Reymond 's 
current  of  rest  is  called  in  the  terminology  of  Hermann  the  '  demarca- 
tion '  current. 

The  newer  theories,  such  as  Macdonald's,  have  sought  to  take  account 
of  the  recent  developments  of  physical  chemistn,'.  and  it  is  unquestion- 
able that  it  is  here  the  real  explanation  is  to  be  found.  There  is  little 
doubt  that  the  electrical  phenomena  of  the  tissues  are  connected  with 
the  existence  in  them  of  membranes,  envelopes,  or  sheaths,  physiological 
if  not  always  anatomical,  which  are  relati\ely  impermeable  to  certain 
ions.  When  such  a  sheath  is  injured,  these  ions,  carrying  with  them 
their  electrical  charges,  may  be  supposed  to  migrate  with  abnormal 
freedom  through  the  injured  part.  A  new  distribution  of  electricity  is 
thus  established  in  the  tissue,  and  differences  of  potential  depending 
uiKjn  differences  in  the  concentration  of  the  ions  at  different  points  are 
set  up.  Bernstein  and  Tschermak.  from  an  investigation  of  the  thermo- 
d\-namic  relations  of  bio-electrical  currents,  have  come  to  the  conclusior 
that  they  are  analogous  to  the  currents  produced  by  so-called  concentra- 


Fig  301. — Upper  Curve,  Record  ul  iLe 
Electrical  Changes  in  the  Vagtis 
N'er\'e  (so-called  '  Electrovagogram  '), 
taken  with  the  String  Galvanometer. 
The  small  waves  on  it  are  s\-nchronous 
with  the  heart-beats,  while  the  large 
waves  are  s>-nchronous  with  the  respi- 
ratory movements,  the  mechanical 
record  of  which  constitutes  the 
second  curve  (ascent,  inspiratioi.). 
The  lowest  curve  is  a  mechanical 
record  of  the  pulse  (Einthoven). 


THEORIES  OF  DEMARCATION  AND  ACTION  CURRENTS    829 

tion  cells — i.e..  arrangements  of  solutions  of  electrolytes  of  different 
concentration  in  contact  with  each  other.  Since  the  development  of 
the  new  electrical  condition  depends  upon  the  fundamental  structure 
of  the  tissue,  these  modern  views  lead  us  back  to  du  Bois-Reymond's 
doctrine  of  a  pre-existing  electrical  equilibrium  connected  with  the 
essential  physiological  properties  of  muscle  or  nerve.  But  instead  of 
his  electromotive  elements  and  their  definite  arrangement,  we  have 
the  ions  and  their  dciinite  relation  to  the  semi-pormcable  membranes. 

Relation  between  the  Action  Current  and  Functional  Activity. — 
Although  the  negative  variation  is  so  general  an  accompaniment  of 
excitation,  and  is  even  within  tolerably  wide  limits,  in  muscle  and  nerve 
at  least,  pretty  nearly  proportional  to  the  strength  of  the  stimulus,  it 
is  at  present  impossible  to  say  definitely  what  the  chemical  or  physical 
changes  are  which  underlie  it.  Unquestionably  the  electrical  changes 
are  closely  related  to  the  excitatory  process  and  to  the  functional 
activity  of  the  tissues.  In  the  case  of  nerve  some  writers,  indeed, 
assume  that  the  redistribution  of  potential  associated  with  the  excited 
state  is  identical  with  the  nervous  impulse,  but  the  common  view  is 
that  the  negative  variation  is  an  accompaniment  of  some  other  change 
which  constitutes  the  propagated  disturbance.  There  is  at  present  no 
clear  experimental  evidence  sufficient  to  decide  the  question.  From 
time  to  time  attempts  have  been  made  to  show  that  the  two  processes 
can  be  dissociated,  but  none  of  the  experiments  so  far  reported  are 
really  crucial. 

Like  the  demarcation  current,  the  action  current  and  the  excitation 
which  accompanies  it  may  be  due  to  changes  in  the  permeability  of 
membranes  or  changes  in  the  concentration  of  certain  ions. 

Although  the  electromotive  changes  caused  by  excitation  are  much 
more  transient  than  those  caused  by  injury,  everything  suggests  that 
there  must  be  some  deep  analogy  between  the  two  conditions.  Some 
have  supposed  that  what  may  be  called  a  subdued  and  more  or  less 
permanent  excitation  exists  in  the  neighbourhood  of  the  injured  tissue, 
an  excitation  which,  like  some  other  forms,  does  not  spread,  and  that 
this  explains  the  similarity  of  electrical  condition  in  activity  and  injury. 

It  is,  of  course,  clear  that  energy  must  be  transformed  to  produce  an 
electromotive  force  capable  of  doing  work.  It  may  be  assumed  that 
this  energy  is  ultimately  derived  from  the  stock  of  chemical  energy  in 
the  tissue-substance.  But  whether  in  the  final  transformation  the 
electrical  phenomena  are  the  expression  of  chemical  changes  or  of 
physical  (osmotic)  changes,  or  of  both,  we  do  not  know.  In  the  case  of 
muscle  it  is  possible  that  the  liberation  cf  lactic  acid,  which  there  are 
several  reasons  for  regarding  as  essentially  concerned  in  the  initiation 
of  the  mechanical  change,  is  associated  in  some  way  with  the  appearance 
of  tlie  negative  variation.  It  is  known  that  the  latter,  although  it 
begins  before  the  contraction,  and  very  rapidly  reaches  its  maximum, 
declines  more  gradually,  so  that  it  overlaps  the  mechanical  change  of 
form.  This  is  particularly  well  seen  in  veratrinized  muscles  (p.  755),  in 
which  the  electrical  variation,  like  the  contraction,  is  greatly  prolonged 
(Garten). 

Polarization  of  Muscle  and  Nerve. — We  have  already  spoken  of 
electrical  excitation  and  of  the  changes  of  excitabihty  caused  by 
the  passage  of  a  constant  current  (p.  785).  We  are  now  to  see  that 
these  physiological  effects  are  accompanied  by,  and  indeed  very 
closely  related  to,  more  physical  changes  which  the  galvanometer 
or  electrometer  reveals  to  us.     Since  these  throw  light  on  the 


Sjo  electro-ph  ysiolog  y 

physical,  and  therefore  ultimately  on  the  physiological,  structure  of 
the  tissues,  they  have  been  deeply  studied,  especially  in  nerve. 
There  is  no  question  that  they  depend  upon  the  presence  in  the 
tissues  of  membranes  presenting  a  relatively  great  resistance  to  the 
passage  of  ions.  When  a  current  is  passed  by  means  of  unpoJarizable 
electrodes  (Fig.  238,  p.  731)  through  a  muscle  or  nerve  for  several 
seconds,  and  the  tissue  connected  to  the  galvanometer  immediately 
after  this  polarizing  current  is  opened,  a  deflection  is  seen  indicating 
a  current  (negative  polarization  current)  in  the  opposite  direction. 

This  (negative)  polarization,  like  the  polarization  of  the  electrodes 
seen  after  passage  of  a  current  through  any  ordinary  electrolytic  con- 
ductor, dilute  sulphuric  acid,  e.g.,  depends  on  the  liberation  of  ions 
(p.  429)  at  the  kathode  and  anode.  It  is  seen  not  only  in  muscle,  nerve, 
and  other  animal  tissues,  but  also  in  vegetable  structures,  and  indeed, 
to  a  certain  extent,  in  unorganized  porous  bodies  soaked  with  electro- 
lytes. In  muscle  and  nerve,  however,  it  is  particularly  well  marked; 
and  although  it  is  not  bound  up  with  the  life  of  tiie  tissue,  and  may  be 
obtained  when  this  has  become  c]uite  inexcitable,  it  is  nevertheless 
dependent  on  the  preservation  of  the  normal  structure,  for  a  boiled 
muscle  shows  but  little  negative  polarization. 

When  the  polarizing  current  is  strong,  and  its  time  of  closure  short, 
we  obtain,  on  connecting  the  tissue  with  the  galvanometer  after  opening 
the  current,  not  a  negative,  but  a  positive  deflection,  indicating  a 
current  in  the  same  direction  as  that  of  the  polarizing  stream.  This  is 
really  an  action  stream,  due  to  the  opening  excitation  set  up  at  the 
anode  (p.  741).  It  is  only  obtained  when  the  tissue  is  living,  and  is  far 
more  strongly  marked  in  the  anodic  than  in  the  kathodic  region. 

Suppose  that  the  nerve  in  Fig.  302  is  stimulated  by  the  opening  of 
the  battery  B,  and  that,  immediately  after,  the  nerve  is  connected  with 
the  galvanometer  G  by  the  electrodes  E,  Ej.  Suppose,  further,  that 
the  shaded  region  near  the  anode  remains  more  excited  for  a  short  time 
than  the  rest  of  the  nerve,  and  we  have  seen  (p.  787)  that  after  the 
opening  of  a  strong  current  there  is  a  delect  of  conductivity,  especially 
in  the  neighbourhocd  of  the  anode,  which  would  tend  to  localize  excita- 
tion. An  action  current  will  pass  through  the  galvanometer  from  Ej 
to  E,  and  through  the  nerve  in  the  same  direction  as  the  original  stimu- 
lating stream.  Under  certain  conditions  a  state  of  continuous  excita- 
tion in  the  ancdic  region  of  a  nerve  is  shown  by  a  tetanus  of  its  muscle 
(Hitler's  tetanus,  p.  741,  and  Fig.  303). 

Electrotonic  Currents. — If  a  current  be  passed  from  the  battery 
through  a  medullated  nerve  (Fig  304)  in  the  direction  indicated  by 
the  arrows,  while  a  galvanometer  is  connected  with  either  of  the 
extrapolar  areas,  as  shown  in  the  figure,  a  current  will  pass  through 
the  galvanometer,  in  the  same  direction  in  the  nerve  as  the  polar- 
izing current,  so  long  as  the  latter  continues  to  flow. 

These  currents  are  called  electrotonic  (in  the  kathodic  region  katelectro- 
lonic  ,  in  the  anodic,  anelectrotonic).  The  exact  mode  of  their  produc- 
tion is  obscure.  Similar  currents  can  be  detected  in  artificial  models 
consisting  of  a  good  conducting  core  and  a  badiv  conducting  envelope; 
for  example,  a  platinum  wire  in  a  ghiss  tube  filled  with  saturated  zinc 
sulphate  solution,  or  a  zinc  wire  covered  with  cotton-wool  soaked  in 
salt  solution.     In  such  models  it  appears  to  be  essential  that  there 


ELECTROTOKIC  CVRRESTS 


83t 


should  be  polarization  (separation  of  ions)  at  the  i)Oiinclary  between 
the  core  anrl  the  sheath — i.e.,  between  the  wire  and  the  liquid,  where 
the  current  passes  from  the  one  to  the  other. 

A  current  led  into  the  sheath  tries,  so  to  speak,  to  pass  mostly  by 
the  good  ccnductiiiy  wire.       if  this  is  not  pohirizable  -  if  it  is,  e.s,.,  a 


Fig,  30J. — Diagram  to  show  Dis- 
tribution  of  '  Positive  Polar- 
zation  '  after  opening  Polar- 
izing Current.  B,  battery; 
G,  galvanometer.  The  dark 
shading  signifies  that  the  ex- 
citation to  which  the  current 
causing  the  positive  deflection 
after  the  opcTiing  of  the  polar- 
izing current  is  due  is  greatest 
in  the  immediate  neighbour- 
hood of  the  anode,  and  fades 
away  in  the  intrapolar  region. 
■+■  indicates  the  anode,  and 
—  the  kathode  of  the  polariz- 
ing current. 


Fig.  303.— Ritter's  Tetanus. 
A  strong  voltaic  current 
was  passed  for  some  time 
through  the  nerve  of  a 
muscle  -  nerve  preparation. 
On  opening  the  circuit,  the 
muscle  gave  one  strong  con- 
traction, and  then  entered 
into  irregular  tetanus,  which 
continued  for  four  minutes. 
(Only  the  first  part  of  the 
tracing  is  reproduced.) 


zinc  wire  surrounded  by  saturated  zinc  sulphate  solution — there  is 
little  or  no  spreading  of  the  current  outside  the  electrodes:  it  passes  at 
once  into  the  core,  and  so  on  to  the  other  electrode.  If,  howe\er,  there 
is  polarization  when  the  current  passes  from  the  liquid  into  the  wire, 
as  is  the  case  in  the  platinum-zinc  sulphate  or  the  zinc -sodium  chloride 

combinations,  the  stream 
spreads  longitudinally  in 
the  sheath,  since  the 
polarization  introduces  a 
virtual  resistance  at  the 
surface  of  the  wire,  in 
comparison  with  which 
the  difference  in  resis- 
tance of  an  oblique  and  a 
direct  transverse  path 
through  the  liquid  becomes  small.  It  has  been  supposed  that  in 
medullated  nerve  a  similar  polarization  takes  place  at  the  boundary 
between  some  part  of  the  nerve-fibre  which  may  be  called  a  core,  and 
another  part  which  may  be  called  a  sheath — for  instance,  between  the 
axis-cylinder  and  the  medullary  sheath,  or  between  the  latter  and  the 
neurilemma.     It  is  known  that  the  electrical  resistance  of  nerve  in  the 


^€H    ,-f-^"k, .  ,^>. 


Fig.  304. — Diagram  showing  Direction  of  the  Extra- 
polar  Electrotonic  Currents,  -f  is  the  anode 
and  -  the  kathode  of  the  polarizing  current. 


832  ELECTRO-PHYSIOLOGY 

transverse  direction  is  much  greater  (five  to  seven  times)*  than  the 
longitudinal  resistance.  Since  a  rapidly-established  polarization  would, 
by  the  ordinary  methods  of  measurement,  appear  as  a  resistance,  this 
has  been  adduced  as  evidence  of  the  great  capacity  of  nerve  for  polar- 
ization by  a  current  passing  across  the  fibres.  It  is,  however,  probable, 
from  what  we  know  of  the  high  electrical  resistance  of  the  physiological 
envelopes  of  such  cells  as  the  red  blood-corpuscles  (p.  26),  that  the 
great  transverse  resistance  of  nerve,  and  indeed  the  electrotonic  currents, 
are  due  in  part,  if  not  wholly,  to  the  true  resistance  of  one  or  more  of 
its  envelopes  (perhaps  the  medullary  sheath).  Examples  of  such 
differences  of  resistance  even  in  the  fluid  constituents  of  one  and  the 
same  animal  structure  are  not  wanting.  For  instance,  the  specific 
resistance  of  the  yolk  of  a  hen's  egg  may  be  three  times  greater  than 
that  of  the  white. 

The  electrotonic  currents  cannot  spread  beyond  a  ligature;  they  are 
stopped  by  anything  which  destroys  the  structure  of  the  tissue;  they 
are  affected  by  various  reagents.  But  this  does  not  prove  that  they 
are  other  than  physical  in  origin,  for  what  destroys  the  structure  of 
the  tissue  or  modifies  its  molecular  condition  may  destroy  or  diminish 
its  capacity  for  polarization,  or  alter  its  electrical  resistance. 

There  are,  however,  certain  facts  which  indicate  that  physiological 
factors,  as  well  as  physical,  are  concerned.  While  the  currents  obtained 
from  core-models  show  a  general  resemblance  to  the  electrotonic  currents 
of  medullated  nerve,  there  is  one  significant  difference:  in  the  former  the 
katelectrotonic  and  anelectrotonic  currents  arc  of  equal  intensity;  in 
the  latter  the  anelectrotonic  preponderates.  The  most  probable  eX' 
planation  is  that  the  anelectrotonic  current  of  medullated  nerve  is  made 
up  of  two  distinct  electrical  effects,  one  physiological  in  nature,  the  other 
dependent  merely  on  the  structure  and  physical  properties  of  the  fibres, 
while  the  katelectrotonic  current  is  wholly  physical.  It  is  in  favour  of 
this  hypothesis  that  under  the  infironce  of  ether,  which  abolishes  the 
physiological  functions  of  nerve,  the  anelectrotonic  current  diminishes 
till  it  becomes  equal  to  the  kateletrotonic.  Non-medullated  nerves,  in 
which  the  conditions  for  physical  electrotonus,  if  present  at  all,  are  only 
feebly  developed,  and  which  exhibit  no  katelectrotonic  current,  or  only 
a  very  weak  one,  show  an  anelectrotonic  current,  which  is  abolished  by 
ether,  and  seems  to  represent  the  physiological  portion  of  the  anelectro- 
tonic current  of  medullated  nerve. 

A  nerve  may  be  stimulated  by  an  electrotonic  current  produced 
in  nerve-fibres  lying  in  contact  with  it.  A  well-known  illustration 
of  this  is  the  experiment  known  as  the  paradoxical  contraction 
(Practical  Exercises,  p.  84-I). 

The  current  of  action  of  a  nerve  can  also  stimulate  another  nerve 
when  the  excitability  of  both  is  greater  than  normal,  as  is  the  case 
in  the  nerves  of  frogs  kept  in  the  cold.  This  comes  under  the  head 
of  secondary  contraction.  But  the  best-known  form  of  secondary 
contraction  is  where  a  nerve,  placed  on  a  muscle  so  as  to  touch  it  in 
two  points  (Fig.  305),  is  stimulated  by  the  action-current  of  the 
muscle,  and  causes  its  own  muscle  to  contract.     A  secondary  tetanus 

*  Since  a  part  of  the  current  is  conducted  by  the  connective  tissue  and 
other  structures  lying  between  the  nerve-ftbres,  and  the  long;itudinaI  and 
transverse  resistance  of  these  tissues  may  be  supposed  equal,  the  disproportion 
between  the  longitudinal  and  transverse  resistance  of  the  nerve  fibres  them- 
selves is  probably  much  greater  than  this. 


ELECTROTONIC  CURRENTS 


833 


can  be  obtained  in  this  way  by  dropping  a  nerve  on  an  artificially 
tetanized  muscle.  The  beat  of  the  heart  causes  usually  only  a 
single  secondary  contraction  when  the  sciatic  nerve  of  a  frog  is 
allowed  to  fall  on  it  (p.  203).  But  when  the  diphasic  variation  is 
well  marked,  as  it  is  in  an  uninjured  heart,  there  may  be  a  secondary 
contraction  for  each  phase — 
i.e.,  two  for  each  heart-beat. 
Excitation  of  one  muscle  may  in 
the  same  way  cause  secondary 
contraction  of  another  with 
which  it  is  in  close  contact. 


I 


Fig.  305.  —  Secondary  Coutrax:- 
tioa.  The  nerve  of  muscle  M 
touches  muscle  M'  at  a  and  h. 
Stimulation  of  the  nerve  of  M' 
at  S  causes  contraction  of  M. 


Fig.  306. — :  ;  r^'  rd  from  Rab- 

bit's Heart  {(j'.trh).  the  lieart  was  ex- 
posed and  beating  in  situ.  Contacts,  one 
on  base  of  right  ventricle,  the  other  on 
right  apex.  The  commencement  of  the 
beat  is  on  the  left-hand  edge  of  the  dark 
line  V.  The  length  of  the  dark  line  shows 
the  duration  of  the  beat.  Upward  move- 
ment signifies  relative  negativity  (activity) 
of  the  part  at  or  near  the  base  contact. 
Time-trace  at  tou,  one-fifth  second. 


The  electromotive  phenomena  of  the  heart  and  of  the  central  ner- 
vous system  are  naturally  included  under  those  of  muscle  and  nerve. 

Heart. — Records  of  the  electrical  changes  obtained  with  the 
capillary  electrometer  or  string  galvanometer  from  the  exposed 
ventricles  vary  in  certain  details  with  the  position  of  the  two 
contacts.  When  one  contact  is  on  the  base  of  the  ventricles  (in  the 
rabbit)  near  the  auriculo-ventricular  groove,  and  the  other  on  the 
apex  (Fig.  306),  for  each  beat  of  the  ventricle  the  electrometer  record 
shows  (i)  a  sharp  rise,  indicating  relative  negativity  (activity)  of 
the  base ;  (2)  an  equally  sharp  fall,  indicating  relative  negativity  at 
the  apex;  (3)  a  slower  but  marked  rise,  indicating  an  increase  or  a 
fresh  development  of  relative  negativity  at  the  base;  (4)  a  more 
rapid  fall,  which  returns  first  slowly,  then  quickly,  until  (i)  follows 
again  (Gotch).  The  time  between  the  beginning  and  the  top  of 
rise  (i)  I's  believed  to  correspond  to  the  time  of  transmission  of  the 

53 


834 


ELECT  RO-PH  YSIOLOG  Y 


active  state  from  the  base  to  the  apex.  The  rate  of  propagation 
on  the  rabbit's  ventricle  varies  from  i  to  3  metres  a  second,  accord- 
ing to  the  rate  of  the  heart-beat.  Such  observations  have  been  inter- 
preted as  indicating  that  the  excitation,  with  its  accompanying 
electrical  change,  begins  at  the  base,  then  develops  in  the  region  of 
the  apex,  and  finally  involves  the  poition  of  the  ventricles  near  the 
aorta  and  pulmonary  artery,  possibly  extending  even  into  the  roots 
of  these  vessels.  The  full  explanation  of  this  seemingly  erratic 
course  of  the  excitation  wave  is  doubtless  dependent  upon  a  full 
knowledge  of  the  course  and  connections  of  the  conducting  system. 


Fig.  307. — Electrometer  Record  from  Tortoise  Heart  (Gotck).  Out  contact  upon 
the  sinus,  the  other  on  the  ape.x  oi  the  '.entricle.  One  complete  beat  shown. 
Upward  movement  signifies  relative  negativity  of  the  sinus  contact.  The  dark 
line  A  shows  the  auricular  effect,  and  the  dark  line  V  the  ventricular  effect. 
Time-trace  at  top,  one-&fth  second. 

and  this  we  do  not  possess  as  yet.  The  fact  that  the  ventricle  is 
originally  developed  from  a  tube  with  a  venous  and  an  arterial  end, 
and  that  this  tube  later  on  becomes  bent  upon  itself  so  that  the  two 
ends  (the  auricular  or  venous  and  the  aortic  or  arterial)  lie  together 
at  the  base  of  the  ventricle,  probably  affords  the  clue.  It  should 
be  mentioned,  however,  that  this  explanation  of  the  second  rise  of 
the  ventricular  ciu"ve  (the  T-wave,  according  to  Einthoven's  nomen- 
clature. Fig.  313)  is  by  no  means  universally  accepted.  Einthoven, 
who  has  worked  with  the  string  galvanometer,  believes  that  be- 
tween the  first  (R)  and  the  second  (T)  ventricular  waves  the  whole 
of  the  ventricle  is  in  contraction,  and  that  there  is  no  difference  of 


ELECTRO-CA  RDIOGRA  M 


«35 


1 


Fig.  308. — Electro-Cardiograms  from  Man 
(Capillary  Electrometer)  (Einthoven  and 
Lint).  Obtained  from  the  same  individual 
at  rest  (upper  curve),  and  immediately  after 
vigorous  muscular  exercise  (lower  curve). 
The  elevations  A,  C,  D,  indicate  negativity 
of  base  to  ape.x;  the  notches  B  and  C^,  nega- 
tivity of  apex  to  base. 


potential  at  this  time  between  its  various  parts.     The  T-wave  he 
considers  to  be  produced,  when  it  is  present,  merely  because  the 

excitated  state  does  not  dis- 
appear simultaneously  over 
the  whole  ventricle. 

In  the  ventricle  of  the 
frog  and  tortoise  the  same 
order  of  development  of  the 
negative  change  is  seen,  the 
base  first  becoming  rela- 
tively negative,  then  the 
apex,  and  then  the  neigh- 
bourhood of  the  origin  of 
the  aorta  (Fig.  307). 

Under  certain  conditions 
the  action  current  of  the  heart 
may  stimulate  the  phrenic 
nerves,  causing  the  dia- 
phragm to  contract  sjTichro- 
nously  with  the  heart. 

The  Human  Electro- Cardi- 
ogram.— An  electrical  change 
accompanies  each  beat  of  the  human  heart.     Waller  first  showed  how 
this  may  be  demonstrated  by  means  of  the  capillary  electrometer. 

Einthoven  and 
Lint  then  investi- 
gated the  pheno- 
menon on  a  large 
numberof  persons. 
From  the  photo- 
graphic records  of 
the  movements  of 
the  meniscus  they 
constructed  the 
true  electro  -  car- 
diographic  curves* 
(Fig.  309;,  which 
express  the  actual 
changes  in  the  po- 
tential difference 
between  the  two 
points  led  ofif. 
They  distinguished 
in  every  one  of 
these  constructed 
electro-cardio- 
grams five  points 
or  cusps,  three  of 
which  indicate  re- 
lative    negativity 


Fig.  309, — Constructed  Elec- 
tro-Cardiograms from  Man 
(EinthovenandLint).  Time 
is  laid  off  along  the  hori- 
zontal, and  electromotive 
force  along  the  vertical  axis, 
the  same  space  being  allot- 
ted to  ten  millivolts  (i.e., 
Y^  volt)  as  to  one  second. 


Fig.  310. —  Illustrating  the 
Position  of  Favourable  and 
Unfavourable  Leads  for 
the  Human  Electro- 
Cardiogram  (Waller). 


*  In  all  accurate  work  with  the  capillary  electrometer  such  curves  must  be 
obtained  by  construction  from  the  direct  photographic  records,  which  do  not 
themselves  give  an  absolutely  true  picture  of  the  variations. 


836 


ELECT  RO-PH  YSIOLOG  Y 


of  tlie  base  of  the  heart  to  the  apex,  and  two  negativity  of  the  apex  to 
the  base.  The  capillary  electrometer  hns  now  been  superseded  by  the 
string  galvanometer  (p. '726)  for  the  investigation  of  the  human  electro- 
cardiogram (Figs.  311-315).  But  a  sample  of  the  records  obtained  by 
the   former   method    (Fig.    308),  witli   the   corresponding  constructed 


Fig.  311. — Human  Electro-Cardiogram 
(String  Galvanometer)  (Einthoven). 
Led  off  from  the  two  hands,  i  mm. 
of  the  abscissa  corresponds  to  00 1 
second. 


Fig.  312. — Human  Electro-Cardio- 
gram (String  (ialvanoraeter) 
(Einthoven).  Led  off  from  right 
hand  and  left  foot. 


0,1  Sec 


FJ§-  313- — Schematic  Representation  of  Electro-Cardiogram  (String  Galvanometer) 
(Einthoven).  Five  points  are  lettered  at  which  the  curve  changes  sign.  P  cor- 
responds to  the  auricular  contraction;  the  other  four  are  included  in  the  ven- 
tricular cycle. 


Fig.  314.— Electro-Cardiogram  from  Man  (String  Galvanometer)  (Lewis).  From  a 
case  of  paroxysmal  tachycardia.  The  heart-rate  was  200  a  minute.  The  upper 
notched  line  is  the  time-trace  in  one-fifth  seconds. 


electro -cardiograms,  (Fig.  309)  is  reproduced  for  their  historical  interest. 
In  their  main  features  it  is  obvious  that  they  agree  with  the  records 
obtained  by  the  string  galvanometer.  The  electro-cardiograms  are 
distinctly  affected  by  exercise  and  by  the  position  of  the  body,  and  very 
markedly  in  disease.    The  galvanometer  may  be  connected  with  the  two 


ELECTRO-CA  R  DIOCRA  M 


837 


liands,  or,  bettor,  wilh  the  ri},'lit  hand  and  the  loft  foot.  Tlic  two  feet 
arc  the  most  unfavourable  oombination.  The  reason  is  obvious  from 
the  (lireetion  of  the  long  axis  of  the  heart,  which  determines  the 
direction  of  the  lines  of  flow  of  currents  due  to  differences  of  potential 
between  base  and  apex  (I'Mg.  },\o). 

Relation  of  the  Waves  of  the  Electro-Cardiogram  to  the  Mechanical 
Events  in  the  Cardiac  Cycle.  Tlioro  is  ovidonco  that  the  excitation  pro- 
cess with  its  associated  electrical  change  spreads  over  the  auricle  from  the 
sinus  mxle,  followed  at  each  point  by  the  mechanical  change  or  contrac- 
tion, in  such  a  manner  that  the  portions  nearer  the  node  begin  to  relax 
before  the  more  distal  units  have  finished  contracting.  When  a  tracing 
of  the  approximation  of  two  distant  points  of  the  auricle  is  taken, 
the  total  shortening  represents  the  algebraic  sum  of  the  contractions 
and   relaxations  of  all  the   muscular   units  between   the   two   points. 


'^^^m^J' 


Fig-  315— Upper  curve,  pressure  in  right  auricle.  Second  curve  from  top,  right 
auricular  myogram;  the  down-stroke  corresponds  to  contraction.  Third  curve, 
ventricular  sounds.  Bottom  curve,  electrocardiogram,  lead  //  (left  hind  and 
right  fore  leg)  (Wiggers). 

Electrical  effects  obtained  by  leading  off  from  the  heart  in  any  particu- 
lar way  must  also  be  more  or  less  complex  resultants  of  the  changes  at 
different  points.  Certain  general  relations,  however,  have  been  estab- 
lished between  the  mechanical  events  and  the  electro-cardiogram.  In 
Fig;  31.5  are  shown  simultaneous  records  of  the  contraction  of  the 
auricle  (auricular  myogram),  the  intra-auricular  pressure,  the  heart 
sounds  and  the  electro-cardiogram  (Wiggers).  The  first  electrical 
variation,  commencing  at  i,  is  seen  to  precede  the  rise  of  pressure  in 
the  auricle,  2,  by  a  definite  interval  (about  002  sec),  and  the  onset  of 
the  mechanical  shortening  ,3,  by  a  somewhat  greater  interval  (o-o^  sec). 
The  length  of  these  intervals  is,  of  course,  not  precisely  the  same  in 
different  experiments. 

The  relation  of  the  beginning  of  the  rise  of  intra-auricular  pressure 
and  of  the  beginning  of  the  mechanical  systole  of  the  auricles  to  the 


838  ELECTRO-PHYSIOLOGY 

P  wave  of  the  electro-cardiogram  (the  wave  specially  associated  with 
the  passage  of  excitation  over  the  auricle)  is  also  slightly  variable. 
Roughly,  the  apex  of  the  P  wave  may  be  taken  as  mdicating  the  onset 
of  the  auricular  systole.  The  relation  l^etwcen  the  end  of  the  auricular 
systole,  4,  and  the  electro-cardiogram,  is  still  more  variable,  but  in 
general  it  falls  not  far  from  the  summit  of  the  R  wave  (a  wave  specially 
associated  with  the  passage  of  the  excitation  over  the  ventricle).  This 
shows  that  the  auricular  systole  still  continues  at  a  time  when  the  ex- 
citation process  has  already  made  considerable  progress  in  the  ventricle. 
The  mechanical  contraction  of  the  ventricle,  as  shown  in  Fig.  315,  bv 
the  position  of  the  vibrations  corresponding  to  the  first  sound,  follows 
very  promptly  the  completion  of  the  auricular  svstole. 

Central  Nervous  System. — It  was  discovered  by  du  Bois-Rej-mond 
that  the  spmal  cord,  like  a  nerve,  shows  a  current  of  rest  between  longi- 
tudinal surface  and  cross-section,  and  that  a  current  of  action  is  caused 
by  excitation.  Setschenow  stated  that  when  the  medulla  oblongata 
of  the  frog  was  connected  with  a  galvanometer,  spontaneous  variations 
occurred  which  he  supposed  due  to  periodic  functional  changes  in  its 
grey  matter.  Gotch  and  Horsley  have  made  experiments  on  the  spinal 
cords  of  cats  and  monkeys.  Leading  off  from  an  isolated  portion  of 
the  dorsal  cord  to  the  capillary  electrometer,  and  stimulating  the 
'  motor  '  region  of  the  cortex  cerebri,  they  obtained  a  persistent  nega- 
tive variation  followed  by  a  series  of  intermittent  variations.  This 
agrees  remarkably  with  the  muscular  contractions  in  an  epileptiform 
convulsion  started  bv  a  similar  excitation  of  the  cortex,  which  consist 
of  a  tonic  spasm  followed  by  clonic  or  phasic  (interrupted)  contractions. 
By  means  of  the  galvanometer,  the  same  observers  have  made  in- 
vestigations on  the  paths  by  which  impulses  set  up  at  different  points 
travel  along  the  cord.     To  these  we  shall  have  to  refer  again  (p.  893). 

Electrical  Phenomena  of  Glands. — These  have  been  studied  with  any 
care  chiefly  in  the  submaxillary  gland  and  in  the  skin,  although  the 
liver,   kidney,  spleen,  and   other   organs  also 
show    currents    when    injured.      In    the    sub- 
maxillary gland  the  hilus  is  galvanometrically 
positive  to  any  point  on  the  external  surface 
of  the  gland  :   a  current  passes  from  hilus  to 
surface  through  the  galvanometer,  and  from 
surface  to  hilus  through  the  gland  (Fig.  316). 
Fig.  316. — Current  of  Sub-    When  the  chorda  tvmpani  is  stimulated  with 
maxillary  Gland.  rapidly  -  succeeding      shocks      of      moderate 

strength,  there  is  a  positive  variation — i.e..  the 
hilus  becomes  still  more  positive  to  the  surface.  This  variation  can 
be  abolished  by  a  small  dose  of  atropine. 

Skin  Currents. — So  far  as  has  been  investigated,  the  integument  of  all 
animals  shows  a  permanent  current  passing  in  the  skin  from  the  external 
surface  inwards.  This  is  feebler  in  skin  which  possesses  no  glands.  In 
skin  containing  glands  the  current  is  chiefly,  but  not  altogether,  secre- 
tory. As  such,  it  is  affected  by  influences  which  affect  secretion,  a 
positive  variation  being  caused  by  excitation  of  secretorv  nerves — e.g., 
in  the  pad  of  the  cat's  foot  by  stimulation  of  the  sciatic.  The  deflection 
obtained  when  a  finger  of  each  liand  is  led  off  to  the  galvanometer, 
which  was  at  one  time  looked  upon  as  a  proof  of  the  existence  of  currents 
of  rest  in  intact  muscles,  is  due  to  a  secretion  current. 

Of  more  doubtful  origin  is  the  current  of  ciliated  mucous  membrane, 
which  has  the  same  direction  as  that  of  the  skin  of  the  frog  and  the 
mucous  membrane  of  the  stomach  of  the  frog  and  the  rabbit — viz.,  from 
ciliated  to  under  surface  through  the  tissue,  or  from  ciliated  surface  to 
cross-section,  if  that  is  the  way  in  which  it  is  led  off.     The  current  is 


ELECTROMOTIVE  PHr:\OMi:XA  OF  THE  EYE 


830 


strengthened  by  induction  shocks,  by  heating,  and  in  general  by  influ- 
ences which  increase  the  activity  of  the  cilia.  Some  circumstances 
point  to  tlie  gobiet-cells  in  the  membrane  as  the  source  of  the  current; 
but,  on  the  whole,  the  balance  of  evidence  is  in  favour  of  the  cilia  V)cing 
the  chief  factor  (Engelmann),  although  the  mucin-sccreting  cells  may 
be  concerned,  too.  Klectrical  changes  associated  with  secretion  have 
been  observed  in  the  frog's  tongue  on  excitation  of  the  glosso-pharyngeal 
nerve. 

Eye-Currents. — If  two  unpolarizable  electrodes  connected  with  a 
galvanometer  are  placed  on  the  excised  eye  of  a  frog  or  rabbit,  one  on 
the  cornea  and  the  other  on  the  cut  optic  nerve,  or  on  the  posterior 
surface  of  the  eyeball,  it  is  found  that  a  current  passes  in  the  eye  from 
optic  nerve  to  cornea,  the  fundus  of  the  eye  being  therefore  negative 
as  regards  the  cornea  (Fig.  317).  The  current  has  the  same  direction 
if  the  anterior  electrode  is  placed  on  the  an- 
terior surface  of  the  retina  itself,  the  front  of 
the  eyeball  being  cut  away,  or  if  one  electrode 
is  in  contact  with  the  anterior  and  the  other 
with  the  posterior  surface  of  the  isolate,  d 
retina.  There  is  nothing  of  special  interest  in 
this;  but  the  important  point  is  that  if  light  be 
now  allowed  to  fall  upon  the  eye,  or  upon  the 
isolated  retina,  characteristic  electrical  changes 
are  caused.  These  are  spoken  of  as  the  photo- 
electric reaction,  and  are  best  studied  by  means 
of  the  string  galvanometer.  The  features  of 
the  curve  representing  the  photo-electric  reaction  vary  with  the  duration 
and  intensity  of  the  illumination  and  with  the  previous  condition  of  tlie 
eye  as  regards  illumination.  A  careful  analysis  of  the  curves  obtained 
under  different  conditions  supports  the  hypothesis  that  there  occur  in 
the  eye  three  separate  processes,  which  may  for  convenience  be  con- 
sidered to  depend  upon  the  existence  in  the  retina  of  three  separate 
photo-chemical  substances.  When  light  of  moderate  intensity  is 
allowed  to  act  upon  an  eye  which  has  not  shortly  before  been  exposed 


3 17. — E  ye  -Current . 


Pig,  318.— Photo-Electric  Reaction  of  Frog's  Eye  (Einthoven  and  Jolly).  The 
duration  of  the  flash  (of  green  light)  wasooi  second.  The  eye  had  been  pre- 
viously in  the  dark,  i  millimetre  of  the  abscissa  corresponds  to  05  second, 
I  millimetre  of  the  ordinate  to  10  microvolts.    Curve  to  be  read  from  left  to  right. 

to  strong  light,  a  form  of  curve  is  obtained  which  seems  to  represent 
the  combined  reaction  of  the  three  substances  (Einthoven  and  Jolly) 
(Fig.  318).  After  a  latent  period  a  small  preliminary  negative  deflec- 
tion A  is  observed  (downward  movement  of  the  string).     This  is  at  once 


840 


ELECTROPHYSIOLOGY 


followed  by  a  mivch  larger  upward  movement  (positive  variation)  in 
the  same  direction  as  the  resting  effect,  the  fundujp  becoming  relatively 
more  negative  to  the  cornea  than  before.  After  the  peak  B  has  been 
reached,  the  curve  sinks  first  rapidly,  then  more  gradually,  but  soon 
mounts  again,  and  reaches  a  second  maximum  C,  vhich  is  higher  than  B 
(second  positive  variation).  Finally,  the  curve  descends  to  its  original 
level.*  The  photo-electric  reaction  is  substantially  the  same  in  all 
vertebrate  eyes  hitherto  investigated.  In  the  cephalopcd  retina,  too, 
the  only  imj)ortant  electrical  change  on  illumination  is  in  the  same 
direction  as  the  resting  effect. 

The  reaction  depends  upon  the  retina  alone,  nnd  does  not  occur 
when  it  is  removed.  Blenching  of  the  visual  purple  docs  not  much 
affect  it,  so  that  it  is  not  connected  with  chemical  changes  in  this 
substance.     Its  seat  must  be  the  layer  of  rods  find  cones,  since  in  the 


Fig.  319. — Diagram  showing  iJircction  of  Shock  in  Gyninotus. 

cephalopods  the  structure  called  the  retina  contains  only  this  layer,  the 
other  layers  of  the  vertebrate  retina  being  represented  in  the  optic  nerve 
and  ganglion  (Beck).  Of  the  spectral  colours,  yellow  light  causes  the 
largest  variation;  blue,  the  least;  but  white  light  is  more  powerful  than 
either  (Dewar  and  McKendrick).  (For'  visual  purple,' seeC  hap.  XVIII.) 
Electric  Fishes. — Except  lightning,  the  shocks  of  these  fishes  were 
probably  the  first  manifestations  of  electricity  observed  by  man.  The 
Torpedo,  or  electrical  ray,  of  the  coasts  of  Europe  was  known  to  the 
Crocks  and  Romans.     It  is  mentioned  in  the  writings  of  Aristotle  and 

Pliny,  and  had  the  honour  of 
being  described  in  verse  1,500 
years  before  Faraday  made  the 
first  really  exact  investigation 
of  the  shock  of  the  Gymnotus, 
or  electric  eel,  of  South  America. 
Another  of  the  electric  fishes, 
Malapterurus  clectricus,  al- 
though found  in  many  of  the 
African  rivers,  the  Nile  in  par- 
ticular, and  known  forages,  was 
scarcely  investigated  till  fifty 
years  ago. 

In  all  these  fishes  there  is  a 
special  bilateral  organ  immediately  under  the  skin,  called  the  electrical 
organ.  It  is  in  this  that  the  shock  is  developed.  It  consists  of  a 
series  of  plates  arranged  parallel  to  each  other.  To  one  side  of  each 
plate  a  branch  of  the  electrical  nerve  supplying  each  lateral  half  of 

*  In  the  figure  the  last  portioD  of  the  curve  while  it  is  still  slowly  descending 
has  not  been  reproduced. 


320. — Diag.-am    showing    Direction    of 
Shock  in  Malapterurus. 


ELECTRIC  FISHES  841 

the  organ  is  tlistrilnitcd,  so  that  each  half  of  the  organ  represents  a 
battery  of  many  cells  arranged  in  series. 

In  C.ymnotus  the  plates  are  vertical,  and  at  right  angles  to  the  long 
axis  of  the  fish,  and  the  nerves  are  distributed  to  their  posterior  surface  ; 
the  shock  passes  in  the  animal  from  tail  to  head.  In  Malapterurus, 
although  the  direction  of  the  plates  is  the  same,  and  the  nerve-supply 
is  also  to  the  posterior  surface,  the  shock  passes  from  head  to  tail. 

In  Torpedo,  the  plates  or  septa  dividing  the  vertical  hexagonal  prisms 
of  which  each  lateral  half  of  the  organ  consists  are  horizontal ;  the  nerve- 
supply  is  to  the  lower  or  ventral  surface ;  and  the  shock  passes  from  belly 
to  back  through  the  organ.  In  all  electric  fishes  the  discharge  is  dis- 
continuous; an  active  fish  may  give  as  many  as  200  shocks  per  second. 

The  electrical  nerve  of  Malapterurus  is  peculiar.  It  consists  of  a 
single  gigantic  nerve-fibre  on  each  side,  arising  from  a  giant  nerve-cell. 
The  fibre  has  an  enormously  thick  siieath,  the  axis-cylinder  forming  a 
relatively  small  part  of  the  whole;  and  the  branches  which  supply  the 
plates  of  the  organ  are  divisions  of  this  single  axis-cylinder. 

The  electromotive  force  of  the  shock  of  the  Gymnotus  may  be  very 
considerable;  and  even  Torpedo  and  Malapterurus  are  quite  able  to 
kill  other  fish,  their  enemies  or  their  prey.  Indeed,  Gotch  has  esti- 
mated the  electromotive  force  of  i  cm.  of  the  organ  of  Torpedo  at 
5  volts.  Schonlein  finds  that  the  electromotive  force  of  the  whole 
organ  may  be  equal  to  that  of  31  Daniell  cells,  or  0-08  volt  for  each 
plate,  and  it  is  one  of  the  most  interesting  questions  in  the  whole  of 
electro-physiol'jgy,  how  they  are  pro- 
tected from  their  own  currents .  There 
is  no  doubt  that  the  current  density 
inside  the  fish  must  be  at  least  as 
great  as  in  any  part  of  the  water  sur- 
rounding it,  and  probably  much 
greater.  The  central  nervous  system 
and  the  great  nerves  must  be  struck 
by  strong  shocks,  yet  the  fish  itself  is  Fig.  321.— Diagram  showing  Uirec- 
not  injured;  nay,  more,  the  young  in  tion  of  Shock  in  Torpedo, 

the  uterus  of  the  viviparous  Torpedo 

are  unharmed.  The  only  explanation  seems  to  be  that  the  tissues  of 
electric  fishes  are  far  less  excitable  to  electrical  stimuli  than  the  tissues  of 
other  animals;  and  this  is  found  to  be  the  case  when  their  muscles  or 
nerves  are  tested  with  galvanic  or  induction  currents.  It  requires  ex- 
tremely strong  currents  to  stimulate  them ;  and  the  electrical  nerves  are 
more  easily  excited  mechanically,  as  by  ligaturing  or  pinching,  than  elec- 
trically. In  general,  too,  the  shock  is  more  readily  called  forth  by  reflex 
mechanical  stimulation  of  the  skin  than  by  electrical  stimulation.  But 
that  the  organ  itself  is  excitable  by  electricity  has  been  shown  by  Gotch. 
He  proved  that  in  Torpedo  a  current  passed  in  the  normal  direction 
of  the  shock  is  strengthened,  and  a  current  passed  in  the  opposite 
direction  weakened,  by  the  development  of  an  action  current  in  the 
direction  of  the  shock.  And,  indeed,  a  single  excitation  of  the  electrical 
nerve  is  followed  by  a  series  of  electrical  oscillations  in  the  organ,  which 
gradually  die  away.  The  latent  period  of  a  single  shock  is  about 
oJo  second.  The  skate  must  be  included  in  the  list  of  electric  fishes. 
Although  its  organ  is  relatively  small,  and  its  electromotive  force  rela- 
tively feeble,  yet  it  is  in  all  respects  a  complete  electrical  organ.  It 
is  situated  on  either  side  of  the  vertebral  column  in  the  tail.  The 
plates  or  discs  are  placed  transversely  and  in  vertical  planes.  The 
nerves  enter  tlieir  anterior  surfaces;  the  shock  passes  in  the  organ  from 
anterior  to  posterior  end.  Gotch  and  Sanderson  have  estimated  the 
maximum  electromotive  force  of  a  length  of  i  cm.  of  the  electrical 
organ  of  the  skate  at  about  half  a  volt. 


842  ELECT  RO-PH  YSIOLOG  Y 

WTiether  the  electrical  organ  is  the  homologue  of  muscle  or  of  nerve- 
ending,  or  whether  it  is  related  to  either,  has  Ix^cn  much  discussed. 
Our  surest  guide  in  a  question  of  this  sort  is  the  study  of  development; 
and  researches  along  this  line  have  shown  that  there  are  two  kinds  oi 
electrical  organ,  one  being  modified  muscle  (as  in  Gymnotus,  Torpedo, 
and  the  skate) ;  the  other  transformed  skin-glands  (as  in  Malapterurus). 
The  scantv  blood-supply  of  the  electrical  organs  in  comparison  with  that 
of  muscle  is  noteworthy.  In  no  case  do  bloodvessels  enter  the  substance 
of  the  plates. 

PRACTICAL  EXERCISES  ON  CHAPTER  XV. 

1.  Galvani's  Experiment. — Pith  a  frog  (brain  and  cord).  Cut  through 
the  backbone  above  the  urostyle.  and  clear  away  the  anterior  portion 
of  the  body  and  the  viscera.  Pass  a  copper  hook  beneath  the  two 
sciatic  plexuses,  and  hang  the  legs  bj-  the  hook  on  an  iron  tripod.  If 
the  tripod  has  been  painted,  the  paint  must  be  scraped  away  where  the 
hook  is  in  contact  with  it.  Now  tilt  the  tripod  so  that  the  legs  come 
in  contact  with  one  of  the  iron  feet.  Whenever  this  happens,  the 
circuit  for  the  current  set  up  by  the  contact  of  the  copper  and  iron  is 
completed,  the  nerves  are  stimulated,  and  the  muscles  contract  (p,  822). 

2.  Make  a  muscle-nerve  preparation  from  the  same  frog.  Crush  the 
muscle  near  the  tendo  AchilMs.  so  as  to  cause  a  strong  demarcation 
current.  Cut  off  the  end  of  the  sciatic  nerve.  Then  lift  the  nerve 
with  a  small  brush  or  thin  glass  rod,  and  let  its  cross-section  fall  on  or 
near  the  injured  part  of  the  muscle.  Everj-time  the  nerve  touches  the 
muscle  a  part  of  the  demarcation  current  passes  through  it,  stimulates 
the  nerve,  and  causes  contraction  of  the  muscle  (p.  822). 

3.  Secondary  Contraction. — Make  two  muscle-nerve  preparations. 
Lay  the  cross-section  of  one  of  the  sciatic  nerves  on  the  muscle  of  the 
other  preparation  (Fig.  305.  P.  833^.  Place  under  the  nerve  near  its 
cut  end  a  small  piece  of  glazed  paper  or  of  glass  rod,  and  let  the  longi- 
tudinal surface  of  the  nerve  come  in  contact  with  the  muscle  beyond 
this.  Lay  the  nerve  of  the  other  preparation  on  electrodes  connected 
with  an  induction  machine  arranged  for  single  shocks,  with  a  Daniell 
cell  and  a  spring  key  in  the  primary-  circuit  (Fig.  283,  p.  808).  On 
closing  or  opening  the  key  both  muscles  contract.  Arrange  the  induc- 
tion machine  for  an  interrupted  current.  When  it  is  thrown  into  one 
nerve,  both  muscles  are  tetanized;  the  nerve  lying  on  the  muscle  whose 
nerve  is  directly  stimulated  is  excited  by  the  action  current  of  the  muscle. 

4.  Demarcation  Current  and  Current  of  Action  with  Capillary  Elec- 
trometer.—  (a)  Study  the  construction  of  the  capillan,-  electrometer 
(Fig.  235,  p.  729).  Raise  the  glass  reservoir  by  the  rack  and  pinion 
screw,  so  as  to  bring  the  meniscus  of  the  mercury'  into  the  field.  Place 
two  moistened  fingers  on  the  binding-icrews  of  the  electrometer,  of)en 
the  small  key  connecting  them,  and  notice  that  the  mercury-  moves,  a 
difference  of  potential  between  the  two  binding-screws  being  caused 
by  the  moistened  fingers. 

(b)  Demarcation  Current. — Set  up  a  pair  of  unpolarizable  electrodes 
(Fig.  238.  p.  731).  Fill  the  glass  tubes  about  one-third  full  of  kaolin 
mixed  with  physiological  salt  solution  till  it  can  be  easily  moulded. 
To  do  this,  make  a  piece  of  the  clay  into  a  little  roll,  which  will  slip  down 
the  tube.  Then  with  a  match  push  it  down  until  it  forms  a  firm  plug. 
Next  put  some  saturated  zinc  sulphate  solution  in  the  tubes,  above  the 
clay,  with  a  fine-pointed  pipette.  Fasten  the  tubes  in  the  holder  fixed 
in  the  moist  chamber  (Fig.  322).  Now  amalgamate  the  small  pieces  of 
zinc  wire  (p.  197)  which  are  to  be  connected  with  the  binding-screws  of 
the  chamber.  (Or  use  Porter's  '  boot  '  electrodes.  These  are  made  of 
unglazed  potter's  clay.     In  use  the  leg  of  the  boot  is  half-filled  with 


PRACTICAL  EXERCISES 


843 


saturated  zinc  sulphate  solution,  into  which  dips  a  thick  amalgamated 
zmc  wire,  in  the  toot  ot  the  boot  is  a  hollow  (or  well)  which  is  filled 
with  physiological  salt  solution  and  serves  to  keep  the  feet  well  moist- 
ened with  the  salt  solution.  The  nerve  is  laid  on  the  feet  of  the  boots. 
When  not  in  use  the  boots  should  be  kept  in  physiological  salt  solution.) 
The  zincs  are  now  placed  in  the  tubes,  dipping  into  the  zinc  sulphate. 
A  piece  of  clay  or  blotting-paper  moistened  with  physiological  salt  solu- 
tion is  laid  across  the  electrodes  to  complete  the  circuit  between  their 
points,  and  they  are  connected  with  the  electrometer  to  test  whether 
they  have  been  properly  set  up.  There  ought  tc  be  little,  if  any,  move- 
ment of  the  mercury  on  opening  the  side-key  of  the  electrometer.  If  the 
movement    is     large,  ___^==* 

the  electrodes  are 
'polarized,'  and  must 
be  set  up  again.  The 
second  pair  of  bind- 
ing -  screws  in  the 
chamber  are  con- 
nected with  a  pair  of 
platinum -pointed 
electrodes  on  the  one 
side,  and  on  the  other, 
through  a  short-cir- 
cuiting key,  with  the 
secondary  coil  of  an 
induction  machine  ar- 
ranged for  tetanus. 

Next  pith  a  frog 
(cord  and  brain),  and 
make  a  muscle-nerve 
preparation.  Injure 
the  muscle  near  the 
tendo  Achillis.  Lay 
the  injured  part  over 
one  unpolarizable 
electrode,  and  an  un- 
injured part  over  the 
other.  Put  a  wet  sponge  in  the  chamber  to  keep  the  air  moist,  and  place 
the  glass  lid  on  it.  Focus  the  meniscus  of  the  mercury,  and  open  the 
key  of  the  electrometer;  the  mercury  will  move,  perhaps  right  out  of  the 
field.  Note  the  direction  of  movement,  and,  remembering  that  the 
real  direction  is  the  opposite  of  the  apparent  direction,  and  that  when 
the  mercury  in  the  capillary  tube  is  connected  with  a  part  of  the  muscle 
which  is  relatively  positive  to  that  connected  with  the  sulphuric  acid, 
the  movement  is  from  capillary  to  acid,  determine  which  is  the  galvano- 
metrically  positive  and  which  the  negative  portion  of  the  muscle  (p.  823) . 

(c)  Action  Current. — Now,  without  disturbing  its  position  on  the 
electrodes,  fasten  the  muscle  to  the  cork  or  paraffin  plate  in  the  moist 
chamber  by  pins  thrust  through  the  lower  end  of  the  femur  and  the 
tendo  Achillis.  Lay  the  nerve  on  the  platinum  electrodes.  Open  the 
key  of  the  electrometer,  and  let  the  meniscus  come  to  rest.  This 
happens  very  quickly,  as  the  capillary  electrometer  has  but  little  inertia. 
If  the  meniscus  has  shot  out  of  the  field,  it  must  be  brought  back  by 
raising  or  lowering  the  reservoir.  Stimulate  the  nerve  by  opening  the 
key  in  the  secondary  circuit ;  the  meniscus  moves  in  the  direction  oppo- 
site to  its  former  movement. 

{d)  Repeat  {b)  and  (c)  with  the  nerve  alone,  laying  an  injured  part 
(crushed,  cut,  or  overheated)  on  one  electrode,  and  an  uninjured  part 
on  the  other.     Of  course,  the  nerve  does  not  need  to  be  pinned. 


B'      B 

Fig.  322. — Moist  Chamber.  E,  unpolarizable  electrodes 
supported  in  the  cork  C;  M,  muscle  stretched  over  the 
electrodes  and  kept  in  position  by  the  pins  A,  B,  stuck 
in  the  cork  plate  P;  B,  binding-screws  connected  with 
galvanometer  or  capillary  electrometer.  The  othei 
pair  of  binding-screws  serves  to  connect  a  pair  of 
stimulating  electrodes  inside  the  chamber  with  the 
secondary  coil  of  an  induction  machine. 


844  ELECTRO-  PH  YSIOLOG  Y 

Clean  the  iinpolarizablc  electrodes,  and  be  sure  to  lower  the  reservoir 
of  the  elcclronicttr  ;  otherwise  the  mercury  ma}'  reach  the  point  of  the 
capillary  tube  and  run  out. 

In  4  a  galvanometer  (p.  72G)  may  be  used  with  advantage  by 
students,  if  one  is  available,  instead  of  the  electrometer,  the  un- 
polarizable  electrodes  being  connected  to  it  through  a  short-circuit- 
ing key.  The  spot  of  light  is  brought  to  the  middle  of  the  scale  by 
moving  the  control-magnet;  or  if  a  telescope -reading  is  being  used,  the 
zero  of  the  scale  is  brought  by  the  same  means  to  coincide  with  the 
vertical  hair-line  of  the  telescope.  The  short-circuiting  key  is  then 
opened. 

5.  Action  Current  of  Heart. — Pith  a  frog  (brain  and  cord).  Excise 
the  heart,  and  lay  the  base  on  one  unpolarizable  electrode,  and  the 
apex  on  the  other,  having  a  sufficiently  large  pad  of  clay  on  the  tips  of 
the  electrodes  to  insure  contact  during  the  movements  of  the  heart,  or 
having  little  cups  hollowed  in  the  clay  and  filled  with  physiological  salt 
solution,  into  which  the  organ  dips.  Connect  the  electrodes  with  the 
capillary  electrometer  and  open  its  key.  At  each  beat  of  the  heart  the 
mercurj^  will  move  (p.  H^s). 

6.  Electrotonus.^Set  up  two  pairs  of  unpolarizable  electrodes  in  the 
moist  chamber.  Connect  two  of  them  with  a  capillary  electrometer 
(or  galvanometer),  and  two  with  a  battery  of  three  or  four  small  Daniell 
cells,  as  in  Fig,  304.  Lay  a  frog's  nerve  on  the  electrodes.  When  the 
key  in  the  battery  circuit  is  closed,  the  mercury  (or  the  needle  of  the 
galvanometer)  moves  in  such  a  direction  as  to  indicate  that  in  the  extra- 
polar  regions  parts  of  the  nerve  nearer  to  the 
anode  are  relatively  positive  to  parts  more  re- 
mote, and  parts  nearer  to  the  kathode  are  rela- 
tively negative  to  parts  more  remote.  The 
direction  of  movement  of  the  mercury  (or  gal- 
vanometer needle)  must  be  made  out  first  for  one 
direction  of  the  polarizing  current.  Then  the 
latter  must  be  reversed,  and  the  movement  of 
the  mercury  (or  needle)  on  closing  it  again  noted 
(P    830). 

7.  Paradoxical  Contraction. — Pith  a  frog  (brain 
and  cord).  Dissect  out  the  sciatic  nerve  down  to 
the  point  where  it  splits  into  two  divisions,  one 
for  the  gastrocnemius  b,  and  the  other  for  the 
peroneal  muscles  a.  Divide  the  peroneal  branch 
as  low  down  as  possible,  and  make  a  muscle-nerve 
preparation  in  the  usual  way.  Lay  the  central 
3^3- — Paradoxical  end  of  the  peroneal  nerve  on  electrodes  con- 
Contraction,  nected  through  a  simple  key  with  a  battery  of  two 
Daniell  cells.  When  the  peroneal  nerve  is  stimu- 
lated, the  gastrocnemius  muscle  contracts.  This  result  is  not  due  to  the 
current  of  action,  for  it  is  not  obtained  with  mechanical  stimulation 
of  the  nerve.  But  it  is  not  the  result  of  an  escape  of  current,  for  if  the 
peroneal  nerve  be  ligatured  between  the  point  of  stimulation  and  the 
bifurcation,  no  contraction  is  obtained.  The  contraction  is  really  due 
to  a  part  of  the  electrotonic  current  set  up  in  the  peroneal  nerve  passing 
tlxrough  the  fibres  for  the  gastrocnemius,  where  they  lie  side  by  side 
in  the  trunk  of  the  sciatic. 

8.  Alterations  in  Excitability  (and  Conductivity)  produced  in  Nerve 
by  the  Passage  of  a  Voltaic  Current  through  it. — Set  up  two  pairs  of 
unpolarizable  electrodes  in  the  moist  chamber.  Connect  a  batter)'  of 
two  or  three  Daniell  cells,  arranged  in  series  through  a  simple  key 


PRACTICAL  EXERCISES  845 

with  the  side-cups  of  a  Pohl's  commutator  with  cross-wires  in.  Con- 
nect the  commutator  to  one  pair  of  the  unpolarizable  electrodes  ('  the 
polarizing  electrodes  '),  as  in  Fig.  324.  The  other  pair  of  unpolarizable 
electrodes  ('  the  stimulating  electrodes  ')  are  to  be  connected  through  a 
short-circuiting  key  with  the  secondary  of  an  induction  machine 
arranged  for  tetanus.  A  single  Daniell  is  put  in  the  primary  coil. 
Pith  a  frog  (brain  and  cord),  make  a  muscle-nerve  preparation,  pin 
the  lower  end  of  the  femur  to  the  cork  plate  in  the  moist  chamber, 
attach  the  thread  on  the  tendo  Achillis  to  the  lever  connected  with  the 
chamber  through  the  hole  in  the  glass  provided  for  this  purpose,  and 
arrange  the  nerve  on  the  electrodes  so  that  the  stimulating  pair  is 
between  the  muscle  and  the  polarizing  pair.  By  moving  the  secondary, 
seek  out  such  a  strength  of  stimulus  as  just  suffices  to  cause  a  weak 
tetanus  when  the  polarizing  current  is  not  closed.  Set  the  drum  off 
(slow  speed),  and  take  a  tracing  of  the  contraction.  Then  close  the 
polarizing  current  with  a  Pohl's  commutator  so  arranged  that  the 
anode  is  next  the  stimulating  electrodes — i.e.,  the  current  ascending  in 
the  nerve.  Again  open  the  short-circuiting  key  in  the  secondary;  the 
contraction  will  now  be  weaker  than  before,  or  no  contraction  at  all 
may   be  obtained.     Allow  the   preparation   two   minutes   to   recover, 


Fig.  3-4- — Arrangement  for  showing  Changes  of  Excitability  produced  by  the  Voltaic 
Current.  M,  muscle;  N,  nerve;  Ej.  Eg.  electrodes  connected  with  secondary 
coilS;  E3,  E4,  unpolarizable  electrodes  connected  with  Pohl's  commutator  (with 
cross-wires)  C;  B',  'polarizing'  battery;  B,  'stimulating'  battery  in  primary 
circuit  P;  K,  K",  simple  keys;  K',  short-circuiting  key. 

then  stimulate  again,  as  a  control,  without  closing  the  polarizing 
current.  If  the  contraction  is  of  the  same  height  as  at  first,  close  the 
polarizing  current  with  the  bridge  of  the  commutator  reversed,  so 
that  the  kathode  is  now  next  the  stimulating  electrodes.  On  stimu- 
lating, the  contraction  will  now  be  increased  in  height.  (See  Figs.  273, 
274.  P-  786.) 

9.  Pfliiger's  Formula  of  Contraction  (p.  788). — To  demonstrate  this, 
connect  two  unpolarizable  electrodes,  through  a  spring  key  and  a 
commutator,  with  a  simple  rheocord  (Fig.  286,  p.  810),  so  as  to  lead 
off  a  twig  of  a  current  from  a  Daniell  cell.  The  unpolarizable  elec- 
trodes are  placed  in  a  moist  chamber.  A  muscle-nerve  preparation 
is  arranged  with  the  nerve  on  the  electrodes  and  the  muscle  attached 
to  a  lever.  The  effects  of  make  and  break  of  a  weak  current,  assending 
and  descending,  can  be  worked  out  with  the  simple  rheocord.  The 
effects  of  a  medium  current  will  probably  be  obtained  wath  a  single 
Daniell  connected  directly  with  the  electrodes  through  a  key.  The 
effects  of  a  strong  current  will  be  got  when  three  or  four  Daniells  are 
connected  with  the  electrodes.  Care  must  be  taken  to  keep  the  prepara- 
tion in  a  moist  atmosphere,  and  more  than  one  preparation  may  be 
needed  to  verify  the  whole  formula. 


846  ELECTRO-PHYSIOLOGY 

10.  Formula  of  Contraction  for  (Human)  Nerves  in  Situ. — Connect 
eight  or  ten  drv  nils  in  sirii-s  *  ("oniai  t  oiu-  trriinii.tl  ot  llir  battt-ry 
to  a  Kirye  phitc  electrode,  and  the  oilier  lo  a  sin. ill  electrode,  butli 
covered  with  cotton,  flannel,  or  sponge,  moistened  with  salt  soluti  n 
Include  in  the  circuit  a  simple  key  for  making  or  breaking  the  current, 
and  a  commutator  for  changing  its  direction  at  will.  Leave  the  key 
open.  Place  the  large  electrode  behind  the  shoulder  (or  on  the  back 
of  the  neck),  and  the  small  electrode  over  the  ulnar  nerve  at  the  elbow 
between  the  internal  condyle  and  the  olecranon.  Arrange  the  com- 
mutator so  that  the  small  electrode  shall  be  the  kathode.  Close,  and 
then  open  the  key.  If  no  contraction  occurs  at  closing,  the  battery 
is  too  weak,  and  more  cells  must  be  added.  If  contraction  occurs  at 
closing,  but  not  at  opening,  reverse  the  commutator,  making  the  small 
electrode  the  anode,  and  observe  whether  contraction  now  occurs  at 
closing,  at  opening,  or  at  both.  Note  also  the  relative  strength  of  the 
various  contractions.  If  the  current  is  '  weak,'  the  only  contraction 
will  be  a  closing  one  when  the  kathode  is  over  the  nerve.  If  the  current 
is  of  '  medium  '  strength,  a  closing  kathodic  contraction  and  both 
opening  and  closing  anodic  contractions  will  be  obtained.  With  '  strong  ' 
currents  contractions  will  occur  at  closing  and  at  op)ening,  whether  the 
kathode  or  the  anode  is  over  the  nerve.  The  contractions  will  vary 
in  strength,  as  described  on  p.  789.  To  work  out  the  different  cases 
of  the  formula  summarized  in  the  table,  the  number  of  cells  must  be 
increased  or  diminished. 


Weak  Currents. 

Medium  Currents. 

Strong  Curr«nts. 

KCC 

KCC 
ACC 
AOC 

KCC 
ACC 
AOC 
KOC 

The  abbreviations  KCC,  ACC,  are  used  respectively  for  kathodic 
closing  contraction  and  anodic  closing  contraction;  KOC,  AOC,  for 
kathodic  opening  contraction  and  anodic  opening  contraction.  KCC 
is  stronger  than  KOC,  and  ACC  tlian  AOC.  KCC  is  stronger  than 
ACC,  and  AOC  than  KOC.  Therefore,  as  the  strength  of  the  current 
is  increased,  in  the  case  of  normal  tissues,  KCC  is  first  obtained,  then 
ACC,  then  AOC.  and  finally  KOC. 

II.  Ritter's  Tetanus. — Lay  the  nerve  of  a  muscle-nerve  preparation 
on  a  pair  of  unpolarizable  electrodes  connected  through  a  simple  key 
with  a  battery  of  three  or  four  small  Daniells.  Connect  the  muscle 
with  a  lever.  Pass  an  ascending  current  (anode  next  the  muscle)  for 
a  few  minutes  through  the  nerve,  and  let  the  writing-point  trace  on 
a  slowly-moving  drum.  When  the  current  is  closed  there  may  be  a 
single  momentary  twitch,  or  the  muscle  may  remain  somewhat  con- 
tracted (galvanotonus)  as  long  as  the  current  is  allowed  to  pass,  or  it 
may  continue  to  contract  spasmodically  ('  closing  tetanus  ').  When 
the  current  is  opened  the  muscle  will  contract  once,  and  then  immedi- 
ately relax,  or  there  may  be  a  more  or  less  continued  tetanus  (Ritter's 
or  '  opening  tetanus  ').  If  opening  tetanus  is  obtained,  divide  the 
nerve  between  the  electrodes:  the  tetanus  continues.  Divide  it  be- 
tween the  anode  and  the  muscle:  the  tetanus  at  once  disappears.  This 
shows  that  the  seat  of  the  excitation  which  causes  the  tetanus  is  in 
the  neighbourhood  of  the  anode  (p.  831). 

♦  If  the  laboratory  possesses  a  batteiy  (with  rheostat),  such  as  is  used  by 
neurologists,  the  experiment  is  more  conveniently  performed  with  this. 


CHAPTER  XVI 

THE  CENTRAL  NERVOUS  SYSTEM 

In  other  divisions  of  our  subject  we  have  been  able  to  follow  to  a 
greater  or  less  extent  the  processes  which  take  place  in  the  organs 
described.  The  chemistry  and  the  physics  of  these  processes  have 
bulked  more  largely  in  our  pages  than  the  anatomy  and  histology 
of  the  tissues  themselves.  In  dealing  with  the  central  nervous 
system,  we  must  adopt  a  method  the  very  reverse  of  this.  Its  ana- 
tomical arrangement  is  excessively  intricate.  The  events  which 
take  place  in  that  tangle  of  fibre,  cell,  and  fibril  are,  on  the  other 
hand,  almost  unknown.  So  that  in  the  description  of  the  physiology 
of  the  central  nervous  system  we  can  as  yet  do  little  more  than 
trace  the  paths  by  which  impulses  may  pass  between  one  portion 
of  the  system  and  another,  and  from  the  anatomical  connections 
deduce,  with  more  or  less  probability,  the  nature  of  the  physiological 
nexus  which  its  parts  form  with  each  other  and  the  rest  of  the  body. 
And  here  it  may  be  well  to  remark  that,  although  for  convenience 
of  treatment  we  have  considered  the  general  properties  of  nerves 
in  a  separate  chapter,  there  is  not  only  no  fundamental  distinction 
between  the  central  nervous  system  and  the  outrunners  which 
connect  it  with  the  periphery,  but  obviously  a  central  nervous 
system  would  be  meaningless  and  useless  without  afferent  nerves 
to  carry  information  to  it  from  the  outside,  and  efferent  nerves  along 
which  its  commands  may  be  conducted  to  the  peripheral  organs. 

Section  I. — Structure  of  the  Central  Nervous  System — 
Histological  Elements. 

In  unravelling  the  complex  structure  of  the  central  nervous 
system,  we  avail  ourselves  of  information  derived  (i)  from  its  gross 
anatomy;  (2)  from  its  microscopical  anatomy;  (3)  from  its  develop- 
ment; (4)  from  what  we  may  call,  although  the  term  is  open  to  the 
criticism  of  cross-division,  its  physiological  and  pathological 
anatomy. 

Certain  tracts  of  white  or  grey  matter  are  differentiated  from  each 
other  by  the  size  of  their  fibres  or  cells.  For  example,  the  postero- 
midian  column  of  the  spinal  cord   has  small    fibres,  the  direct  cere- 

847 


848  THE  CENTRAL  NERVOUS  SYSTEM 

bellar  tract  large  fibres;  the  large  pyramidal  cells  (giant  cells  or  cells 
of  Betz),  in  what  we  shall  afterwards  have  to  distinguish  as  the  '  motor 
area  '  (p.  950)  of  the  cerebral  cortex,  are  the  cells  of  origin  of  fibres  of 
the  pyramidal  tract  subserving  the  volitional  movements  of  the  limbs 
and  trunk.  The  pyramidal  cells  of  the  '  face  area  '  are  comparatively 
small.  In  general,  an  efferent  or  motor  nerve-cell  is  larger  the  longer 
its  axon  is — e.g..  tlie  largest  of  all  the  pyramidal  cells  in  the  '  motor  ' 
region  are  found  in  the  portion  known  as  the  '  leg  area,'  from  which 
the  pyramidal  fibres  have  to  pass  all  the  way  down  the  cord  to  the 
segments  from  which  the  spinal  nerves  going  to  the  lower  limbs  arise. 

The  recent  work  of  Brodman  and  of  Campbell  has  shown  that  the 
cerebral  cortex  may  be  histologically  differentiated  into  regions  which 
correspond  to  a  great  extent  to  the  various  functional  regions  mapped 
out  by  physiological  methods  (p.  958). 

The  study  of  development  enables  us  not  only  to  determine  the 
homology,  the  morphological  rank,  of  the  various  parts  of  the  brain 
and  cord,  but  also,  by  comparison  of  animals  of  different  grades  of 
organization,  sometimes  to  decide  the  probable  function  and  physio- 
logical importance  of  a  strand  of  nerve-fibres  or  a  column  of  nerve- 
cells.  It  is  of  special  value  in  helping  us  to  differentiate  the  various 
areas  of  grey  matter  on  the  surface  of  the  brain,  and  to  trace  the  various 
tracts  or  paths  into  which  the  white  matter  of  the  central  nervous 
system  may  be  divided.  For  the  medullary  sheath  is  not  developed 
at  the  same  time  in  all  the  tracts,  and  a  strand  of  nerve-fibres  in  which 
it  is  wanting — e.g..  the  pyramidal  tract  (p.  878),  which  is  the  last  of 
the  spinal  tracts  to  become  myelinated — is  readily  distinguished  under 
the  microscope. 

Then,  again — and  this  is  what  we  propose  to  include  under  the 
fourth  head — experimental  ph3-siology  and  clinical  and  pathological 
observation  throw  light  not  only  on  the  functions,  but  also  en  the 
structure,  of  the  central  nervous  system.  For  instance,  complete  or 
partial  sectioH,  or  destruction  by  disease,  of  the  white  fibres  of  the 
cord  or  brain,  or  of  the  nerve-roots,  or  removal  of  portions  of  the  grey 
matter,  is  followed  by  degeneration  in  definite  tracts.  And  since,  as 
we  have  already  seen,  degeneration  of  a  nerve-fibre  is  caused  when  it 
is  cut  off  from  the  cell  of  which  it  is  a  process,  the  amount  and  dis- 
tribution of  such  degeneration  teaches  us  the  extent  and  position  of 
the  central  connections  of  the  given  tract.  Con\ersely,  the  cells  in 
which  a  tract  of  nerve-fibres  arises  may  sometimes  be  identified  by 
the  alterations  in  the  chromatin  (p.  859)  and  other  changes  which  occur 
in  them  after  section  of  their  axons.  Particularly  in  young  animals, 
removal  of  a  peripheral  organ — an  eye  or  a  limb — or  section  of  its 
nerves,  may  be  followed  by  atrophy  of  portions  of  the  central  nervous 
system  immediately  related  to  it. 

'  Softening  '  of  a  definite  portion  of  the  white  or  grey  matter  may 
also  in  certain  cases  be  caused  by  depriving  it  of  its  blood-supply  by 
the  injection  of  artificial  emboli,  and  the  resulting  degenerations  may 
then  be  studied.  For  instance,  fine  particles  like  lycopodium  spores 
are  injected  into  the  abdominal  aorta  between  the  origins  of  the  renal 
and  inferior  mesenteric  arteries.  They  are  prevented  by  clamps  from 
entering  these  ves.sels,  and,  passing  through  the  lumbar  arteries,  stick 
in  the  branches  of  the  anterior  spinal  artery,  and  cause  softening 
mainly  of  the  grey  matter  of  the  lumbar  portion  of  the  cord.  When 
the  abdominal  aorta  of  a  rabbit  is  temporarily  compressed  (for  about 
an  hour)  below  the  origin  of  the  renal  arteries,  the  grey  matter  of  the 
corresponding  portion  of  the  cord  is  so  seriously  injured  that  it  and 
the  fibres  that  arise  from  it  degenerate,  while  the  fibres  whose  cells  of 


DEVELOPMENT 


449 


3-25.  —  Formation    of    the     Neural 
Canal  at  an  Early  Stage  (Beard). 


6rif];iri  arc  not  situated  in  this  part  of  the  grey  matter  are  not  affected, 
or  at  least  completely  recover. 

C'ertain  tracts  may  also  be  marked  out  by  means  of  the  electrical 
variation,  which  gives  token  of 
the  passage  of  nervous  impulses 
along  them  when  portions  of  the 
central  nervous  system  or  peri- 
pheral nerves  are  stimulateej 
(Horslcy  and  Gotch). 

Development  of  the  Central 
Nervous  System. — ^Vcry  early  iu 
development  (Fig.  325)  the  keel 
of  the  vertebrate  embryo  is  laid 
down  as  a  groove  or  gutter  in  tho 
ectoderm  of  the  blastodermic  area 
(Chap.  XIX.).  The  walls  of  this 
'  medullary  '  or  '  neural  '  groove 
grow  inwards,  and  at  length  there 
is  formed,  by  their  coalescence,  the  '  neural  canal  '  (Fig.  326),  which 
expands  at  its  anterior  end  to  form  four  cerebral  vesicles  ^Fig.  327). 
Thus  there  is  a  continuous  tunnel  from 
end  to  end  of  the  primary  cerebro -spinal 
axis;  and  this  persists  as  the  central 
canal  of  the  spinal  cord  and  the  ven- 
tricles of  the  brain,  whose  ciliated 
epithelium  represents  the  ectodermic 
lining  of  the  primitive  neural  canal.  In 
the  adult  portions  of  the  canal  may 
become  obliterated  from  an  overgrowth 
of  the  lining  cells,  and  the  cilia  are,  if 
present  at  all,  less  distinct  than  in  the 
child,  and  far  less  distinct  than  in  the 
lower  animals.  From  the  wall  of  this 
canal  is  formed  the  cerebro-spinal  axis, 
in  which  developing  nerve-cells  or  neuro- 


~4G 


y 


^JijQ,-' 


:■  ."'in- 


l^\ 


Fig.  326. — Neural  Canal  at  a  Later 
Stage  (Beard).  C.  neural  canal; 
G,  posterior  spinal  ganglion. 


Fig.  327. — Diagram  to  illustrate 
the  Formation  of  the  Cerebral 
Vesicles.  A.  i  indicates  the 
cavity  of  the  secondary  fore- 
brain,  which  eventually  becomes 
the  lateral  ventricles.  In  B  the 
secondary  fore-brain  has  grown 
backwards  so  as  to  overlap  the 
other  vesicles.  I,  first  cerebral 
vesicle  (primary  fore-brain  or 
'tween  brain) ;  II,  second  cerebral 
vesicle  (mid-brain);  III,  third 
cerebral  vesicle  (hind-brain);  IV, 
fourth  cerebral  vesicle  (after- 
brain). 


blasts  soon  become  differentiated  from  the  supporting  cells  or  spongio- 
blasts, and  wander  outwards  from  the  neighbourhood  of  the  central  canal 
(Fig.  338)  till  their  further  progress  is  checked  by  the  barrier  of  the  mar- 

54 


850  THE  CENTRAL  NERVOUS  SYSTEM 

ginal  veil,  a  closely-woven  network  or  thicket,  into  which  the  processes  of 
the  spongioblasts  break  up  at  the  outside  of  the  primitive  ccrcbro-spinal 
axis.  Although  the  neuroblasts  themselves  are  unable  to  penetrate 
the  marginal  veil,  the  axis-cylinder  processes  of  some  of  them  do  so, 
and  form  the  motor  roots  of  the  spinal  nerves.  The  neuroblasts  from 
which  the  fibres  of  the  white  columns  of  the  cord  are  dc\xloped  are 
apparently  unable  to  send  their  axons  through  the  marginal  veil. 
They  are  accordingly  forced  to  assume  a  longitudinal  direction,  and 
in  this  way  the  central  grey  matter  becomes  covered  with  a  sheath  of 
longitudinal  white  fibres.  For  a  time  only  motor  nerve-cells  and  the 
fibres  connected  with  them  are  developed  in  the  cerebro-spinal  axis. 
The  ganglia  on  the  posterior  roots  arise  from  a  series  of  ectodermic 
thickenings  or  sprouts  from  the  neural  crest  which  runs  along  the  dorsal 
aspect  of  the  neural  canal.  These  sprouts  contain  the  neuroblasts 
which  develop  into  the  spinal  ganglion  cells  with  the  posterior  root- 
fibres.  From  each  pole  of  each  neuroblast  a  process  grows  out,  one 
towards  the  periphery,  which  forms  a  peripheral  nerve-fibre,  the  other 
centrally  to  connect  the  cell  with  the  cord.  From  the  after-brain  (or 
myelencephalon)  is  developed  the  medulla  oblongata  or  spinal  bulb, 
from  the  hind-brain  (or  metencephalon)  the  cerebellum  and  pons, 
from  the  mid-brain  (or  mesencephalon)  the  corpora  quadrigemina  and 
crura  cerebri.  The  fore-brain,  or  primary  fore-brain  (thalamencepha- 
lon),  gives  rise  of  itself  only  to  the  third  ventricle  and  optic  thalamus; 
but  a  secondary  fore-brain  (telencephalon)  buds  off  from  it  and  soon 
divides  into  two  chambers,  from  the  roof  of  which  the  cerebral  hemi- 
spheres, and  from  the  floor  the  corpora  .striata,  are  derived.  Their 
cavities  persist  as  the  lateral  ventricles,  which  communicate  with  the 
third  ventricle  by  the  foramen  of  Monro.  The  olfactory  tracts  are 
formed  as  buds  from  the  secondary  fore-brain. 

To  complete  the  story  of  the  development  of  the  brain,  it  may  be 
added  that  the  retina  is  really  an  expansion  of  its  nervous  substance. 
A  hollow  process,  the 'optic  vesicle,  buds  out  on  each  side  from  the 
primary  fore-brain.  A  button  of  ectoderm,  which  afterwards  becomes 
the  lens,  grows  against  the  vesicle  and  indents  it  so  that  it  becomes 
cup-shaped,  the  inner  concave  surface  of  the  cup  representing  the 
retina  proper,  the  outer  convex  surface  the  choroidal  epithelium.  The 
stalk  becomes  the  optic  nerve. 

Histological  Elements  of  the  Central  Nervous  System. — The  central 
nervous  system  is  built  up  (i)  of  true  nervous  elements,  (2)  of  sup- 
porting tissue.  The  nervous  elements  have  usually  been  described  as 
consisting  of  nerve-fibres  and  nerve-cells,  but  the  antithesis  of  a  time- 
honoured  distinction  must  not  lead  us  to  forget  that  the  essential 
part  of  a  nerve-fibre,  the  axis-cylinder,  is  a  process  of  a  nerve-cell, 
and  the  medullary  sheath  a  structure  whose  integrity  is  intimately 
related  to  that  of  the  axis-cylinder.*  In  strictness,  the  term  '  nerve- 
cell  '  ought  to  include  not  only  the  cell-body,  but  all  its  processes,  out 
to  their  last  ramifications.  But  the  habit  of  speaking  of  the  position 
of  the  cell-bodyt  as  that  of  the  nerve-cell  is  so  ingrained,  that  it  seems 
better  to  continue  the  use  of  the  latter  term  in  its  old  signification,  and 
to  speak  of  the  cell  and  branches  together  as  a  neuron  (also  spelled 
neurone). 

*  While  the  medullary  sheath,  like  the  axis-cylinder,  seems  to  be  as  regards 
its  nutrition  under  the  control  of  the  nerve-cell,  and  must  therefore  be  looked 
upon  as  an  integral  portion  of  the  neuron,  although  not  essential  for  its  de- 
velopment, the  neurilemma  in  respect  both  of  its  nutrition  and  iits  develop- 
ment appears  to  be  an  independent  structure. 

\  Foster  and  Sherrinpton  call  the  cell-body  the  perikaryon. 


HISTOLOGICAL  ELEMENTS 


851 


The  Neurons.— A  typical  ncrvc-cell  (Figs.  328,  330,  33-i)  is  a  knot  of 
granular  protoplasm,  containing  a  large  nucleus,  inside  of  which  lies 
a  highly  refractive  nucleolus.  A  centrosome  and  attraction  sphere 
(p.  5)  have  also  been  found  in  some  nerve-cells,  though  not  as  yet 
demonstrated  in  all.  Pigment  may  also  be  present,  especially  in  old 
age.  By  certain  methods  of  staining  it  may  be  shown  that  fibrils 
(neuro-fibril.s)  run  through  the  protoplasm  of  the  cell,  forming  a  felt- 
work  in  it,  and  entering  the  dendrites  on  the  one  hand  and  the  axis- 
cylinder  process  on  the  other  (Figs.  328,  331,  335)-  In  the  axis- 
cylinaers  of  nerve-fibres  the  fibrils  (Fig.  329)  appear  to  preserve  their 

identity  down  to  the  distribution  of 
the  fibre.  In  the  ground  substance 
between  the  fibrils  lie  round,  an- 
gular, or  spindle-shaped  bodies 
(Nissl's  bodies)  which  stain  with 
basic  dyes  (Fig. 340).*  These  bodies 
vary  in  appearance  in  different 
kinds  of  nerve-cells,  and  in  the 
same  nerve-cell  under  different  con- 
ditions. According  to  Macallum, 
they  contain  organically  combined 
iron.  In  a  multipolar  cell,  like  those 


-Anterior  Horn  Cell  from  Man 
showing  Fibrils  (Bethe). 


Fig.  329.  —  MeduUated  Nerve- 
Fibre  showing  Fibrils  of  Axis- 
Cylinder  (Bethe).  The  fibrils  are 
seen  passing,  without  interrup- 
tion, across  a  node  of  Ranvier. 


in  the  anterior  horn  of  the  spinal  cord,  several  processes — it  may  be  five 
or  six,  or  even  more — pass  off  from  the  cell-body  (Frontispiece).  The 
most  complete  pictures  of  them  are  given  by  preparations  impregnated 
according  to  the  method  of  Golgif  (Figs.  330,  333).     One  of  the  pro- 

*  In  Nissl's  method  the  sections  are  stained  in  a  solution  of  methylene  blue, 
and  decolourized  in  aniliu-alcohol. 

t  The  method  depends  upon  the  deposition  of  mercury,  or  silver,  in  or 
around  the  cell-bodies  and  their  processes  in  tissues  which  have  been  hardened 
in  bichromate  of  potassium  and  then  soaked  in  a  solution  of  mercuric  chloride 
or  silver  nitrate.  In  Pal's  improvement  of  Golgi's  method  a  solution  of  sodic 
sulphide  follows  the  mercuric  chloride. 


852 


THE  CENTRAL  NERVOUS  SYSTEM 


cesses  of  most  nerve-cells  is  distinguished  from  the  rest  by  the  fact 
that  it  maintains  its  original  diameter  for  a  comparatively  great 
distance  from  the  cell,  and  gives  off  comparatively  few  branches. 
This  process,  which  in  favourable  preparations  can  be  traced  on  till  it 
becomes  the  axis-cylinder  of  a  nerve-fibre,  is  called  the  axis-cylinder 
process,  or  more  shortly  the  axon.  The  few  slender  brai  ches  that  come 
off  from  it,  usually  at  right  angles,  are  called  collaterals.  The  collaterals 
consist  essentially  of  one  or  more  fibrils  of  the  axon.  Both  the  main 
thread  of  the  axon  and  the  collaterals  end  by  breaking  up  into  an 
arborescent  system  of  fibrils  or  telodendrion .  The  telodendrions  vary 
greatly  in  appearance  from  simple  end -brushes  to  far-branching 
thickets,  or  such  special  end-organs  as  motor  plates  (Fig.  335)  or 
muscular  spindles.  The  rest  of  the  processes  of  the  cell,  which  are 
termed  dendrites  or  protoplasmic  processes,  very  rapidly  diminish  in 
diameter,    as  they    pass  away   from  the  cell     by   breaking    up   into 


Fig.  3 JO. — Multipolar  Nerve-Cell:  Golgi  Preparation  (Barker,  after  Kolliker). 
n,  axon;  c,  collaterals. 

fibrils  like  the  branches  of  a  tree.  The  Nissl  bodies  extend  for  some 
distance  into  the  dendrites,  but  not  into  the  axon.  The  dendrites 
of  some  cells,  especially  the  pyramidal  cells  of  the  cerebral,  and 
the  Purkinje's  cells  of  the  cerebellar  cortex,  have  small  swellings, 
the  so-called  lateral  buds  or  gemmtiles,  on  their  course.  Their  signifi- 
cance is  unknown.  The  dendrites  terminate  at  a  little  distance  from 
the  cell,  where  they  come  into  relation  with  the  end -arborizations  of 
the  axons  of  other  neurons.  In  this  way  two  or  more  neurons  are 
linked  together  to  form  a  nervous  path.  According  to  the  view  most 
commonly  held  (neuron  hypothesis),  the  relation  is  not  one  of  actual 
anatomical  continuity,  but  the  processes  come  so  close  together  that 
nerve  impulses  are  able  to  pass  across  from  the  terminal  brush  of  the 
axon  of  one  nervous  element  to  the  dendrites  or  cell-body  of  another. 
This  kind  of  junction  is  called  a  synapse. 

It  has  been  suggested  that  the  contact  may  be  rendered  more  or  less 
close  through  amoeboid  movements  of  the  dendrites,  and  that  in  this 


HISTOLOGICAL  ELEMENTS 


85^ 


way  the  nervous  impulse  may  be  switched  like  a  railway-train  from 
one  path  to  another.  But  there  is  no  experimental  basis  for  this  some- 
what crude,  if  fascinating,  hypothesis.  Sherrington  has  suggested 
that  the  presence  of  a  '  membrane  '  at  the  synapse  may  limit  the  con- 
duction and  determine  its  direction.  Some  membranes,  such  as  frog's 
skin,  are  known  to  possess  a  so-called  irreciprocal  permeability  for 
certain  substances,  permitting  them  to  pass  more  easily  in  one  direc- 
tion than  the  other,  and  it  is  conceivable  that  a  membrane  at  the 
synapse  might  have  a  similar  action  in  respect  to  the  movement  of  ions 
concerned  in  the  propagation  of  the  nervous  excitation.     Whatever 


Fig.  331— Nerve-Cells  of  Hirudo  (Schafer. 
after  Apathy).  A,  vinipolar  motor  cell; 
a,  network  of  neuro-fibrils  near  the  sur- 
face of  the  cell;  b.  near  the  nucleus  n; 
c,  afferent,  d,  efferent  neuro-fibril.  B,  bi- 
polar  sensory  cell  a  with  its  nucleus  n  ; 
cu,  cuticle;  ep,  epidermis  cells  between 
which  a  neuro-fibril  passes  up  from  its 
branched  ending  near  the  surface  of  the 
skin  to  the  nerve-cell,  where  it  forms  a 
network,  which  gives  off  a  fibril  passing 
towards  the  central  nervous  system. 


Fig.  332.— Large  Pyramidal  Cell  of 
Cerebral  Cortex  (Barker,  after  Bech- 
terew).     a,  axon;  b,  dendrite. 


the  nature  of  the  relation  between  two  superposed  neurons  may  be,  it 
does  not  permit  the  conduction  of  nerve-impulses  indiscriminately'  in 
both  directions.  For  instance,  stimulation  of  the  central  end  of  the 
posterior  root  of  a  spinal  nerve  causes  an  electrical  response  (p.  824) 
in  the  anterior  root  of  the  same  segment,  while  no  electrical  change  is 
produced  in  the  posterior  root  by  stimulation  of  the  anterior.  We  shall 
see  later  on  (p.  872)  that  some  of  the  fibres  of  the  posterior  root  and 
their  collaterals  end  by  arborizing  around  the  dendrites  of  the  cells  01 
the  anterior  horn.     The  excitation  is,  therefore,  able  to  pass  from  the 


854 


THE  CENTRAL  NERVOUS  SYSTEM 


telodcndrions  of  the  posterior  root-fibres  through  the  dendrites  of  the 
anterior  horn  cells  towards  their  cell-bodies,   but  not  in  the  opposite 


Fig.  333- — • — e  shows  the  development  of  the  pyramidal  nerve-cells  of  the  cerebral 
cortex  in  a  typical  mammal;  a,  neuroblast  with  commencing  axon;  b,  dendrites 
appearing;  d,  commencing  collaterals.  A — D  shows  the  different  degree  of  com- 
plexity in  the  fully-developed  pyramidal  cells  in  different  vertebrates:  A,  frog; 
B,  lizard;  C.  rat;  D,  man  (Donaldson,  after  Ram6n  y  Cajal). 

direction,  and  in  general  the  direction  of  conduction  is  from  the  den- 
drites towards  the  cell-body. 

Some   investigators   believe  that   the   fibrils   already   spoken   of  as 
forming  a  felt-work  in  the  protoplasm  of  the  nerve-cell  may  run  right 


Fig.  334— Cells  from  the  Gasserian  Ganglion  of  a  Developing  Guinea-Pig. 
originally  bipolar  cells  are  seen  changing  into  cells  apparently  unipolar, 
same  process  occurs  in  the  cells  of  the  spinal  ganglia  (Van  Gehuchten). 


The 
The 


through  from  one  cell  to  another,  thus  constituting  an  actual  anatomical 
connection  between  the  neurons,  and  that  .such  a  connection  may  be 
established  also  by  fibrils  which  do  not  enter  the  cells  at  all,  but  run  in 
the  intercellular  substance  of  the  grey  matter.     Such  a  continuity  of 


//  IS  TO  I.  OG I CA  L  EL  EM  EN  TS 


fibrils  from  cell  to  cell  has 
been  demonstrated  in  some 
of  the  invertebrates  —  e.g., 
in  annelids  (Fig.  331) — 
where  previously  the  best 
examples  of  strictly  iso- 
lated neurons  were  sup- 
posed to  be  found  (Apathy)- 
The  supporters  of  the 
theory  of  continuity  look 
upon  the  cell-body  as 
merely  necessary  for  the 
nutrition  of  the  nerve-net, 
but  deny  that  it  is  neces- 
sary for  the  conduction  of 
nerve-impulses.  If  this  is 
the  case,  it  is  obvious  that 
the  neurons  can  no  longer 
be  considered  as  functional 
units  in  which  the  law  of 
isolated  conduction  of 
nerve-impulses  (p.  793) 
holds  good.  Nor  is  it  by 
any  means  so  easy  to  un- 
derstand as  on  the  neuron 
hypothesis  such  facts  as  the 
strict  limitation  of  Wal- 
lerian  degeneration  to  the 
boundaries  of  the  neurons 
directly  affected,  or  the 
strict  limitation  of  the 
silver  reduction  in  Golgi 
preparations  to  single  neu- 
rons. It  is,  of  course,  true 
that  the  simplicity  and 
order  introduced  by  the 
neuron  hypothesis  into  our 
conceptions  of  the  nervous 
conduction  paths  by  no 
means  prove  its  accuracy. 
Yet  they  are  reasons  for 
not  lightly  abandoning  it, 
and  it  has  recently  been 
corroborated  by  important 
new  evidence  on  the  growth 
of  nerve-cells  on  artificial 
media  outside  of  the  body 
(p.  802;  Fig.  337.  P-  8.57)- 
Varieties  of  Neurons. — 
Nearly  all  the  nerve-cells 
of  the  cerebro-spinal  axis 
agree  with  the  cells  of  the 
anterior  horn  in  the  posses- 
sion of  an  axon  and  one  or 
more  dendrites,  although 
sometimes  the  dendrites 
are  scanty  in  number  and 


Pig  ^35. — Scheme  of  Lower  Motor  Neuron 
(Barker),  a,  h,  axon-hilljck  (the  portion  of  the 
cell  from  which  the  axon  comes  off),  containing 
no  Nissl  bodies,  and  showing  fibrillation;  ax, 
axis-cylinder  or  axon;  m,  medullary  sheath, 
outside  of  which  is  the  neurilemma;  c,  cell- 
substance  (cytoplasm),  showing  Nissl  bodies  in 
a  lighter  ground  substance;  d,  protoplasmic 
processes  or  dendrites  containing  Nissl  bodies; 
n,  nucleus;  «',  nucleolus;  n,  R,  node  of  Rauvier; 
s.f.  side  fibril;  n  of  n,  nucleus  of  the  neurilemma; 
tel.,  motor  end-plate;  m',  striped  muscle-fibre; 
s.  I ,  incisure. 


856 


THE  CENTRAL  NERVOUS  SYSTEM 


insignificant  in  size.  In  the  cerebral  cortex  the  typical  cells  are  ol 
pyramidal  shape.  From  the  base  comes  off  the  axon,  and  from  the 
angles  dendritic  processes,  a  particularly  massive  dendrite  proceeding 
from  the  apex  of  the  pyramid  towards  the  surface  of  the  brain. 

Sometimes  an  axon,  instead  of  ending  in  an  arborization  which 
comes  into  relation  with  the  dendrites  of  another  nerve-cell,  or,  as  is 
more  frequently  the  case,  with  the  dendrites  of  more  than  one  cell, 
breaks  up  into  a  sort  of  basket-work  of  fibrils  surrounding  the  cell- 
body.  The  cells  of  Purkinje,  for  instance,  in  the  cerebellum  are  sur- 
rounded by  such  pericellular  baskets  {L'ig.  336).  The  cells  of  the  spinal 
ganglia  have  two  axons,  which  in  the  embryo  arise  one  from  each  end 
of  the  bipolar  cell,  but  in  the  adult,  in  all  vertebrates  except  some 
fishes,  are  connected  to  the  cell  by  a  single  process  (Fig.  334)-  It  has 
been  commonly  held  that  the   unipolar  cell  with  a  single  T-shaped 

process  is  developed  from  a  bipolar  cell, 
which  grows  towards  one  side,  so  that  the 
two  processes  come  together  and  fuse. 
Such  observations  as  that  of  Harrison  on 
the  bifurcation  of  the  growing  end  of  the 
main  process  of  isolated  nerve-cells  culti- 
vated in  vitro  suggest  an  alternative  and 
a  simpler  explanation  —  viz.,  that  the 
T-shaped  process  is  derived  from  the 
splitting  of  a  single  chief  process.  If  this 
be  the  case,  one  of  the  original  processes 
at  the  poles  probably  undergoes  a  retarded 
development  or  disappears,  since  the  great 
majority  of  the  spinal  ganglion  cells  with 
the  T-shaped  process  appear  to  have  no 
dendrites.  Another  kind  of  cell  which 
seems  undoubtedly  to  be  of  nervous  nature 
is  the  '  granule-cell.'  Granule-cells  are 
much  smaller  than  the  ner\-e-cells  we  ha\'e 
been  describing.  Their  processes  are  much 
less  easily  followed,  but  all  appear  to  give 
off  an  axon  and  several  dendrites.  They 
contain  a  relatively  large  nucleus  (5  to  8  /.t 
in  diameter),  with  only  a  mere  fringe  of 
cell-substance.  The  nucleus,  unlike  that 
of  a  large  nerve-cell,  stains  deeply  with 
haematoxylin.  Some  parts  of  the  grey 
matter  are  crowded  with  these  granule-cells — e.g.,  the  nuclear  layer 
of  the  cerebellum  and  the  substantia  gelatinosa,  or  substance  of 
Rolando,  which  caps  the  posterior  horn  in  the  cord.  In  other  parts 
they  are  more  thinly  scattered,  but  probably  they  are  as  widely  diflused 
as  the  large  nerve-cells  proper,  and  no  extensive  area  of  the  grey  matter 
is  wholly  without  them. 

Although  there  are  several  varieties  of  granules  (Hill),  they  all 
agree  in  this,  that  their  axons  run  a  comparatively  short  course,  and 
never,  or  rarely,  pass  beyond  the  grey  matter.  Another  kind  of  neuron 
which  is  also  confined  to  the  grey  matter,  and  is  typically  seen  in  the 
cortex  of  the  cerebrum  and  cerebellum,  presents  the  peculiarity  of  an 
axon  which  branches  into  an  intricate  network  immediately  after 
commg  off  from  the  cell  (cell  of  Golgi's  second  type).  Unlike  the  long 
axon  of  the  typical  large  nerve-cell,  the  axis-cylinder  process  of  this 
Golgi  cell  remains  unmcdullated. 

The  sympathetic  ganglion  cells  are  developed  from  immature  neuro- 


Fig.  336. — Pericellular  Baskets 
(Schafer,  after  Cajal).  Two 
cells  of  Purkinje  from  the 
cerebellum  are  seen  sur- 
rounded by  end  ramifications 
forming  a  basket-work,  b,  de- 
rived from  the  branching  of 
axons  of  small  nerve-cells  in 
the  molecular  layer;  a,  axon. 


HISTOLOGICAL  ELEMENTS 


8S7 


blasts  that  migrate,  in  the  course  of  development,  from  the  rudiments 
of  the  s[)inal  ganglia,  and  gatliering  in  clumps  form  the  ganglia  of  the 
sympathetic  cliain  (His).  They  agree  in  general  with  the  cells  of  the 
cerebro-spinal  axis  in  jjossessing  an  axon  and  one  or  more,  commonly 
several,  dendrites,  although  a  few  of  them  are  devoid  of  dendrites. 
The  great  majority  of  the  axons  remain  unmedullated,  but  a  few 
acquire  a  very  fine  medullary  sheath. 

The  epithelium  lining  the  central  canal  of  the  cord  and  the  ventricles 
of  the  brain  has  also  been  considered  by  some  as  of  nervous  nature. 
The  fact  that  the  deep  ends  of  the  cells  are  continued  into  processes 
which  pierce  far  into  the  grey  substance  has  been  supposed  to  lend 
weight  to  this  opinion,  but  there  is  no  good  ground  for  it. 

Growth  of  Neurons. — The  growth  of  a  neuron  from  origin  to  com- 
pletion is  a  comparatively  slow  process  in  the  higher  animals.  Early 
in  foetal  life  (about  the  third  or  fourth  week  in  man)  certain  round 
germinal  cells  make  their  appearance  amid  the  columnar  ectodermic 
cells  surrounding  the  neural  canal.  From  their  division  are  formed, 
in  the  first  months  of  embryonic  life,  the  primitive  nerve-cells  or 
neuroblasts.     These  soon  elongate  and   push  out  processes,   first  the 


Fig.  33,7. — Isolated  nerve-cells  from  the  spinal  cord  of  a  tadpole  growing  in  clotted 
Ivmph.  A,  B,  C,  are  cells  in  different  stages  of  growth.  The  lower  view  of  C 
was  drawn  under  the  microscope  4I  hours  later  than  the  upper  (Harrison). 


axon  or  axons,  and  then  the  dendrites  (Fig.  333).  The  formation  of 
the  axons  from  the  nerve-cell  is  most  clearly  followed  in  isolated 
cultures  (Fig.  337).  As  development  goes  on,  the  cell-body  grows 
larger,  and  the  processes  longer  and  more  richly  branched.  The  axon 
and  its  collaterals,  when  it  has  any,  in  the  case  of  the  great  majority  of 
the  nervous  elements  of  the  brain  and  cord,  ultimately  acquire  a 
medullary  sheath,  although,  as  we  have  said,  the  time  at  which  medul- 
lation  is  completed  varies  in  different  groups  of  elements,  and  in  some 
nervous  tracts  it  is  even  wanting  at  birth.  At  birth,  too,  the  branches 
of  many  of  the  cells  are  less  numerous,  and  the  connections  between 
different  nervous  elements  therefore  less  intimate  than  they  will  after- 
wards become.  For  many  years  the  processes,  and  particularly  the 
axons,  continue  not  only  to  grow  longer,  but  to  grow  thicker  as  well. 
The  cell-body  also  enlarges,  and  the  quantity  of  material  in  it  that 
stains  with  basic  dyes  increases.  In  the  growing  (lumbar)  spinal 
ganglia  of  the  white  rat  the  increase  in  volume  of  the  largest  cell- 
bodies  is  very  closely  correlated  with  the  increase  in  area  of  the  cross- 
section  of  the  nerve-fibres  growing  out  of  them.  The  cross-section 
of  the  axis-cylinder  is,  and  remains,  almost  exactly  equal  to  the  area 


SjS 


THE  CENTRAL  NERVOUS  SYSTEM 


of  the  medullar}'  sheath  (Dofialdson).  Even  after  puberty  is  reached 
the  anatomical  organization  of  the  nervous  system  may  still  continue 
to  advance,  although  at  an  ever-slackening  rate,  and  the  finishing 
touches  may  only  be  given  to  its  architecture  in  adult  life.  In  old 
age  the  nervous  elements  decay  as  the  body  does.  The  cell- 
body  diminishes  in  size ;  the  stainable  material  lessens  in  amount ; 
vacuoles  form  in  the  protoplasm  and  pigment  accumulates;  the  nucleus 
shrinks;  the  nucleolus  is  obscured  or  may  di.sappear  altogether.  At 
the  same  time  the  processes  of  the  cell,  and  especially  the  dendrites, 
tend  to  atrophv  (Fig-  339)- 

Nutrition  of  the  Neuron. — We  have  already  seen  that  when  an  axon 
is  cut  off  from  its  cell-body,  it  and  its  medullary  sheath,  when  it 
possesses  one,   undergo  a  rapid  degeneration.     It  was  long  supposed 


Fig.  338.  —  Section 
through  Half  of  Neural 
Tube  (Barker,  after 
His).  The  pear- 
shaped  neuroblasts  are 
seen  migrating  out- 
wards. The  axons  of 
some  of  them  are  seen 
pushing  their  way  out 
through  the  marginal 
veil  as  the  anterior 
root  of  a  spinal  nerve. 


Ii^ 


Fig.  339. — I.  spinal  ganglion  cells  of  a  still-bom  male 
child;  2,  of  a  man  ninety-two  years  old  ( x  250) 
— N,  nuclei;  3,  nerve-cells  from  the  antennary 
ganglion  of  a  honey-bee  just  emerged  in  the  per- 
fect form ;  4.  of  an  old  honey-bee.  The  nucleus  is 
black  in  the  figure.  In  3  it  is  very  large,  in  4  it 
is  shrunken  and  the  cell-substance  contains 
vacuoles  (Hodge). 


that  no  change  took  place  in  the  nerve-cell.  The  researches  of  recent 
years  have  shown  that  not  only  does  loss  of  the  specific  function  and 
trophic  influence  of  the  cell-body  affect  the  nutrition  of  the  axon,  but 
loss  of  function  of  the  axon  reacts  on  the  cell-body.  In  many  cases 
at  least,  when  a  nerve-fibre  is  divided  from  its  cell,  characteristic 
changes  are  produced  in  the  latter  and  in  its  dendritic  processes,  and 
they  are  scarcely  less  rapid,  although  usually  less  profound,  and  far 
more  transient  than  the  degeneration  in  the  peripheral  portion  of  the 
nerve-fibre.  The  cell-body  and  the  nucleus  swell.  Many  of  the  Nissl 
bodies  (Fig.  340)  disintegrate,  and  are  reduced  to  a  finely  granular 
condition.  After  a  time  much  of  the  disintegrated  chromatic  sub- 
stance disappears  altogether.     The  nucleus  may  be  displaced  to  one 


HISTOLOGICAL  ELEMENTS 


859 


side  of  the  cell.  Certain  changes  in  the  neurofibrils  of  the  cell  may 
accompany  the  changes  in  the  chromatin.  In  rabbits  after  division 
of  the  facial  nerve  the  alterations  in  its  nucleus  of  origin  have  been 
found  to  reach  a  maximum  in  about  three  weeks,  after  which  there  is  a 
tendency  to  recovery  on  the  part  of  the  majority  of  the  cells,  even  when 
regeneration  of  the  nerve  has  been  prevented  by  cutting  out  a  portion 
of  it.  Some  of  the  cells  may  completely  atrophy  and  disappear. 
Similar  changes  have  been  found  by  Warrington  in  the  motor  cells  ol 
the  anterior  horn  after  section  of  the  posterior  (dorsal)  spinal  roots. 
Since  in  this  case  no  anatomical  injury  has  been  inflicted  on  the  motor 
neurons,  it  has  been  surmised  that  the  cause  of  the  alterations  is  the 
loss  of  impulses  which  normally  reach  them  along  their  dendrites.  In 
short,  we  may  say.  with  Marinesco,  that  the  functional  and  anatomical 
integrity  of  the  neuron  depends  on  the  integrity  of  all  its  constituent 
parts,  and  of  the  neurons  which  carry  to  it  functional  excitations — i.e., 
excitations  connected  with  its  proper  physiological  work.  The  neuron, 
in  fact,  lives  by  its  function,  or,  in  common  language,  by  doing  its 
work.     Yet  the  anatomical  tokens  of  mere  disuse,  as  in  the  motor  cells 


Fig.  340. — Cells  from  the  Nuclei  of  the  Oculo-Motor  Nerves  of  the  Cat  Thirteen  Days 
alter  Division  of  the  Root-Fibres  on  one  Side:  Nissl's  Stain  (Barker,  after  Flatau). 
a,  normal  cell  from  side  on  which  the  roots  were  not  cut;  b,  cell  from  side  operated 
upon.  Only  a  few  Nissl  bodies  are  present  in  b,  and  the  nucleus  is  displaced  to 
one  side  of  the  cell. 

of  the  anterior  horn  after  division  of  the  cord  at  a  higher  level,  are  less 
distinct  than  those  which  follow  section  of  the  axon.  Therefore  it 
must  be  concluded  that  the  latter,  although  not  indispensable  for  the 
nutrition  of  the  cell  as  the  cell  is  for  the  axon,  exerts  an  influence  upon 
it.  Similar  changes  in  the  chromatin  may  also  be  produced  in  nerve- 
cells  by  a  period  of  anaemia,  in  extensive  superficial  burns,  in  tetanus 
caused  by  the  injection  of  bacterial  cultures,  in  acute  alcoholic  poisoning, 
in  fatigue,  and  in  other  ways.  According  to  Wright,  the  inhalation 
of  ether  or  chloroform  (in  dogs)  so  alters  the  chromatic  substance 
that  it  loses  its  affinity  for  aniline  dyes.  In  long-continued  anaesthesia 
the  nucleus  is  also  affected,  while  the  nucleolus  is  the  last  part  of  the 
cell  to  suffer.  A  greater  alteration  occurs  in  the  cells  in  the  three  hours 
between  the  sixth  and  ninth  hours  of  anaesthesia  than  in  the  five  hours 
between  the  first  and  sixth.  Although  the  changes  are  transitory,  the 
cells,  after  a  narcosis  of  nine  hours,  being  practically  normal  in  Jorty- 
eight  hours,  they  indicate  that  the  duration  of  safe  surgical  anaesthesia 
has  a  limit  measured  by  hours. 

It  is  probable  that  the  alterations  in  the  chromatic  substance  should 


Rfio 


THE  CENTRAL  NERVOUS  SYSTEM 


not  be  looked  upon  as  the  token  of  any  specific  lesion;  they  are  the 
common  structural  response  of  the  cell  to  injurious  influences  of  the 
most  varied  nature. 

Grey  and  White  Matter. — Nerve-cells  are  the  most  distinctive  his- 
tological feature  of  tlie  grey  nervous  substance.  Sown  thickly  in  the 
cerebral  cortex,  the  basal  ganglia,  the  floor  of  the  fourth  ventricle,  and 
the  cervical  and  lumbar  enlargements  of  the  cord,  they  are  scattered 
more  sparingly  wherever  the  grey  matter  extends.  They  also  occur 
in  the  spinal  ganglia,  and  their  cerebral  homologues  (such  as  the  Gas- 
serian  ganglion),  in  the  ganglia  of  the  sympathetic  system,  and  the 
sporadic  ganglia  in  general.  But  wide  as  is  their  distribution,  and 
great  as  is  the  size  of  the  individual  cells,  some  of  which  have  a  diameter 
of  140/Z,  or  even  more,  they  yet  make  up  but  a  small  portion  of  the  whole 
of  the  central  nervous  substance,  the  total  weight  of  the  9,000  millions  of 
nerve-cell  bodies  in  the  human  brain  being  less  than  27  grammes 
(Donaldson).  And  although  it  is  not  to  be  wondered  at  that  objects 
so  notable  when  \  iewed  under  the  microscope  should  have  struck  the 

imagination  of  physiologists,  it  is  probable 
that  the  \-ery  high  powers  which  it  is  so 
common  to  attribute  exclusively  to  them 
are.  in  part  at  least,  shared  with  the  network 
or  feltwork  formed  by  their  processes. 

The  grey  matter,  in  addition  to  this  ex- 
ceeding!}'delicate  feltwork  of  non-medullated 
fibres  and  filaments  representing  the  den- 
drites and  such  axons  and  collaterals  as 
terminate  within  itself,  contains  also,  as  may 
be  seen  in  preparations  stained  by  Weigert's 
method,*  great  numbers  of  exceedingly  fine 
medullated  fibres,  many  of  which  are  the 
collaterals  of  fibres  that  are  passing  out  to  the 
white  matter. 

Only  medullated  nerve-fibres  are  met  with 
in  the  white  matter  of  the  cerebro-spinal  axis. 
They  are  commonly  stated  to  be  devoid  of  a 
neurilemma  (or  neurolemma),  and  in  the  sense 
that  there  is  no  continuous  separate  mem- 
branous sheath  corresponding  to  the  sheath 
of  Schwann  of  the  peripheral  medullated 
fibres  this  is  correct.  Sheath  cells,  however, 
are  present,  and  form  a  reticulum  around  each  fibre  in  the  meshes 
of  which  myelin  is  contained.  In  diameter  the  medullated  fibres  of 
the  white  matter  vary  from  2  /*  to  20  /i.  In  Malapterums  electricus 
the  fibre  in  the  cord  which  supplies  the  electrical  organ  is  of  immense 
size;  and  in  the  anterior  column  of  many  fishes  may  also  be  seen  a 
single  gigantic  fibre  on  each  side  with  a  diameter  of  nearly  100  jx.  It 
cannot  be  said  that  any  relation  between  the  functions  of  neurons 
and  the  calibre  of  their  axons  has  been  definitely  established.  Many 
afferent  fibres,  it  is  true,  are  small — this  is  notably  the  case  with  the 
fibres  of  the  posterior  column,  and  many  motor  fibres  are  large.  But 
the  di.stinction  can  by  no  means  be  generalized,  for  the  fibres  of  the 
direct  cerebellar  tract  (p.  866),  which  certainly  are  afferent,  are  amongst 
the  largest  in  the  spinal  cord  ;  and  the  vaso-motor  fibres,  which  pass  from 
the  cord  by  the  anterior  (ventral)  roots  (Fig.  341)  into  the  sympathetic, 
are  smaller  than  the  fibres  of  the  posterior  column.  Even  the  motor 
*  Weigert's  is  a  special  method  of  staining  the  medullary  sheath  with 
hematoxylin. 


Fig.  341. — Transverse  Section 
of  a  Bundle  of  Nerve- 
Fibres  from  the  Anterior 
(Ventral)  Root  of  the  First 
Coccygeal  Nerve  of  the  Cat 
(Dale).  The  great  differ- 
ence  in  the  diameter  of  the 
fibres  is  well  shown.  The 
small  fibres  are  vaso-motor. 


HISTOLOGICAL  ELEMENTS  86i 

nerve-fibres  of  striated  muscles  vary  considerably  in  diameter,  those  of 
the  tongue,  e.g.,  being  smaller  than  those  of  the  mus'jles  of  the  limbs. 
Further,  the  mcdullated  fibres  of  the  brain  are,  without  reference  to 
function,  in  general  finer  than  the  fibres  of  the  cord.  As  a  rule  the 
fibres  whose  course  is  the  longest  arc  the  thickest,  but  the  rule  is  often 
broken.  For  example,  the  average  diameter  of  the  fibres  going  to  the 
thigh  of  the  frog  is  greater  than  that  of  the  fibres  going  to  the  lower 
part  of  the  limb  (Dunn).  The  cause  of  these  differences  in  the  size  of 
nerve-fibres  is  quite  unknown.  It  is  more  likely  to  be  morphological 
than  ph\-siological. 

Supporting  Tissue. — The  protective  membranes  of  the  central  nervous 
system  consist  of  ordinar^^  connective  tissue  derived  from  the  meso- 
derm. The  supporting  framework  which  interpenetrates  the  nervous 
substance  consists  of  a  peculiar  form  of  tissue  derived  from  the  ecto- 
derm, and  called  neuroglia.  The  whole  cerebro-spinal  axis  is  wrapped 
in  four  concentric  sheaths.  Next  the  walls  of  the  bony  hollow  in  which 
it  lies  is  the  dura  mater.  Next  the  nervous  substance  itself,  following 
the  convolutions  of  the  brain  and  the  fissures  of  the  cord,  and  giving 
off  bloodvessels  to  both,  is  the  pia  mater.  Between  the  dura  and 
the  pia,  separated  from  ;he  latter  by  a  jacket  of  cerebro-spinal  fluid, 
is  the  double  layer  of  the  arachnoid.  The  comparatively  coarse  septa 
that  run  into  the  nervous  substance  as  if  coming  off  from  the  pia  mater 
are  the  main  beams  in  the  scaffolding  of  non-nervous  material  with 
which  that  substance  is  interwoven,  and  by  which  it  is  supported. 
The  interstices  are  filled  in  by  a  thick-set  feltwork  of  interlacing  neurog- 
lia fibres,  which  lie  close  against  the  small  glia  cells.  In  preparations 
impregnated  by  the  Golgi  method  many  of  the  neuroglia  fibres  appear 
to  be  processes  running  out  from  the  attenuated  cell-body  like  the 
arms  of  a  microscopic  crab  or  spider.  But  this  is  a  deceptive  appear- 
ance, as  has  been  shown  by  means  of  special  methods  in  which  the 
neuroglia  fibres  are  alone  stained  {Weigert,  Huber,  etc.).  They 
generally  lie  in  close  contact  with,  or  embedded  in,  the  protoplasm 
of  the  neuroglia  cells,  from  which  they  have  become  differentiated 
structurally  and  chemically,  but  sometimes  they  may  detach  themselves 
entirely  from  the  cells  and  lie  free  in  the  intervening  tissue.  The 
neuroglia  is  present  in  greatest  abundance  in  the  grey  matter  immedi- 
ately surrounding  the  central  canal  of  the  cord  and  the  ventricles  of 
the  brain  (the  ependyma,  as  it  is  called),  from  which  long  neuroglia 
fibres  pass  out  radially,  giving  off  branches  on  their  course,  and  ending 
in  little  knobs  or  enlargements  attached  to  the  pia  mater. 


Section  II. — General  Arrangement  of  the  Grey  and  White 
Matter  in  the  Central  Nervous  System. 

(i)  Around  the  central  canal,  as  we  have  seen,  a  tube  of  grey 
matter  sheathed  with  white  fibres  is  developed.  This  tube,  from 
oi)tic  thalamus  to  conus  medullaris,  may  be  conveniently  referred  to 
as  the  central  grey  axis  or  stem,  which,  in  the  lowest  vertebrates — e.g., 
fishes — is  much  the  most  important  part  of  the  central  nervous 
system . 

(2)  On  the  outer  surface  of  the  anterior  portion  of  the  neural 
axis,  but  not  in  the  part  corresponding  to  the  spinal  cord,  is  laid 
down  a  second  sheet  or  mantle  of  cortical  grey  matter.     Between 


862  THE  CENTRAL  NERVOUS  SYSTEM 

this  and  the  primitive  grey  stem  are  interposed  (a)  the  sheath  of 
white  fibres  that  clothes  the  latter,  and  connects  its  various  parts, 
and  (6)  a  new  development  of  white  matter  (corona  radiata,  cere- 
bellar peduncles),  which  serves  to  bring  the  cortex  into  relation 
with  the  primitive  axis,  and  through  it  with  the  rest  of  the  body. 

Although  there  are  histological  and  developmental  differences 
between  the  cerebral  and  the  cerebellar  cortex,  we  may,  for  some 
purposes,  classify  them  together  as  cortical  formations.  Anl  we 
may  also  include  under  this  head  the  corpora  striata,  which,  although 
for  descriptive  purposes  generally  grouped  with  the  optic  thalami 
and  the  other  clumps  of  grey  matter  at  the  base  of  the  brain,  as  the 
basal  ganglia,  are  to  be  regarded  as  cortical  in  character.  As  we 
mount  in  the  vertebrate  scale  the  cortex  formation  of  the  secondary 
fore-brain  and  hind-brain  acquires  prominence. 

In  other  words,  the  grey  matter  developed  in  the  roof  of  the  cerebral 
vesicles  I.  and  III.  (Fig.  327)  (the  grey  matter  of  the  cerebral  and  cere- 
bellar cortex)  comes  to  overshadow  the  superficial  grey  matter  hitherto 
present  only  in  the  roof  of  vesicle  II.  (in  the  corpora  bigemina).  And 
this  cortex  formation  becomes  larger  in  amount,  and,  in  the  case  of 
the  cerebral  grey  matter,  more  richly  convoluted,  the  higher  we  ascend, 
until  it  reaches  its  culmination  in  man.  As  the  anterior  cerebral 
vesicles  develop,  they  spread  continually  backward,  until  at  length  the 
cerebral  hemispheres  cover  over,  and  almost  completely  surround,  the 
primary-  fore-brain  and  the  mid-  and  hind-brains,  so  that  the  anterior 
portion  of  the  primitive  stem  comes,  as  it  were,  to  be  invaginated  into 
the  second  wider  tube  of  cortical  grey  matter.  This  development  of 
the  cortical  grey  substance  is  accompanied  with  a  corresponding 
development  of  nerve-fibres,  for  an  isolated  nerve-cell  (apart,  of  course, 
from  possible  embryonic  rudiments  which  have  not  undergone  com- 
plete development)  is  no  more  conceivable  than  a  railway-station  the 
track  from  which  leads  nowhere  in  particular,  or  a  harbour  on  the  top 
of  a  hill. 

But  it  is  to  be  particularly  observed  that  the  new  formation  does 
not  supplant  the  old,  but  works  through  and  directs  it.  The  neuro- 
blasts of  the  cortex  do  not  throw  out  their  axons  to  make  direct  junc- 
tion with  muscles  and  sensory  surfaces.  Such  junction  the  cortex 
finds  already  established  between  the  primitive  cerebro-spinal  axis  and 
the  peripherJ^  It  joints  itself  on  by  nerve-fibres  to  the  cells  of  the 
central  stem;  and  we  have  reason  to  believe  that  no  single  axon  in  an 
ordinary  spinal  or  cranial  nerve*  runs  all  the  way  from  the  periphery 
to  the  cortex,  and  no  axon  of  a  cortical  nerve-cell  all  the  way  from  the 
cortex  to  the  periphery,  but  that  the  connection  is  made  by  a  cliain 
of  at  least  two  neurons,  the  cell-body  of  one  of  which  is  situate  in  this 
primitive  grey  tube. 

The  fibres  from  the  cortex  of  each  cerebral  hemisphere  (corona 
radiata),  radiating  out  like  a  fan  below  the  grey  matter,  are  gathered 
together  into  a  compact  leash  as  they  sweep  down  through  the  isthmus 
of  the  brain  in  the  internal  capsule,  to  join  the  crura  cerebri.  The 
cortex  of  each  cerebellar  hemisphere,  and  the  ribbed  pouch  of  grey 

*  The  olfactory  and  possibly  to  some  extent  the  optic  nerves  are  exceptions 
to  this  statement.  Their  relation  to  the  cortex,  as  is  ea,sily  under.stood  from 
the  manner  of  their  development  (p.  850),  is  different  from  that  of  the  other 
nerves. 


GREY  AND  WHITE  MA  ITER  IN  THE  SPINAL  CORD 


863 


matter,  known  as  tlic  corpus  dentatum,  which  is  buried  in  its  white 
core,  arc  also  connected  l)y  strands  of  fibres  with  the  central  stem  and 
the  cerebral  mantle.  The  restiform  body  or  inferior  peduncle  brings 
the  cerebellum  into  communication  with  the  spinal  cord.  The  superior 
peduncle  by  one  path,  and  the  middle  peduncle  by  another,  connect  it 
with  the  cerebral  cortex.  A  great  transverse  commissure,  the  corpus 
callosum,  unites  the  cerebral  hemispheres  across  the  middle  line,  while 
transverse  fibres,  that  break  through  the  middle  lobe  or  worm,  form 
a  similar  though  far  less  massive  junction  between  the  two  hemispheres 
of  the  cerebellum. 

The  fibres  of  the  nervous  system  may  be  divided  into  (i)  fibres 
connecting  the  peripheral  organs  with  nerve-cells  in  the  central  grey 
axis;  (2)  fibres  connecting  nerve-cells  in  this  central  axis  with  cells 
in  the  external  or  cortical  grey  tube;  and  (3)  fibres  linking  cortex 
with  cortex,  or  central  ganglia  with  each  other.  In  the  third  group 
are  included  {a)  fibres  which  connect  portions  of  the  cortex  on  the 
same  side  (association  fibres) ;  {b)  fibres  which  connect  portions  on 
opposite  sides  of  the  middle  line  (commissural  fibres) ;  (c)  fibres  which 
connect  the  central  grey  matter  at  different  levels — e.g.,  the  proprio- 
spinal  or  endogenous  fibres  of  the  cord.  Our  first  task  is,  therefore, 
to  trace  the  peripheral  nerves  to  their  cells  of  origin  or  centres  of 
reception*  in  the  nervous  stem.  And  although  there  is  reason  to 
believe  that  the,  whole  of  the  peripheral  nerves,  cerebral  and  spinal 
(with  the  exception  of  the  olfactory  and  optic,  which  are  rather 
portions  of  the  brain  than  true  peripheral  nerves),  form  a  morpho- 
logical series,  it  will  be  well  to  begin  with  the  spinal  nerves,  since 
their  motor  and  sensory  fibres  are  gathered  into  different  and  definite 
roots,  whose  course  within  the  cord  is,  in  general,  more  easily  traced 
than  the  course  of  the  cerebral  root-bundles  within  the  brain. 

Section  III. — Arrangement  of  the  Grey  and  White  Matter 
IN  THE  Spinal  Cord. 

The  grey  matter  of  the  spinal  cord  is  arranged  on  each  side  in  a 
great  unbroken  column  of  roughly  crescentic  section,  joined  with 
its  fellow  across  the  middle  line  by  a  grey  bar  or  bridge,  which 
springs  from  the  convexity  of  the  crescent,  and  is  pierced  from  end 
to  end  by  the  central  canal.  The  anterior  horn  of  the  crescent, 
although  it  varies  in  shape  at  different  levels  of  the  cord,  is,  in 
general,  broad  and  massive,  in  comparison  with  the  slender  and 
tapering  posterior  horn.  In  the  lower  cervical  and  upper  dorsal 
region  a  moulding  or  projection,  forming  a  lateral  horn,  springs 
from  the  fluted  outer  side  of  the  grey  substance.  Within  the  grey 
matter  nerve-cells  are  found,  sometimes  so  regularly  arranged  that 
they  form  veritable  cellular  or  vesicular  strands.     Of  these  the  best 

*  The  centre  or  nucleus  of  reception  of  a  nerve  contains  the  nerve-cells 
around  which  its  axons  terminate;  the  nucleus  of  origin  of  a  nerve  contains 
the  cells  from  which  its  axons  arise. 


864 


Thin  CENTRAL  NERVOUS  SYSTEM 


marked  are — (i)  The  tract  or  tracts  made  up  by  the  cells  of  the 
anterior  horn  (Fig.  342),  which  practically  run  from  end  to  end  of  the 
cord,  swell  out  in  the  cervical  and  lumbar  enlargements,  where  the 
cells  arc  very  numerous  and  of  great  size  (70  /j,  to  140  jj,  in  diameter), 
and  contract  to  a  thin  thread  in  the  thoracic  region,  where  they  are 
relatively  few,  scattered,  and  small.  In  the  enlargements  there 
are  several  groups  of  these  cells  corresponding  with  the  segments 

of  the  limbs,  the  movements 
\  /  of    the    hand,    forearm,    and 

upper  arm  being  each  repre- 
sented by  a  group  in  the 
cervical,  and  those  of  the  foot, 
leg,  and  thigh  by  groups  in 
the  lumbar  swelling.  In  the 
rest  of  the  cord  only  two 
well-marked  groups  of  cells 
are  present  in  the  anterior 
horn,  a  mesial  and  a  lateral. 
(2)  Clarke's  column,  whose 
cells,  mostly  of  good  size  and 
somewhat  rounded  in  outline, 
are  situated  at  the  inner  side 
of  the  root  of  the  posterior 
horn  just  where  it  joins  on  to 
the  grey  cross-bar.  It  gradu- 
ally increases  in  size  from 
above  downwards,  usually 
appearing  first  at  the  level  of 
the  seventh  or  eighth  cervical 
nerve,  attaining  its  maximum 
development  at  the  eleventh 
or  twelfth  dorsal  and  dis- 
appearing altogether,  as  a 
continuous  strand,  at  the  level 
of  the  second  or  third  lumbar 
nerves.  Scattered  nerve-cells, 
however,  constituting  the  so- 
called  cervical  and  sacral  nuclei  of  Stilling,  are  frequently  found 
occupying  the  same  po.sition  towards  the  upper  and  lower  ends  of 
the  cord,  and  may  be  looked  upon  as  isolated  portions  of  Clarke's 
column.  (3)  A  tract  of  small  cells  called  the  intermedia-lateral 
tract,  lateral  cell  column,  or  lateral  horn,  situated  at  the  outer  edge 
of  the  grey  matter,  about  midway  between  the  anterior  and  pos- 
terior horns.  It  is  best  marked  in  the  thoracic  region,  up  to  about 
the  second  thoracic  segment,  although  in  the  corresponding  situa- 
tion there  are  scattered  cells  in  the  lumbar  swelling  and  the  cervical 


StilUr)gs  CerULCol 
r?ucleus 
-  CeruLCoi 
Lnlargewevt 


lateral  Cell- column 
Ccolurnn  of^  p)e  enter - 
medio -lateral  tract) 

Stclliops  dorsal 

nucleus  orClark&'5 
Column 

Ce]h  aj  1he.  drilkrior 
Cornu 


Scattered  ceils  of' 

iKttermedio-lc^era^ 
tract 

lurnhdr Enlargement 

StilUno's  Sacral 
nuec&us 


Fig.  342. — Diagram  of  Grey  Tracts  of  Cord. 


GREY  AND   WHITE  MATTER  IN  THE  SPINAL  CORD        S65 

cord.  There  is  reason  to  believe  that  the  axons  of  cells  of  the  inter- 
medio-lateral  tract,  which  pass  out  as  small  medullated  fibres  in 
the  anterior  roots,  form  tiie  preganglionic  segments  of  the  efferent 
vascular  and  visceral  nerves  (p.  185)-  (4)  The  cells  of  the  posterior 
horn,  which,  although  numerous,  are  smaller  than  those  of  the 
anterior  horn.  Throughout  the  whole  cord,  however,  two  small 
groups  of  cells  may  be  distinguished,  one  on  the  lateral  side  of  the 
horn,  about  its  middle,  and  the  other  on  the  mesial  side,  a  little 
in  front  of — i.e.,  ventral  to — the  edges  of  the  substance  of  Rolando. 
Both  of  these  groups  are  broken  up  by  the  passage  through  them 
of  bundles  of  fibres  which  form  a  network,  and  they  are  therefore 
called  respectively  the  group  of  the  lateral  and  the  group  of  the 
posterior  reticular  formation. 

The  white  matter  of  the  cord  is  anatomically  divided  by  the 
position  of  the  nerve-roots  and  the  anterior  and  posterior  fissures 


Fig.  343. — Diagrammatic  Section  of  the  Spinal  Cord  in  the  Cervical  and  Lumbar 
Enlargements,  to  show  Tracts  of  Fibres  (Starr),  i,  antero-median  column; 
2,  antero-lateral  column;  3,  ascending  antero-lateral  or  Gowers'  tract;  4,  mar- 
ginal tract  (ground  bundle,  consisting  of  short  endogenous  fibres);  5,  lateral  or 
crossed  pyramidal  tract;  6,  direct  cerebellar  tract;  7,  tract  of  Lissauer;  8,  ex- 
ternal portion,  and  9,  root  zone,  of  Burdach's  column;  ro,  comma  tract;  11,  pos- 
terior commissural  tract;  12,  Goll's  column;  13,  septo-marginal  tract. 

into  three  columns  on  each  side :  the  anterior,  lateral,  and  posterior 
columns.  The  first  two,  since  they  are  not  separated  by  a  perfectly 
definite  boundary,  are  often  grouped  together  as  the  antero-lateral 
column.  In  the  cervical  region  it  may  be  seen  with  the  microscope 
that  the  posterior  white  column  is  almost  bisected  by  a  septum 
running  in  from  the  pia  mater  towards  the  grey  commissure.  The 
inner  half  is  called  the  postero- median  column,  or  column  of  Goll ; 
the  outer  half  the  postero-external  column,  or  column  of  Burdach 
(Fig.  343).  No  localization  of  any  of  the  other  conducting  paths 
in  the  cord  is  possible  by  gross  anatomical  examination;  but  by 
means  of  the  developmental  method  and  the  method  of  degenera- 
tion the  columns  of  Goll  and  Burdach  can  be  followed  throughout 
the  cord,  and  several  similar  areas  can  be  mapped  out.  We  shall 
only  mention  those  that  are  physiologically  the  most  important. 

55 


866  THE  CENTRAL  NERVOUS  SYSTEM 

WluMi  the  spinal  cord  is  divided,  and  the  animal  allowed  to  survive 
for  a  time,  certain  tracts  arc  picked  out  by  the  degeneration  of  their 
fibres,  although  in  every  degenerated  tract  some  fibres  remain  un- 
affected. We  luay  distinguish  the  tracts  that  degenerate  above 
the  lesion  (ascending  degeneration)  from  those  that  degenerate 
below  the  lesion  (descending  degeneration). 

Ascending  Tracts. — Above  the  lesion  degeneration  is  found  both 
in  the  posterior  and  the  antero-lateral  columns.  Immediately 
above  the  section  nearly  the  w^hole  of  the  posterior  column  is  in- 
volved. Higher  up  the  degeneration  clears  away  from  Burdach's 
tract,  and,  shifting  inwards,  comes  to  occupy  a  position  in  the 
column  of  Goll.  In  the  antero-lateral  column  two  degenerated 
regions  are  seen,  both  at  the  surface  of  the  cord,  one  a  compact, 
sickle-shaped  area  extending  forwards  from  the  neighbourhood  of 
the  line  of  entrance  of  the  posterior  roots,  and  the  other  an  area  of 
scattered  degeneration,  embracing  many  intact  fibres,  and  complet- 
ing the  outer  boundary  of  the  column  almost  to  the  anterior  median 
fissure.  The  compact  area  is  called  the  dorsal  or  direct  cerebellar 
tract,  or  tract  ofFlechsig  {or  the  fasciculus  cerebello-spinalis) ,  the  diffuse 
area  the  antero-lateral  ascending  tract,  or  tract  of  Gowers,  or  ventral 
cerebellar  tract  (or  the  fasciculus  antero-lateralis  snperficialis).*  The 
dorsal  cerebellar  tract  is  distinguished  by  the  large  size  of  its  fibres. 
It  is  only  distinct  in  the  dorsal  and  cervical  regions  of  the  cord.  The 
tract  of  Lissauer,  or  posterior  marginal  zone,  is  another  small  ascend- 
ing tract  at  the  outer  side  of  the  tip  of  the  posterior  horn.  It  is 
made  up  of  fine  fibres  from  the  posterior  roots  which  soon  pass  into 
the  posterior  column., 

Descending  Tracts. — When  the  cord  is  divided,  say,  in  the  upper 
dorsal  or  cervical  region,  the  following  tracts  degenerate  below  the 
lesion : 

(i)  A  small  group  of  fibres  close  to  the  antero-median  fissure, 
which  has  received  the  name  of  the  direct  pyramidal  tract — pyramidal 
1  ecause  higher  up  in  the  medulla  oblongata  it  forms  part  of  the 
pyramid;  direct,  because  it  does  not  cross  over  at  the  decussation  of 
the  pyramids,  but  continues  down  on  the  same  side.  In  the  stan- 
dard anatomical  nomenclature  it  is  termed  the  fasciculus  cercbro- 
spinalis  anterior.  The  direct  pyramidal  tract  is  only  present  in  man 
and  the  higher  apes. 

(2)  A  tract  of  degenerated  fibres  in  the  posterior  part  of  the 
lateral  column.  This  is  the  lateral  or  crossed  pyramidal  tract  (or  the 
fasciculus  cerebro-spiualis  lateral  is),  and  is  much  larger  than  the  direct. 
In  the  medulla  it  also  lies  within  the  pyramid,  but,  unlike  the  direct 
pyramidal  tract,  it  crosses  to  the  opposite  side  of  the  cord  at  the 
decussation.  The  pyramidal  tracts  are  also  called  corticospinal  to 
indicate  their  origin  and  termination. 

♦  Some  WTiters  employ  the  terms  dorsal  and  ventral  s/>imo  cerebellar 
tracts. 


GREY  AND  WHITE  MATTER  IN  THE  SPINAL  CORD        867 


{},\  A  tract  of  scattered  degeneration  lying  along  the  margin  of  the 
cord  in  the  anterior  portion  of  the  antero-lattTal  column,  and  partly 
overlajiping  the  tract  of  (iowers.  It  is  called  the  antcro-lateral 
descend i Hi:,  tract,  or  tract  of  Loewcnthal,  or  the  vestibulo-spinal  tract. 

(4)  The  prcpyramidal  (or  rubrospinal)  tract,  or  M onakoxv' s  tract 
(also  called  the  fasciculus  intermcdio-lateralis),  \ymg  immediately  in 
front  of  the  crossed  pyramidal  tract. 

(5)  A  small,  comma-shaped  island  of  degeneration  {comma  tract) 
can  be  followed  downwards  for  a  short  distance  in  the  middle  o! 
Burdach's  column.    It  is  only 


and 


D.  C 


D.P 


V.B 


seen    in    the    cervical 
upper  thoracic  regions. 

Less  well  known  descending 
tracts  are^  - 

(6)  The  olivo  -  spinal  and 
thalamico  -  spinal  tracts  (or 
Helweg's  bundle)  in  the  antero- 
lateral column  opposite  the 
head  of  the  anterior  horn. 
This  tract  docs  not  pass  down 
beyond  the  lower  cervical  re- 
gion. The  olivo-spinal  tract 
appears  to  consist  of  fibres 
running  down  from  the  olivary 
body  into  the  cord,  while  the 
thalamico-spinal  tract  is  made 
up  of  descending  fibres  origina- 
ting in  the  optic  thalamus. 
This  is  an  important  tract  in 
the  lower  vertebrates,  but  not 
in  man. 

(7)  The  tract  of  Marie  in  the 
anterior  column  is  chiefly  a 
continuation  into  the  cord  of 

the  posterior  longitudinal  bundle,  one  of  the  conspicuous  tracts  of  the 
brain-stem  or  upper  portion  of  the  cerebro-spinal  axis  (p.  885).  It 
contains  both  ascending  and  descending  fibres. 

When  we  have  deducted  the  long  ascending  and  descending  tracts 
which  have  been  described,  there  still  remains  in  the  antero-lateral 
column  a  balance  of  white  matter  unaccounted  for.  This  white 
substance,  which  does  not  degenerate  for  any  great  distance  either 
above  or  below  a  lesion,  is  called  the  antero-lateral  ground-bundle, 
and  lies  chiefly  in  the  form  of  an  incomplete  ring  around  the  grey 
matter.  For  descriptive  purposes  it  is  sometimes  distinguished  as 
the  anterior  ground-bundle  (or  fasciculus  anterior  proprius)  in  the 
anterior  column,  and  the  lateral  ground-bundle  (or  fasciculus  lateralis 
proprius)  in  the  lateral  column.  It  is  believed  to  consist  of  fibres 
(endogenous  or  proprio-spinal  fibres)  which  run  only  a  comparatively 
short  course  in  the  cord,  and  serve  to  connect  nerve-cells  at  different 
levels.     Some   of  these  endogenous   fibres  are  ascending,   others 


Fig.  344. — Scheme  of  Cross-Section  of  Spinal 
Cord  (Donaldson,  after  Lenhossek).  On  the 
left  side  only  the  afferent  fibres  are  shown; 
the  efferent  fibres  and  the  spinal  cells  on  the 
right  side.  D.R.,  posterior  (dorsal)  root; 
V.R.x  anterior  (ventral)  root;  C.P.,  crossed 
pyramidal  fibres;  C,  direct  cerebellar  tract; 
A.L.,  antero-lateral  tract;  D.C.,  posterior 
columns. 


868 


THE  CENTRAL  NERVOUS  SYSTEM 


descending.     The  sepio-marginal  bundle  consists  also  largely  of  fibres 
which  begin  and  end  in  the  cord  (proprio-spinal  fibres).  Some  endog- 


Figr  345.— Medulla  Oblongata,  Pons  and 
•  Corpora  Quadrigemina  (Dorsal  or  Pos- 
terior    View)     (Sappey).     i,    corpora 
quadrigemina;     2,    nates;     3,     testes; 
4,  anterior  brachium  uniting  the  nates 
to  the  lateral  geniculate  body;  5.  pos- 
terior brachium  uniting  the  testes  to 
the  internal  geniculate  body  6;  7,  pos- 
terior   commissure;    8,    pineal    gland 
pulled  forward  to  show  nates;  9,  su 
perior  peduncle  of  the  cerebellum;  10 
II,  12,  valve  of  Vieussens;  13,  troch 
lear  nerve;  14,  lateral  sulcus;  15,  fillet 
16,  superior,   17,  middle,  and   18,  in 
ferior,    peduncle    of    the   cerebellum 
19,  floor  of  fourth  ventricle;  20,  audi 
tory  nerve;  21,  spinal  cord;  22,  postero 
median  column,  continued  in  the  me 
dulla  as  the  funiculus  gracilis;  23,  the 
clava,  the  continuation  of  the  funiculus 
gracilis. 


Fig.  346. — Medulla  Oblongata,  Pons 
and  Crura  Cerebri  (Ventral  or  .in- 
terior View).  I,  infundibuluin; 
2,  tuber  cinereum;  3,  corpus  mam- 
millare;  4,  cerebral  peduncle  or  crus 
cerebri;  5,  pons;  6,  middle  peduncle 
of  cerebellum;  7,  pyramid;  8,  decus- 
sation of  pyramids;  9,  olive;  10,  tu- 
bercle of  Rolando  ;  11,  e.\ternal 
arcuate  fibres;  12,  upper  end  of  cord; 
13,  ligamentum  denticulatum;  14, 
dura  mater  of  cord;  15,  optic  tract; 
16,  chiasraa;  17,  third  nerve;  18, 
fourth  nerve;  19,  fifth  nerve;  30, 
sixth  nerve;  21,  seventh  nerve;  22. 
eighth  nerve;  23,  nerve  of  VVrisberg 
(portio  intermedia),  which  unites 
with  the  facial;  24,  glosso-pharyn- 
geal  nerve;  25,  vagus;  26,  spinal 
accessory;  27,  hypoglossal;  28,  29, 
30,  first,  second,  and  third  pairs  of 
cervical  spinal  nerves. 


enous  fibres  may  also  be  intermingled  with  the  fibres  of  certain  of 
the  long  tracts,  both  in  the  antero-lateral  and  posterior  columns,  and 


GREY  AND  WHITE  MATTER  IN  CEREBROSPINAL  AXIS     860 

Sherrington  has  shown  (in  Xhv  do^)  lli;i.t  long  proprio-spinal  fibres 
passing  down  in  the  lateral  colunm  connect  the  upper  with  the  lower 
parts  of  the  cord  (p.  908). 

The  next  question  which  arises  is:  How  are  the  long  tracts  con- 
nected below — i.e.,  with  the  periphery — and  above — i.e.,  with  the 
higher  parts  of  the  central  nervous  system  ?  The  answer  to  this 
question,  partly  derived  from  clinical  records  and  partly  from 
experimental  results,  is  in  the  case  of  some  of  the  tracts  unexpectedly 
full  and  minute,  though  meagre  in  regard  to  others.  But  to  render 
it  intelligible  it  is  necessary,  first  of  all,  to  describe  briefly — 


Section  IV. — Arrangement  of  Grey  and  White  Matter 
IN  the  Upper  Portion  of  the  Cerebro-Spinal  Axis. 

In  the  medulla  oblongata  the  grey  and  white  matter  of  the  spinal 
cord  is  rearranged,  and,  in  addition,  new  strands  of  fibres  and  new 
nuclei  of  grey  substance  make  their  appearance.  Of  these  nuclei  the 
most  conspicuous  is  the 
dentate  nucleus  of  the  in- 
ferior olive,  which,  covered 
by  a  crust  of  white  fibres, 
appears  as  a  projection  on 
the  antero-latcral  surface 
of  the  medulla.  In  front 
of  the  olive,  between  it 
and  the  continuation  of 
the  anterior  median  fis- 
sure, is  another  projec- 
tion, the  pyramid,  which 
looks  like  a  prolongation 
of  the  anterior  column  of 
the  cord,  but  is  made  up 
of  very  different  consti- 
tuents. Dorsal  to  the 
olive  is  the  restiform  body 
or  inferior  peduncle  of  the 
cerebellum,  and  behind 
the  restiform  body  lie  two  pjg.  347._Medulla  Oblongata  and  Cerebellum,  with 
thin  columns,  \\\e  funicn-  Fourth  Ventricle  (Hirschfeld).  i,  mesial  groove 
Itis  cuneatus.  which  con-  of  floor  of  ventricle  running  down  to  the  calamus 
tinues  the  postero-exter-  scriptorius;  2,  stria3  acustica-;  3,  inferior  peduncle 
nal  column  of  the  cord,  of  the  cerebellum;  4,  clava;  5,  superior  peduncle 
a.nd  the  funic itlus  gracilis,  crossing  the  inferior  and  passing  to  its  internal 
which  continues  the  pos-  side;  7.  7.  lateral  sulcus;  8,  corpora  quadrigemina. 
tero-internal  column.    In 

these  funiculi  are  contained  collections  of  small  or  medium-sized  nerve- 
cells  termed  respectively  the  nucleus  cuneatus  and  the  nucleus  gracilis. 
The  rearrangement  of  the  constituents  of  the  cord  is  due  mainly  to  two 
causes:  (i)  The  opening  up  of  the  central  canal  to  form  the  fourth 
ventricle,  and  the  folding  out,  on  either  side,  of  the  grey  matter  which 
lies  posterior  to  it  in  the  cord;  (2)  the  breaking  up  of  the  grey  matter 
of  the  anterior  horn  by  strands  of  fibres  as  they  sweep  through  it  from 
the  lateral  pyramidal  tract  to  take  up  a  position  in  the  p^Tamid  of  the 
opposite  side  (decussation  of  the  pyramids),  and  a  little  higher  up  by 


870  THE  CENTRAL  NERVOUS  SYSTEM 

fibres  passing  across  the  middle  line  from  the  gracile  and  cuncate  nuclei 
(sensory  decussation  or  decussation  of  the  fillet).  The  mosaic  of  grey 
and  white  matter  formed  in  the  medulla  by  the  interlacing  of  longi- 
tudinal and  transverse  fibres  with  each  other  and  with  tlie  relics  of  the 
anterior  horn,  is  called  the  reticular  formation  (formatio  reticularis). 
It  occupies  the  anterior  and  lateral  portions  of  the  bulb  behind  the 
pyramids  and  olivary  bodies,  and  is  continued  upwards  in  the  dorsal 
portion  of  the  pons  and  crura  cerebri,  and  downwards  for  a  little  way 
into  the  upper  part  of  the  cervical  cord. 

The  cercbro-spinal  axis  passes  up  from  the  medulla  through  the  pons, 
encircled  and  traversed  by  the  transverse  pontine  fibres  derived  from 
the  middle  cerebellar  peduncle  or  commissure,  which  enclose  every- 
where between  them  numerous  collections  of  nerve-cells  {nuclei  ponti's). 
Enlarged  by  the  accession  of  many  of  these  fibres  which  come  from  the 
cortex  of  the  cerebellum  on  the  opposite  side,  as  well  as  of  fibres  from  the 
nuclei  of  the  cranial  nerves  that  take  origin  in  this  neighbourhood  (fifth 
and  eighth),  the  central  nervous  stem  bifurcates  above  the  pons  into  the 
two  divergent  crura  cerebri.  From  each  crus  a  great  sheet  of  fibres 
passes  up  betrween  the  optic  thalamus  and  the  caudate  nucleus  of  the 
corpus  striatum  on  the  one  hand,  and  the  globus  pallidus  of  the  lenticular 
nucleus  on  the  other,  as  the  internal  capsule,  from  which  they  are  dis- 
persed, in  the  corona  radiata,  to  the  cerebral  cortex.  Both  in  the  upper 
part  of  the  pons  and  in  the  crus  a  ventral  portion,  or  crusta,  containing 
the  fibres  of  the  pyramidal  tract,  and  a  dorsal  portion,  or  tegmentum, 
can  be  distinguished,  the  line  of  separation  being  marked  in  the  crus  by 
a  collection  of  grey  matter,  called  from  its  usual,  though  not  invariable, 
colour  the  substantia  nigra  (Fig.  352),  A  portion  of  the  tegmentum  is 
continued  below  the  optic  thalamus. 


Section  V. — Connections  of  the  Long  Paths  of  the  Cord. 

Coming  back  now  to  our  question  as  to  the  connections  of  the  long 
tracts  of  the  cord,  let  us  consider,  first  of  all, 

The  Connections  of  the  Postero-Median  and  Poster©- External 
Columns. — When  a  single  posterior  root  is  divided,  say,  in  the  dorsal 
region,  between  the  cord  and  the  ganglion,  its  fibres,  as  we  have 
already  seen  (p.  797),  degenerate  above  the  section.  Since  the  cell- 
bodies  of  these  neurons  lie  in  the  ganglion,  if  a  series  of  microscopic 
sections  of  the  spinal  cord  be  made,  well-marked  degeneration  will 
be  found  at  the  level  of  entrance  of  the  root  on  the  same  side  of  the 
cord,  while  below  that  level  there  will  be  only  a  few  degenerated 
fibres  in  the  comma  tract.  Immediately  above  the  plane  of  the 
divided  root  the  degeneration  will  be  confined  to  Burdach's  column 
and  to  its  external  border.  Higher  up  it  will  be  found  in  the  internal 
portion  of  Burdach's  and  the  external  rim  of  Goll's  column.  Still 
higher  up  the  degenerated  fibres  will  be  confined  to  the  postero- 
median column ;  the  postero-external  will  be  free  from  degeneration. 

When  a  number  of  consecutive  posterior  roots  are  cut,  the  whole 
of  the  postero-external  column  in  the  sections  immediately  above 
the  highest  of  the  divided  roots  will  be  found  occupied  by  degene- 
rated fibres,  while  Goll's  column  may  be  free  from  degeneration,  or 


CONNECTIONS  OF  THE  LONG  PATHS  OF  THF  CORD 


871 


f—yr^ 


degenerated  only  at  its  outer  border.     Higher  up  degeneration  will 
be  found  to  have  involved  tiie  whole  of  the  postero-median  column, 
and  to  liave  cleared  away  altogether  from  the  postero-external. 
Tlie  degeneration  in  the  column  of  (ioll  may  be  traced  along  the 
whole  length  of  the  cord  to  the  medulla,  although  the  number  of 
degenerated  fibres  diminishes  as  we  pass  upward.     The  explanation 
of  these  appearances  is  as  follows:   It  may  be 
seen  in  preparations  of  the  cord  impregnated  by 
Golgi's  method  that  the  fibres  of  the  posterior 
roots  soon  after  their  entrance  into  the  cord 
divide  into  two  processes,  one  of  which  runs  up 
and  the  other  down  in  the  posterior  column,  or 
in  the  adjoining  portion  of  the  posterior  horn. 
From  both  of  these  collaterals  are  given  off  at 
intervals  to  the  grey  matter.     The  descending 
branches  run  downwards  only  for  a  short  dis- 
tance, and  the  degeneration  in  the  comma  tract 
seen  after  section 
of  the  cord  is  due 
to  the  division  of 
these    branches. 
Many   of    the   as- 
cending   branches 
pass  up  for  a  short 
distance     in     the 
postero-external 
column,   sweeping 
obliquely  through 
it  to  gain  the  tract 
of    Goll.     In    this 
tract  some  of  them 
run    right    on    to 
the    medulla    ob- 
longata, to  end  by 
arborizing   among 
the    cells    of    the 
nucleus      gracilis. 
Other  fibres,  both 
of    Goll's    and    of 
Burdach's     tract, 
end     at      various 
levels  in  the  cord, 
their  collaterals,  and  ultimately  the  main  branches  themselves, 
coming  into  relation  with  nerve-cells  in  the  grey  matter.     When  the 
cervical  posterior  roots  are  cut,  many  of  the  degenerated  fibres 
remain  in  Burdach's  column  up  to  the  medulla,  where  they  terminate 


^-^ 


Fig.  348.— Diagrams 
of  Degeneration  at 
Difierent  Levels  in 
the  Cord  after  Sec- 
tion of  a  Number  of 
Posterior  Roots  of 
Nerves  forming  the 
Lumbo-Sacral  Plex- 
us (Mott). 


Fig.  349. — Branching  of  Posterior 
Root-Fibres  in  Cord  (Donald- 
son, after  Cajal).  Collaterals, 
Col,  are  seen  coming  off  from 
the  two  main  branches  of  the 
root -fibres.  DR,  and  ending  in 
arborizations.  CC,  cells  in  the 
grey  matter  of  the  cord,  whose 
axons  also  give  off  collaterals. 


872  THE  CENTRAL  NERVOUS  SYSTEM 

in  the  nucleus  cuneatus.  In  the  posterior  cohimn,  then,  the 
numerous  fibres  of  the  posterior  roots  which  do  not  end  in  the  spinal 
cord  are  arranged  in  layers,  the  fibres  from  the  lower  roots  being 
nearest  the  median  fissure  (in  the  postero-median  column),  and  those 
from  the  higher  roots  farthest  away  from  it  (in  the  postero-extemal 
column.  Thus,  in  a  section  througli  the  upper  cervical  region  Goll's 
column  is  almost  entirely  composed  of  fibres  from  the  posterior  limb, 
while  the  column  of  Burdach  consists  of  fibres  from  the  anterior 
limb.  Other  collaterals  from  the  posterior  root-fibres,  and  many 
of  the  main  root-fibres  themselves,  run  into  the  anterior  horn  and 
terminate  in  arborizations  around  its  cells;  some  pass  into  the 
posterior  horn,  and  doubtless  come  into  relation  with  its  scattered 
cells  and,  in  the  dorsal  region,  with  the  cells  of  Clarke's  column. 
Some  of  the  posterior  root-fibres  and  their  collaterals  also  form 
synapses  with  the  cells  of  the  intermedio-lateral  tract.  Other 
collaterals  and  probably  some  axons  cross  the  middle  line  in  the 
anterior  and  posterior  commissures  and  end  in  the  grey  matter  of  the 
opposite  side. 

Connections  of  the  Direct  or  Dorsal  Cerebellar  Tract. — Since  the 
dorsal  or  direct  cerebellar  tract  does  not  degenerate  after  section  of 
the  posterior  nerve-roots,  but  does  degenerate  above  the  level  of  the 
lesion  after  section  of  the  spinal  cord,  the  nerve-cells  from  which  its 
axons  arise  must  be  situated  somewhere  or  other  in  the  cord.      Now, 
it  has  been  observed  that  the  vesicular  column  of  Clarke  first  becomes 
prominent  in  the  lower  dorsal  region,  and  that  in  this  same  region 
the  direct  cerebellar  tract  begins.     Atrophy  of  the  cells  of  Clarke's 
column  has  sometimes  in  disease  been  shown  to  accompany  de- 
generation of  the  direct  cerebellar  fibres.     After  an  experimental 
lesion  of  these  fibres  in  animals,  some  of  the  cells  of  the  vesicular 
column  show  the  changes  in  the  Nissl  bodies  and  the  other  changes 
which  we  have  already  described  as  occurring  in  nerve-cells  whose 
axons  have  been  cut.     After  two  or  three  months  these  cells  may 
be  found   almost   completely  atrophied  (Schafer).     Finally,  axis- 
cylinder  processes   have   been   seen   sweeping   out   from    Clarke's 
column  into  the  direct  cerebellar  tract  (Mott).     The  evidence,  then, 
is  complete  that  the  cells  of  origin  of  this  tract  are  in  Clarke's  column. 
Clarke's  cells  are  surrounded  by  arborizations,  some  of  which,  as 
previously  stated,  represent  the  terminations  of  posterior  root-fibres 
and  of  their  collaterals.     The  neurons  whose  axons  run  in  the  dorsal 
cerebellar  tract  arc  therefore  the  second  link  in  an  afferent  path. 
The  direct  cerebellar  tract  runs  right  up  to  the  cerebellum  through 
the  restiform  body,  without  crossing  and  without  being  further 
interrupted  by  nerve-cells.     The  restiform  body  ends  parti v  in  the 
dentate  nucleus  of  the  cerebellum,  partly  in  the  vermis,  and  among 
the  fibres  which  end  in  the  vermis  are  those  of  the  direct  cerebellar 
tract.     In  the  dorsal  cerebellar  tract  there  is  a  definite  stratification 


CONNECTIONS  OF  THE  LOSG  PATHS  OF  THE  CORD 


873 


of  the  fibres:  the  fibres  from  the  lowest  segments  of  the  cord  lie 
outermost;  beneath  these  come  fibres  from  the  lowest  thoracic  seg- 
ments, then  fibres  from  the  higher  thoracic  segments;  and,  internal 
to  all,  fibres  from  the  topmost  thoracic  and  lowest  cervical  segments. 

Connections  of  the  Antero-Lateral  Ascending  Tract. — According  to 
Schafcr.  tlic  axons  of  this  tract  arc  prf)bably  connected  with  cells 
situated  in  the  middle  and  posterior  parts  of  the  grey  crescent,  mainly 


Fig.  350. — Transverse  Section  of  Medulla 
Oblongata  at  the  Level  of  the  Decussa- 
tion of  the  Fillet  (Halliburton,  after 
Schwalbe).  a.m.f,  anterior,  and  p.m./, 
posterior,  median  fissure;  /.a  and  f.a^, 
external  arcuate  fibres;  f.a',  internal 
arcuate  fibres  becoming  external;  n.a.r, 
nuclei  of  arcuate  fibres;  py,  pyramid; 
o,  0',  lower  end  of  nucleus  of  olive;  /.r, 
formatio  reticularis;  n.l,  lateral  nucleus; 
n.g,  nucleus  gracilis;  f.g,  funiculus  gra- 
cUis;  n.c,  nucleus  cuneatus;  n.c',  external 
cuneate  nucleus; /.c,  funiculus  cuneatus; 
g,  substance  of  Rolando;  c.c,  central  canal 
surroundedby  grey  matter;  n.  A'7,  nucleus 
of  spinal  accessory;  n.XII,  of  hypoglos- 
sal; a.V,  ascending  root  of  fifth  nerve; 
s.d,  the  decussation  of  the  fillet,  or 
superior  decussation. 


Fig.  351 — Transverse  Section  of  Medulla 
Oblongata  at  about  the  Middle  of  the 
Olive  (Sch.valbe).  f.l.a,  anterior  median 
fissure;  n.a.r,  arcuate  nucleus;  p.,  pyra- 
mid; n.XII,  h\'poglossal  nucleus;  XII, 
root  bundle  of  hypoglossal  ner\-e  coming 
off  from  the  surface ;  at  6  it  rims  between 
the  pyramid  and  the  dentate  nucleus  of 
the  olive,  0;  f.a.e,  external  arcuate  fibres; 
n.l,  lateral  nucleus;  a,  arcuate  fibres  going 
to  restiform  body  c.r,  partly  through  the 
substantia  gelatinosa  g,  partly  superficial 
to  the  ascending  root  of  the  fifth  nerve 
a.V;  X,  root-bundle  of  vagus;  n.X ,  n.X', 
two  portions  of  vagus  nucleus;  f.r,  for- 
matio reticularis:  n.g,  nucleus  gracilis; 
n.c,  nucleus  cuneatus;  n.t,  nucleus  of  the 
funiculus  teres;  n.am,  nucleus  ambiguus; 
f,  raphe;  0',  0",  accessory  olivary  nucleus; 
p.o.l,  peduncle  of  the  olive. 


on  the  opposite  side  of  the  cord .  although  also  on  the  same  side.  None  of 
the  fibres  of  the  tract  can  come  directly  from  the  posterior  nerve-roots, 
since  no  degeneration  is  seen  in  it  on  section  of  the  roots  alone. 

The  antero-lateral  ascending  tract  passes  up  through  the  medulla, 
where  some  of  its  fibres  perhaps  form  synapses  with  the  cells  of  the 


'74 


THE  CENTRAL  \ERVOUS  SYSTEM 


lateral  nucleus,  a  collection  of  grey  matter  in  the  lateral  portion  of  the 
spinal  bulb.  But  its  main  strand  runs  on  unbraken  through  the 
medulla,  in  front  of  the  rcstiform  body,  and  behind  the  olive,  and  after 
reaching  the  upper  part  of  the  pons  bends  back  over  and  in  company 
with  the  superior  peduncle  as  the  ventral  spino-cerebcUar  bundle,  to 
end  in  the  worm  of  the  cerebellum  (Fig.  363). 

A  few  fibres  of  Gowers'  tract  may  pass  by  the  middle  peduncle  to  the 
opposite  cerebellar  hemisphere,  bome  of  its  fibres  do  not  go  to  the 
cerebellum  at  all.  One  group  can  be  followed  to  the  corpora  quadri- 
gemina  {spiyio-tectal  fibres),  and  another  by  way  of  the  tegmentum  of  the 
crus  cerebri  to  the  optic  thalamus  {spino-thalamic  fibrss). 

Through  the  relay  of  the  gracile  and  cuncate  nuclei,  the  postero- 
internal and  postero-external  columns  of  the  cord  are  further  con- 
nected on  the  one  hand  with  the  cerebrum,  and  on  the  other  with  the 
cerebellum.  The  cells  of  the  nuclei  give  oft  fibres  (internal  arcuate 
fibres)  which,  sweeping  in  wide  arches  across  the  mesial  raphe  to  the 

opposite  side,  take  up 
a  position  behind  the 
pyramid  in  the  tract  of 
the  filld,  a  bundle  of 
fibres  which  becomes 
more  compact,  and 
therefore  more  distinct, 
as  it  passes  brainwards. 
Receiving  fibres  from 
other  sources  on  its 
way,  and  also  giving 
off  fibres,  it  runs  up- 
wards through  the  dor- 
sal or  tegmental  portion 
of  the  pons.  In  the  mid- 
brain it  divides  into 
two  portions,  the  lateral 
fillet,  also  called  the 
lower  fillet  or  fillet  of  Reil,  and  the  intermediate,  also  called  the  upper 
fillet.  The  lateral  fillet  contains  mainly  fibres  arising  in  the  cochlear 
nucleus  of  the  auditory  never,  and  ends  in  grey  matter  of  the  pos- 
terior corpus  quadrigeminum,  and  partly  in  the  mesial  geniculate 
body.  It  appears  to  be  a  path  for  the  conduction  of  auditory 
impulses.  The  intermediate  fillet  contains  chiefly  the  fibres  that 
come  off  from  the  gracile  and  cuneate  nuclei,  but  is  enlarged  by  the 
accession  of  fibres  from  the  sensory  nuclei  of  the  cranial  nerves.  It 
terminates  in  the  lateral  nucleus  of  the  optic  thalamus  by  forming 
synapses  with  nerve-cells,  whose  axons,  passing  through  the  posterior 
limb  of  the  internal  capsule  and  the  corona  radiata,  continue  the 
afferent  path  to  the  cerebral  cortex. 

Not  all  of  the  axons  from  the  cells  of  the  cranial  sensory  nuclei  run 


Fig-  35-- — Diagrammatic  Transverse  Section  of 
Crura  Cerebri  and  Aqueduct  of  Sylvius,  a,  an- 
terior corpora  quadrigemina  6,  aqueduct;  c,  red 
nucleus;  d,  fillet;  e,  substantia  nigra;/,  pyramidal 
tract  in  the  crusta  of  the  crura  cerebri:  g,,  fibres 
from  frontal  lobe  of  cerebrum;  h,  fibres  from  tem- 
poro-occipital  lobe ;  i,  posterior  longitudinal  bundle. 


CONNECTIOSS  OF  THE  LONG  PATHS  OF  THE  CORD        873 


in  the  fillet.  Many  of  them  occupy  a  position  in  the  reticular  forma- 
tion of  the  tegmentum  dorsal  to  the  tillet  as  they  pass  through  the 
pons  and  mid-brain  to  end  in  the  thalamus  and  the  region  below  it 
(sub-thalamic  region).  From  the  sensory  nucleus  0^  the  fifth  nerve 
a  separate  bundle  of  fibres  ascends  to  the  thalamus,  in  the  tegmen- 
tum of  the  mid-brain  lateral  to  the  posterior  longitudinal  bundle. 
Connections  of  the  Pyramidal  Tracts. — When  the  cortex  in  and  in 
front  of  the  fissure  of  Rolando  is  destroyed  by  disease  in  man,  or 
removed  by  operation  in  animals,  it  is  found  that  in  a  short  time 
degeneration  has  taken  place  in  the  fibres  of  the  corona  radiata  which 
pass  off  from  this  area.  The  degeneration  can  be  followed  down 
through  the  genu  and  the  anterior  two-thirds  of  the  posterior  limb 
of  the  internal  capsule  r 

(Fig-  353)  and  the 
crusta  of  the  cerebral 
peduncle  of  the  corre- 
sponding side  into  the 
medulla  oblongata. 
Below  the  decussation 
of  the  pyramids  it  is 
found  that  the  degene- 
ration has  involved  the 
two  pyramidal  tracts, 
and  only  these  —  the 
crossed  pyramidal 
tract  on  the  side  oppo- 
site the  cortical  lesion, 
the  direct  pyramidal 
tract  on  the  same  side 
— and  that  the  cross- 
section  of  the  two  de- 
generated tracts  goes 
on  continually  dimin- 
ishing as  we  pass  down  the  cord.  (We  overlook  for  the  moment,  in 
the  interest  of  simplicity  of  statem.ent,  the  fact  that  some  degenerated 
fibres  are  found  in  the  crossed  pyramidal  tract  on  the  same  side  as  the 
lesion.)  This  is  proof  positive  that  the  cell-bodies  of  the  neurons  whose 
axons  run  in  these  tracts  are  situated  in  the  cerebral  cortex.  They 
have  indeed  been  identified  with  certain  of  the  large  pyramidal  cells 
(the  so-called  giant  cells  or  cells  of  Betz)  in  the  cortex  of  the "  motor  ' 
region  in  front  of  the  Rolandic  fissure  (p.  950).  For  after  division 
of  the  motor  pyramidal  fibres  in  the  upper  cervical  region  of  the  cord 
(in  monkeys)  changes  in  the  chromatin  (so-called  chromatolysis)  and 
atrophy  of  these  large  cells  occur.  The  same  has  been  found  to  be 
true  in  man  in  cases  where  the  cord  was  injured  by  fracture  of  the 
spine  in  such  a  way  as  to  interrupt  the  tract  (as  well  as  other  tracts) 


MID.  BRAIN 
Fig.  353. — Pyramidal  Path  (after  Gowers).    Degenera- 
tion after  destruction  of  the  '  motor  '  area  of  the 
right  cerebral  hemisphere.     The  degenerated  areas 
are  indicated  by  the  shading. 


876  THE  CENTRAL  NERVOUS  SYSTEM 

couiplcU'ly  and  permanently,  without  entailing  death  for  a  consider- 
able time  (Holmes  and  May).  The  fact  that  after  destruction  of  the 
cortex  or  the  path  in  its  course  the  degeneration  below  th<;  lesion  does 
not  spread  to  the  anterior  roots  shows  that  at  least  one  relay  of 
nerve-cells  intervenes  between  the  pyramidal  fibres  and  the  root- 
ftbres.  The  results  both  of  normal  and  morbid  histology  enable  us 
to  identify  the  cells  of  the  anterior  horn  as  the  cells  of  origin  of  the 
axons  of  the  anterior  root- fibres.     For 

(i)  Axis-cylinder  processes  have  been  actually  observed  passing  out 
from  certain  of  the  so-called  motor  cells  of  the  anterior  horn  to  become 
the  axis-cylinders  of  the  anterior  root. 

(2)  In  the  pathological  condition  known  as  anterior  poliomyelitis, 
the  cells  of  the  anterior  horn  degenerate,  and  so  do  the  anterior  roots 
of  the  affected  region,  the  motor  fibres  of  the  spinal  nerves,  and  the 
muscles  supplied  lay  them. 

(3)  As  already  mentioned  (p.  858),  comparatively  transient  but 
decided  changes  occur  in  the  anterior  horn  cells  on  section  of  the  corre- 
sponding anterior  roots. 

(4)  An  enumeration*  has  been  made  in  a  small  animal  (frog)  of  the 
cells  of  the  anterior  horn  and  of  the  anterior  rcot-fibres,  and  it  has  been 
found  that  the  numbers  agree  in  a  remarkable  manner.  From  all  this 
it  cannot  be  doubted  that  most,  at  any  rate,  of  the  cells  of  the  anterior 
horn  are  connected  with  fibres  of  the  anterior  root.  But  since  the 
number  of  fibres  in  the  pyramidal  tracts  (about  80,000  in  each  half  of 
the  human  cord)  falls  far  short  of  the  number  of  fibres  in  the  anterior 
roots  (not  less  than  200,000  in  man  on  each  side),  it  is  necessary  to 
suppose  either  that  one  pyramidal  fibre  may  be  connected  with  several 
cells  or  that  all  the  anterior  root-fibres  are  not  in  functional  connection 
with  the  pyramidal  tract. 

There  is  no  reason  to  assume  any  such  connection  in  the  case  of  the 
fine  meduUated  root-fibres  arising  in  the  lateral  horn  and  going  to  the 
visceral  and  vascular  muscles. 

While  there  is  no  doubt  that  anterior  root-fibres  and  pyramidal 
fibres  of  the  brain  and  cord  form  segments  of  the  same  nervous  path, 
the  connection  between  the  pyramidal  fibres  and  the  cells  of  the 
anterior  horn  has  not  yet  been  anatomically  demonstrated.  Many  of 
the  pyramidal  fibres  pass  into  the  grey  matter  between  the  anterior 
and  posterior  horns  or  near  the  base  of  the  posterior  horn.  The 
anterior  horn  cells  are  surrounded  by  arborizations.  Some  of  these 
are  probably  the  terminations  of  axons  whose  cell-bodies  are  situated 
in  the  posterior  horn,  others  the  terminations  of  posterior  root-fibres 
or  their  collaterals.  Many  of  them  very  likely  represent  the  end 
arborizations  of  pyramidal  fibres  or  their  collaterals.  Some  ob- 
servers, however,  suppose  that  the  pyramidal  fibres  do  not  come  into 
immediate  relation  with  the  anterior  horn  cells,  but  that  another 
neuron  is  intercalated  between  them  and  the  cells. 

The  pyramidal  fibres  are  unquestionably  paths  for  voluntary 
motor  impulses  passing  down  from  the  cortex  to  the  cord.     But 

•  Such  enumerations  can  be  made  with  great  accuracy  from  photographs 
of  sections  of  the  nerves  (Hardesty,  Dale).     (See  Fig.  341,  p.  860.) 


CONNECTIONS  OF  THI-l  LONG  J'.iriJS  OF  THE  CORD        877 

they  are  not  the  only  cortico-spinal  efferent  paths,  and  in  many 
animals  they  are  not  even  the  most  important  paths  for  voluntary 
movements.  It  is  the  more  skilled  and  delicate  movements  which 
the  pyramidal  tract  subserves  in  man,  and  it  is  these  movements 
which  arc  permanently  lost  when  the  tract  is  destroyed.  The  size 
of  the  path  is  proportioned  to  the  degree  of  development  of  the 
brain.  Thus,  it  is  larger  in  the  monkey  than  in  the  dog,  larger  in  the 
anthropoid  apes  than  in  the  lower  monkeys,  and  larger  in  man  than 


Fig-  354- — Paths  from  Cortex  in  Corona  Radiata  (Starr).  A,  tract  from  frontal  con 
volutions  to  nuclei  of  pons  and  so  to  cerebellum;  B,  motor  pyramidal  tracts 
C,  afferent  tract  for  tactile  sensations  {represented  in  the  diagram  as  separated 
from  B  by  an  interval  for  the  sake  of  clearness);  D,  visual  tract;  E,  auditory 
tract;  F,  G,  H,  superior,  middle,  and  inferior  cerebellar  peduncles;  J,  fibres 
from  the  auditory  nucleus  to  the  posterior  corpus  quadrigeminum ;  K,  decussa- 
tion of  the  pyramids  in  the  bulb;  FY,  fourth  ventricle.  The  roman  numerals 
indicate  the  cranial  nerves. 

in  even  the  highest  of  the  apes.  In  the  lower  mammals  it  is  exceed- 
ingly small.  While  in  man  the  pyramidal  tracts  constitute  nearly 
12  per  cent,  of  the  total  cross-section  of  the  cord,  they  make  up 
little  more  than  i  per  cent,  in  the  mouse,  3  per  cent,  in  the 
guinea-pig,  5  per  cent,  in  the  rabbit,  and  nearly  8  per  cent,  in  the  cat. 
In  some  mammals,  as  the  rat,  mouse,  guinea-pig,  and  squirrel,  the 
pyramidal  tracts  lie,  not  in  the  antero-lateral,  but  in  the  posterior 
columns.  In  vertebrates  below  the  mammals  the  pyramidal  system 
does  not  exist  as  a  collection  of  neurons  which  send  their  axons  with- 


R78 


THE  CENTRAL  NERVOUS  SYSTEM 


out  interruption  down  from  the  cortex  to  the  cord.  In  liirds,  e.f^., 
after  the  removal  of  a  hemisphere,  the  degeneration  does  not  extend 
below  the  mid-brain  (Boyce). 


Section  VI. — Paths  from  and  to  the  Cortex. 

Thus  far  we  have  been  able  to  map  out  two  great  paths  from 
the  cerebral  cortex  to  the  periphery — one  efferent,  the  other  afferent, 
(i)  The  great  efferent  or  motor  pyramidal  path,  which,  starting  in 
the  cortex  in  front  of  the  fissure  of  Rolando,  where  its  axons  give  off 
numerous  collaterals  to  the  grey  matter  soon  after  emerging  from 
the  cells,  and  sweeping  down  the  broad  fan  of  the  corona  radiata, 

passes  through  the  narrow 
isthmus  of  the  internal  cap- 
sule into  the  crusta  of  the 
crus  cerebri,  and  thence  into 
the  pons  (Figs.  354,  355).  At 
this  level,  the  fibres  destined 
to  make  connection  with  the 
motor  nuclei  of  the  cranial 
nerves  in  the  grey  matter 
underlying  the  aqueduct  of 
Sylvius  and  the  fourth  ven- 
tricle terminate.  Most  of 
these  fibres  decussate  to  make 
physiological  connection  with 
nuclei  on  the  opposite  side, 
but  some  join  nuclei  on  the 
same  side.  The  question 
whether  they  arborize  di- 
rectly around  the  cells  of  the 
motor  nuclei  or  make  junc- 
tion with  them  through 
another  intercalated  neuron 
is  precisely  in  the  same 
position  as  the  corresponding 
question  for  the  spinal  pyra- 
midal path  (p.  876).  On  their 
way  through  the  pons  they  send  off  collaterals  to  the  nuclei 
pontis,  as  they  do  higher  up  to  the  grey  matter  of  the  basal 
ganglia  of  the  cerebrum  and  the  substantia  nigra,  and  the  path 
may  be  continued  to  the  motor  nuclei  by  axons  arising  here. 
There  is  no  proof,  however,  that  this  is  the  case.  The  rest  of 
the  pyramidal  fibres  run  on  into  the  pyramid  of  the  bulb, 
where  the  greater  part  (usually  about  90  per  cent.)  of  the  fibres 
decussate,  appearing  in  the  c^Tvical  cord  as  the  massive  crossed 


Fig.  355. — Motor  Pyramidal  Tracts  (Diagram- 
matic) (Halliburton,  after  Gowers).  The 
convolutions  are  supposed  to  be  cut  in 
vertical  transverse  section,  the  internal 
capsule,  I,  C,  and  the  crus  in  horizontal 
section.  O,  TH,  optic  thalamus;  CN,  cau- 
date nucleus;  L2  and  L3,  middle  and  ex- 
ternal portions  of  lenticular  nucleus;  f,a,  I. 
fibres  from  the  face,  arm.  and  leg  areas  of 
the  cortex  respectively;  E,  S,  Sylvian  fis- 
sure. The  genu  or  knee  of  the  internal 
capsule  is  indicated  by  the  asterisk. 


PATHS  FROM  AND  TO  THE  CORTEX 


879 


pyiiiinuhil  liiicl  ot  the  o[)p()sitc  side.  A  few  (usually  about  10  per 
cent.)  reniiiin  on  tlie  same  side  as  the  slender  direct  pyramidal  tract. 
The  size  of  this  tract  varies  much  in  different  individuals,  and  it 
is  occasionally  absent.  Its  breadth  constantly  diminishes  as  it 
proceeds  down  the  cord,  and  it  disappears  before  the  middle  of  the 
thoracic  region  is  reached,  its  fibres  continually  decussating  across 
the  anterior  white  commissure  and  plunging  into  the  opposite 
anterior  horn.  They 
either  end  among  its 
cells,  or,  passing  through 
it,  reinforce  the  crossed 
pyramidal  tract.  The 
fibres  of  t  his  crosse d  t  ract 
are,  in  their  turn,  con- 
tinually passing  off  into 
the  grey  matter  to  make 
connection  (p.  876)  with 
the  cells  of  the  anterior 
horn,  whose  axis-cylin- 
der processes  enter  the 
anterior  roots  of  the 
spinal  nerves.  The  losses 
which  it  suffers  as  it 
descends  the  cord  may 
be  in  some  slight  degree 
compensated  by  the  bi- 
furcation of  some  of  its 
fibres  (geminal  fibres), 
but  ultimately  the  whole 
tract  forms  synapses 
with  cells  in  the  grey 
matter,  and  dwindles 
away  as  the  lumbar  re- 
gion is  reached(Fig.  343). 
A  certain  number  of  the 
pyramidal  fibres  do  not 
decussate  either  in  the 
bulb  or  in  the  cord. 
These  are  called  homo- 
lateral fibres.  They  run 
down  in  the  lateral  py- 
ramidal tract,  and  are 
represented  by  the  fibres 
that  degenerate  in  that 
tract  after  a  lesion  in  the  '  motor  '  area  of  the  same  side  (p.  875)- 
This  would  explain  the  escape  in  hemiplegia  (parah'sis  of  one  side 


Fig.  356. — Horizontal  Section  through  the  Right 
Hemisphere  to  show  the  Constituents  of  the 
Internal  Capsule  (von  Monakow).  A,  knee  of 
corpus  callosum :  B,  anterior,  B',  posterior,  horn  of 
lateral  ventricle;  C,  knee  of  internal  capsule; 
S.  sensory  fibres;  V,  visual  tract;  AH,  Amnion's 
horn;  Calc,  calcarine  fissure;  T,  first,  T',  second, 
temporal  convolution;  OR,  optic  radiation;  Aud, 
auditory  tract ;  D,  retrolenticular  region  of  internal 
capsule;  lo.  lenticulo-optic  division  of  internal 
capsule;  CI,  claustrum;  op.,  operculum;  I,  island 
of  Rcil;  E,  external  capsule;  Is,  lenticulo-striate 
division  of  internal  capsule;  F,  fibres  from  frc-ntal 
lobe;  F',  inferior  part  of  third  frontal  convolution; 
Tk,  optic  thalamus;  Put,  putamen. 


88o  THE  CENTRAL  NERVOUS  SYSTEM 

fiSrpiJlsCAlIoSum,. 


?-^^L^(sU5ff. 


^Lt.ntkuliLi-Ngckus 


'P'tjiTAf'fcflcrcItJs 


6mo-Ccirri(il  fibrd 


Crosstd  Sensory  Fibres 
/pAin.  Hti.t&  Cold\ 
ITouch  &  Pressure/ 

—foferlorOUw 


5f)ino-Cer€belUr 
Tracts 

(Co-ordinfiitton  & 
Muscular  Tont 


De£(>  ftftuafe  Fibres 


Dorsal  Column  (direct) 
/stnst  of  posifion      '\ 
\  '       "   moi/tmcnf/ 


S^nd.lGan^li'on  _. 
Sf>iri&.l  Nerve  Jl:< 

Fig.  337. — Ascending  Nerve  Tracts  (after  Holmes), 


PATHS  FROM  AND  TO  THE  CORTEX  881 

of  the  botly)  of  those  muscles  which  are  accustomed  to  work  with 
the  corresponding  muscles  on  the  opposite  side — e.g.,  the  respiratory 
muscles,  these  being  innervated  to  some  extent  from  both  cerebral 
hemispheres. 

(2)  A  great  afferent  or  sensory  path  by  which  some  at  least  of  the 
impulses  carried  up  through  the  posterior  roots  of  the  spinal  nerves, 
after  passing  through  various  relay's  of  nerve-cells,  reach  the  cortex 
of  the  cerebellum ;  or  the  upper  portions  of  the  central  grey  tube,  the 
corpora  quadrigemina  and  optic  thalamus;  or,  finally  (through  the 
tegmentum  and  the  posterior  limb  of  the  internal  capsule  behind  the 
motor  fibres),  the  cerebral  cortex  itself. 

The  efferent  pyramidal  path  from  the  cortex  to  the  periphery  is 
broken  by  at  most  two  relays  of  nerve-cells — those  intercalated  cells 
to  which  reference  has  already  been  made  (p.  876),  if  they  really 
exist,  and  the  motor  cells  of  the  anterior  horn.  The  afferent  path  to 
the  cerebral  cortex  is  interrupted  by  at  least  three  relays  with  axons 
of  considerable  length.  One  of  the  cells  is  situated  in  the  ganglion 
on  the  posterior  root,  another  in  the  medulla  oblongata,  a  third  in  the 
optic  thalamus ;  and  on  some  of  the  routes  another,  or  even  more  than 
one,  is  intercalated  between  the  medulla  and  the  cortex  (Fig.  357). 

The  Internal  Capsule. — We  have  already  recognized  the  pyramidal 
tract  and  the  afferent  tegmental  path  as  constituents  of  the  internal 
capsule.  The  cranial  fibres  of  the  pyramidal  tract  occupy  mainly 
the  genu  or  knee,  the  spinal  fibres  the  posterior  limb  as  far  back  as 
the  posterior  border  of  the  lenticular  nucleus  (Fig.  356). 

The  fibres  from  the  various  motor  areas  are  to  a  certain  extent 
arranged  in  order  in  the  capsule,  those  for  the  eyes  and  head  lying 
farthest  forward,  those  for  the  leg  farthest  back,  while  the  fibres 
going  to  the  face,  arm  and  trunk  occupy  intermediate  positions. 
The  separation,  however,  is  far  from  complete,  the  fibres  of  neigh- 
bouring regions  being  considerably  intermixed  (Hoche).  As  the 
tracts  pass  downwards  the  intermingling  becomes  continually 
greater  (Simpson  and  Jolly)  (Figs.  358,  359)-  The  afferent  fibres 
from  the  thalamus  to  the  cortex,  which  we  have  described  as  the 
last  segment  of  the  afferent  tegmental  path,  lie  in  the  posterior  part 
of  the  posterior  limb.  But  here  again  there  is  no  absolutely  sharp 
line  of  demarcation.  Some  motor  fibres  are  intermingled  with  the 
sensory  in  the  posterior  part  of  the  capsule,  for  lesions  of  this  region 
produce  a  certain  degree  of  paralysis  as  well  as  anaesthesia  on  the 
opposite  side  of  the  body.  A  pure  capsular  hemiansesthesia — that 
is,  a  loss  of  sensation  on  the  opposite  side  due  to  a  lesion  in  the 
internal  capsule  and  unaccompanied  by  motor  defect — does  not 
appear  to  exist.  Accordingly  the  common  statement  that  the  efferent 
(motor)  path  occupies  the  anterior  two-thirds,  and  the  afferent 
(sensory)  path  the  posterior  third  of  the  posterior  limb  of  the 
internal  capsule,  while  true  in  a  general  sense,  is  not  strictly  correct. 

56 


8S2 


THE  CENTRAL  NERVOUS  SYSTEM 


The  destination  of  the  afferent  fibres  of  the  internal  capsule  has 
not  been  definitely  settled.  There  is  no  doubt  that  they  pass  up  to 
the  convolutions  around  the  fissure  of  Rolando  (central  convolu- 
tions), and  there  is  reason  to  believe  that  some  of  them  terminate  in 
the  *  motor  '  region  in  front  of  that  fissure,  although  many  of  the 
fibres  concerned  in  tactile  sensations  seem  to  end  in  the  ascending 
parietal  convolution. 

But  we  have  not  yet  exhausted  the  constituents  of  the  internal 

capsule.  Two  great  cones  of  fibres 
sweep  down  into  it,  one  from  the 
frontal,  the  other  from  the  occipital 
and  temporal  portions  of  the  cerebral 
c6rtex.  The  first  passes  through  its 
anterior  limb,  the  second  behind  the 
sensory  path  in  its  posterior  limb. 
The  cells  of  origin  of  the  frontal  fibres 
are  known,  and  those  of  the  occipital 
and  temporal  fibres  are  supposed,  to 
be  situated  in  the  cortex.  They  are 
therefore  efferent  fibres  as  regards 
the  cortex  (cortifugal).  Running  on 
through  the  crust  a  of  the  cerebral 
peduncle  (Fig.  352),  the  frontal  tract 


Fig-  358. — Pyramidal  Tract  in  In- 
ternal Capsule  (Simpson  and 
Jolly).  Horizontal  section 
through  right  cerebral  hemi- 
sphere, cutting  fibres  of  internal 
capsule  transversely  at  an  upper 
level  a  little- below  the  upper 
surface  of  the  lenticular  nucleus. 
The  extent  of  the  degeneration 
following  destruction  of  the 
whole  of  the  right  '  motor  '  cor- 
te.x,  except  the  '  head  and  eyes  ' 
area  (in  one  of  the  lower  mon- 
keys), is  shown.  Note  over- 
lapping of  fibres  from  face,  arm, 
and  leg  areas,  as  shown  by  ex- 
periments in  which  one  or  other 
of  these  areas  was  alone  re- 
moved. 

internal,  the  occipito-temporal  external,  they  end  in  the  grey 
matter  of  the  pons,  and  serve  as  one  segment  of  an  extensiv-e 
connection  between  the  cerebral  and  the  cerebellar  cortex  of  the 
opposite  side,  the  other  segment  being  formed  by  neurons  whose 
cell-bodies  are  situated  in  the  pons,  and  whose  axons,  crossing 


Fig-  359- — Pyramidal  Tract  in  Internal 
Capsule  at  Lower  Level  (Simpson  and 
Jolly).  CN',  head  of  caudate  nucleus: 
OT,  optic  thalamus;  CI,  claustrum. 


PATHS  FROM  AND  TO  THE  CORTEX 


ftfl:? 


the  middle  line,  pursue  their  cours(!  through  the  middle  cerebellar 
peduncle,  to  terminate  in  the  superficial  grey  matttT  of  the  cere- 
bellum. It  is  evident  that  thi>  junction  of  the  cerebral  cortex  with 
this  pontine  grey  matter,  through  and  into  which  so  many  nerve- 
tracts  pass,  multiplies  the  number  of  possible  routes  by  which 
impulses  may  travel  between  one  part  of  the  brain  and  another. 
The  corpus  callosum  forms  a  mighty  link  between  the  two  cerebral 
hemispheres.  And  intertwined  in  the  corona  radiata  with  the 
callosal  fibres  are  other  systems,  of  which  it  is  especially  necessary 
to  mention  the  afferent  {cortipetal)  fibres  that  join  the  optic  thalamus 
with  nearly  every  part  of  the  cerebral  cortex.  Such  fibres  pass  from 
the  cells  of  the  grey  matter  of  the  thalamus  to  the  frontal  and  parietal 


Fig.  300. — Association  Fibres  (after  Starr).  Cerebral  hemisphere  seen  from  the  side 
A,  A,  association  fibres  between  adjacent  convolutions;  B,  between  frontal  and 
occipital  lobes;  C,  cinguluui,  connecting  frontal  and  toniporosphenoidal  lobes; 
D,  uncinate  fasciculus  between  frontal  and  temporal  regions;  E,  inferior  longi- 
tudinal bundle  between  occipital  and  temporo-sphenoidal  lobes;  O.T.,  optic 
thalamus;  C.N.,  caudate  nucleus. 

regions  through  the  anterior  border  of  the  internal  capsule  in  front  of 
the  frontal  fibres  previously  described  as  running  in  the  anterior 
limb  of  the  capsule  to  the  pons;  and  from  the  thalamus  to  the  occi- 
pital region  through  the  extreme  posterior  border  of  the  internal 
capsule,  behind  the  occipital  fibres  that  proceed  to  the  pons.  The 
fibres  that  connect  the  thalamus  with  the  occipital  cortex  are 
spoken  of  as  the  optic  radiation.  Some  of  the  fibres  of  the  optic 
radiation,  however,  proceed,  not  from  the  thalamus,  but  from  the 
anterior  corpus  quadrigeminum  and  the  lateral  geniculate  body. 
The  thalamus  is  also  connected  with  the  cortex  of  the  temporal  lobe, 
udth  the  cerebellum,  and  through  the  fillet  with  the  posterior  part  of 
the  tegmental  system,  the  medulla  oblongata  and  the  spinal  cord 
(p.  874).  Fibres  also  pass  from  the  inner  and  deeper  part  of  the 
thalamus  to  the  lenticular  nucleus  of  the  corpus  striatum.     The 


884 


THE  CENTRAL  NERVOUS  SYSTEM 


thalamus  must  be  regarded  as  a  great  sensory  centre  througli  which 
afferent  impulses  stream  on  their  way  to  all  parts  of  the  cortex. 

The  fibres  which  connect  the  cerebral  cortex  with  lower  levels  of 
the  central  nervous  system  are  sometimes  grouped  together  as 
projection  fibres  in  contradistinction  to  the  commissural  and  associa- 
tion fibres.  A  large  proportion  of  the  fibres  of  the  corona  radiata  are 
projection  fibres,  including  efferent  groups  (pj-ramidal  tract,  fronto 

pontine  fibres,  temporo- 
pontine fibres)  and  afferent 
groups  (the  fillet  system, 
thalamo-cortical  fibres  from 
the  grey  matter  of  the 
thalamus  to  the  cortex,  in- 
cluding the  optic  radiation). 

Section  VII. — Connections 
OF  Brain  Stem  with  Cord 
— Connections  of  Cere- 
bellum. 

Connections  of  the  Vestibulo- 
spinal or  Antero-Lateral  De- 
scending Tract.  —  The  main 
origin  of  these  fibres  is  the 
nucleus  of  Deiters,  a  collection 
of  large  multipolar  nerve-cells 
in  the  floor  of  the  fourth  ven- 
tricle near  the  inner  auditory 
nucleus.  This  nucleus  consti- 
tutes an  important  intermedi- 
ate station  between  the  cere- 
bellum and  the  cord.  Its 
cells  give  off  axons  which  paiss 
into  the  posterior  longitudinal 
bundle  of  the  bulb  and  pons, 
mostly  to  the  bundle  of  the 
same  side,  but  partly  into  that 
of  the  opposite  side.  Here  the 
fibres  bifurcate  into  an  ascend- 
ing branch,  which  passes  up  to 
the  oculo-motor  nucleus,  and  a 
descending  (vestibulo  -  spinal) 
branch,  which  passes  down- 
wards to  the  spinal  cord  and 
enters   the   antero-latera!    de- 


Fis;.    361. — Fibres   connecting    Frontal    and 

Temporo-Occipital  Lobes  with  Cerebellum, 
etc.  (Diagram)  (after  Gowcrs).  Fr,  frontal, 
Oc,  occipitallobc;  interrupted  lines  indicate 
fibres  (TOC)  connecting  cerebellum  and 
temporo-occipital  cortex,  and  fronto-cere- 
bellar  fibres  (FC).  On  left  side  the  position 
of  these  two  groups  of  fibres  and  of  motor 
(p^Tamidal)  tract,  PY,  in  the  crus,  is  indi- 
cated by  letters.  The  p>Tamidal  tract  is 
seen  on  the  right  passing  down  from  the 
Rolandic  area  through  posterior  limb  of 
internal  capsule  IC  (the  genu  or  knee  of 
which  is  indicated  by  asterisk)  to  decussate 
in  the  bulb.  AF,  ascending  frontal  convolu- 
tion: AP,  ascending  parietal  convolution; 
FR,  fissure  of  Rolando;  IPF,  intraparietal 
fissure;  PCF,  precentral  fissure;  Ipt,  crossed 
pyramidal,  apt,  direct  pyramidal  tract. 


scending  tract.  The  fibres  of 
this  tract  ultimately  pass  into  the  anterior  horn,  where  most  of  them 
end  by  arborizing  amongst  the  cells  of  the  horn.  Higher  up  corre- 
sponding fibres  from  the  posterior  longitudinal  bundle  arborize  in  the 
cr.'.nial  motor  nuclei. 

Connections  of  the  Rubro-Spinal  Tract. — These  fibres,  as  the  name 
gi\cn  to  the  bundle  implies,  originate  in  the  red  nucleus  and  run  down 
into  the  cord.     A  little  distance  from  their  cells  of  origin  they  cross  the 


CONNECTIONS  OF  CEREBELLUM 


88  = 


median  line,  and  then  pass  down  first  in  the  tegmentum,  and  below  that 
in  the  lateral  column  of  the  bulb  and  cord.  On  their  way  they  come 
into  relation  with  the  motor  nuclei  of  the  cranial  nerves,  and  in  the 
cord  with  the  cells  of  the  anterior  horn.  It  is  obvious  that  in  contrast 
to  the  projection  fibres  the  fibres  of  the  rubro-spinal,  vt;stibulo-si)inal, 
olivo-spinal,  and  thalamico-spinal  tracts  (p.  867)  and  the  posterior 
longitudinal  bundle  connect  the  brain  stem  or  cerebral  axis  with  the 
cord,  or  different  levels  of  the  brain  stem  with  each  other. 

Connections  of  the  Grey  Matter  of  the  Cerebellum  with  the  Periphery 
and  other  Parts  of  the  Central  Nervous  System. — Numerous  as  are  the 
nervous  ties  of  the  cerebral  cortex,  those  of  the  grey  matter  of  the 
cerebellum  are,  in  proportion  to  its  mass,  still  more  extensive,  particu- 
larly as  regards  afferent  fibres,  and  perhaps  not  less  important. 

Speaking  broadly,  we  may  say  that  the  restiform  body  or  inferior 
peduncle  connects  chiefly  the  dentate  nucleus  and  the  grey  matter  of 
the  worm  with  the  spinal  cord  and  medulla  oblongata,  and  through 
them  with  the  periphery.     The  fibres  which  it  receives  from  the  direct 


S  Auc^ 


Fig.  362. — Direct  Sensory  Cerebellar 
Path  of  Edinger.  D,  Deiters' 
nucleus;  v,  median  nucleus  of 
auditory  nerve;  /,  nucleus  of  the 
roof;  g.  nucleus  globosus. 


Fig.  363- — Diagram  of  Dorsal  and  Ventral  Spino 
Cerebellar  Tracts  entering  Cerebellum  (^Iott). 
P.C.Q.,  posterior  corpora  quadrigemina;  s.v., 
superior  vermis  of  cerebellimi;  d.a.c,  v.a.c, 
dorsal  and  ventral  ascending  cerebellar  tracts. 


cerebellar  tract  (dorsal  spino-cerebellar  tract)  of  its  own  side  it  carries 
to  the  worm.  These  fibres  occupy  the  outer  portion  of  the  peduncle. 
The  fibres  which  reach  the  restiform  body  from  the  olivary  nucleus  of 
the  opposite,  and  alro  in  smaller  numbers  from  that  of  the  same  side, 
run  mainly  to  the  hemisphere.  All  these  fibres  are  afferent  in  relation 
to  the  cerebellum  (cerebello-petal).  An  uncrossed  afferent  connection 
also  exists  between  the  cerebellum  and  the  vestibular  branch  of  the 
auditory  nerve,  through  certain  of  its  nuclei  of  reception,  and  also 
between  it  and  the  nuclei  of  other  cranial  nerves,  such  ai  the  trigeminus 
and  the  vagus.  The  fibres  pass  up  in  the  inner  portion  of  the  inferior 
peduncle  (direct  sensory  cerebellar  path  of  Edinger,  Fig.  362)  to  the 
nucleus  of  the  roof  (nucleus  tecti)  and  nucleus  globosus.  Some  efferent 
fibres  (cerebellofugal)  also  run  down  from  the  cerebellum  in  the  inferior 
peduncle,  including  fibres  from  the  nucleus  tecti  of  the  opposite  side 
which  are  on  their  way  to  the  medulla  oblongata. 


886 


THE  CENTRAL  NERVOUS  SYSTEM 


The  middle  peduncle  is  in  the  main  a  link  between  the  cerebellar 
cortex  and  the  cerebral  cortex  of  the  opposite  side,  through  the  relay 
of  the  pontine  grey  matter.  Most  of  the  fibres  in  it  are  afferent  in  rela- 
tion to  the  cerebellum,  their  cells  of  origin  being  situated  in  the  nuclei 
of  the  pons,  and  sending  their  axons  across  the  middle  line  to  end  in  the 
cerebellar  cortex. 

The  superior  peduncle  connects  chiefly  the  dentate  nucleus  of  one 
side  with  the  cortex  of  the  opposite  cerebral  hemisphere  through  the 
red  nucleus  of  the  tegmentum  of  the  crus  cerebri  and  the  optic  thalamus 
on  the  opposite  side.  The  great  majority,  or  perhaps  all,  of  its  fibres 
are  efferent  fibres  as  regards  the  cerebellum — i.e.,  their  cells  of  origin  lie 
in  the  dentate  nucleus.     Running  upwards  and  forwards  in  the  superior 

peduncle  towards  the  mid- 
brain they  cross  the  middle 
line  below  the  corpora 
quadrigemina,  and  then 
bifurcate  into  ascending 
and  descending  branches. 
The  ascending  branches  end 
mainly  in  connection  with 
cells  in  the  red  nucleus,  but 
some  of  them  pass  on  to 
the  optic  thalamus,  with 
which  cells  of  the  red 
nucleus  are  also  connected. 
The  thalamus,  as  we  have 
seen,  is  in  its  turn  exten- 
sively connected  with  the 
cerebral  cortex  and  the 
red  nucleus  (by  the  efferent 
tract  of  Monakow)  with  the 
grey  matter  uf  the  cord. 
The  descending  branches 
of  the  fibres  of  the  superior 
peduncle,  entering  the  re- 
ticular formation  of  the 
pons,  pass  down,  it  is  said, 
to  make  connection  with 
the  motor  nuclei  of  the 
cranial  and  spinal  nerves.. 
The  tract  of  Gowers,  as 
previously  stated,  comes 
into  relation  with  the  su- 
perior peduncle,  passing 
backwards  along  its  mesial  border  to  the  worm.  Since  the  cortex  of  the 
cerebellum  is  linked  to  the  dentate  nucleus,  the  superior  peduncle  affords 
an  indirect  connection  betrween  it  and  the  cerebral  cortex.  Through 
the  restiform  body  afferent  impulses  pass  up  to  the  cerebellum.  From 
the  cerebellum  they  may  proceed  to  the  cerebrum.  So  that  the  path  by 
the  restiform  body,  dentate  nucleus,  and  superior  peduncle  may  form  an 
alternative  route  for  afferent  impressions  ascending  from  the  periphery  to 
the  great  brain — a  path  broken  by  at  least  four  relays  of  nerve-cells. 
The  cerebellar  hemisphere  may  be  connected  by  an  efferent  path  through 
the  nucleus  of  Deiters  and  the  descending  antero-lateral  tract  with  the 
motor  roots  of  the  same  side.  Another  efferent  path  (from  the  dentate 
nucleus)  may  be  constituted  by  the  fibres  of  the  superior  peduncle  and 
Monakow's  bundle. 


Fig.  364. — Paths  of  Middle  Cerebellar  Peduncle 
(Mingazzini).  The  scheme  indicates  the  afferent 
and  efferent  paths  which  run  through  the  middle 
cerebellar  peduncle,  connecting  cerebellum  with 
opposite  side  of  cerebrum,  a,  fibre  coming  from 
a  cell  in  the  nuclei  pontis  and  going  to  the  cere- 
bellar cortex;  6,  fibre  from  a  cell  in  cortex  of 
opposite  cerebral  hemisphere  making  connection 
in  the  pons  with  a  (a  and  b  together  constitute 
an  afferent  path  to  the  cerebellum);  c,  a  fibre 
springing  fiom  a  Purkinje's  cell  in  the  cerebellar 
cortex  and  making  connection  in  the  pons  with 
a  cell  d,  which  sends  its  axon  to  the  cerebral 
cortex  of  the  opposite  side,  c  and  d  constitute 
an  efferent  path  from  cerebellum  to  opposite 
cerebral  hemisphere;  e,  f,  represent  a  path 
coming  from  the  cerebellar  cortex,  which  crosses 
the  middle  line  in  the  pons,  and  then  ascends 
till  it  loses  itself  in  the  forraatio  reticularis. 


FUNCTIONS  OF  CENTRAL  NERVOUS  SYSTEM  887 

We  have  purposely  omitted  to  enumerate  other  paths  by  which 
the  various  tracts  of  grey  matter  in  the  brain  are  brought  into  com- 
munication with  each  other,  and  our  knowledge  of  such  connections 
is  no  doubt  far  from  complete.  When  we  add  that  not  only  are  the 
cerebral  hemispheres  united  by  many  ties  to  the  subordinate  portions 
of  the  cerebro-spinal  axis  and  to  each  other,  but  that  cortical  areas 
of  one  and  the  same  hemisphere  are  in  communication  by  short 
connecting  loops  of  '  association  '  fibres  (Fig.  360),  it  will  be  seen  that 
the  linkage  of  the  various  parts  of  the  central  nervous  system  is 
extremely  complex;  that  an  excitation,  blocked  out  from  one  path, 
may  have  the  choice  of  many  alternative  routes;  and  that  the  ap- 
parent simplicity  and  isolation  of  the  pyramidal  tracts  must  not  be 
allowed  too  far  to  govern  our  views  of  the  possibilities  open  to  a 
nervous  impulse  once  it  has  been  set  going  in  the  labyrinth  of  the 
nervous  network.  Nor  is  it  only  by  the  main  channel  of  the  axis- 
cylinder  that  nervous  impulses  can  be  conducted,  they  can  also  pass 
along  the  collaterals.  And  the  actual  route  taken  by  a  given  impulse 
is  determined  not  only  by  anatomical  relations,  but  also  by  molec- 
ular conditions,  particularly  in  the  terminal  fibrils  of  the  axons, 
collaterals  and  dendrites,  and  in  the  substance,  if  such  a  substance 
there  be,  which  intervenes  between  the  end  arborizations  of  a  neuron 
and  the  dendrites  or  cell-bodies  of  the  neurons  with  which  they  lie  in 
contact.  So  that  a  road  open  at  one  moment  may  be  closed  at 
another.  (See  p.  902.)  W'e  ma}'  suppose  that  the  greater  the  number 
of  connections  between  the  cells  of  the  central  nervous  system,  the 
greater  is  the  complexity  of  the  processes  which  may  be  carried  on 
within  it.  And,  indeed,  comparison  of  the  brains  of  different  animals 
shows  that  it  is  not  so  much  by  excess  in  the  number  of  nerve-cells 
as  by  the  increased  complexity  of  linkage,  that  a  highly-developed 
brain  differs  from  a  brain  of  lower  type;  the  higher  the  brain,  the 
more  richly  branched  are  the  dendrites  and  the  terminations  of  the 
axons  and  their  collaterals,  and,  therefore,  the  greater  is  the  numbei 
of  possible  paths  between  one  nerve-cell  and  another. 


Section  VIII. — Functions  of  the  Central  Nervous  System — 
(i)  The  Spinal  Cord  (including  the  Medulla  Oblongata). 

Much  of  our  knowledge  of  the  functions  of  the  central  nervous 
system  and  of  its  divisions  has  been  gained  by  the  removal  or 
destruction  of  more  or  less  extensive  tracts  of  nervous  substance,  or 
the  cutting  off  of  connection  between  one  part  and  another.  But  it 
is  well  to  warn  the  reader  at  the  very  outset  that  in  no  other  part  of 
physiology  is  such  caution  required  in  making  deductions  as  to  the 
working  of  the  intact  mechanism  from  the  phenomena  which  mani- 
fest themselves  after  such  lesions. 


888  THE  CENTRAL  NERVOUS  SYSTEM 

In  tlie  first  place,  every  operation  of  any  magnitude  on  the  brain  or 
cord  is  immediately  followed  by  a  depression  of  the  functional  power  of 
the  ner\()us  tissue  distal  to  the  lesion,  a  depression  which  may  extend 
far  from  the  actual  seat  of  injury  and  manifest  itself  by  various  phe- 
nomena, which  arc  grouped  together  under  the  name  of  '  shock,'  better 
termed  spinal  or  cerebro-spinal  shock,  to  distinguish  it  from  the  cardio- 
vascular or  surgical  shock  already  mentioned  (p.  192).  Thus,  when  the 
spinal  cord  of  a  dog  is  divided,  e.g.,  in  the  dorsal  region,  all  power,  all 
vitality-,  one  might  almost  say,  seems  to  be  for  ever  gone  from  the 
portion  of  the  body  below  the  level  of  the  section.  The  legs  hang  limp 
and  useless.  Pinching  or  tickling  them  calls  forth  no  reflex  movements. 
The  vaso-motor  tone  is  destroyed,  and  the  vessels  gorged  with  blood. 
The  urine  accumulates,  overfills  the  paralyzed  bladder,  and  continually 
dribbles  away  from  it.  The  sphincter  of  the  anus  has  lost  its  tone,  and 
the  faeces  escape  involuntarily.  And  if  w^e  were  to  continue  our  observa- 
tions only  for  a  short  time,  a  few  hours  or  days,  we  should  be  apt  to 
appraise  at  a  very  low  value  the  functions  of  that  part  of  the  cord 
which  still  remains  in  connection  with  the  paralyzed  extremities.  But 
these  symptoms  are  essentially  temporary'.  They  are  the  immediate 
results  of  the  section;  they  are  not  permanent  '  deficiency  '  phenomena. 
And  if  we  wait  for  a  time,  we  shall  find  that  this  torpor  of  the  lower 
dorsal  and  lumbar  cord  is  far  from  giving  a  true  picture  of  its  poten- 
tialities; that,  cut  off  as  it  is  from  the  influence  of  the  brain,  it  is  still 
endowed  with  marvellous  powers.  If  we  wait  long  enough,  we  shall 
see  that,  although  voluntaiy  motion  never  retiims,  reflex  movements 
of  the  hind-limbs,  complex  and  co-ordinated  to  a  high  deg-ree,  are  readily 
induced.  A  few  months  after  transection  of  the  cord  it  is  easy  to  show 
that,  although  the  dog  cannot  use  the  hind  limbs  for  continuous  pro- 
gression, the  machinen,'  for  executing  the  appropriate  movements  exists 
in  the  cord.  When,  for  example,  the  animal  is  held  in  the  proper 
position  and  given  a  slight  push  forwards,  it  may  take  two  or  three  steps 
before  its  legs  give  way.  The  regulation  of  the  movements  necessary 
for  the  maintenance  of  "equilibrium  cannot  be  achieved  when  the  control 
of  the  higher  centres  is  eliminated.  In  water,  where  the  problem  of 
the  maintenance  of  the  normal  position  is  solved  by  the  mechanical 
properties  of  the  medium,  the  dog  can  use  the  hind-legs  in  swimming. 
The  tone  of  the  resting  muscles  below  the  lesion  is  even  somewhat 
greater  than  normal.  Vaso-motor  tone  also  comes  back.  The 
functions  of  defaecation  and  micturition  are  normally  performed. 
Erection  of  the  penis  and  ejaculation  of  the  semen  take  place  in  a  dog. 
A  man  with  complete  paralysis  below  the  loins  and  destitute  of  all 
sensation  in  the  paralyzed  region  has  been  known  to  become  a  father 
(Brachet).  Pregnancy  carried  on  to  labour  at  full  term  has  been 
observed  in  a  bitch  whose  cord  was  completely  divided  above  the 
lumbar  enlargement.  The  severity  and  duration  of  spinal  shock  are 
greater  in  the  monkey  than  in  the  dog,  in  man  than  in  the  monkey,  and 
in  the  whole  mammalian  group  than  in  the  lower  vertebrates.  The 
mechanism  of  its  production  has  been  much  discussed,  and  will  be 
referred  to  on  another  page  (p.  912). 

We  cannot  doubt  that  the  spinal  cord  takes  an  important  share  in 
the  recovery  of  function  after  shock.  But  here  again  it  would  be 
erroneous  to  conclude  that  everything  is  due  to  the  cord.  For  Goltz 
and  Ewald  have  been  able  to  keep  dogs  alive  for  long  periods  after 
preliminary  section  of  the  cord  in  the  cervical  region  and  subsequent 
removal  of  large  portions  of  it.  They  find  th.^t  even  after  destruction 
of  the  lumbar  and  sacral  regions  of  the  cord  the  external  sphincter  of 
the  anus,  striped  and  even  voluntary  muscle  though  it  be,  regains  its 


FUNCTIONS  OF  THE  SPINAL  CORD  8^ 

tone,  allhougli  it  is  temporarily  lost  after  tlic  first  cervical  section. 
The  bladder  ultimately  recovers  the  power  of  emptying  itself  spon- 
taneously and  at  regular  intervals.  A  pregnant  bitch  in  which  the 
lumbar  enlargement  and  the  whole  cord  below  it  to  the  cauda  equina 
had  been  removed,  and  therefore  all  the  nerve-roots  supplying  fibres 
to  the  uterus  cut,  whelped  in  a  normal  manner,  and  the  corresponding 
mammary  glands  behaved  exactly  as  the  rest.  Digestion  went  on  as 
usual  when  practically  nothing  of  the  cord  except  its  cervical  portion 
was  left.  Certain  vaso-motor  phenomena  were  also  observed  which 
suggest  that  the  sympathetic  system,  independently  of  the  cerebro- 
spinal system,  is  itself  possessed  of  regulative  powers  (p.  183). 

Secondly,  we  must  not  run  into  the  opposite  error,  and  assume, 
without  proof,  that  all  the  functions  which  the  brain  or  cord  is  capable 
of  manifesting  under  abnormal  circumstances  are  actually  exercised  by 
either  when,  under  ordinary  conditions,  it  is  working  along  with  and 
guiding,  or  being  guided  by,  the  other.  For  example,  in  many  animals 
certain  of  the  reflex  powers  of  the  cord  are,  if  not  increased,  at  all  events 
more  freely  exercised  when  the  controlling  influence  of  the  higher  centres 
has  been  cut  off  than  when  the  central  nervous  system  is  intact. 

Thirdly,  there  is  another  class  of  phenomena  which  we  must  make 
allowance  for,  and  perhaps  more  frequently  in  the  case  of  pathological 
lesions  in  man  than  in  experimental  lesions  in  the  lower  animals.  This 
is  the  class  of  '  irritative  '  phenomena.  The  irritation  set  up  by  a  blood- 
clot  or  a  collection  of  pus,  or  in  any  other  way,  in  a  wound  of  the  grey 
or  white  matter,  may  cause  a  stimulation  of  nervous  tracts  by  which, 
for  a  time,  the  '  deficiency  '  effects  of  the  lesion  may  be  masked. 

In  the  fourth  place,  we  must  not  hastily  conclude  that,  when  no 
obvious  deficiency  seems  to  follow  the  removal  of  a  portion  of  the  central 
nervous  system,  the  function  of  that  portion  must  necessarily  be  of 
such  a  nature  as  to  give  rise  to  no  objective  sigiis.  For  there  is  reason 
to  believe  that,  to  a  certain  extent,  the  function  of  one  part  may,  in  its 
absence,  be  vicariously  performed  by  another. 

Bearing  in  mind  the  cautions  we  have  just  been  emphasizing,  we 
may  broadly  distinguish  between  the  functions  of  the  cord  (including 
the  bulb)  and  those  of  the  brain  proper  by  saying  that  the  cord  is 
essentially  the  seat  of  reflex  actions,  the  brain  the  seat  of  automatic 
actions  and  conscious  processes.  But  neither  of  these  conceptions 
is  entirely  correct.  Both  err  by  defect  and  by  excess.  The  brain, 
it  is  true,  is  pre-eminently  automatic.  The  movements  which  are 
started  in  the  grey  matter  of  the  cerebral  cortex  are  pre-eminently 
voluntary  (p.  946),  but  we  cannot  deny  to  the  brain  the  possession  of 
reflex  powers  as  well.  The  movements  in  which  the  only  nerve 
centres  concerned  are  those  of  the  spinal  cord  are  above  all  reflex 
(p-  897)-  But  some  of  its  centres,  and  especially  those  lying  in  the 
medulla  oblongata — e.g.,  the  respirator^'  centre — are,  much  as  they 
are  influenced  bj''  afferent  impulses,  capable  of  discharging  auto- 
matic impulses  too.  And  while  consciousness  is  certainly  bound  up 
with  integrity  of  the  brain,  and  in  all  the  higher  mammals  is  asso- 
ciated with  cerebral  activity  alone,  it  has  been  plausibly  maintained 
that  the  spinal  cord,  even  of  such  an  animal  as  the  frog,  may  also  be 
endowed  with  something  which  might  be  called  a  kind  of  hushed 
consciousness.     Whether  this  be  so  or  not  for  the  frog,  with  its 


Sgo 


THE  CENTRAL  NERVOUS  SYSTEM 


distinct  though  relatively  ill-developed  cere',jral  hemispheres,  it 
would  seem  by  no  means  unlikely  in  the  case  of  fishes  and  animals 
below  them,  which  are  practically  devoid  of  a  cerebral  cortex 
altogether. 

The  functions  of  the  spinal  cord  may  be  classified  thus: 

1.  The  conduction  of  impulses  set  up  elsewhere — either  in  the 

brain  or  at  the  periphery. 

2.  The  modification  of  impulses  set  up  elsewhere  (reflex  action). 

3.  The  origination  of  impulses  (?). 

Ce/ebral 


Fibre  for 
Head  ^ 


z)e  cassation 
of  Pyramids  " 

Ft,6re  ofDtrect t  . 

Pi/ramidal  tract 

JVerue  -  Cells  ^-  _  -  .'igf^ 
of  Ant  Horn   -^-^^^^^"^^i 
Terminal  ArSonsotton.  VX-^C 
qfoPj/fomdaL  Fibre.  ,  /^.JjgiC 
around  cell  of 
Ant  //orn 


(yncrossed  Tibr^ 
Spioat 


Anterior 

Boot 

Fibres 


Fig-  365- — Some  Possible  Paths  of  Efferent  Impulses  in  the  Central  Nervous  System 
(Schematic).  Details  are  omitted  from  the  scheme.  For  instance,  each  pyra- 
midal fibre  is  represented  as  arborizing  around  one  anterior  cornual  cell  only, 
and  no  collaterals  are  shown.  The  hypothetical  intercalated  neurons  between 
the  pyramidal  fibres  and  the  anterior  horn  cells  (p.  876)  are  not  shown. 

I.  Conduction  of  Nervous  Impulses  by  the  Cord. — The  old  con- 
troversy as  to  whether  the  white  fibres  of  the  spinal  cord  are  directly 
excitable  has  long  been  settled  in  the  affirmative. 

The  inquiry  was  complicated  by  the  presence  of  the  spinal  roots, 
which,  since  the  experiments  of  Charles  Bell,  have  been  known  to  be 
capable  of  excitation  by  artificial  stimuli.  But  at  length  the  difficulty 
was  overcome  in  this  way:   The  posterior  (dorsal)  portion  of   several 


FUNCTIONS  OF  THE  SPINAL  CORD  SQI 

segments  of  the  cord  with  the  attached  posterior  roots  and  the  grey 
matter  was  excised.  Long  strands  of  the  white  matter  of  the  anterior 
(ventral)  portion  of  the  cord  were  isolated,  and  laid  on  electrodes,  and 
contractions  of  muscles  were  seen  to  follow  stimulation,  even  when  the 
anterior  roots  nearest  the  stimulating  electrodes  had  been  cut,  and  every 
precaution  taken  to  avoid  escape  of  current  on  to  the  distant  anterior 
roots  of  the  nerves  supplying  the  muscles.  Indeed,  apart  from  direct 
experimental  evidence,  the  fact  that  the  white  fibres  of  the  brain  are 
universally  admitted  to  be  excitable  by  artificial  means  would  be  of 
itself  almost  sufficient  to  decide  the  question,  for  we  know  of  no  essential 
difference  between  the  cerebral  and  the  spinal  fibres.  But  the  con- 
ditions must  rarely  occur  under  which  direct  stimulation  of  white  fibres 
in  their  course  is  possible  in  the  intact  body ;  and  the  only  impulses  with 
which  we  need  concern  ourselves  here  are  those  that  reach  the  con- 
ducting paths  from  grey  matter  in  the  cord  itself  or  in  the  brain,  or  from 
the  peripheral  organs. 

What  sort  of  impulses  do  the  various  tracts  of  the  spinal  cord 
conduct  ?  For  the  dorsal  or  posterior  roots  this  question  was  first 
fully  answered  by  Magendie;  for  the  ventral  or  anterior  roots, 
although  with  a  certain  degree  of  ambiguity,  by  Sir  Charles  Bell. 
Bell  observed  that  when,  in  an  animal  just  killed,  he  mechanically 
stimulated  the  anterior  roots,  muscular  contractions  were  obtained 
at  each  touch  of  the  forceps.  He  concluded  that  the  anterior  roots 
are  motor  and  sensory,  while  the  posterior  roots  are  '  vegetative  ' — 
i.e.,  connected  with  the  functions  of  the  viscera,  the  so-called 
'  vegetative  '  organs.  But  although  he  is  often  credited  with  the 
discov-ry  of  the  functions  of  the  posterior  roots  as  well,  he  was  not 
the  first  to  make  the  decisive  experiment  necessary  to  show  that  they 
are  the  conductors  of  sensory  impulses.  It  was  after  Magendie's 
discovery  that  only  a  portion  of  the  nerves  are  sensitive,  and  that 
there  are  nerves  '  which  are  like  tendons,  aponeuroses,  or  cartilages 
in  insensibility,'  that  Bell  formulated  the  law  that  the  anterior  roots 
are  purely  motor,  the  posterior  purely  sensory.  This  law,  often 
termed  Bell's  Law,  is  more  correctly  denominated  the  Magendie- 
Bell  Law. 

When  the  posterior  roots  are  divided,  loss  of  sensation  occurs  in 
the  region  to  which  they  are  distributed.  If  only  one  root  is  cut, 
the  loss  of  sensation  is  never  complete  in  any  part  of  the  skin ;  and 
Sherrington  has  found  that  the  cutaneous  areas  of  distribution  of 
consecutive  nerve-roots  are  not  perfectly  independent,  but  to  some 
extent  overlap.  Stimulation  of  the  peripheral  end  of  the  divided 
posterior  root  has  no  effect.  Stimulation  of  the  central  end  gives 
rise,  if  the  animal  be  conscious,  to  evidences  of  pain,  and  other  signs 
of  the  passage  of  afferent  impulses — e.g.,  a  rise  in  blood-pressure. 
The  latter  may  also  be  observed  when  the  animal  is  anaesthetized. 

Referred  Pain. — The  posterior  roots  contain  sensory  fibres  not  only 
for  the  skin,  but  also  for  the  deeper  structures  and  the  viscera.  The 
afferent  fibres  reach  the  viscera  by  the  sympathetic,  the  vagus,  and  the 
pelvic  nerves  or  nervi  erigentes.     Clinical  observations  have  thrown 


892  THE  CENTRAL  NERVOUS  SYSTEM 

much  light  upon  the  distribution  of  the  visceral  fibres  and  their  rela- 
tion to  the  cutaneous  sensory  nerves.  It  has  long  been  known  that 
in  disease  of  an  internal  organ  the  pain  is  often  referred  to  some  super- 
ficial piirt.  It  has  now  been  demonstrated  that  each  organ  is  related 
to  a  more  or  legs  definite  region,  or  more  than  one  region,  of  the  skin. 
In  disease  of  the  organ  there  is  in  this  area  increased  excitability 
(hyperalgesia)  or  tenderness  to  slight  mechanical  stimuli,  and  often 
also  increased  excitability  for  heat  or  cold,  and  the  reflexes  elicited  by 
stimulation  are  exaggerated  (Head,  Dana). 

The  bond  of  connection  appears  to  be  the  origin  from  the  same  spinal 
segments  of  the  autonomic*  sensory  fibres  of  any  viscus  and  the  sensory 
supply  of  the  correspcnding  cutaneous  area.  The  common  anatomical 
origin  seems  to  carry  with  it  a  physiological  correlation,  either  because 
the  irritation  of  the  visceral  fibres  spreads  in  the  cord  to  the  somatic 
afferent  fibres  which  enter  the  corresponding  segments,  or  because  of 
some  action  higher  up  in  the  cerebral  centres,  the  nature  of  which  will 
be  best  considered  along  with  the  general  topic  of  the  localization  of 
sensor}^  impressions  (Chapter  XVIII.). 

Recurrent  Sensibility. — Although  muscular  contraction  is  the 
most  conspicuous  event  that  follows  stimulation  of  the  peripheral  end 
of  an  anterior  nerve-root,  it  is  by  no  means  the  only  one.  It  is 
frequently  observed,  though  not  in  all  kinds  of  animals,  that  here, 
too,  pain  is  caused.  That  this  pain  is  not  due  to  the  muscular  con- 
traction is  proved  by  the  fact  that  it  can  still  be  elicited  when  the 
nerve-trunk  is  divided  between  the  junction  of  the  roots  and  the 
periphery.  The  real  explanation  of  the  phenomenon  is  that  certain 
fibres  from  the  posterior  roots  ('  recurrent  fibres,'  see  footnote  on 
p.  797)  bend  up  for  some  distance  into  the  anterior  roots,  and  then 
turn  round  again  and  pursue  their  course  to  their  peripheral  dis- 
tribution in  the  mixed  nerve,  or  run  on  in  the  motor  roots  to  supply 
the  sheath  surrounding  them  (nervi  nervorum),  and  even  the  mem- 
branes of  the  spinal  cord. 

The  afferent  impulses  that  enter  tlje  cord  along  the  posterior  roots 
have  the  choice  of  many  paths  by  which  they  may  reach  the  brain. 
The  following  are  a  few  of  the  routes  whicli  they  may  follow: 

(i)  They  may  pass  directly  up  through  the  postero-median  column. 
If  they  take  this  route,  their  course  will  be  first  interrupted  by  nerve- 
cells  in  the  gracile  or  cuneate  nuclei  in  the  medulla  oblongata.  Thence 
they  may  find  their  way  across  the  middle  line  b)'  the  arcuate  fibres  of 
the  upper  or  sensory  decussation,  and,  sweeping  along  the  fillet  and  the 
sensory  path  in  the  hinder  part  of  the  posterior  limb  of  the  internal 
capsule,  finally  arrive  at  the  cerebral  cortex.  Between  the  gracile  and 
cuneate  nuclei  and  the  cortex  they  pass  through  nerve-cells  in  the  optic 
thalamus. 

(2)  They  may  pass  up  by  the  direct  cerebellar  tract  and  restiform 
body  to  the  grey  matter  of  the  cerebellar  worm.  If  they  take  this 
route  their  course  will  be  interrupted  very  soon  after  their  entrance  into 

*  Langley  uses  the  term  autonomic  nervous  system  to  include  the  nerve 
supply  of  heart  muscle,  all  unstriated  muscle,  and  all  gland  cells  ia  the  body. 
It  embraces,  in  addition  to  the  sympathetic,  cranial  autonomic  fibres  in 
several  of  the  cranial  nerves  and  sacral  autonomic  fibres  in  the  nervi  erigentes 
(see  Chapter  XVII.). 


FUNCTIONS  OF  THE  SPINAL  CORD  893 

the  cord  in  the  cells  of  Clarke's  column.  Since  the  supcrhcial  grey 
matter  of  the  vermis  is  connected  by  association  fibres  with  the  dentate 
nucleus,  and  the  dentate  nucleus  by  the  superior  peduncle  with  the  oppo- 
site cerebral  hemisphere,  this  is  also  a  possible  path  to  the  great  brain. 

(3)  They  may  reach  the  antero-latcral  ascending  tract  of  the  same 
side  through  its  cells  of  origin  in  the  spinal  grey  matter,  and,  passing 
through  the  medulla  and  pons  to  the  superior  peduncle  of  the  cere- 
bellum, enter  the  grey  matter  of  the  superior  worm. 

(4)  They  may  cross  the  middle  line,  after  entering  the  cord,  through 
axons  or  collaterals  (p.  872)  which  run  in  the  anterior  and  also  in  the 
posterior  commissure,  enter  one  of  the  ascending  tracts  on  the  other 
side — e.g.,  the  tract  of  Gowers — and  continue  without  further  decus- 
sation up  to  their  central  destination. 

(5)  They  may  spread  from  neuron  to  neuron  in  the  tangle  of  the  grey 
matter  itself,  and  pass  out  again  at  a  different  level  into  one  of  the 
white  tracts  on  the  same  or  on  the  opposite  side  of  the  cord. 

Efferent  impulses  from  the  brain  may  travel — 

(i)  Through  the  direct  or  crossed  pyramidal  tract. 

(2)  From  one  side  of  the  cerebral  cortex  to  the  other,  and  then  down 
the  pyramidal  tracts  corresponding  to  that  side  (?). 

(3)  From  the  frontal  part  of  the  cerebral  cortex,  through  the  anterior 
limb  of  the  internal  capsule  to  the  grey  matter  in  the  pons,  and  thence 
to  the  cerebellum  by  its  middle  peduncle. 

(4)  From  the  occipital  or  temporal  cortex,  in  the  hinder  rim  of  the 
internal  capsule,  to  the  pontine  grey  matter,  and  through  the  middle 
peduncle  to  the  cerebellum.  From  the  cerebellum  they  may  possibly 
pass  down  to  the  nucleus  of  Deiters  and  thence  along  the  antero-lateral 
descending  tract  tx)  the  anterior  horn  of  the  cord,  and  indirectly  to  the 
periphery. 

All  the  paths  enumerated,  as  well  as  others  to  which  it  would  be 
tedious  to  formally  refer,  and  which  the  ingenuity  of  the  reader  may 
profitably  be  employed  in  constructing  for  himself,  from  the  data 
already  given,  are  to  be  looked  upon  as  possible  channels  for  the 
passage  of  impulses  between  the  brain  and  the  periphery.  But  it 
must  be  distinctly  pointed  out  that  what  is  certain  is  in  this  case 
much  more  limited  than  what  is  possible.  Among  the  efferent  paths 
it  is  certain  that  the  pyramidal  tracts  are  conductors  of  voluntary 
motor  impulses,  and  that  in  most  individuals  the  great  majority  of 
such  impulses  decussate  in  the  medulla  oblongata,  only  a  small 
minority  in  the  cord.  For  a  lesion  involving  the  pyramidal  tract 
above  the  decussation  of  the  pyramids  causes  paralysis  of  the  oppo- 
site side  of  the  body,  a  lesion  below  the  decussation  paralj^sis  of  the 
same  side.  It  is  certain  that  when  one  pyramidal  tract  has  been 
destroyed,  in  many  animals  at  least,  the  resulting  paralysis  is  soon 
recovered  from,  at  any  rate  to  a  great  extent,  and  it  is  possible  that 
in  this  case  the  motor  cortex  on  the  side  of  the  lesion  has  placed  itself 
again  in  communication  with  the  paralyzed  muscles  through  its 
commissural  connections  with  the  opposite  hemisphere.  This, 
however,  is  not  the  only  alternative,  for,  as  already  pointed  out,  the 
pyramidal  tracts  are  not  the  only  cortico-spinal  paths  which  can 


894  THE  CENTRAL  NERVOUS  SYSTEM 

subserve  volitional  movements,  and  division  of  the  anterior  portion 
of  the  antero-lateral  column  may  cause  deeper  and  more  permanent 
paralysis  than  division  of  the  pyramidal  tract. 

In  the  dog  total  section  of  the  pyramids  is  not  followed  by  com- 
plete paralysis  of  voluntary  movements,  and  stimulation  of  the 
cortical  motor  areas  can  still  ehcit  characteristic  movements.  It  is 
obvious  that  impulses  emanating  from  the  cortex  can  reach  the 
motor  nuclei  of  the  cord  by  other  routes  than  the  long  pyramidal 
fibres,  possibly  by  paths  with  several  segments,  of  which,  for 
example,  the  rubro-spinal  tract  (p.  867)  may  be  one.  Just  as  an 
important  business  house  may  find  it  useful  or  indispensable  to 
supplement  or  replace  the  common  telegraph  service  by  private  wires 
in  the  interest  of  more  prompt  and  satisfactory  communication  with 
its  principal  correspondents,  while  still  utilizing  the  ordinary  channels 
to  some  extent,  so  the  higher  brains  may  be  supposed  to  have 
developed  more  and  more  the  direct  service  of  the  pyramidal  tract 
to  tighten  the  grip  of  the  cortex  upon  the  motor  nuclei  of  the  cerebro- 
spinal axis,  while  still  availing  themselves,  although  in  diminishing 
degree  as  their  evolution  proceeds,  of  the  more  primitive  indirect 
paths. 

Decussation  of  the  Sensory  Paths. — On  the  other  hand,  it  is  certain 
that  pathological  or  traumatic  lesions,  apparently  involving  the 
destruction  of  one  lateral  half  of  the  cord  in  man  and  experimental 
iemisections  in  some  mammals,  are  followed  by  symptoms  which 
suggest  that  some  kinds  of  sensory  impulses  decussate  chiefly  in  the 
spinal  cord — viz.,  diminution  or  loss  of  sensibility  to  pain  and  to 
changes  of  temperature  on  the  opposite  side  below  the  level  of  the 
lesion,  with  little  or  no  impairment,  and  often  increase  of  sensibility 
(hyperesthesia)  on  the  same  side.  Tactile  sensibility  is  lost  on  the 
side  of  the  lesion,  and  likewise  the  muscular  sense. 

The  first  general  description  of  this  symptom-complex  was  given  by 
Brown-Sequard.  On  the  basis  of  clinical  observations  in  man,  he 
came  to  the  conclusion  that  unilateral  lesions  of  the  cord,  equivalent 
approximately  to  a  semisection,  are  associated  with  muscular  paralysis 
below  the  level  of  the  lesion  on  the.  same  side,  and  loss  of  cutaneous 
sensibility  on  the  opposite  side,  while  on  the  side  of  the  lesions  there 
may  be  an  augmentation  of  sensibility.  He  interpreted  these  facts  as 
meaning  that  the  sensory  path  decussates  soon  after  its  entrance  into 
the  cord.  The  sensory  path  from  the  left  side  is  therefore  spared  by  a 
lesion  of  the  left  side  of  the  cord,  but  interrupted  by  a  lesion  of  the 
right  side  of  the  cord.  The  left  and  right  motor  paths,  having  already 
decussated  in  the  bulb,  are  cut  by  lesions  in  the  left  and  right  halves  of 
the  cord  respectively.  Long  afterwards  Brown-Scquard  saw  cause  to 
retract  this  interpretation  of  the  facts  observed  by  him,  but  the  majority 
of  subsequent  observers  have  considered  his  original  hypothesis  more 
satisfactory'  than  his  later  ones.  While  it  may  be  true  that  in  man  it  has 
not  been  rigidly  demonstrated  that  the  symptoms  are  associated  with 
a  clean-out  lesion  precisely  limited  to  one-half  of  the  cord,  clinical 
observation  has  on  the  whole  tended   to  confirm  the  view  that  an 


FUNCTIONS  OF  THE  SPINAL  CORD  895 

important  portion  of  tlic  sensory  path  decussates  in  the  cord.  But  it 
is  a  curious  circumstance  that  experimental  physiologists  have  for  tlie 
most  part  obtained  contradictory  results.  Thus  Mott,  working  with 
monkeys,  found  that  the  different  kinds  of  sensation,  far  from  being 
abolished,  are  as  a  rule  impaired  in  a  smaller  degree  on  the  side  opposite 
to  the  semisection  than  on  the  same  side,  while  Ferrier  and  Turner 
obtained  on  the  whole  a  contrary  result,  and  one  that  corresponded 
closely  with  Brown-Scquard's  original  description.  The  discovery  that 
no  ascending  degeneration,  or  only  a  trifling  amount,  is  to  be  found  on 
the  opposite  side  of  the  cord,  either  after  semisection  or  after  division 
of  posterior  roots,  does  not  of  itself  enable  us  to  decide  the  question. 
For  while  this  latter  fact  shows  that  few  or  none  of  the  afferent  fibres 
cross  the  middle  line  to  enter  the  long  conducting  paths  before  being 
interrupted  by  nerve-cells,  it  by  no  means  proves  that  afferent  impulses 
do  not  decussate  in  the  cord.  The  long  paths  of  the  posterior  column, 
indeed,  do  not  decussate  below  the  level  of  the  bulb.  The  dorsal  and 
ventral  spino-cerebellar  tracts  are  also,  in  the  main  at  least,  uncrossed 
spinal  paths.  A  portion  of  the  afferent  impulses  must  therefore  be 
carried  up  to  the  cerebrum  and  the  cerebellum  without  decussating  in 
the  cord.  But  nobody  can  tell  how  massive  a  link  between  the  two 
halves  of  the  cord  may  be  formed  by  the  grey  matter  and  the  endogenous 
fibres  of  the  white  columns  and  their  collaterals.  We  know  that  some 
afferent  impulses  do  decussate  far  below  the  level  of  the  medulla.  For, 
(i)  A  part  of  the  action  current  (p.  838)  crosses  the  middle  line  and 
ascends  in  the  opposite  half  of  the  cord  when  the  central  end  of  one 
sciatic  is  stimulated  (Gatch  and  Horsley).  (2)  Crossed  reflex  move- 
ments are  possible;  and  when  excitation  ot  the  central  end  of  the  sciatic 
is  followed  by  contraction  of  the  muscles  of  the  opposite  fore-limb,  the 
afferent  impulses  must  either  decussate  in  the  lumbar  cord,  and  then 
run  up  on  the  opposite  side  to  the  level  of  the  brachial  plexus,  or  must 
ascend  on  the  same  side  and  cross  over  somewhere  between  the  plane 
of  the  sciatic  and  the  brachial  nerve-roots.  The  only  other  hypothesis 
on  which  crossed  reflex  action  can  be  explained — but  a  hypothesis  for 
which  there  is  not  a  tittle  of  evidence — is  that  the  afferent  impulse 
always  acts  on  the  few  motor  cells  whose  axis-cylinder  processes  pass 
over  to  the  opposite  side,  and  there  enter  anterior  nerve-roots.  But 
while,  for  these  reasons,  it  cannot  be  denied  that  some  afferent  impulses 
decussate  in  the  cord,  it  would  be  an  error  to  conclude  that  all  do  so  in 
any  animal,  or  that  all  animals  are  in  this  respect  alike.  It  is  indeed 
extremely  probable  that  in  different  species  of  animals,  and  even  in 
individuals  of  the  same  species,  there  are  considerable  differences  in 
the  extent  of  the  sensory  decussation  in  the  cord,  just  as  there  are  in  the 
extent  of  the  motor  decussation  in  the  bulb.  In  some  animals  the 
greater  part  of  the  sensory  path  may  decussate  in  the  cord :  in  others  the 
greater  part  may  decussate  in  the  bulb,  or  higher  up.  The  lack  of 
agreement  in  the  experimental  results  may  be  due  partly  to  this  cause. 
When  it  is  further  remembered  how  difficult  it  sometimes  is  to  interpret 
the  account  which  a  man  gives  of  his  sensations,  and  to  recognize 
precisely  the  degree  and  nature  of  sensory  defects  produced  by  disease 
in  the  human  subject,  it  will  not  be  thought  surprising  that  experi- 
ments on  animals,  from  the  time  of  Galen  onwards,  should  have  yielded 
evidence  which,  although  perhaps  now  at  length  tending  to  a  definite 
result,  is  still  unfinished  and  in  part  confhcting. 

If,  leaving  them  out  of  account,  not  as  valueless  but  as  still 
difficult  of  interpretation,  we  attempt  to  draw  any  general  conclusion 


896  THE  CENTRAL  NERVOUS  SYSTEM 

from  the  clinical  observations  which,  however  imperfect,  are  in  such 
questions  our  surest  guide,  it  can  only  be  this,  that  in  man  some 
of  the  sensory  impulses,  and  particularly  those  connected  with  the 
cutaneous  sensations  of  pain  and  temperature,  decussate,  in  part  at 
least,  in  the  cord.  But  there  is  also  evidence  that  tactile  afferent  im- 
pulses, including  those  coming  from  the  muscles  and  related  to  the 
muscular  sense,  and,  it  may  be,  some  of  the  impulses  associated  with 
pain,  decussate,  not  in  the  cord,  but  in  the  bulb. 

The  Paths  for  Different  Kinds  of  Sensory  Impressions. — If  this  is  the 
state  of  our  knowledge  where  the  problem  is  merely  to  determine  the 
crossing-place  of  afferent  impulses  which  are  certainly  known  to  cross, 
it  is  only  to  be  expected  that  we  should  be  still  more  in  the  dark  as 
regards  the  routes  by  which  different  kinds  of  afferent  impulses  thread 
their  way  through  the  maze  of  conducting  paths  in  the  neural  axis  to 
reach  their  planes  of  decussation  and  gain  the  '  sensory  crossway  '  in 
the  internal  capsule.  Some  authors  have  indeed  cut  the  Gordian  knot 
by  assuming  that  any  kind  of  sensory  impression  may  travel  up  any 
afferent  path.  Direct  stimulation  of  a  naked  nerve-trunk,  it  has  been 
argued  in  favour  of  this  view,  gives  rise  to  a  sensation  of  pain;  stimula- 
tion of  the  skin  in  which  the  end-organs  of  the  nerve  lie  gives  rise  to  a 
sensation  of  touch  or  a  sensation  of  temperature,  according  as  the 
stimulus  is  a  mild  mechanical  or  a  thermal  one,  the  contact  of  a  feather 
or  of  a  hot  test-tube.  Why,  it  has  been  asked,  should  we  imagine  that 
the  difference  in  the  result  of  stimulation  depends  on  a  difference  in  the 
.  nerve-fibres  excited,  and  not  on  a  difference  in  the  kind  of  impulses  set 
up  in  the  same  nerve-fibres  ?  This  is  a  question  which  we  shall  have 
again  to  discuss.  But  apropos  of  our  present  problem,  we  may 
say  that  there  is  very  clear  proof  from  the  pathological  side  that  a 
limited  lesion  in  the  conducting  paths  of  the  central  nervous  system 
may  be  associated  with  defect  or  total  loss  of  one  kind  of  sensation ,  while 
all  the  other  kinds  remain  intact.  And  there  seems  no  other  tenable 
hypothesis  than  that  in  such  cases  the  pathological  change  has  picked 
out  a  particular  group  of  fibres,  either  collected  into  a  single  strand  or 
scattered  among  unaltered  fibres  of  different  function.  For  example, 
in  syringo-myelia,  a  condition  in  which  cavities  are  formed  in  the  grey 
matter  of  the  cord  secondary  to  a  new  gro\\i;h  of  the  neuroglia  surround- 
ing the  central  canal,  a  frequent  symptom  is  the  loss  in  a  certain  region 
of  sensibility  to  pain  and  to  changes  of  temperature,  while  tactile 
sensibility  is  unaffected  (dissociation  of  sensations).  Again,  in  loco- 
motor ataxia,  a  disease  in  which  inco-ordination  of  movement  and 
derangement  cf  the  mechanism  of  equilibration  are  prominent  symptoms, 
degeneration  in  the  posterior  column  of  the  cord  is  a  most  constant 
lesion.  And  there  is  strong  evidence  that  afferent  impulses  from 
muscles  and  tendons,  which  either  give  rise  to  impressions  belonging  to 
the  group  of  tactile  sensations,  or  produce  no  effect  in  consciousness,  and 
which,  according  to  the  most  widely  accepted  doctrine,  serve  as  the 
basis  of  the  muscular  sense,  and  play  an  important  part  in  the  main- 
tenance of  equilibrium  (p.  941),  pass  up  in  the  posterior  column.  It 
may  also  conduct  tactile  impressions  from  the  skin.  A  case  has  been 
observed  where  a  man  received  a  stab  which  di\ided  the  whole  of  one 
side  of  the  cord  and  the  posterior  column  of  the  other  side.  Sensibility 
to  touch  was  lost  on  both  sides  of  the  body  below  the  level  of  the  injun,-. 
sensibility  to  pain  only  on  the  side  opposite  to  the  main  lesion.  In 
another  case,  in  which'  some  small  syphilitic  tumours  (gummata)  iu 


FUNCTIONS  OF  THE  SPINAL  CORD  807 

the  lateral  column  on  the  left  side  caused  marked  degeneration  in  the 
left  direct  cerebellar  tract,  the  tract  of  Gowers,  and  the  crossed  pyram- 
idal tract,  without  affecting  the  posterior  columns,  tactile  sensibility 
was  only  slightly  impaired  in  the  opposite  leg,  while  the  sensibility  for 
pain  and  temperature  was  much  enfeebled.  In  the  left  leg,  which  was 
paralyzed,  there  was  slight  hyperassthesia.  These  observations  indicate 
that  impressions  of  pain  and  temperature  pass  up  in  the  antero-lateral 
column,  either  in  the  tract  of  Gowers,  or  in  the  direct  cerebellar  tract,  or 
in  botli  (Dejerine  and  Thomas). 

But  it  does  not  follow  that  they  cannot  ascend  by  other  p>aths  as 
well.  It  appears,  indeed,  that  the  grey  matter  of  the  cord,  or,  rather, 
short  endogenous  fibres  arranged  in  series  in  the  antero-lateral  column 
so  as  to  connect  the  grey  matter  at  different  levels,  constitute  such  a 
path,  and  that  impulses  which  give  rise  to  pain  can  be  propagated  along 
a  cord  in  which  hardly  a  vestige  of  white  substance  remains  uncut.  In 
man  the  path  for  pain  and  temperature  impressions  along  these  short 
endogenous  fibres  seems  to  be  mainly  or  entirely  a  crossed  path.  The 
afferent  paths  for  such  vaso-motor  reflexes  as  are  elicited  by  stimulation 
of  the  central  end  of  the  sciatic  ascend  in  the  lateral  column,  and  the 
impulses  largely  cross  the  middle  line  in  the  cord.  The  posterior 
columns  have  nothing  to  do  with  the  conductioxi  of  painful  impressions, 
for  division  of  them  causes  not  anaesthesia,  but  rather  hyperaesthesia, 
while  if  they  are  left  intact,  and  the  rest  of  the  cord,  including  the  grey 
matter,  divided,  the  animal  is  insensitive  to  pain  below  the  level  of  the 
lesion.  Just  as  man  differs  from  lower  animals  in  the  completeness 
with  which  certain  of  the  sensory  impressions  decussate  in  the  cord,  so 
differences  exist  in  the  degree  of  localization  of  the  different  kinds  of 
impressions  in  particular  tracts.  One  of  the  outstanding  differences  is 
that  in  animals  it  seems  to  be  easier  for  a  still  intact  path  to  be  substi- 
tuted for  a  severed  path  as  a  conductor  of  impulses  which  normally 
traverse  the  latter.  The  rapiditj'  with  which  sensation  is  restored 
below  the  lesion  after  semisection  of  the  cord  in  animals  is  an  illustration 
of  this.  Another  difference,  which  can  be  explained  in  the  same  way,  is 
that  a  sharply-marked  dissociation  of  sensations — retention  of  tactile 
sensibility,  for  example,  with  loss  of  sensibility  to  pain  or  to  pain  and 
temperature  changes — either  cannot  be  produced  experimentally  in 
animals,  or  is  very  difi&cult  to  realize. 

The  impulses  which  descend  the  cord  give  token  of  their  arrival  at  the 
periphery  by  causing  either  contraction  of  voluntary  muscles,  or  con- 
traction of  the  smooth  muscular  fibres  of  arteries,  or  secretion  in  glands. 
They  all  pass  down  in  the  antero-lateral  column,  but  the  path  of  the 
voluntary  impulses  in  the  pyramidal  tracts  is  the  best  known  and  most 
sharply  defined. 

2.  Modification  of  Impulses  set  up  elsewhere  (Reflex  Action). — 
The  spinal  cord,  although  it  is  a  conductor  of  nervous  impulses 
originating  elsewhere,  is  by  no  means  a  mere  conductor.  Many  of 
the  impulses  which  fall  into  the  cord  are  interrupted  in  its  grey 
matter.  Some  of  the  efferent  impulses  proceeding  from  the  brain 
are  perhaps  modified  in  the  cord,  and  then  transmit  ted  to  the  muscles. 
Some  of  the  afferent  impulses  are  modified,  and  then  transmitted  to 
the  brain ;  some  are  mo(H  fied,  and  deflected  alt  ogel  her  into  an  efferent 
path.  These  last  are  the  impulses  which  give  rise  to  reflex  effects. 
A  reflex  action  has  sometimes  been  defined  as  an  action  carried  out 
in  the  absence  of  consciousness:  not  necessarily,  however,  in  the 

57 


89S  THE  CENTJi-AL  NERVOUS  SYSTEM 

absence  of  general  consciousness,  but  in  the  absence  of  consciousness 
of  the  particular  act  itself.  But  the  term  is  now  more  correctly 
used  so  as  to  embrace  all  kinds  of  actions  which  are  not  directly 
voluntary,  whether  the  individual  is  conscious  of  them  or  not.  For 
example,  when  the  sole  of  rhe  foot  is  tickled,  the  leg  is  irresistibly 
and  involuntarily  drawn  up  by  reflex  contraction  of  its  muscles;  yet 
the  person  is  perfectly  cognizant  both  of  the  movement  and  of  the 
sensation  which  accompanies  the  afferent  impulse.  Many  reflex 
actions  usually  associated  with  sensations  proceed  normally  when 
consciousness  is  entirely  in  abeyance;  during  sleep  most  of  the 
ordinary  reflexes  can  be  elicited. 

Anatomical  Basis  of  Reflex  Action. — Since  the  essence  of  reflex  action 

is  that  the  arrival  of  afferent  impulses  in  the  spinal  cord  or  brain  causes 
the  discharge  of  efferent  impulses,  there  must  be  some  connection 
between  the  incoming  and  the  outgoing  nerve-fibres.  In  unicellular 
animals,  such  as  amoeba,  there  is  no  differentiation  of  any  special 
nervous  or  conducting  path.  A  stimulus  applied  at  one  point  may 
cause  contraction  anywhere.  Even  in  the  lowest  multicellular  animals 
or  metazoa — e.g.,  in  the  sponges — there  is  no  special  nervous  tissue. 
In  some  species  of  hydra,  however,  many  of  the  surface  or  ectodermic 
cells  (p.  6)  possess  deeply-placed  contractile  or  muscular  processes, 
and  stimulation  of  the  surface  cells  is  followed  by  contraction  of  these 
processes.  We  may  imagine  that  the  first  l:>eginnings  of  an  actual 
nervous  system  may  have  arisen  by  a  further  differentiation  of  such 
an  ectodermic  cell  into  a  receptive  portion  at  the  surface,  a  deeper  con- 
tractile portion,  and  an  intermediate  strand  of  protoplasm  connecting 
the  two,  and  capable  of  conducting  the  excitation  from  surface  to 
muscular  process.  In  such  a  reflex  arc  the  nervous  link  would  consist 
only  of  the  conducting  strand  analogous  to  the  nerve  fibre  joining  the 
receptive  or  sensory  .element  to  the  contractile  element,  and  the  dis- 
tinction between  afferent  and  efferent  fibre  would  not  exist.  When 
development  has  gone  a  step  further,  and  the  neuro-muscular  process 
is  interrupted  by  a  second  epithelial  cell  transformed  into  a  nerve-cell, 
the  afferent  fibre  enters  one  pole  and  the  efferent  fibre  leaves  the  other 
pole  of  the  same  cell.  It  is  this  condition  which  we  actually  find  when 
the  nervous  system  first  emerges  in  the  animal  scale  as  an  unmistakably 
differentiated  structure — namely,  in  the  Coelcnterates  in  such  forms  as 
the  jellyfishes.  Here  the  three  types  of  cell,  receptive  or  sensory  cell, 
reactive  or  central  cell,  and  motor  or  contractile  cell,  arc  connected 
together  by  conducting  paths  or  nerve-fibres.  In  a  simple  reflex  action 
three  events  can  be  distinguished :  stimulation  of  a  receiving  mechanism, 
conduction  of  the  excitation,  and  the  consequent  reaction  or  end -effect. 
'I"he  receiving  mechanism  or  receptor  may  consist  of  ordinary  sensory 
nerve-endings  in  the  skin,  or  of  special  sense-endings,  as  in  the  retina 
or  internal  ear.  The  conducting  mechanism  or  conductor  in  all  except 
the  very  simp'.est  nervous  systems  is  made  up  of  at  least  two  neurons, 
one  the  afferent  portion  of  the  reflex  arc  connected  with  the  receptor, 
the  other  the  efferent  portion  of  the  arc,  connected  with  the  organ, 
sometimes  termed  the  effector  organ — a  muscle,  e.g.,  or  a  gland — which 
accomplishes  the  end-effect.  The  transference  of  the  excitation  from 
the  afferent  to  the  efferent  neuron  takes  place  across  the  intervening 
synapre.  The  simple  isolated  reflex  arc,  as  thus  described,  although 
a  convenient  abstraction,  corresponds  but  little  to  anything  which 
actually  exists  in  one  of    the   higher   animals.     With  increasing  com- 


FUNCTIONS  OF  THE  SPINAL  CORD  899 

plexity  of  organization  the  nervous  impulse  passing  up  an  afferent 
fibre  is  in  general  otfcrccl,  instead  of  a  single  efferent  path,  a  choice  of 
many  potential  routes  when  it  reaches  the  spinal  coril.  We  have 
previously  (p.  872)  described  the  course  taken  by  the  fibres  of  the 
posterior  roots  on  entering  the  cord.  It  is  obvious  tluit  through  the 
main  fibres  and  their  collaterals  an  extensive  connection — partly  direct, 
partly  by  the  link  of  intermediate  neurons — is  established  with  the 
motor  cells  on  both  sides  of  the  cord.  But  the  facts  of  physiology 
demonstrate  an  even  ampler  connection  than  the  mere  anatomical 
study  of  the  distribution  of  the  root-fibres  would  suggest.  Indeed,  the 
phenomena  of  strychnine-poisoning  seem  to  show  that  every  afferent 
fibre  is  potentially  connected  with  the  motor  mechanisms  of  the  whole 
cord,  or  at  least  with  a  very  large  proportion  of  them.  For  in  a  frog  under 
the  influence  of  this, drug,  stimulation  of  the  smallest  portion  of  the  skin 
will  cause  violent  and  general  convulsions,  which  are  unaffected  by  de- 
struction of  the  brain,  but  cease  at  once  on  destruction  of  the  cord  (p.  904)- 

In  an  unpoisoned  reflex  frog — that  is,  a  frog  in  wliich  interference 
with  the  single  spinal  reflexes  has  been  prevented  by  section  of  the  bulb 
or  destruction  of  the  brain — the  movements  resulting  from  stimulation 
of  a  given  receptive  area  are  by  contrast  surprisingly  limited,  localized, 
and  constant.  Thus,  a  harmful  stimulus  of  a  certain  intensity  applied 
to  a  toe  will  elicit  time  after  time  a  raising  of  the  leg — in  other  words, 
an  excitation  of  muscles  whose  motor  nerves  arise  from  cells  in  the  same 
region  of  the  cord  into  which  the  afferent  fibres  from  the  receptive  skin 
area  enter.  The  localization  of  the  reflex  is  in  this  case  without  doubt 
dependent  upon  the  fact  that  the  connections  of  the  afferent  fibres  with 
the  group  of  efferent  neurons  in  question  are  more  direct  and  more 
intimate  than  with  any  other  group.  This  anatomical  isolation  of  a 
given  reflex  arc  is  never  complete,  but  so  far  as  it  goes  it  may  be 
assumed  to  be  constant  and  incapable  of  variation.  Under  normal 
conditions  the  anatomical  isolation  is  always  supplemented  by  a 
physiological  isolation ,  which  is  susceptible  of  variation  in  the  direction 
either  of  increase  or  of  diminution. 

It  is  therefore  a  question  of  great  interest  how  the  isolated  con- 
duction of  the  impulses  in  a  given  reflex  arc,  in  so  far  as  it  depends  upon 
the  physiological  condition  of  the  arc  and  of  its  connections,  is  normally 
achieved.  The  best  answer  which  can  at  present  be  given  is  that  it  is 
not  equally  easy  for  a  reflex  excitation  to  pass  across  all  the  synapses 
which  are  potentially  open  to  it,  and  that  a  lowering  of  the  resistance 
of  the  synapses  in  the  favoured  path  is  probably  quite  as  important  a 
factor  in  the  isolation  as  an  increase  of  the  resistance  in  those  which 
are  to  be  barred.  Following  the  path  of  least  resistance,  the  excitation 
traverses  the  synapse  or  synapses  which  it  is  easiest  for  it  to  break 
through.  What  property  of  the  synapse  is  associated  with  resistance 
to  the  passage  of  the  impulse  is  unknown.  But  it  is  a  variable  property, 
and  when  a  general  reduction  in  the  resistance  is  produced,  as  by  strych- 
nine or  tetanus  toxin,  an  excitation  impressed  upon  a  single  afferent 
path  may  force  a  great  many  synapses  normally  impervious  to  it. 

While  it  is  convenient  in  a  preliminary  survey  to  speak  of  the  resist- 
ance to  spreading  of  the  excitation  in  the  cord  being  diminished  by 
strychnine  or  by  tetanus  toxin,  we  shall  see  presently  that  more  than 
this  is  involved  (p.  903). 

Principle  of  the  Common  Path. — In  considering  the  architecture 
of  the  cerebro-spinal  nervous  system  as  a  basis  of  reflex  action,  one 
feature  is  of  such  importance  as  to  deserve  special  mention.     The 


900  THE  CENTRAL  NERVOUS  SYSTEM 

afferent  neurons,  running  from  the  receptive  surfaces  to  the  centres, 
constitute  eucli  for  its  own  receptive  point-a  '  private  '  path  which 
can  only  be  used  by  impulses  arising  at  that  point,  and  not  by 
impulses  arising  at  any  other  point.  Through  its  central  connec- 
tions an  afferent  neuron  from  a  single  point  may  be  put  into  com- 
munication with  numerous  efferent  neurons,  and  thus  with  numerous 
and  distant  effector  organs  (muscles  or  glands).  Conversely,  the 
efferent  portion  of  a  single  reflex  arc  can  convey  reflex  excitations 
originating  in  numerous  and  distant  receptive  fields.  It  is  the  sole 
path  which  all  efferent  impulses — let  them  originate  where  they  may 
— must  use  to  reach  the  end-organ  in  question.  It  is  therefore  not  a 
private  but  a  public  path,  and  may  be  termed  in  this  relation  the 
final  common  path  (Sherrington). 

The  existence  of  the  common  path  is  of  great  importance  in  under- 
standing the  manner  in  which  reflexes  are  compounded  together,  a 
problem  absolutely  fundamental  in  nervous  co-ordination.  One 
consequence  of  the  existence  of  a  common  path  is  that  when,  among 
the  receptors  which  may  use  it,  two  are  simultaneously  stimulated 
which,  when  separately  excited,  produce  opposite  effects  upon  the 
effector  organ,  only  one  of  the  effects  is  produced.  In  other  words, 
impulses  which  produce  the  two  opposed  effects  can  be  successively, 
but  cannot  be  simultaneously,  sent  along  the  common  path.  Thus, 
■'  excitation  of  the  central  end  of  the  afferent  root  of  the  eighth  or 
seventh  cervical  nerve  of  the  monkey  evokes  reflexly  in  the  same 
individual  animal  sometimes  flexion  at  the  elbow,  sometimes  ex- 
tension. If  the  excitation  be  preceded  by  excitation  of  the  first 
thoracic  root,  the  result  is  usually  extension ;  if  by  excitation  of  the 
sixth  cervical  root,  it  is  usually  flexion.  Yet  though  the  same  root 
may  thus  be  made  to  evoke  reflex  contraction  of  the  flexors  or  of  the 
extensors,  it  does  not  evoke  contraction  in  both  flexors  and  extensors 
in  the  same  reflex  response.  .  .  .  The  flexor-reflex,  when  it  occurs, 
seems,  therefore,  to  exclude  the  extensor- re  flex,  and  vice  versa. 
Either  the  one  or  the  other  results,  but  not  the  two  together  ' 
(Sherrington).  It  is  obvious  that  this  is  an  advantageous  arrange- 
ment. An  algebraical  summation  of  the  opposed  effects  by  the 
common  path  would  result  in  a  useless  action  which  was  neither 
effective  flexion  nor  effective  extension,  a  compromise  and  not  a 
co-ordination.  The  conditions  which  determine  which  of  two  or 
more  competing  reflexes  shall  obtain  possession  of  the  final  common 
path  are  considered  on  p.  9<^2. 

Role  of  the  Receptor  in  Reflex  Action.— The  role  of  the  receptor  in 
the  reflex  arc  is  above  all  to  sift  out  from  the  various  kinds  of  im- 
pressions impinging  upon  the  receiving  surface  the  particular  kind 
to  which  the  appropriate  response  is  the  reflex  action  in  question. 
As  w^ill  be  pointed  out  in  greater  detail  in  the  study  of  the  special 
senses,  each  kind  of  afferent  end-organ  has  become  adapted  to  a 


FUNCTIONS  OF  THE  SPINAL  CORD  901 

special,  or,  as  it  is  termed,  an  '  adequate  '  stimulus,  so  that  it  is 
easily  affected  by  this,  and  with  difficulty  or  not  at  all  by  other 
modes  of  stimulation.  Thus,  light  is  the  adequate  stimulus  of  the 
end-organ  of  the  optic  nerve,  heat  that  of  the  end-organs  of  the 
nerves  by  which  we  perceive  the  sensation  of  warmth,  mechanical 
pressure  that  of  the  nerves  by  which  we  perceive  the  sensation  of 
pressure.  Other  kinds  of  stimuli  are  either  entirely  inactive  or  much 
less  effective  in  evoking  tlie  particular  sensory  response.  There  is 
every  reason  to  believe  that  the  receptor  in  the  reflex  arc  occupies  the 
same  position  in  regard  to  adequate  stimuli  as  it  does  when  it  func- 
tions as  a  sense-organ. 

Sherrington  has  shown  that  the  different  kinds  of  nerve-endings 
in  one  and  the  same  area  of  the  skin  (in  the  dog)  must  be  assumed  to 
possess  totally  different  spinal  connections,  since  the  movements 
elicited  by  stimuli  suitable  for  one  form  of  nerve-ending  are  quite 
different  from  those  elicited  by  stimuli  suitable  for  another. 

The  '  extensor-thrust  '  is  a  reflex  obtained  in  the  hind-leg  of  the 
dog.  and  characterized  by  a  brief,  strong  extension  at  the  hip,  knee, 
and  ankle.  It  is  only  ehcited  by  a  certain  kind  of  mechanical  stimu- 
lation, best  in  the  spinal  dog — i.e.,  in  a  dog  whose  brain  has  been 
desti-oyed  or  severed  from  the  cord  some  time  before — by  pushing  the 
tip  of  the  finger  between  the  plantar  cushion  and  the  pads  of  the  toes. 
The  stimulus  is  similar  to  that  which  normally  liberates  the  reaction 
— namely,  the  pressure  of  the  ground  on  the  sole  of  the  foot  during 
locomotion.  The  reflex  cannot  be  obtained  by  electrical  stimula- 
tion or  by  any  kind  of  direct  stimulation  of  afferent  nerve-trunks. 
The  same  is  true  of  the  pinna-reflex  in  the  cat — i.e.,  the  backward 
crumpling  of  the  ear  ehcited  by  squeezing  or  tickling  its  tip.  The 
scratch-reflex,*  a  scratching  movement  of  the  hind-foot,  is  much 
more  easily  elicited  in  the  spinal  dog  by  mechanical  stimulation 
(rubbing,  tickling,  or  tapping)  applied  to  the  skin  of  the  back  behind 
the  shoulder  than  by  electrical  stimulation,  which  often  fails  to 
evoke  it  at  all.  The  puzzhng  fact  that,  according  to  surgical  ex- 
perience, many  of  the  internal  organs — e.g.,  the  ureters  and  bile- 
ducts — can  be  handled,  cut,  and  sutured  without  pain,  while  the 
passage  of  a  renal  calculus  or  a  gall-stone  may  cause  excruciating 
agony,  becomes  explicable  in  view  of  the  apparently  slight  difference 
which  sometimes  distinguishes  an  adequate  from  an  inadequate 
stimulus.  Thus  Sherrington  has  shown  that  very  distinct  reflex 
eftects — e.g.,  a  rise  of  blood-pressure — can  be  obtained  by  sudden 
distension  of  the  bile-duct  by  the  injection  of  salt  solution  into  its 
lumen.  Distension  is  here  the  adequate  form  of  mechanical  stimu- 
lation, and  it  is  the  form  induced  by  the  passage  of  a  calculus,  while 
nerve-cutting,  although  a  mechanical  stimulus,is  not  an  adequate  one. 

*  The  scratch-reflex  is  very  easily  obtained  in  cats  during  resuscitation 
after  a  period  of  cerebral  anaemia. 


902  THE  CENTRAL  NERVOUS  SYSTEM 

Characteristic  Properties  of  the  Reflex  Arc. — Conchiction  in  reflex 
arcs  shows  certain  pecuHarities  when  compared  with  the  conduction 
in  nerve-trunks  already  studied  (p.  781):  (i)  The  direction  of  the 
reflex  conduction  cannot  be  reversed.  There  is  an  absolute  block 
on  the  passage  of  impulses  backwards  through  a  synapse.  (2)  The 
velocity  of  conduction  over  the  whole  reflex  arc  is  much  smaller 
than  over  a  nerve-trunk  of  equal  length.  Both  of  these  differences 
depend  mainly  on  the  fact  that  the  impulses  must  be  transmitted 
from  one  neuron  to  another,  and  very  likely  on  a  fundamental 
property  of  the  synapse.  The  delay  or  '  lost  time  '  in  the  discharge 
of  the  efferent  impulses  which  constitute  the  reflex  response  to  the 
excitation  of  an  afferent  path  increases  with  the  complexity  of  the 
response — ^that  is,  with  the  number  of  neurons  and  tlierefore  of 
synapses  involved  in  it.  (3)  The  reflex  arc  is  easily  fatigued,  easily 
affected  by  deprivation  of  oxygen  and  by  drugs,  in  comparison  with 
the  nerve-trunk.  This  difference  is  due  to  the  portion  of  the  arc 
in  the  grey  matter,  including  the  synapse  or  synapses.  Fatigue 
expresses  itself  by  an  increase  in  the  degree  of  block  or  resistance  to 
the  passage  of  impulses  along  the  arc.  (4)  The  reflex  end-effect  may 
much  outlast  the  stimulus — in  other  words,  a  marked  '  after-dis- 
charge '  is  characteristic  of  reflexes.  The  more  intense  the  stimulus 
which  liberates  the  end-effect,  the  greater  is  the  duration  of  the  after- 
discharge.  For  example,  the  '  crossed  extension  reflex  '  (extension 
at  the  knee,  ankle,  and  hip,  produced  in  the  spinal  dog  by  stimula- 
tion of  the  skin  of  the  opposite  or  contralateral  hind-limb),  when 
provoked  by  a  stimulus  of  more  than  a  certain  intensity,  may  outlast 
the  stimulation  by  ten  or  fifteen  seconds,  and  the  after-discharge 
may  be  stronger  than  any  other  part  of  the  reflex  (Sherrington). 
(5)  A  succession  of  impulses  may  easily  pass  along  a  reflex  arc  when 
one  of  the  series  would  fail  to  pass  (temporal  summation).  This 
does  not  occur  in  a  nerve-trunk.  The  first  stimulus,  though  itself 
unable  to  produce  the  reflex  effect,  facilitates  the  action  of  succeeding 
stimuli,  so  that  summation  of  the  impulses  occurs  in  the  cord 
(Stirling).  A  stimulus — e.g.,  a  make-induction  shock,  far  too  weak 
to  produce  the  scratch-reflex  when  applied  once  only  to  a  point  of 
that  area  of  skin  from  which  the  reflex  is  normally  elicited — has  been 
seen  to  cause  the  reflex  after  more  than  forty  shocks  had  been 
delivered  at  the  rate  of  eighteen  per  second.  The  facilitation  of  the 
passage  of  an  impulse  by  the  previous  passage  of  impulses  along  the 
same  reflex  path  recalls  a  somewhat  similar  phenomenon  already 
alluded  to  in  connection  with  the  conduction  of  the  propagated 
disturbance  in  nerve-fibres  (p.  791),  although  in  the  case  of  the  reflex 
arc  the  effect,  it  may  be  supposed,  is  exerted  upon  the  fields  of 
conjunction,  including  the  synapses,  between  the  different  neurons. 
There  is  reason  to  believe  that  summation  in  the  reflex  arc  is  mainly 
achieved  by  the  removal  of  block  or  resistance.    The  phenomenon  of 


FUNCTIONS  OF  THE  SPINAL  CORD  903 

facilitation  is  probably  of  great  importance  in  the  acquirement  of 
new  reactions  and  in  rendering  these  acquisitions  stable.  It  is  prob- 
ably one  of  the  main  physiological  foundations  of  habit,  and  there- 
fore of  education.  In  this  connection  it  is  important  to  note  that 
the  very  same  repetition  of  stimuli  which  leads  to  facilitation  leads 
to  fatigue  when  the  stimuli  are  applied  in  too  rapid  succession, 
(6)  The  rhythm  and  intensity  of  the  reflex  end-effect  correspond 
much  less  closely  with  the  rhythm  and  intensity  of  the  stimulus  than 
in  nerve-trunks.  (7)  The  phenomena  of  refractory  period  (p.  155), 
inhibition  and  '  shock,'  are  much  more  conspicuous  in  the  reflex  arc 
than  in  nerve-trunks. 

Inhibition  in  Reflex  Action. — Special  emphasis  must  be  laid  upon 
the  part  plaved  b\-  inhibition  in  reflex  actions.  For  the  proper 
carrying  out  of  many  reflex  movements  it  is  necessary  not  only  that 
the  appropriate  effector  organ,  the  appropriate  muscle,  or  group  of 
muscles,  should  be  caused  to  contract  at  the  proper  time,  but  that 
their  contraction,  or  that  of  other  muscles,  should  be  diminished  or 
abolished  by  inhibition,  or  even  rendered  for  a  certain  period  im- 
practicable by  the  establishment  somewhere  in  the  reflex  arc  of  a 
refractory  state,  which  is  itself  a  phenomenon  of  inhibition.  There  is 
good  evidence  that  this  is  a  central  inhibition — i.e.,  it  depends  on 
some  process  occurring  in  the  spinal  portion  of  the  reflex  arc. 

As  an  example  of  the  numerous  class  of  reflexes  in  which  the 
excitation  of  certain  muscles  is  accompanied  by  the  inhibition  of 
their  antagonists  (reciprocal  inhibition),  we  may  take  the  '  flexion 
reflex,'  the  flexion  at  the  knee,  hip,  and  ankle  of  the  hind-limb 
readily  elicited  in  the  spinal  dog  by  '  nocuous  '  or  harmfui  stimuli 
(such  as  a  prick,  a  strong  squeeze,  chemical  agents,  or  excessive 
heat),  or  by  electrical  stimuh  applied  to  the  skin  of  the  limb  or  of 
any  afferent  nerve  of  the  limb. 

Sherrington  has  shown  that  when  the  legs  of  the  animal  are  so 
prepared  that  only  the  flexors  can  act  on  one  knee,  and  only  the 
extensors  on  the  other,  stimulation  of  symmetrical  points  on  the 
two  sides  in  the  area  of  skin  (receptive  field)  from  which  the  flexion 
reflex  can  be  evoked  causes  contraction  (excitation)  of  the  flexors  and 
simultaneous  relaxation  (inhibition)  of  the  tone  of  the  extensors.  The 
same  is  true  when  corresponding  afferent  nerve-twigs  are  stimulated  ^ 
on  the  two  sides.  From  this  it  is  inferred  that  each  of  the  nerve- fibres 
from  the  receptive  field  of  the  reflex  divides  in  the  cord  into  two  sets 
of  end-branches  {e.g.,  collaterals) — a  set  which  produces  excitation 
when  it  is  stimulated,  and  another  set  which  produces  inhibition. 

Reversal  of  Reflexes. — The  difference  in  action  is  specific  in  the 
sense  that  no  mere  change  in  the  kind  or  intensity  of  stimulation 
affects  it.  Yet  there  are  facts  which  show  that  the  specificity  is  not 
absolutely  immutable,  and  that  a  change  of  conditions  in  the  spinal 
cord  may  permit  excitation  of  a  given  group  of  muscles  to  be  pro- 


904  THE  CENTRAL  NERVOUS  SYSTEM 

duced  by  the  stimulation  of  an  aft'ercnt  path  which  is  primarily 
inhibitory  for  them.  One  of  the  most  striking  illustrations  of  this 
possibility  is  seen  in  the  action  of  strychnine.  Stimulation  of  the 
internal  saphenous  nerve  below  the  knee — say  in  a  dog  after  removal 
of  the  cerebrum — is  known  always  to  produce  inhibition  of  tl.e 
portion  of  the  quadricei)s  extensor  whose  contraction  causes  the 
knee-jerk. 

If  now  the  animal  be  poisoned  by  a  small  dose  of  strychnine, 
stimulation  of  the  nerve  causes  no  longer  reflex  relaxation,  but  reflex 
contraction  of  the  muscle.  This  fact  indicates  that  the  essential 
action  of  strychnine  is  something  different  from  a  mere  reduction  of 
the  resistance  to  the  spread  of  impulses  in  the  cord  (Sherrington). 
Tetanus  toxin  produces  a  similar  effect,  though  more  slowly. 

The  reversal  of  the  depressor  reflex  on  the  blood-pressure  has  been 
previously  alluded  to  (p.  i88).  A  different  type  of  reversal,  and  one 
of  most  interest  in  connection  with  the  co-ordination  of  reflexes,  is 
illustrated  by  such  observations  as  the  following:  The  extensor 
thrust  is  only  obtained  by  the  adequate  form  of  stimulation  de- 
scribed on  p.  901,  when  the  hind-limb  is  in  a  condition  of  flexion. 
When  the  leg  is  passively  extended  at  the  time  when  the  stimulus  is 
applied,  the  response  is  not  the  extensor  thrust,  but  flexion  of  the 
leg  and  thigh  (direct  flexion  reflex).  The  passive  assumption  of  a 
condition  of  flexion  at  the  knee  and  thigh  appears,  accordingly,  to 
favour  the  extensor  reaction  (Sherrington).  The  observations  of 
Magnus  have  shown  that  such  relations  are  general;  for  example, 
the  reaction  is  usually  extension  when  the  opposite  posterior  limb 
is  flexed  at  the  time  of  stimulation,  and  flexion  when  the  opposite 
leg  is  extended.  In  the  spinal  cat,  stimulation  applied  to  the  tail, 
especially  near  the  root,  elicits  always  a  stroke  towards  the  side  on 
which  at  the  time  of  stimulation  the  muscles  are  extended.  The 
phenomenon  is  dependent  upon  the  integrity  of  the  afferent  nerves 
of  the  passively  extended  or  flexed  muscles  whose  position  influences 
the  reflex,  and  of  the  afferent  nerves  of  the  tendons  and  fascia  re- 
lated to  them.  The  condition  of  the  reflex  centres  is  in  some  way 
influenced  by  impulses  conducted  along  those  afferent  paths. 

Not  only  is  the  tone  of  the  extensors  diminished  or  abolished 
during  the  activity  of  the  flexors,  but  the  contraction  of  the  knee 
extensors  evolved  by  striking  the  patellar  tendon,  which  is  called 
the  knee-jerk,  either  fails  to  appear,  or  appears  but  feebly,  when  the 
flexion  reflex  is  simultaneously  elicited,  even  when  the  mechanical 
antagonism  of  the  flexor  contraction  has  been  eliminated  by  pre- 
viously detaching  the  flexors  from  the  knee. 

The  Knee-jerk. — This  is  sometimes  termed  a  pseudo-reflex.  For 
certain  authorities  believe  that  the  mechanism  by  which  it  is  pro- 
duced is  different  from  that  concerned  in  tlie  reflex  blinking  of  the 
eyelid,  or  the  reflex  retraction  of  the  testicle,  or  the  drawing-up  of 


FUNCTIOiWS  01-   THE  SPINAL  CORD  905 

the  foot  wiien  tlie  sole  is  tickled.  The  knee-jerk  is  obtained  in 
undiminished  strength  when  the  nerves  of  the  ligamentum  patellae 
have  been  divided.  It  is  therefore  not  a  reflex  movement  caused  by 
stimulation  of  afferent  nerves  coming  from  the  tendon,  and  the  name 
'  tendon-reflex  '  is  clearly  a  misnomer.  But  that  it  is  related  in  some 
way  or  other  to  afferent  impulses  is  certain,  for  division  of  the 
posterior  roots  that  enter  into  the  anterior  crural  nerve  abolishes 
the  knee-jerk.  The  phenomenon,  according  to  these  authors  who 
deny  that  it  is  a  true  reflex,  comes  under  the  head  of  what  is  called 
myotatic  irritabilit}' — that  is,  it  depends  on  mechanical  stimulation 
of  the  slightly-stretched  muscle  by  the  pull  of  the  tendon  when  it  is 
struck.  It  is  necessary  for  this  stimulation  that  the  muscle  should 
be  to  a  certain  extent  tonically  contracted.  So  that  when  the 
afferent  fibres  are  interrupted,  or  the  grey  matter  of  the  cord  dis- 
organized, and  the  reflex  tone  abolished,  the  knee-jerk  disappears. 
The  strongest  objection  to  considering  it  an  ordinary  reflex  is  the 
shortness  of  the  interval  which  elapses  between  the  tap  and  the  jerk, 
which,  according  to  some  observers,  is  not  much  greater  than  the 
latent  period  of  the  quadriceps  muscle  for  direct  electrical  stimula 
tion,  as  measured  under  the  ordinary  conditions  of  its  contraction. 
There  is  no  doubt  that  the  interval  is  very  brief,  although  somewhat 
conflicting  results  have  been  obtained  by  different  observers  for  the 
corrected  latency — that  is,  the  period  between  stimulus  and  response 
minus  the  latent  period  of  the  muscle.  In  man  this  period  seems 
to  be  about  002  second.  In  a  dog  with  divided  spinal  cord  the 
interval  was  found  to  be  0014  to  002  second  (Applegarth) ;  in  the 
rabbit  only  0008  to  0005  second  (Waller  and  Gotch).  Recent 
observations  in  which  the  electrical  response  of  the  muscle  as  re- 
corded by  the  string  galvanometer  was  employed  instead  of  the 
contraction  have  3aelded  results  not  very  different  from  those 
obtained  by  the  older  methods,  ooii  to  0-015  second  according  to 
Synder.  Taking  account  of  the  newer  observations  on  the  velocity 
of  the  nervous  impulse  (p.  793),  it  would  appear  that  the  interval  is 
not  really  too  short  to  prevent  the  knee-jerk  from  being  classified 
as  a  true  reflex  contraction,  although  a  very  brief  one.*  The  rein- 
forcement of  the  knee-jerk  is  referred  to  under  another  heading 
(p.  911).  It  is  admitted  that,  in  addition  to  the  direct  stimu- 
lation of  the  muscle  on  the  same  side,  the  tendon-tap  may  cause 
also  a  true  reflex  knee-jerk  on  the  opposite  side,  the  interval  between 
tap  and  contraction  being  about  ^  second. 

Spread  or  Irradiation  of  Reflex  Action. — As  the  strength  of  the 
stimulus  which  has  been  evoking  a  gi\en  reflex  movement  is  in- 
creased, the  reflex  effect  becomes  more  and  more  extensive,  spreading 
out  or  irradiating  in  various  directions.     If,  for  example,  the  reflex 

*  There  is  really  now  no  good  reason  for  regarding  the  knee-jerk  as  anj^hing 
else  than  a  true  reflex.  The  term  pseudo-reflex  and  other  terms  implj-ing 
that  the  knee-jerk  is  not  a  reflex  should  therefore  be  dropped. 


9o6  THE  CENTRAL  NERVOUS  SYSTEM 

in  question  is  tlie  flexion  reflex  elicited  by  stimulation  of  the  plantar 
surface  of  the  hind-foot  in  the  spinal  animal,  increase  of  the  stimulus 
will  cause,  in  addition  to  flexion  of  the  same  hind-foot,  extension  of 
the  opposite  hind-limb,  then  in  the  homonymous  fore-limb  {i.e.,  the 
limb  on  the  same  side)  extension  at  the  elbow  and  retraction  at  the 
shoulder,  then  certain  definite  movements,  the  details  of  which  need 
not  detain  us  here,  in  the  opposite  fore-limb,  and  ultimately  also 
definite  movements  of  the  head  and  tail  (Sherrington).  Obviously 
there  is  a  certain  orderliness  in  the  spread  of  the  reflexes;  they 
follow  a  certain  regular  march;  the  irradiation  in  the  tangle  of  the 
spinal  paths  is  not  an  indiscriminate  one.  The  same  fact  emerges 
quite  as  clearly  when  other  reflexes  are  studied  in  a  similar  way;  and 
certain  laws  or  rules  which  define  the  spread  of  the  impulses  in  spinal 
reflexes  have  been  deduced.  For  descriptive  purposes,  in  dealing 
with  reflex  action,  it  is  convenient  to  consider  each  lateral  half  of 
the  cord  as  divisible  into  regions  each  related  on  the  one  hand  to  a 
certain  area  of  the  receptive  surface  (skin),  and  on  the  other  to 
certain  muscles.  Such  regions  are  those  of  the  neck,  including  the 
pinna  (cervical),  the  fore-limb  (brachial),  the  trunk  (thoracic),  the 
hind-limb  (crural),  and  the  tail  (caudal).  According  to  their  rela- 
tion to  these  regions  the  spinal  reflexes  can  be  classified  as  '  short  ' 
or  '  long.'  The  short  spinal  reflexes  are  those  in  which  the  muscular 
response  takes  place  in  the  same  region  as  the  application  of  the 
stimulus.  The  long  reflexes  are  those  evoked  when  the  stimulus  is 
applied  to  the  receptive  field  of  one  region,  and  the  response  occurs 
in  the  musculature  of  another  region.  For  the  short  reflexes 
Sherrington  has  given  a  number  of  rules,  which  may  be  stated  as 
follows:  (i)  The  closer  together  their  spinal  segments,  the  easier  is 
it  for  stimulation  of  a  given  efferent  root  to  excite  reflex  contractions 
of  muscles  supplied  by  a  given  afferent  root.  (2)  For  each  afferent 
root  there  exists  in  its  own  spinal  segment  (of  course,  on  its  own  side 
of  the  cord)  a  reflex  motor  path  of  as  low  a  threshold  {i.e.,  as  easily 
set  into  action)  and  of  as  high  potency  {i.e.,  producing  as  great  a 
reflex  effect)  as  any  open  to  it  anywhere.  It  has  been  shown  that 
the  afferent  nerves  of  a  skeletal  muscle  are  derived  from  the  spinal 
ganglion  corresponding  to  the  segment  of  the  cord  containing  its 
motor  cells.  (3)  Motor  mechanisms  for  the  skeletal  musculature 
lying  in  the  same  region  of  the  cord,  and  in  the  selfsame  spinal 
segment,  show  markedly  unequal  accessibility  to  the  local  afferent 
channels  as  judged  by  the  reflex  contractions  produced.  For 
example,  the  reflex  contraction  of  the  flexors  of  the  knee  on  the 
stimulated  side,  and  of  the  extensors  of  the  opposite  knee,  is  in 
many  animals  much  more  easily  elicited  than  contraction  of  the 
extensors  of  the  homonymous  and  the  flexors  of  the  contralateral 
{i.e.,  opposite)  side.  This,  however,  is  not  because  the  last-named 
extensors  and  flexors  are  really  incapable  of  being  reflexly  affected 
through  the  afferent  fibres  of  the  corresponding  spinal  segments,  but 


FUNCTIONS  OF  THE  SPINAL  CORD  907 

because  the  reflex  effect  produced  by  them  is  in  tliis  case  not  con- 
traction, but  inhibition.  (4)  The  groups  of  motor  cells  contempor- 
aneously discharged  by  spinal  reflex  action  innervate  synergic 
muscles  (muscles  which  act  in  the  same  direction  in  effecting  a 
harmonious  movement),  and  not  antergic  muscles  (which  antagonize 
each  other). 

This  disproves  the  old  idea  that  the  movements,  caused  by  ex- 
citation of  an  efferent  spinal  root,  are  co-ordinated  synergic  move- 
ments, since  at  many  joints  the  flexors  and  extensors  both  receive 
motor  fibres  from  one  and  the  same  root,  and  stimulation  of  the 
root  must  simultaneously  excite  antagonistic  muscles.  '  The 
collection  of  fibres  in  a  motor  spinal  root  does  not  represent  a  reflex 
figure — i.e.,  a  number  of  simple  reflexes  occurring  simultaneously — 
nor  does  the  receptive  field  of  a  reflex  correspond  with  the  distribu- 
tion of  an  afferent  root.' 

(5)  It  follows  from  (i),  (2),  and  (4)  that  the  spinal  reflex  move- 
ment which  can  be  elicited  in  and  from  any  one  spinal  region  will 
exhibit  much  uniformity  even  when  the  exciting  stimulus  is  applied 
at  different  and  distant  points  within  the  receptive  field.  The 
flexion  reflex  of  the  hind-limb,  e.g.,  will  have  the  same  general  char- 
acter— i.e.,  flexion  of  each  of  the  three  main  joints — whatever  part 
of  the  surface  of  the  limb  is  stimulated.  Yet  the  flexion  movement 
will  be  strongest  at  the  joint  whose  flexors  are  innervated  by  motor 
cells  situated  in  a  spinal  segment  near  the  entrance  of  the  afferent 
fibres  from  the  stimulated  skin  area. 

For  the  long  spinal  reflexes  it  is  less  easy  to  deduce  definite  rules, 
for  they  can  be  less  easily  and  constantly  evoked  than  the  short 
reflexes.  The  so-called  laws  of  spread  formulated  by  Pfliiger  for 
the  long  spinal  reflexes,  and  based  mainly  on  observations  made 
in  the  brainless  frog  and  on  clinical  records  in  cases  of  spinal  lesion 
in  man,  need  not  be  stated  here.  For  Sherrington  has  shown  that 
they  require  serious  modification.  Especially  is  this  true  of  Pfliiger's 
fourth  law,  that  the  reflex  irradiation  spreads  always  more  easily 
up  in  the  direction  of  the  medulla  oblongata,  so  that  stimulation  of 
a  fore-limb  does  not  cause  reflex  contraction  of  a  hind-limb,  although 
excitation  of  a  hind-limb  may  cause  movement  of  one  or  both  fore- 
limbs.  This  law  does  not  hold  in  the  mammal.  As  a  rule,  indeed, 
irradiation  takes  place  more  easily  down  than  up  the  cord.  Excita- 
tion of  the  skin  of  the  pinna  easily  causes  reflex  movements  of  the 
limbs,  while  the  reverse  is  rare.  Reflex  movements  of  the  hind- 
limb  in  the  spinal  animal  are  more  easily  evoked  by  stimulation  of 
the  fore-limb  than  movements  of  the  fore-limb  by  stimulation  of 
the  hind.  It  is  easier  for  the  irradiation  to  cross  the  cord  from 
hind-limb  to  hind-limb  than  to  pass  up  from  hind-  to  fore-limb; 
but  it  is  often  easier  for  irradiation  to  occur  down  the  cord  from 
fore-  to  hind-Hmb  than  across  the  cord  from  one  fore-limb  to  the 
other.    Afferent  channels  from  the  skin  of  the  shoulder,  through 


9o8  THE  CENTRAL  NERVOUS  SYSTEM 

which  the  scratch-reflex  is  discharged  (in  the  dog),  are  freely  con- 
nected with  efferent  paths  to  the  muscles  of  the  hip,  knee,  and  ankle 
by  an  uncrossed  path  descending  the  lateral  column  (Sherrington). 
In  cats,  after  temporary  occlusion  of  the  cerebral  circulation,  which 
throws  the  brain  out  of  gear,  it  is  easy  to  elicit  movements  of  the 
hind-legs  by  pinching  the  fore-paws  or  the  skin  of  the  upper  part 
of  the  body.  The  scratch-reflex  can  also  be  very  readily  evoked, 
and  in  great  intensity,  by  stimulating  the  pinna,  and  is  not  confined 
to  the  side  stimulated.  In  anaemia  of  the  brain  and  (cervical)  cord 
and  subsequent  resuscitation,  homolateral  reflexes  {i.e.,  on  the 
same  side  as  the  stimulus)  are  submerged  later  and  emerge  sooner 
than  contralateral  refle.xes  whose  centres  lie  in  the  area  which  was 
rendered  ansemic  (Pike,  (iuthrie,  and  Stewart). 

Co-Ordination  of  Reflexes. — The  co-ordination  or  orderly  combina- 
tion of  muscular  actions  for  the  production  of  appropriate  and  har- 
monious movements  is  one  of  the  most  important  functions  of  the 
central  nervous  system.  Both  the  brain  and  the  cord  take  a  share 
in  this  co-ordination.  The  role  of  the  brain  \\'ill  be  considered  later 
on,  but  it  is  essential  to  recognize  now  that  many  of  the  movements 
which  the  brain  directs  represent  spinal  reflexes  already  synthesized, 
compounded,  or  co-ordinated  in  a  very  high  degree.  This  is  the 
reason  why,  in  the  spinal  animal,  the  inexperienced  observer  may 
sometimes  be  startled  by  the  apparently  '  purposive  character  '  of 
a  reflex  movement— the  scratch-reflex  in  the  dog  or  cat,  e.g.,  or  the 
extensive  reflex  movements  of  the  hind-legs  of  a  brainless  frog 
when  the  skin  is  pinched  or  painted  with  dilute  acid,  so  plainly 
directed  to  the  seat  of  irritation.  When  a  drop  of  acid  is  applied 
to  the  flank  of  such  a  frog,  it  will  attempt  to  wipe  it  off  with  the 
foot  which  is  situated  most  conveniently.  If  this  foot  be  held,  it 
will  use  the  other.  These  reactions  are  necessarily  purposive  in 
character,  since  they  have  been  evolved  with  reference  to  the  ad- 
vantage of  the  organism  as  a  whole.  They  are  the  sort  of  complex 
reactions  which  the  intact  animal  would  have  had  to  improvise 
by  the  combination  of  a  considerable  number  of  simple  movements 
when  it  was  executing  such  defensive  reactions,  with  the  conscious 
purpose  of  escaping  from  the  irritant,  w-ere  they  not  already  present 
as  purposive  reflexes  in  the  ready-made  condition. 

In  the  combining  of  reflexes  we  may  distinguish  between  simul- 
taneous combination — i.e.,  the  combination  of  reflex  actions  taking 
place  at  the  same  time — and  successive  combination — i.e.,  the 
combination  of  reflexes  in  such  a  way  that  they  follow  each  other 
in  an  orderly  sequence.  The  facts  already  mentioned  in  speaking 
of  irradiation  afford  a  partial  explanation  of  the  co-ordination  of 
reflexes  by  simultaneous  combination.  The  movements  are  orderly 
and  harmonious  because  the  spread  of  the  reflexes  is  not  indis- 
criminate, but  follows  a  definite  '  march,'  determined  partly  by  the 


FUNCTIONS  OP  THE  SPINAL  CORD  O09 

anatomical  relations  of  afferent  and  efferent  paths,  partly  by  the 
varying  resistance  of  the  synapses  or  other  structures  whose  proper- 
ties lix  the  threshold  value  of  the  excitation  by  which  an  arc  can  be 
forced.  In  general  it  is  not  enough  that  the  channel  of  the  final 
common  paths  (p.  899)  to  the  muscles  whose  contraction  produces 
the  reflex  movement  should  be  thus  open  to  the  afferent  arcs  that 
elicit  the  movement;  they  must  be  closed  to  other  afferent  arcs 
which  might  disturb  the  reflex.  Not  only  so:  there  is  evidence 
that  very  frequently  the  final  common  paths  are,  so  to  say,  more 
widely  opened  to  the  afferent  arcs  in  question  by  the  '  reinforcing  ' 
or  '  facilitating  '  influence  of  allied,  though  it  may  be  distant, 
afferent  arcs,  which  are  simultaneously  excited  (p.  911).  Further, 
the  final  common  paths  to  antagonistic  muscles  must  also  be 
temporarily  closed.  The  closing  of  these  central  connections,  or 
rather  the  raising  of  their  threshold  sufficiently  to  bar  the  impulses 
from  passing  through  the  door,  is  an  inhibitory  phenomenon.  Ex- 
citation of  the  desired  movements  and  inhibition  of  antagonistic 
movements  go  hand-in-hand  in  the  simultaneous  combination  of 
reflexes.  It  is  obvious  that  if  a  movement  is  to  be  efficiently  exe- 
cuted, it  cannot  be  the  result  of  a  compromise  between  competing 
reflexes.  A  segment  of  a  limb  can  be  either  flexed  or  extended,  but 
cannot  at  the  same  time  undergo  both  flexion  and  extension.  In 
the  interests  of  an  effective  movement,  one  or  the  other  must  give 
way  utterly.  The  reflex  which  eventually  prevails  makes  a  clear 
field  for  itself  by  inhibiting  all  other  reflexes  which  do  not  co-operate 
with  it.  For  example,  if  the  receptive  area  of  skin  from  which  the 
scratch  reflex  is  elicited  be  stimulated  and  a  painful  stimulation  be 
at  the  same  time  applied  to  the  foot,  we  do  not  obtain  a  mixed 
scratch  and  flexion  reflex,  which  would  result  in  a  confused  and 
ineffective  combination  of  movements,  but  a  pure  scratch  or  flexion 
reflex,  as  a  rule  the  latter. 

The  successive  combination  of  reflexes  is  well  illustrated  by  the 
contraction  of  the  oesophagus  in  deglutition.  First  one  portion  of 
the  tube  and  then  the  next  below  are  involved  in  the  reflex  action. 
The  combination  consists  in  the  orderly  sequence.  The  manner  in 
which  this  is  secured  in  this  class  of  reflex  action  has  been  lumin- 
ously discussed  by  Sherrington,*  but  details  cannot  be  given  here. 
While  only  aUied  reflexes — i.e.,  such  as  mutually  reinforce  and 
therefore  harmonize  with  each  other — can  be  simultaneously  com- 
bined, and  antagonistic  reflexes  cannot,  both  allied  and  antagonistic 
reflexes  can  be  successively  combined.  An  example  of  the  succes- 
sive combination  of  allied  reflexes  is  the  series  of  scratch  reflexes 
caused  by  a  parasite  travelling  across  the  receptive  field  of  the 
reflex.     An  example  of  the  successive  combination  of  antagonistic 

*  '  Integrative  Action  of  the  Nervous  System,'  to  which  work  the  advanced 
student  is  referred. 


/ 


910  THE  CENT.^AL  NERVOUS  SYSTEM 

reflexes  is  afforded  when  either  the  scratch  reflex  or  the  flexion 
reflex  is  induced  and  caused  to  interrupt  the  other  while  it  is  pro- 
ceeding. The  transition — e.g.,  from  flexion  to  scratch  reflex — is 
made  without  any  period  of  confusion.  Thus,  if  the  scratch  reflex 
has  been  induced  and  is  being  executed,  and  the  foot  is  then  pain- 
fully stimulated,  the  scratch  reflex  immediately  ceases,  and  the 
flexor  reflex  takes  its  place.  When  the  flexor  reflex  has  termin- 
ated, the  scratch  reflex  may  be  resumed.  The  same  holds  good  for 
other  antagonistic  reflexes.  In  many  cases  the  avoidance  of  con- 
fusion is  due  to  the  inhibition  of  the  first  reflex,  or  often  to  inhibition 
of  the  set  of  muscles  which  were  active  in  the  first  reflex  combined 
with  excitation  of  their  antagonists  (so-called  interference).  It  is 
obvious  that  this  is  an  adaptation  of  great  importance. 

Influence  of  the  Brain  on  the  Spinal  Reflexes. — The  spinal  reflexes 
can  be  influenced  by  impulses  descending  from  the  higher  centres. 
For  (a)  it  is  a  matter  of  common  experience  that  a  reflex  movement 
may  be  to  a  certain  extent  controlled,  or  prevented  altogether  by  an 
effort  of  the  will,  and  it  is  worthy  of  remark  that  only  movements 
which  can  be  voluntarily  produced  can  be  voluntarily  inhibited. 
(b)  Long-continued  muscular  contractions  may  be  caused  in  animals 
after  removal  of  the  cerebral  hemispheres  by  stimulation  of  afferent 
nerves — for  example,  by  scratching  the  mucous  membrane  of  the 
mouth  in  a  '  brainless  '  frog  or  Necturus.     (c)  By  stimulation  of 
certain  of  the  higher  centres  reflex  movements  which  would  other- 
wise be  elicited   may  be  suppressed  or  greatly  delayed.     If   the 
cerebral  hemispheres  are  removed  from  a  frog,  and  one  leg  of  the 
animal  dipped  into  dilute  acid,  a  certain  interval,  the  (uncorrected) 
reflex  time,  will  elapse  before  the  foot  is  drawn  up  (p.  996).     If, 
now,  a  crystal  of  common  salt  be  applied  to  the  optic  lobes,  or 
corpora  bigemina, or  the  upper  part  of  the  spinal  cord,  and  theexperi- 
ment  repeated,  it  will   be   found  either  that  the  interval  is  much 
lengthened  or  that  the  reflex  disappears  altogether.     Stimulation 
of  the  optic  lobes  relaxes  the  reflex  sexual  embrace  of  the  male  frog 
when  it  is  present.     From  such  experiments  it  has  been  concluded 
that  centres  which  can  inhibit  the  spinal  reflexes  are  situated  in  the 
thalamus,  the  corpora  bigemina  and  the  medulla  oblongata  of  the 
frog.     In   mammals,   also,   there  is  evidence  of  the  existence   of 
mechanisms  in  the  brain,  the  excitation  of  which  diminishes  the 
reflex  excitability  of  the  cord.     For  example,  stimulation  of  the 
frontal  convolutions  in  the  dog  causes  a  diminution  in  the  height 
of  reflex  contractions   of  the  limbs.      Strong   stimulation   of  an 
afferent  nerve    may  abolish  or  delay  a  reflex  movement  which  is 
being    elicited    through    other   receptors,     (d)  If   such    inhibitory 
mechanisms  exist,  it  is  to  be  supposed  that  elimination  of  the  brain 
will  render  it  easier  to  elicit  reflexes  from  the  cord.     Experiment 
shows  that  this  is  actually  the  case.     An  animal  like  a  frog  responds 


t-UNCTIONS  Of  THE  SPINAL  CORD  gii 

to  stimuli  by  retlcx  movements  more  readily  after  the  medulla 
oblongata  has  been  divided  from  the  spinal  cord  or  the  brain  re- 
moved. In  the  dog  the  scratch  reflex  is  elicited  more  easily  after 
removal  of  the  cerebral  cortex  or  its  elimination  by  cerebral 
anaemia.  In  the  guinea-pig,  after  extirpation  of  the  cortex  of  one 
hemisphere,  the  scratch  reflex  is  more  readily  evoked  on  the  side 
of  the  lesion  (Brown). 

That  the  brain  exerts  more  than  a  merely  inhibitory  influence  on 
the  production  of  reflex  movements  is  suggested  by  many  facts. 
The  knee-jerk,  for  example,  is  increased  or  '  reinforced  '  if  an  instant 
before  the  tendon  is  struck  the  patient  makes  a  voluntary  movement 
or  is  acted  on  by  a  sensory  stimulus  (Bowditch  and  Warren).     In 
health  it  varies  in  strength  with  many  circumstances  which  affect 
the  activity  of  the  central  nervous  system  as  a  whole  (Lombard, 
etc.).     It  often  disppears  in  pathological  lesions,  situated  high  up 
in  the  cord  in  man,  and  is  markedly  impaired  after  high  section  of 
the  cord  in  dogs.     In  hemiplegia  (paralysis  of  one  side  of  the  body, 
caused  by  disease  in  the  brain)  the  cutaneous  reflexes  on  the  para- 
lyzed side  may  sometimes  be  absent  for  years.     Some  observers 
have  even  gone  so  far  as  to  say  that  under  normal  conditions  the 
so-called  spinal  reflexes  are  really  cerebral — in  other  words,  that 
the  afferent  impulses  run  up  to  the  brain  and  there  discharge  efferent 
impulses,  which  pass  down  to  the  motor  cells  of  the  anterior  horn 
and  cause  their  discharge.     It  may  be  admitted  that  there  is  no 
physiological  ground  for  supposing  that  the  afferent  impulses  which 
have  to  do  with  the  reflex  contraction  of  the  muscles  of  the  leg 
when  the  sole  is  tickled,  stop  short  at  the  motor  cells  of  those  spinal 
segments  from  which  the  efferent  nerves  come  off,  while  the  af* 
ferent  impulses  which  have  to  do  with  the  sensation  of  tickling  pass 
up  to  the  brain.     The  probability  is  that  under  ordinary  circum- 
stances such  afferent  impulses  pass  up  the  cord  in  long  afferent 
paths,  as  well  as  directly  towards  the  motor  cells  along  those  fibres 
of  the  posterior  roots  and  their  collaterals  which  bend  forward  into 
the  anterior  horn  at  the  level  of  their  entrance  into  the  cord.     And 
the  only  question  is  whether,  as  a  matter  of  fact,  the  spinal  motor 
cells  are  most  easily  discharged  by  the  impulses  that  reach  them 
directly,  or  by  the  impulses  that  come  do\yn  to  them  by  the  round- 
about way  of  the  brain,  and  the  efferent  fibres  that  connect  it  with 
the  cord.     It  is  evident  that  the  answer  to  this  question  need  not 
be  the  same  for  all  kinds  of  animals.     It  may  well  be  that  in  the 
higher  animals,  in  which  the  cortex  has  undergone  a  relatively  great 
development,  the  spinal  motor  mechanisms  are  more  easily  dis- 
charged from  above  than  from  below,  while  in   lower  animals  the 
opposite  may  be  the  case.    When  the  cord  is  cut  off  from  the  brain 
the  afferent  impulses  may  overflow  more  easily  into  the  spinal  motor 
cells  since  their  alternative  path  is  blocked.      In  the  frog,  where 


512  THE  CENTRAL  NERVOUS  SYSTEM 

there  is  already  a  beaten  track  between  the  posterior  root-fibrea 
and  the  cells  of  the  anterior  horn,  this  overflow  may  be  established 
immediately  after  section  of  the  cord,  and  may  of  itself  lead  to  an 
exaggeration  of  the  reflexes.  In  animals  like  the  dog  a  longer  time 
may  be  necessary  before  the  unaccustomed  route  from  the  end 
arborizations  of  the  afferent  axons  and  their  collaterals  to  the 
dendrites  or  the  bodies  of  the  motor  cells  becomes  natural  and  easy; 
in  man  a  still  longer  interval  may  be  required.  Moore  and  Oertel 
have  made  a  careful  comparative  study  of  reflex  action  after  com- 
plete section  of  the  cord  in  the  cervical  or  upper  dorsal  region,  and 
conclude  that  the  spinal  reflexes  in  the  higher  animals  are  far  more 
dependent  on  the  upper  portions  of  the  central  nervous  system  than 
in  the  frog. 

Spinal  Shock. — The  phenomena  of  spinal  shock  and  its  varying 
severity  in  different  animals  may  be  accounted  for  by  the  rupture  of 
the  paths  normally  used  in  the  reflexes.  The  theory  that  the  shock  is 
due  to  an  inhibition  set  up  by  the  mechanical  injury  is  untenable.  For 
shock  affects  only  the  portion  of  the  central  nervous  system  distal  (or 
aboral)  to  the  lesion.  Wlien  a  dog  is  allowed  to  live  after  transection 
of  the  cord  in  the  lower  cervical  region  till  shock  has  been  recovered 
from,  a  second  transection  distal  to  the  first  is  followed  by  only  slight 
and  very  transient  depression  of  the  reflex  power,  although  the  direct 
effect  of  the  second  injury  ought,  of  course,  to  be  as  great  as  that  of  the 
first.  Finally,  according  to  Sherrington,  the  condition  of  the  spinal 
reflex  arcs  in  shock  diflers  from  the  condition  caused  by  inhibition,  and 
resembles  rather  a  general  spinal  fatigue  in  which  conduction  along  the 
arc  and  especially  across  the  synapses  is  difficult  and  uncertain.  This 
condition  is  supposed  to  be  due  to  the  loss  of  a  '  tonic  '  influence  of 
higher  centres,  assumed  to  be  necessary  for  the  maintenance  of  the 
normal  conductivity  of  the  arc.  These  cranial  centres,  if  they  exist,  or, 
at  least,  the  most  efficient  of  them,  must  be  assumed  to  be  situated 
distal  to  the  cerebral  cortex,  probably  in  the  pons  or  mid-brain.  For 
section  just  behind  the  pons  causes  much  more  severe  shock  than 
removal  of  the  cerebral  hemispheres. 

Peripheral  Reflex  Centres. — The  question  whether  any  reflex  centres 
exist  outside  cf  the  spinal  cord  and  brain,  and  especially  in  the  sympa- 
thetic ganglia,  has  been  the  subject  of  a  lengthy  controversy.  That 
the  spinal  ganglia  cannot  act  as  reflex  centres  is  generally  acknowledged, 
and  it  is  not  difficult  to  see  that,  for  anatomical  reasons,  this  must  be  so. 
A  reflex  arc  must,  so  far  as  we  know,  in  all  highly-organized  animals 
include  at  least  two  neurons.  There  is  no  proof  that  an  afferent 
impulse  can  ascend  an  axon  to  a  cell-body  and  there  excite  an  efferent 
impulse,  which,  descending  the  same  axon  in  a  separate  set  of  fibrils, 
gives  rise  to  a  reflex  contraction,  or  a  reflex  secretion.  Now,  the  cells 
of  a  spinal  gangUon  represent  the  original  neuroblasts  from  which  the 
posterior  root-fibres  grew  out  as  processes  towards  the  cord  on  the  one 
side  and  the  periphery  on  the  other.  A  sensory  fibre  passing  into  the 
ganglion  makes  connection  with  a  cell  by  a  T-shaped  junction  and 
passes  on  its  course  again.  No  afferent  fibres  run  from  tlie  nerve-trunk 
into  the  ganglion,  to  end  in  arborizations  around  the  ganglion  cells, 
and  no  efferent  fibres  arise  from  ncrvc-cells  in  the  ganglion  to  pass  out 
into  the  trunk.  For  although  a  shghtly  greater  number  of  mcduUatcd 
fibres  of  small  calibre  is  found  in  a  spinal  nerve-trunk  immediately 


FUNCTIONS  OF  THE  SPINAL  CORD  yij 

distal  to  the  junction  of  the  roots  than  in  both  roots  taken  together,  this 
appears  to  be  due  to  tlie  passago  into  tlic  nerve  (from  tlie  grey  ramus 
communicans)  of  mcdullated  fibres  which  end  in  the  bloodvessels  or 
other  tissue  of  the  ganglion  (Dale).  Here  it  is  evident  that  there  is  no 
possibility  of  a  complete  reflex  arc.  Indeed,  it  is  not  certain  that  the 
normal  afferent  impulses  pass  through  the  bodies  of  the  spinal  ganglion 
cells  at  all.  For  (i)  a  negative  variation  can  be  observed  in  the  j)osterior 
roots  above  the  ganglia  on  stimulation  of  the  trunk  of  a  fr  g's  sciatic 
nerve  more  than  two  days  after  the  death  of  the  animal,  when  the 
ganglion  cells  may  be  supposed  to  have  completely  lost  their  vitality. 
and  when  no  reflex  negative  variation  can  be  detected  in  the  central 
stump  of  a  severed  anterior  root  on  excitation  of  the  sciatic  or  the 
corresponding  posterior  root.  Such  a  reflex  action  current  is  normally 
obtainable  from  a  fresh  preparation.  (2)  When  the  blood-supply  of  the 
posterior  root-fibres  and  the  ganglion  is  cut  off  without  killing  the  frog, 
the  nerve  impulse  is  still  conducted  by  the  fibres,  as  is  shown  by  the 
reflex  movements  elicited  on  stimulation  of  the  central  end  of  the  sciatic, 
at  a  time  when  the  nerve-cells  show  marked  histological  alterations. 

(3)  Prolonged  excitation  of  the  posterior  roots  or  the  mixed  nerve  causes 
no  noticeable  microscopical  changes  in  the  ganglion  cells  (Stcinach).* 

(4)  The  application  of  nicotine  to  a  spinal  ganglion  does  not  hinder  the 
passage  of  impulses  through  the  corresponding  afferent  fibres.  If  it 
acts  on  spinal  ganglion  cells  as  it  does  on  sympathetic  ganglion  cells 
(p.  182),  this  must  be  because  the  impulses  do  not  require  to  traverse 
the  ganglion. 

Axon-Reflexes. — In  the  ordinary  sympathetic  ganglia, f  also,  it  is 
doubtful  whether  the  anatomical  foundation  for  a  reflex  arc  exists,  and 
the  most  careful  physiological  experiments  have  failed  to  connect  them 
with  any  reflex  function.  Sokownin,  indeed,  observed  that  stimulation 
of  the  central  end  of  the  hypogastric  nerve  caused  contractions  of  the 
bladder,  and  he  considered  these  movements  to  be  reflex,  the  centre 
being  the  inferior  mesenteric  ganglion.  Langley  and  Anderson  have 
also  found  that  when  all  the  nervous  connections  of  the  inferior 
mesenteric  ganglion,  except  the  hypogastric  nerves,  are  cut,  stimulation 
of  the  central  end  of  one  hypogastric  causes  contraction  of  the  bladder, 
the  efferent  path  being  the  other  hypogastric.  In  addition,  they  have 
observed  an  apparent  reflex  excitation  of  the  nerves  which  supply  the 
erector  muscles  of  the  hairs  (pilo-motor  nerves)  through  other  sympa- 
thetic ganglia.  They  believe,  however,  that  in  neither  case  is  the  action 
truly  reflex,  but  that  it  is  caused  by  stimulation  of  the  central  ends  of 
motor  fibres,  which  come  off  from  the  spinal  cord,  and  in  passing  through 
the  ganglion  give  off  collateral  branches  to  some  of  its  cells.  In  the 
case  of  the  inferior  mesenteric  ganglion  the  spinal  fibres  passing  down 
in  the  left  hypogastric  would  send  branches  to  arborize  around  ganglion 
cells  which  give  origin  to  fibres  of  the  right  hypogastric,  and  vice  versa. 
When  the  central  end  of  the  left  hypogastric  is  stimulated  the  excitation 
is  conducted  up  the  spinal  fibres,  and  so  reaches  their  branches,  and, 
through  the  ganglion  cells,  the  sympathetic  fibres  of  the  right  hypogastric, 
which  convey  it  to  the  muscles  of  the  bladder  (see  sartorius  or  gracilis  ex- 
periment of  Kiihne,  p.  792) .    Other  examples  of  such  axon-reflexes  exist. 

*  Hodge  obtained  changes.  In  such  experiments  it  is  necessary  that  thf 
ganglion  should  not  be  directly  excited  by  electrotonic  currents  or  escape  of 
the  stimulating  current. 

t  The  ganglion  cells  of  Auerbach's  and  Meissner's  plexus  in  the  intestine 
are  not  of  ordinary  sympathetic  type,  and,  as  has  been  previously  pointed 
out,  it  is  probable  that  they,  or  some  of  them,  are  true  reflex  centres  for  the 
stomach  and  intestines. 

58 


914  THE  CESTRAL  NERVOUS  SYSTEM 

Reflex  Time. — W'lien  a  reflex  movement  is  evoked,  a  measurable 
period  ela})ses  between  the  application  of  the  stimulus  and  the 
commencement  of  the  movement.  This  inter\'al  may  be  called  the 
uncorrected  reflex  time  or  the  latent  period  of  the  reflex.  A  part  of 
the  interval  is  taken  up  in  the  transmission  of  the  afferent  impulse 
to  the  reflex  centre,  a  part  in  the  transmission  of  the  efferent  impulse 
to  the  muscles,  a  part  represents  the  latent  period  of  muscular 
contraction,  and  the  remainder  is  the  time  spent  in  the  centre,  or 
the  true  reflex  time.  Ordinarily  this  time,  though  absolutely  short, 
is  relatively  so  great  that  the  total  latent  period  of  a  reflex  is  much 
longer  than  when  a  similar  length  of  nerve-trunk  is  interposed  be- 
tween the  point  of  application  of  the  stimulus  and  the  muscle. 
When  the  conjunctiva  or  eyelid  is  stimulated  on  one  side  both  eye- 
lids  blink.  This  is  a  typical  reflex  action  reduced  to  its  simplest 
expression,  and  the  true  reflex  time  is  correspondingly  short — only 
about  ^\j  second  (50  <r*).  An  additional  yj^  second  (10  a)  is  con- 
sumed in  the  passage  of  the  afferent  impulse  along  the  fifth  ner\'e 
to  the  medulla  oblongata,  of  the  efferent  impulse  from  the  medulla 
to  the  orbicularis  palpebrarum  along  the  seventh  nerve,  and  in  the 
latent  period  of  the  muscle.  \\'hen  a  naked  ner\'e,  like  the  sciatic, 
is  stimulated,  the  true  reflex  time  is  reduced  to  j^  to  -^  second.  As 
estimated  by  Tiirck's  method  (p.  996),  the  uncorrected  reflex  time 
is  greatly  lengthened,  it  ma}-  be  to  several,  or  even  many,  seconds. 
For  here  it  is  evident  that  the  time  taken  by  the  acid  to  soak 
through  the  skin  and  reach  the  nen'e-endings  in  strength  sufficient 
to  stimulate  them  is  included.  But  even  when  the  peripheral 
factors  remain  constant,  the  central  factor  may  var\'.  With  strong 
stimulation,  eg.,  the  reflex  time  is  shorter  than  with  weak  stimula- 
tion. With  weak  stimuli  the  latent  period  of  the  flexion  reflex  in 
the  dog  is  usually  60  cr  or  120  a--  It  may  even  be  as  long  as  200  a. 
With  strong  stimuli  it  may  be  as  little  as  30  a-  Even  22  a  has  been 
seen,  which  is  little  more  than  for  ner\^e-trunk  conduction.  Fatigue 
of  the  nerve-centres  delays  the  passage  of  impulses  through  them; 
and  strychnine,  while  it  increases  the  excitability  of  the  cord,  also 
lengthens  the  reflex  time. 

Reflexes  in  Disease. — In  order  that  a  reflex  action  may  take  place, 
the  reflex  arc— afferent  nerve,  central  mechanism,  and  efferent  nerve — 
must  be  complete;  and,  in  fact,  a  whole  series  of  simple  reflex  move- 
ments exists,  the  suppression,  diminution,  or  exaggeration  of  which 
can  be  used  in  diagnosis  as  tests  of  the  condition  of  the  reflex  arc.  It 
is  customary  to  divide  these  into  superficial  reflexes,  elicited  from 
receptive  fields  on  the  surface  of  the  body  [extero-ceptive  fields),  and  deep 
reflexes,  elicited  from  receptors  in  the  depth  of  the  organism  (proprio- 
ceptive fields),  especially  in  the  muscles  and  the  tendons  and  joints  con- 
nected with  them.  The  extero-ceptive  reflexes  are  normally  excited 
by  extraneous  stimuli  acting  on  the  surface  from  the  environment. 
Ihe  proprio-ceptive  reflexes  arc  normally  excited  by  changes  (muscular 

•  <r  =  oooi  second. 


FUNCTIONS  OF  THE  SPINAL  CORD 


915 


contractions)  occurring  in  the  body  itself,  which  changes  arc  in  turn 
i.sually  initiated  by  excitation  of  surface  receptors  by  the  environment. 
Examples  of  superficial  reflexes  are  the  plantar  reflex  (the  dra\ving-up 
of  the  foot  when  the  sole  is  tickled),  the  cremasteric  reflex  (retraction  of 
the  testicle  when  the  skin  on  tlic  inside  of  the  thigh  just  below  Poupart's 
ligament  is  stroked,  especially  in  boys),  the  gluteal,  abdominal ,  epigastric, 
and  interscapular  reflexes  (contraction  of  the  muscles  in  those  regions 
when  the  skin  covering  them  is  tickled).  The  behaviour  of  the  toes, 
especially  of  the  great  toe,  is  of  considerable  diagnostic  importance. 
Normally,  on  tickling  the  sole,  the  toes 
are  flexed  towards  the  planta ;  but 
when  a  lesion  of  the  pyramidal  tract 
exists,  as  in  hemiplegia,  there  is  dorsal 
instead  of  plantar  flexion,  most  marked 
in  the  case  of  the  great,  toe,  and  the 
toe  moves  more  slowly  than  in  the 
healthy  person  (Babinski'ssign).  This 
is  an  instance  of  reversal  of  a  reflex 
owing  to  the  elimination  of  the  in- 
fluence of  the  cortex.  In  an  epileptic 
fit  there  is  said  to  be  a  temporary 
reversal  of  the  same  reflex,  indicating 
probably  that  the  cortex  is  temporarily 
eliminated  in  consequence  of  fatigue 
due  to  intense  and  prolonged  discharge. 
In  children  during  the  first  few  months 
of  life  stimulation  of  the  sole  causes 
normally  a  dorsal  flexion  of  the  big  toe, 
this  reversal  of  the  normal  reaction  of 
the  adult  persisting  until  the  pyra- 
midal path  has  attained  functional 
completion  (p.  848).  During  sleep 
the  reversed  reaction  (dorsal  flexion) 
is  still  obtained  for  a  time.  Examples 
of  deep  reflexes  are  the  knee-jerk  (a 
sudden  extension  of  the  leg  by  the 
rectus  femoris  and  vastus  medialis 
components  of  the  quadriceps  muscle 
when  the  ligaraentum  patellae  is  sharply 
struck),  the  heel-jerk  or  foot-jerk  (a 
movement  of  the  foot  caused  in  most 
healthy  persons,  though  not  in  all,  by 
tapping  the  tendo  Achillis),  and  the 
periosteal  radial  reflex  (a  movement 
of  flexion  and  slight  pronation  of  the 
forearm  and  hand  elicited  by  tapping 
the  lower  end  of  the  radius).  The 
jaw-jerk  (a  movement  of  the  lower  jaw  when,  with  the  mouth  open, 
the  chin  is  smartly  tapped)  and  ankle-clonus  (a  series  of  spasmodic 
movements  of  the  foot,  brought  about  by  flexing  it  shar])ly  on  the  leg) 
are  phenomena  of  the  same  class,  which  can  be  elicited  only  in 
disease.  Any  condition  which  impairs  the  conducting  power  of  the 
afferent  or  efferent  fibres  of  the  reflex  are  necessarily  diminishes  or 
abolishes  the  reflex  movement,  even  if  the  central  connections  are 
intact.  E.g.,  in  locomotor  ataxia  the  disappearance  of  the  knee-jerk 
is  one  of  the  most  important  diagnostic  signs.  This  disease  involves 
the   posterior  roots  and  the  fibres  that  continue  them  in  the  posterior 


'rttersea/tu/ur 


Epicfastric 


.^hdcmittnl 


kneg-jerh 

AnkU-Clonui 
Plantar- 


Fig.  366. — Diagram  of  Refle.K  Centres 
in  Cord  (after  Hill). 


[2  Cremaster 


5i6  THF  CFNTRAL  NERVOUS  SYSTEM 

column.  The  anterior  nerve-roots  are  perfectly  healthy.  The  grey 
matter  of  the  cord — at  least,  in  the  earlier  stages  of  the  disease 
—is  unaffected.  The  weak  link  in  the  chain  is  the  afferent  path. 
Where  the  presence  of  the  knee-jerk  is  doubtful,  it  is  necessary  to  search 
for  the  most  favourable  position  of  the  limb  for  eliciting  it  before  deter- 
mining that  it  is  absent.  The  patient  may  be  made  to  clasp  his  hands 
tightly  at  the  moment  of  the  tap  to  reinforce  the  jerk  (p.  gii).  In 
anterior  poliomyelitis  (p.  876)  the  afferent  link  is  intact,  but  the  other 
two  are  broken,  and  the  reflexes  also  disappear.  Certain  lesions  which 
partially  cut  off  the  spinal  cord  from  the  higher  centres  without  affecting 
the  integrity  of  the  spinal  reflex  arcs  increase  the  strength  of  reflex 
movements  and  the  facility  with  which  they  are  called  forth.  In 
primary  spastic  paraplegia  (a  paralysis  of  the  legs  and  the  lower  portion 
of  the  body),  which  is  associated  with  degenerative  changes  in  the  lateral 
columns,  the  deep  reflexes  are  all  exaggerated.  But  according  to  the 
best  authorities,  a  lesion  amounting  to  total  transection  of  the  cord  in 
man  abolishes  all  reflexes  below  the  lesion.  In  the  monkey  the  knee- 
jerk  may  be  tried  for  in  vain  for  weeks  after  section  of  the  cord  in  the 
middle  of  the  thoracic  region,  whereas  in  the  rabbit  it  can  be  obtained 
ten  to  fifteen  minutes  after  the  transection.  The  position  of  the  centres 
in  the  cord  for  the  various  reflex  movements  is  shown  in  Fig.  366. 

3.  The  Origination  of  Impulses  in  the  Spinal  Cord  (Automatism). — 
An  action  known  to  be  caused  or  conditioned  by  afferent  impulses 
is  called  a  reflex  action.  There  is  some  evidence  that  the  reflex 
centres  are  continually  in  a  state  of  activity,  and  are  not  simply 
roused  to  activity  by  the  arrival  of  the  afferent  impulses,  which 
discharge  the  reflex.  Their  condition,  when  not  discharging,  seems 
to  represent  a  state  of  balance  between  excitatory  and  inhibitory 
influences,  a  so-called  '  innervation  equilibrium,'  which  can  be  up- 
set in  one  direction  or  the  other,  according  to  the  intensity  of  the 
antagonistic  influences.  A  ph\^siological  action  is  termed  auto- 
matic when  it  depends  upon  a  nervous  outflow  which  seems  to  be 
spontaneous,  in  the  sense  that  it  is  not  brought  about  by  any  evi- 
dent reflex  mechanism,  or,  in  other  words,  is  not  discharged  by 
afferent  impulses  falling  into  the  centre  where  it  arises,  although  it 
may  be  determined  by  substances  in  the  blood.  Automatic  actions 
being  thus  defined  in  a  negative  manner  by  the  defect  of  a  quality, 
there  is  always  a  possibility  that  some  day  or  other  it  may  be  de- 
monstrated that  any  given  action  which  at  present  seems  automatic 
in  its  origin  depends  on  afferent  impulses  hitherto  unnoticed.  As 
a  matter  of  fact,  the  supposed  proofs  of  spinal  automatism  have  in 
more  than  one  case  vanished  with  the  advance  of  knowledge,  and  as 
the  domain  of  purely  automatic  action  has  been  narrowed,  that  of 
reflex  action  has  extended,  until  the  controversy  as  to  the  boun- 
daries between  the  two  seems  not  unlikely  to  be  ended  by  the  ab- 
sorption of  the  automatic  in  the  reflex.  And  as  we  seem  almost 
driven  to  conclude  that  from  the  anatomical  standpoint  the  ner\'ous 
system  is  essentially  a  vast  collection  of  looped  conducting  paths, 
each  with  an  afferent  portion,  an  efferent  portion,  and  connections 
between  them  formed  by  the  end  arborizations  of  the  axons  and 


FUNCTrONS  OF  THE  SPINAL  CORD  917 

tlicii"  collattiiils,  till'  dendrites  and  the  cell-bodies,  so  it  may  be 
that  no  strict  physiological  automatism  really  exists  either  in  cord 
or  brain,  that  every  form  of  physiological  activity — muscular  move- 
ment, secretion,  intellectual  labour,  consciousness  itself — would 
cease  if  all  afferent  impulses  were  cut  off  from  the  nervous  centres. 
Assuredly  no  neuron  is  entirely  isolated  from  other  neurons.  The 
more  the  nervous  system  is  investigated,  the  deeper  grows  the  con- 
viction of  its  essential  solidarity,  the  more  clearly  it  displays  itself 
as  a  single  mechanism,  the  most  distant  parts  of  which  are  intricately 
knit  together.  But  there  are  certain  groups  of  actions  so  widely 
separated  from  the  most  typical  reflex  actions  that,  provisionally 
at  least,  they  may  be  distinguished  as  automatic.  Such  are  the 
voluntary  movements,  and  certain  involuntary  movements,  like 
the  beat  of  the  heart.  And  we  may  proceed  to  inquire  whether  the 
spinal  cord  has  any  power  of  originating  movements  or  other  actions 
of  this  high  degree  of  automatism. 

Muscular  Tone  or  Tonus — Postural  Reflexes. — It  is  generally 
stated  that  so  long  as  a  muscle  is  connected  with  the  spinal  segment 
from  which  its  nerves  arise,  it  is  never  completely  relaxed ;  its  fibres 
are  in  a  condition  of  slight  tonic  contraction,  and  retract  when  cut. 
This  tonus  has  been  clearly  demonstrated  for  some  muscles,  though 
not  for  all.  If  a  frog  whose  brain  has  been  destroyed  is  suspended 
so  that  the  legs  hang  down,  and  one  sciatic  neive  is  cut,  the  corre- 
sponding limb  may  be  observed  to  elongate  a  little  as  compared 
with  the  other,  owing  to  a  slight  relaxation  of  the  flexors.  At  one 
time  this  tone  of  the  muscles  was  supposed  to  be  due  to  the  continual 
automatic  discharge  of  feeble  impulses  from  the  grey  matter  of  the 
cord  along  the  motor  nerves.  But  it  has  been  proved  that  if  the 
posterior  roots  of  the  limb  be  cut,  its  tone  is  completely  lost,  although 
the  anterior  roots  are  intact.  So  that  the  tone  of  the  skeletal 
muscles  in  this  classical  experiment  depends  on  the  passage  of 
afferent  impulses  to  the  cord,  and  must  be  removed  from  the  group 
of  automatic  actions  and  included  in  the  reflexes.  The  subject  is 
considered  here  and  not  with  the  ordinary  reflexes,  partly  to  em- 
phasize by  a  notable  example  the  gradual  abridgement  of  the  sup- 
posed automatic  ftmctions  of  the  cord,  which  has  been  already 
referred  to,  but  partly  because  these  reflexes  have  certain  peculiari- 
ties which  distinguish  them  from  the  reflexes  manifested  by  move- 
ments. It  has  since  been  shown  that  this  reflex  tonus  of  skeletal 
muscle  is  a  postural  reflex — i.e.,  a  reflex  contraction  of  muscles  asso- 
ciated with  the  maintenance  of  the  posture  of  a  part  or  of  the  animal 
as  a  whole.  It  can  be  readily  demonstrated  in  the  decerebrate 
mammal  that  the  tonus  of  the  extensor  muscles  of  the  limbs  is  a 
reflex  sustained  through  the  afferent  fibres  of  the  muscles  themselves, 
including  those  from  the  tendons  and  the  neighbouring  joints  (the 
proprioceptive  system)  and  not  througli  the  cutaneous  nerves.     It 


yl8  TMK  CENTRAL  XERVOUS  SVSTliM 

is  obviously  in  accord  witJi  the  interpretation  ol  the  tonus  as  a 
postural  reflex  that  in  the  mammal  the  extensor  limb  muscles  should 
exhibit  the  phenomenon  and  the  flexors  not,  while  in  the  frog  it  is 
the  reverse.  For  it  is  the  extensors  which  are  concerned  in  the  re- 
flex standing  posture  so  characteristic  of  the  mammal,  while  the 
flexors  of  the  iiind  limbs  are  especially  concerned  in  the  squatting 
posture  so  characteristic  of  the  frog. 

The  postural  reflexes  differ  in  no  essential  way  from  the  reflexes 
previously  studied,  except  that  they  are  directed  to  the  maintenance 
of  posture  and  not  to  the  production  of  movement.  Reflex  postural 
tonus  has  cilso  been  demonstrated  for  other  groups  of  skeletal  muscles, 
of  which  the  most  important  are  the  neck  muscles  concerned  in  the 
position  of  the  head.  The  reflexes  in  this  instance  originate  not  only 
through  the  afferent  fibres  of  the  muscles  themselves,  but  also  from  the 
otic  labyrinth,  in  discussing  the  functions  of  which  the  subject  must  be 
returned  to.  But  it  may  still  be  mentioned  here,  and  it  shows  how 
intricate  is  the  correlation  of  the  postural  reflexes  to  one  another, 
that  not  only  docs  the  labyrinth  influence  the  postural  contraction  of 
the  extensors  of  the  limbs  directly — i.e.,  through  afferent  fibres  from 
the  labyrinth  itself,  but  also  indirectly  through  the  changes  produced 
in  the  posture  of  the  head  and  neck — i.e.,  through  the  afferent  fibres 
of  the  neck  muscles  (Magnus  and  de  Kleijn).  Even  when  the  head  of 
a  normal  rabbit  is  passively  moved  so  that  its  position  relatively  to  the 
body  is  altered,  the  postural  tonus  of  the  muscles  of  the  extremities 
and  even  of  some  of  the  muscles  of  the  trunk,  especially  those  connected 
with  the  lumbar  vertebrae,  is  definitely  affected. 

A  remarkable  property  of  a  muscle  which  exhibits  postural  reflex 
tonus  is  that  its  tension  remains  approximately  unaltered,  even  when 
its  length  is  greatly  changed  by  placing  the  joint  on  which  it  acts  in 
different  postures.  Within  a  wide  range  it  is  able  to  counterbalance 
just  the  same  extending  force  whatever  the  length  of  the  active  muscle 
may  be  (Practical  Exercises,  p.  looo).  This  property  is  dependent  upon 
the  integrity  of  the  reflex  arcs.  A  muscle  which  is  not  under  the 
influence  of  its  nerve  centre  reveals  no  trace  of  this  pecidiarity,  which, 
however,  is  possessed  by  the  smooth  muscle  of  viscera — e.g.,  the  urinary 
bladder  and  the  stomach.  It  has  been  shown  that  these  hollow  organs 
can  hold  very  different  quantities  of  liquid  without  any  great  change 
of  tension.  With  a  larger  volume  of  contents,  indeed,  the  tension 
may  be  even  less  than  with  a  smaller  volume.  It  is  oljvious  that  this 
property  must  play  an  important  part  in  regulating  the  pressure 
within  such  viscera,  so  that  in  the  case  of  the  bladder  —<?./;'.,  the  pres- 
sure may  not  rise  prematurely  to  the  point  at  which  the  desire  to 
micturate  is  aroused.  The  adjustment  of  the  tonus  of  these  smooth 
muscles  docs  not  depend  altogether  upon  the  central  nervous  system,  for 
it  is  still  exhibited,  although  not  so  amply,  by  the  excised  living  stomach. 

Other  characteristics  of  the  reflex  postural  contraction  are  the  long 
periods  for  which  it  usually  endures  without  apparent  fatigue,  and 
what  is  probably  associated  with  this  relative  unfatiguability,  the 
slight  expenditure  of  energy  by  which  it  is  maintained  (Roaf). 

It  is  probable  that  the  tone  of  such  visceral  muscles  as  the  sphincters 
of  the  anus  and  bladder  has  a  reflex  element  analogous  to  postural 
contraction,  and  possible  that  the  same  is  true  of  the  tone  of  the  smooth 
muscular  fibres  of  the  bloodvessels  on  which  the  maintenance  of  the 
mean  blood-pressure  so  largely  depends  (p.  185). 


FUNCTIONS  OF  THF  SPINAx.  CORD  9i9 

Trophic  Tone.-  -  The  degenerative  changes  that  occur  in  muscles, 
nerves,  and  other  tissues  when  their  connection  with  the  central 
nervous  system  is  interrupted  have  been  already  referred  to  (p.  804). 
It  is  possible  to  explain  these  changes  in  some  cases  without  the 
assumption  that  tonic  impulses  are  constantly  passing  out  from  the 
brain  and  cord  to  control  the  nutrition  of  the  pcriplieral  organs; 
and  we  have  seen  that  there  is  no  real  evidence  of  the  existence  of 
specific  trophic  fibres.  But  the  degeneration  of  muscles  after  sec- 
tion of  their  motor  nerves  is  difficult  to  understand,  except  on  the 
hypothesis  that  impulses  from  the  cells  of  the  anterior  horn  influence 
their  nutrition.  The  only  question  is  whether  these  are  the  im- 
pulses to  which  muscular  tone  is  due,  and  therefore  reflex,  or  dif- 
ferent in  nature  and  automatically  discharged.  Now,  degeneration 
of  a  muscle  is  not  usually  caused,  or  at  least  not  lor  a  long  time,  by 
interruption  of  its  afferent  nerve-fibres,  as  in  locomotor  ataxia,  or 
after  section  of  the  posterior  nerve-roots  (Mott  and  Sherrington). 
We  can  hardly  suppose  that  in  any  case  the  trophic  influence  of  the 
cells  of  the  spinal  or  sympathetic  ganglia  to  which  all  other  reflex 
powers  have  been  denied,  is  of  reflex  nature.  And  there  is,  indeed, 
more  evidence  in  favour  of  trophic  tone  being  an  automatic  action 
of  the  cord  than  for  any  of  the  other  tonic  functions  hitherto  con- 
sidered. 

The  evidence  for  respiratory  automatism  upon  which  the  spinal 
cord  has  been  chiefly  credited  with  true  automatic  action  has  pre- 
viously been  given  (p.  284). 

The  '  Centres  '  of  the  Cord  and  Bulb. — We  have  frequently  used  the 
word  '  centre  '  in  describing  the  functions  of  the  spinal  cord,  but  the 
term,  although  a  convenient  one,  is  apt  to  convey  the  idea  that  our 
knowledge  is  far  more  minute  and  precise  than  it  really  is.  When  we 
say  that  a  centre  for  a  given  physiological  action  exists  in  a  definite 
portion  of  the  spinal  cord,  all  that  is  meant  is  that  the  action  can  be 
called  out  experimentally,  or  can  normally  go  on,  so  long  as  this  portion 
of  the  cord  and  the  nerves  coming  to  it  and  leaving  it  are  intact,  and 
that  destruction  of  the  '  centre  '  abolishes  the  action.  For  example,  a 
part  of  the  medulla  oblongata  on  each  side  of  the  middle  line  in  the 
floor  of  the  fourth  ventricle  above  the  calamus  scriptorius  is  so  related 
to  the  function  of  respiration  that  when  it  is  destroyed  the  animal  ceases 
to  breathe.  But  this  respiratory  centre — the  '  noeud  vital  '  of  Flourens 
■ — docs  not  correspond  in  position  with  any  definite  collection  of  grey 
matter,  although  it  includes  the  nuclei  of  origin  of  several  cranial  nerves, 
and  forms  an  important  point  of  departure  for  efferent,  and  of  arrival 
for  afferent,  fibres  connected  with  the  respirator}-  act.  Its  destruction 
involves  the  cutting  off  of  the  impulses  constantlv  travelling  up  the 
vagus  to  modify  the  respiratory  rhythm,  and  of  the  impulses  constantly 
passing  down  the  cord  to  the  phrenics  and  the  intercostal  nerves.  And 
just  as  the  traffic  of  a  wide  region  can  be  paralyzed  at  a  single  blow,  by 
severing  tlie  lines  in  the  neighbourhood  of  a  great  railway  junction,  or 
more  laboriously,  though  not  less  effectually,  by  separate  section  of  the 
same  tracks  at  a  radius  of  a  hundred  miles,  so  destruction  of  the 
respiratory  centre  accomplishes  by  a  single  puncture  what  can  be  also 


920  THE  CENTRAL  NERVOUS  SYSTEM 

performed  by  section  of  all  the  respiratory  nerves  at  a  distance  from 
the  medulla  oblongata.  But  while  nobody  speaks  of  the  destruction  of 
a  '  centre  '  when  a  reflex  action  is  abolished  by  division  oi  the  peripheral 
nerves  concerned  in  it,  there  is  a  tendency,  when  the  same  effect  is 
brought  about  by  a  lesion  in  the  brain  or  cord,  to  invoke  that  mysterious 
name,  and  to  forget  that  the  cerebro-spinal  axis  is  at  least  as  much  a 
stretch  of  conducting  paths  as  a  collection  of  discharging  nervous 
mechanisms. 

It  is,  perhaps,  a  profitless  task  to  enumerate  all  the  so-called  centres 
in  the  bulb  and  cord.  In  addition  to  the  great  vasomotor,  respiratory, 
cardio-inhibitory  and  cardio-augmentor  centres  in  the  bulb,  which 
perhaps,  have  more  right  than  the  rest  to  be  regarded  as  distinct 
physiological  mechanisms,  if  not  as  definitely  bounded  anatomical 
areas,  there  have  been  distinguished  ano-spinal,  vesico-spinal,  and 
genito-spinal  centres  in  the  lumbar  cord,  a  cilio-spinal  centre  for  rlila- 
tatioji_of_jthe_pupiLiii  the  cervical  cord,  and  in  the  medulla  centres  for 
sneezing,  for  coughing,  for  sweating,  "for  sucking,  for  masticating,  for 
swallowing,  for  salivating,  for  vomiting,  for  the  production  of  general 
convulsions,  for  closure  of  the  eyes,  for  the  secretion  of  tears,  and  even  a 
'  diabetes  '  or  '  sugar  '  regulating  centre  (p.  547).  It  has  been  recently 
shown  that  in  the  cat  a  region  of  the  dorsal  cord  between  the  last 
cervical  and  the  third  dorsal  segments  is  capable  of  sustaining  the 
spontaneous  liberation  of  epinephrin  from  the  adrenal  glands  after  the 
cord  has  been  divided  higher  up. 


Section  IX. — The  Crani.^l  Nerves. 

Unlike  the  spinal  nerves,  which  arise  at  not  very  unequal  intervals 
from  the  cord,  the  nuclei  of  the  cranial  nerves,  with  the  exception 
of  the  olfactory  and  optic,  are  crowded  together  in  the  inch  or  two 
of  grey  matter  of  the  primitive  neural  axis  in  tlie  immediate  neigh- 
bourhood of  the  fourth  ventricle  and  the  Sylvian  aqueduct.  Of 
these  nuclei  some  are  the  end  nuclei  or  '  nuclei  of  reception  '  of 
sensory  fibres — that  is  to  say,  collections  of  nerve-cells  around 
which  the  sensory  fibres  break  up  into  terminal  arborizations.  Such 
are  the  sensory  nuclei  of  the  fifth,  the  nuclei  of  the  eighth,  and  the 
sensory  nuclei  of  the  glossopharyngeal  and  vagus  nerves  (Figs,  ^by, 
368).  The  nuclei  of  origin  of  the  motor  fibres  lie,  upon  the  whole, 
in  two  longitudinal  rows — a  median  tow,  which  consists  of  the 
nuclei  of  the  third  and  fourth  nerves  in  the  floor  of  the  aqueduct, 
and  those  of  the  sixth  and  twelfth  nerves  in  the  floor  of  the  fourth 
ventricle;  and  a  lateral  row  comprising  the  motor  nuclei  of  the  fifth, 
seventh,  tenth,  and  eleventh  nerves.  The  clumps  of  grey  matter 
which  make  up  these  nuclei  ma\'  be  considered  as  liomologous  with 
the  grey  matter  of  the  ventral  or  anterior  (including  the  lateral) 
horn  of  the  spinal  cord ;  and  the  motor  fibres  of  the  nerves  themselves 
as  homologous  with  the  anterior  spinal  roots.  Without  going 
further  into  the  thorny  subject  of  the  homologies  of  the  cranial  and 
spinal  nerves,  we  may  point  out  that  while  all  the  spinal  mrv 
contain  both  efferent  and  afferent  fibres,  some  of  the  cranial    nciv 


TIIF.  CRANIAL  MiRVES 


Q2I 


arc  pnrrly  efferent,  sonu'  purely  afferent,  and  otliers  mixed.     So 
that  if  we  are  to  look  upon  tl.c  motor  nerves  as  the  homologues  of 

the  ventral  roots,  the  dorsal 
(posterior)  root- fibres  cor- 
rtsponding  to  them  must  be 
represented  in  tlie  other 
cranial  nerves.  Thus,  the 
sensory  portion  of  the  mixed 
fifth  nerve,  and  the  purely 
afferent  auditory  nerve,  must 
be  supposed  to  contain 
fibres  corresponding  to  seve- 
ral dorsal  roots. 


Fig.  367. — Nuclei  'A  Cranial  Nerves  (Toldt). 
Motor  red,  sensory  blue.  The  numbers 
correspond   to  the  cranial  nerves. 


The  first  or  olfac- 
tory nerve  consists 
of  fine  fibres,  each 
of  which  is  a  process 
of  an  olfactory  cell 
(Fig.  369).  The  ol- 
factory cells,  which 
are  really  peripheral 
nerve-cells,  lie  among 
the  epithelial  cells  in 
the  olfactory  region 
of  the  Schneiderian 
membrane,  the  com- 
mon lining  of  the 
nostrils.  Each  olfac- 
tory cell  gives  off  two 
processes,     a     short 


9 
10 


Fig-  368.— Nuclei  and  Roots  of  Cranial 
Nerves  (Toldt).  Lateral  view.  Motor 
red,  sensory  blue. 


one,  representing  a  dendrite,  which  runs  out  to  the  surface  of  the  mucous 
membrane,  and  a  longer  but  more  slender  process,  representing  an  axon, 


922 


THE  CENTRAL  KEliVOVS  SYSTEM 


wliicli  as  a  fibre  of  tlic  olfactory  nerve  pierces  the  cribriform  plate  of  the 
ethmoid  bone,  and  plunges  into  the  olfactory  bulb. 

In  the  olfactory  bulb  at  least  four  layers  can  be  distinguished — (i)  on 
the  surface,  beneath  the  pia  mater,  the  layer  of  entering  oliactory 
nerve-fibres;  (2)  the  layer  of  olfactory  glomeruli,  peculiar  structures,  each 
of  which  is  made  up  of  an  intricate  basket-like  arboiization  formed  by 
an  olfactory  nervo-fibre,  or,  it  may  be,  more  than  one,  and  a  brush-like 
arborization  belonging  to  a  dendrite  of  one  of  the  mitral  cells  of  the  next 
layer;  (3)  the  molecular  or  mitral  layer,  which  contains  a  number  of 
large  nerve-cells  called,  from  their  most  common  shape,  mitral  cells, 
along  with  smaller  nerve-cells  ('  granules  ')  and  neuroglia ;  (4)  the  nuclear 
layer,  containing  numerous  small  nerve-cells  or  '  granules  '  intermingled 
with  white  fibres.  The  mitral  cells  give  off  axons,  which  pass  through 
the  fourth  layer,  and  then  as  fibres  of  the  olfactory  tract  to  the  grey 
matter  of  the  hippocampal  region  of  the  brain.  The  course  of  the 
impulses  from  the  olfactory  mucous  membrane  to  the  brain  is  lihown  in 
F^u-  369-     The  olfactory  tract,  as  it  runs  back,  divides  into  portions 


Fig-  369-  —  Scheme  of  the  Olfactory  Nervous 
Apparatus  (Cajal).  A.  olfactory  cells;  B.  glomeruli; 
C,  mitral  cells;  D,  olfact(^ry  granule  cell;  E,  lateral 
root  of  olfactory  tract;  F,  cortex  of  brain  in  the 
region  of  the  uncinate  gyrus;  a,  small  cell  of  mitral 
layer;  b,  brush  of  dendrite  of  a  mitral  cell  ending  in  a 
glomerulus;  c,  thorns  or  spines  on  the  processes  of  an  olfactory  granule;  e,  collateral 
coming  off  from  the  axon  of  a  mitral  cell;  /,  collaterals  ending  in  the  molecular  layer 
of  the  uncinate  gyrus;  g,  pyramidal  cells  of  the  cortex;  h,  supporting  epithelial  cells 
of  the  olfactory  mucous  membrane. 

called  its  '  roots.'  Of  these  the  lateral  is  the  most  important,  and  it 
terminates  in  the  hippocampal  and  uncinate  gyri  of  the  same  side. 
Fibres  of  the  olfactory  tract  arc  also  connected  either  directly  or  through 
the  relay  of  another  neuron  with  the  opposite  side  of  the  brain,  especially 
the  opposite  uncinate  gyrus.  The  anterior  commissure  contains 
numerous  fibre*;,  which  connect  the  hippocampal  regions  of  the  two 
sides.  Other  central  comiections  of  the  olfactory  tract  exist,  but  some 
are  imperfectly  known.  The  name  '  rhinencephalon  '  is  given  to  the 
portions  of  the  brain  concerned  with  the  sense  of  smell.  Disturbances 
of  smell  sensation  may  be  caused  by  lesions  in  any  part  of  the  rhinen- 
cephalon, and  also  by  changes  in  the  olfactory  mucous  membrane  and 
olfactory  fibres;  but  the  symptoms  do  not  obtrude  themselves,  and  are 
doubtless  often  overlooked.  Excessive  stimulation  of  the  olfactory 
nerve  by  exposure  to  a  strong  odour  has  been  said  to  cause  complete 
and  permanent  loss  of  smell. 

The  second  or  optic  nerve  (ontains  mainly  afferent  fibres,  which 
arise  from  the  ganglion  cells  of  the  retina,  and  teruiinatc  by  forming 
synapses  with  nerve-cells  in  llic  lateral  or  external  grniculate  body,  the 


TUi:  CRA>!IAL  NERVES 


92.^ 


Corp. 


pulvinar  ^or  posterior  portion)  of  the  optic  thalamus,  and  tlie  anterior 
corpus  quiuliigcminum.  Jn  young  animals  all  these  structures  undergo 
atrophy  after  extirpation  of  the  eyeball.  The  visual  path  is  continued 
from  the  pulvinar  and  the  external  corpus  geniculatum  by  the  axons 
of  these  nerve-cells,  which  proceed  in  the  optic  radiation  (p.  883)  to  the 
occipital  cortex.  The  fibres  which  pass  from  the  retina  to  the  anterior 
corpus  quadrigeminum  are  distinguished  by  their  small  size,  and 
probably  constitute  the  path  of  the  impulses  which  cause  contraction 
of  the  piipil  when  light  falls  on  the  retina.  The  reflex  arc  is  schematic- 
ally shown  in  Fig.  370,  where  optic  nerve-fibres  are  represented  as 
forming  synapses  with  cells  in  the  anterior  corpus  quadrigeminum 
whose  axons  pass  to  the  nucleus  of  the  third  nerve  ami  arbcrize  around 

some  of  its  celts  (Figs.  354,  3^6, 
and  370).  At  the  chiasma  the 
fibres  of  the  optic  nerve  de- 
cussate, partially  in  man  and 
some  mammals,  as  the  rabbit, 
dog,  cat,  and  monkey,  com- 
pletely in  animals  whose  visual 
field  is  entirely  independent  for 
the  two  eyes,  as  in  fishes  and 
birds.  In  man  the  fibres  for 
the  nasal  halves  of  both  retinae 
cross  the  middle  line  at  the 
chiasma,  those  for  the  temporal 
halves  do  not.  This  does  not 
mean,  however,  that  exactly 
half  of  the  optic  nerve-fibres 
decussate.  The  number  of  un- 
crossed fibres  is  smaller  than 
that  of  crossed.  The  chiasma 
also  contains  fibres  in  its  pos- 
terior portion,  which  extend 
from  one  optic  tract  to  the 
other,  but  are  not  connected 
with  the  retinae  or  the  optic 
nerves.  They  are  commissural 
fibres  which  connect  the  two 
mesial  geniculate  bodies  across 
the  middle  line,  and  are  called 
Gudden's  commissure.  A  suffi- 
ciently extensive  lesion  involv- 
ing the  occipital  cortex  on  one 
side,  or  the  posterior  portion 
of  the  optic  thalamus,  or  the 
optic  tract,  causes  hemianopia*  or  defect  of  the  visual  field  on  the 
side  opposite  to  the  lesion,  with  blindness  of  the  corresponding  halves 
of  the  two  retinae.  Thus,  a  lesion  equivalent  to  complete  section  of  the 
right  optic  tract  would  cause  blindness  of  the  nasal  half  of  the  left,  and 
of  the  temporal  half  of  the  right  eye,  and  the  left  half  of  the  field  of 
vision  would  be  blotted  out — the  patient  would  be  unable,  with  his  eyes 
directed  forwards,  to  see  an  object  at  his  left.  Such  a  complete 
hemianopia  is  much  rarer  in  disease  of  the  cortex  than  in  disease  of  the 
*  The  terms  '  hemiopia,'  '  hemianopia,'  '  hemianopsia,'  are  used  with  refer- 
ence sometimes  to  the  blind  side  of  the  retinae,  but  ordinarily  to  the  half  of  the 
visual  field  which  is  deficient  We  shall  always  use  the  word  '  hemianopia  ' 
in  the  latter  sense. 


Nerue 


Fig   370. — Scheme  of  the  Visual  Path  (after 
Schafer). 


924  rW£  CENTRAL  NERVOUS  SYSTEM 

optic  tract.  A  lesion — e.g.,  a  tumour  of  the  pituitarv  body  —involving 
the  whole  of  the  optic  nerve  in  front  of  the  chiasma,  would  cause  com- 
plete blindness  in  the  corresponding  eye.  Sometimes  in  disease  of  the 
optic  nerve  vision  is  not  totally  destroyed  in  the  eye  to  which  it  belongs, 
but  the  field  is  narrowed  by  a  circumference  of  blindness.  In  this  case 
the  pathological  change  involves  the  circumferential  fibres  of  the  nerve. 
When  the  chiasma  is  affected  by  disease,  a  very  frequent  symptom  is 
bitemporal  hemianopia.  blindness  of  the  nasal  halves  of  the  retinip.  with 
loss  of  the  outer  or  temporal  half  of  each  field  of  vision.  The  optic  nerve 
and  tract  contain  a  few  efferent  fibres  for  the  retina,  whose  cell-bodies 
have  not  vet  been  ccrtainlv  located. 

The  third  nerve,  or  ocuio-motor,  arises  from  an  elongated  nucleus, 
or  a  scries  of  nuclei,  containing  large  nerve-cells  in  the  fioor  of  the 
Sj'lvian  aqueduct  below  the  anterior  corpora  quadrigemina.  The  root- 
bundles  coming  off  from  the  most  anterior  of  the  nuclei  carry  fibres  that 
innervate  the  ciliary  muscle,  and  thus  have  to  do  with  the  mechanism 
of  accommodation,  and  also  fibres  that  innervate  the  sphincter  muscle  of 
the  iris,  and  thus  cause  contraction  of  the  pupil  when  light  falls  on  the 
retina.  Both  groups  of  fibres  terminate  by  arborescing  around  sympa- 
thetic cells  in  the  ciliary  ganglion,  from  which  the  path  to  the  (unstriated) 
ciliary  and  sphincter  muscles  is  continued  by  post-ganglionic  fibres. 
Farther  back  in  the  oculo-motor  nucleus  arise  the  motor  fibres  for  four 
of  the  extrinsic  muscles  of  the  eyeball  and  the  elevator  of  the  upper 
eyelid.  In  the  dog  these  fibres  come  off  in  the  following  order,  from 
before  backwards;  internal  rectus,  superior  rectus,  levator  palpebra' 
superioris,  inferior  rectus,  inferior  oblique.  Most  of  the  fibres  of  the 
third  nerve  arise  from  nerve-cells  on  their  own  side  of  the  middle  line, 
but  a  certain  number  decussate  to  enter  the  nerve  of  the  opposite  side. 

Complete  paralysis  of  the  third  nerve  causes  loss  of  the  power  of 
accommodation  of  the  corresponding  eye,  dilatation  of  the  pupil  by  the 
unopposed  action  of  the  sympathetic  fibres,  diminution  of  the  power  of 
mov'ng  the  eyeball,  ptosis,  or  drooping  of  the  upper  iid,  external  squint, 
and  consequent  diplopia,  or  double  vision. 

The  fourth  or  trochlear  nerve  arises  from  the  posterior  part  of  the 
same  tract  of  grey  matter  which  gives  origin  to  the  third  nerve.  It 
supplies  the  superior  oblique  muscle.  Paralysis  of  the  nerve  causes 
internal  squint  when  an  object  below  the  horizontal  plane  is  looked  at, 
owing  to  the  unopposed  action  of  the  inferior  rectus.  There  is  also 
diplopia  on  looking  down.  Unlike  the  other  cranial  nerves,  the  two 
trochlear  nerves  decussate  completely  after  they  emerge  from  their 
nuclei  of  origin. 

The  fifth  or  trigeminus  nerve  appears  on  the  surface  of  the  pons  as  a 
large  sensory  root  and  a  smaller  motor  root.  Its  deep  origin  is  more 
extensive  than  that  of  any  of  the  other  cerebral  nerves,  stretching  a-s  it 
does  from  the  level  of  the  anterior  corpus  quadrigeminum  above  to  the 
upper  part  of  the  spinal  cord  below.  Its  scnsorv  root,  in  fact,  seems  to 
include  the  sensory  divisions  of  several  motor  cranial  nerves. 

The  motor  root  arises  partly  from  a  nucleus  {principal  motor  nucleus) 
in  the  floor  of  the  fourth  ventricle  below  the  pons,  partlv  from  large 
round  nerve-cells  lying  at  the  side  of  the  grey  matter  bounding  the 
aqueduct  of  Sylvius  all  the  way  from  the  anterior  quadrigcminate  body 
to  the  point  at  which  the  motor  root  is  given  off  [accessory  or  superior 
motor  nucleus). 

The  fibres  of  the  sensory  root  have  their  cells  of  origin  in  the  Gasserian 
ganglion,  whence  they  pass  into  the  pons.  Here  thev  bifurcate  into 
ascending  and  descending  branches.  The  ascending  branches  end  in 
the  principal  sensory  micleus,  a  collection  of  grey  matter  at  the  side  of 


THE  CRANIA  I.   NEliVES 


925 


the  principal  motor  nucleus.  The  descending  branches,  turning  down- 
wards into  the  mcthilla  oblongat;i,  terminate  in  a  long  tract  of  scattered 
cells,  constituting  with  the  fibres  the  so-called  spinal  root,  and  extending 
frorn  the  level  of  the  second  cervical  nerve  through  the  medulla  oblon- 
gata and  the  pons,  where  it  is  continued  into  the  principal  sensory  nucleus. 
The  attcrent  path  is  continued  by  the  axons 
of  cells  of  the  sensory  nuclei  (or  nuclei  of 
reception)  of  the  nerve,  many  of  which  cross 
the  middle  line  and  enter  the  intermediate 
fillet  of  the  opposite  side,  and  also  the 
special  ascending  bundle  going  to  the  thala- 
mus. Some  of  the  axons  do  not  decussate, 
but  ascend  in  the  fillet  of  the  same  side. 


TV.  »p.  n.  V. 


371. — Scheme  of  Motor  and  Sensory  Neurons  of  Trigeminus  (Gehuchten). 
G.  s.  G.,  Gasserian  ganglion;  Nu.  m.  m.  n.  V.,  nucleus  of  the  descending  root; 
A^M.  m.  pr.  n.  V.,  chief  motor  nucleus  of  the  fifth  nerve;  Rad.  desc.  mes.  n.  V.. 
accessory  motor  nucleus,  sometimes  called  the  descending  root;  Tr.  sp.  n.  V ., 
tractus  spinalis,  or  spinal  root  of  the  fifth. 

The  motor  fibres  of  the  fifth  nerve  supply  the  muscles  of  mastication 
and  the  tensor  tympani.  The  sensory  fibres  confer  common  sensation 
on  the  face,  conjunctiva,  the  mucous  membranes  of  the  mouth  and  nose, 
and  the  structures  contained  in  them,  and,  according  to  Gowers,  special 
sensation,  through  branches  given  off  to  the  facial  and  glosso-pharyngeal 
nerves,  on  the  organs  of  taste.*     Complete  paralysis  of  the  nerve  causes 

*  It  should  be  stated  that  some  physiologists  believe  that  the  glosso-pharyu- 
geal  is  the  nerve  of  taste,  and  that  none  of  the  taste  fibres  go  to  the  sensory 
nuclei  of  the  fifth  nerve.  The  majority  hold  that  the  glosso-pharyngeal 
supplies  the  posterior  third,  and  the  chorda  tympani  and  lingual  the  anterior 
two-thirds  of  the  tongue  with  gustatory  fibres.  The  removal  of  the  Gasserian 
ganglion  and  the  adjacent  portion  of  the  fifth  nerve  for  severe  and  persistent 
neuralgia,  has  afforded  opportunities  to  test  this  question.  But,  unfortunately 
the  results  described  by  various  observers  do  not  agree,  some  finding  that 
taste  is  unimpaired,  others  that  it  is  abolished.  Gowers  states  that  the  gus- 
taJ:ory  sensations  may  persist  for  some  time  after  the  operation,  although 
ultimately  (in  two  or  three  weeks)  they  disappear.  It  has  been  shown  by 
Harris  that  when  alcohol  is  injected  into  the  third  division  of  the  fifth  nerve 
at  the  foramen  ovale  or  into  the  Gasserian  ganglion,  immediate  loss  of  taste 
develops  in  a  very  large  proportion  of  cases  in  the  anterior  half  of  the  tongue 
on  that  side.  Taste  fibres  are  therefore  certainly  present  in  the  fifth  nerve 
at  this  level. 


926  THE  CENTRAL  NERVOUS  SYSTEM 

loss  of  movement  in  the  muscles  of  mastication,  sometimes  impaired 
hearing,  and  loss  of  common  sensation  in  the  area  supplied  by  it.  Lose 
or  impairment  of  taste  in  the  corresponding  half  of  the  tongue  is  also 
often  seen  in  disease  involving  the  sensory  root,  althf)ugh  not  in 
affections  of  the  trunk  of  the  nerve,  since  the  taste  fibres  leave  it  near 
its  origin  (Cowers).  Both  taste  and  touch  are  lost  in  the  monkey  in  the 
anterior  two-thirds  of  the  tongue  after  intracranial  section  of  the 
trigeminus  (Sherrington). 

Vaso-motor  changes  are  occasionally,  and  '  trophic  '  changes  fre- 
cjuently,  observed  in  disease  of  the  fifth  nerve.  The  trophic  disturbance 
is  most  conspicuous  in  the  eyeball  (ulceration  of  the  cornea,  going  on, 
it  may  be,  to  complete  disorganization  of  the  eye).  These  effects  are 
partly  due  to  the  loss  of  sensation  in  the  eye,  with  the  consequent  risk  of 
damage  from  without,  and  the  unregarded  presence  of  foreign  bodies 
and  accumulation  of  secretion  within  the  lids  (p.  805). 

The  sixth  or  abducens  nerve  takes  origin  from  a  nucleus  in  the  floor 
of  the  fourth  ventricle  at  the  level  of  the  posterior  portion  of  the  pons. 
It  supplies  the  external  rectus  muscle  of  the  eyeball.  Paralysis  of  it 
causes  internal  squint.  It  is  generally  described  as  a  purely  motor 
nerve,  but  this  is  incorrect.  It  has  been  shown  that  the  sixth,  as  we'll 
as  the  third  and  fourth,  cranial  nerves  contain  a  considerable  number 
of  afferent  fibres,  whose  receptive  nerve-endings  are  situated  in  the 
recti  and  ublicjui  muscles  and  their  tendons. 

Xhe  motor  fibres  of  the  seventh  or  facial  nerve  arise  from  a  nucleus 
in  the  reticular  formation  of  the  medulla  oblongata,  and  running  up 
some  distance  into  the  pons.  They  supply  the  muscles  of  the  face ;  and 
when  these  are  greatly  developed,  as  in  the  trunk  of  the  elephant,  the 
nerve  reaches  very  large  proportions.  Since  the  fibres  which  connect 
the  cerebral  cortex  with  the  nucleus  decussate  about  the  middle  of  the 
pons,  a  lesion  above  this  level  which  causes  hemiplegia  paralyzes  the 
face  on  the  same  side  as  the  rest  of  the  body — i.e.,  on  the  side  opposite 
the  lesion.  But  the  paralysis  is  confined  to  the  muscles  of  the  lower 
portion  of  the  face,  and  affects  especially  the  muscles  about  the  mouth. 
Sometimes  the  pyramidal  tract  and  the  facial  nerve,  or  nucleus,  are 
involved  in  a  common  lesion.  In  this  case  paralysis  of  the  face  is  on 
the  side  of  the  lesion,  and  is  total,  while  the  rest  of  the  body  is  para- 
lyzed on  the  opposite  side.  Paralysis  of  the  seventh  nerve  is  more 
common  than  that  of  any  other  nerve  in  the  body.  It  is  often  caused 
by  an  inflammator}-  process  in  the  nerve  itself  (neuritis).  The  symp- 
toms of  complete  facial  palsy  are  very  characteristic.  The  face  and 
forehead  on  the  paralyzed  side  are  smooth,  motionless,  and  devoid  of 
expression.  The  eve  remains  open  even  in  sleep,  owing  to  paralysis 
of  the  orbicularis  palpebrarum.  A  smile  becomes  a  grimace.  An 
attempt  to  wink  with  both  eyes  results  in  a  grotesque  contortion.  The 
mouth  appears  like  a  diagonal  slit  in  the  face,  its  angle  being  drawn 
up  on  the  sound  side,  and  the  patient  cannot  bring  the  lips  sufficiently 
close  together  to  be  able  to  blow  out  a  candle  or  to  whistle.  Liquids 
escape  from  the  mouth,  and  food  collects  between  the  paralyzed  buc- 
cinator and  the  teeth.  The  labial  consonants  are  not  properly  pro- 
nounced. Taste  may  be  lost  in  the  anterior  two-thirds  of  the  tongue 
when  the  nerve  is  injured  above  the  exit  of  the  gustatory  fibres  in  the 
chorda  tympani,  but  not  when  the  lesion  is  in  the  nucleus  of  origin,  or 
anywhere  above  it.  Hearing  is  sometimes  impaired  because  the 
auditory  and  facial  nerves,  lying  close  together  for  part  of  their  course, 
are  apt  to  suffer  together,  but  perhaps  also  because  the  stapedius 
muscle  is  supplied  by  the  seventh. 


THE  CRAKJAL  NERVES 


927 


The  seventh  nerve  is  not  purely  motor.  From  the  cells  of  a  ganglion 
on  it  corresponding  to  a  spinal  ganglion  (the  geniculate  ganglion) 
afferent  fibres  arise,  which  pass  in  the  pays  intermedia  or  nerve  of 
VVrisberg  into  the  pons  between  the  seventh  and  eighth  nerves,  and 
there  bifurcate  into  nscending  and  descending  branches,  like  other 
afferent  fibres  originating  in  ganglia  of  the  spinal  type.  The  descend- 
ing brandies  enter  the  fasciculus  solitarius,  and  end  by  arborizing 
around  nerve-cells  in  the  upper  part  of  that  bundle.  The  peripheral 
axons  of  the  nerve-cells  in  the  geniculate  ganglion  enter  the  large  super- 
ficial petrosal  nerve  and  the  chorda  tympani,  in  which  they,  or  some 
of  them,  perhaps  represent  taste  fibres. 

The  eighth  or  auditory  nerve  enters  the  medulla  oblongata  by  two 
roots  (a  dorsal  and  a  ventral),  one  of  which  passes  in  on  each  side  of 


vin 


Fig-  372-— Scheme  of  Path  of  Auditory  Impulses  (.Lewandowsky).  Sp,  ganglion 
spirale;  G,  accessory  nucleus;  T,  acoustic  tubercle;  Tr,  trapezium;  H,  Heid's 
fibres;  St,  striae  acustics;  tr,  trapezoid  nucleus;  Os,  upper  olive;  LI,  lateral  fillet, 
with  its  nucleus,  nL;  P,  commissure  of  the  lateral  fillets;  Qp,  posterior  corpora 
quadrigemina,  with  Cq,  their  commissure,  and  Bq,  the  brachia;  Gm,  mesial  or 
internal  geniculate  body;  R,  cerebral  cortex. 

the  restiform  body.  The  cells  of  origin,  both  of  the  dorsal  and  of  the 
ventral  root,  are  situated  in  the  internal  ear,  the  former  in  the  ganglion 
spirale,  or  ganglion  of  Ccrti,  which  is  embedded  in  the  bony  spiral  of 
the  cochlea,  the  latter  in  the  ganglion  vestibulare,  or  ganglion"of  Scarpa, 
which  lies  in  the  vestibule.  These  cells  correspond  to  the  ganglion 
cells  on  the  posterior  root  of  a  spinal  nerve,  but,  unlike  them,  they 
remain,  even  in  mammals,  bipolar  throughout  life.  Their  centra'l 
processes  form  the  axons  of  the  eighth  nerve.  Their  peripheral  pro- 
cesses are  distributed  in  the  case  of  the  dorsal  root  to  the  organ  of 
Corti,  in  the  case  of  the  ventral  root  to  the  semicircular  canals  and  the 
vestibule.  For  this  reason  the  dorsal  root  is  often  called  the  cochlear 
division,  and  the  ventral  root  the  vestibular  division  of  the  auditorv 


928  THE  CENTRAL  NEKVOVS  SYSTEM 

nerve.  Ana  the  cochlear  and  vestibular  roots  arc  pliysiologically 
as  well  as  anatomically  distinct.  For  the  cochlea  subserves  the 
function  of  hearing,  tlie  semicircular  canals  and  vestibule  the  function 
of  equilibration.  As  they  enter  the  medulla  oblongata,  the  fibres  of 
the  dorsal  root  bifurcate.  Of  the  two  branches,  one  is  considerably 
thicker  than  the  other.  Many  of  the  thicker  brandies  terminate  by 
arborizing  around  the  cells  of  the  accessory  auditory  nucleus,  whose 
position  is  indicated  by  a  swelling  on  the  ventral  surface  of  the  resti- 
form  body  at  the  junction  of  the  dorsal  and  ventral  roots;  but  some 
pass  over  the  restiform  body  to  end  in  another  nucleus  (lateral  nucleus), 
also  indicated  by  a  swelling  (tuberculum  acusticum)  lying  over  the 
restiform  bod}'.  The  nerve-cells  of  the  acces-sory  nucleus  and  the 
acoustic  tubercle,  therefore,  constitute  nuclei  of  reception  for  the 
dorsal  root-fibres.  The  more  slender  branches  of  the  coclilear  root- 
fibres  run  downwards  for  some  distance  before  breaking  up  into  fibrils. 

The  path  to  the  higher  parts  of  the  brain  is  continued  by  the  axons 
of  nerve-cells  in  the  accessory  nucleus  and  the  acoustic  tubercle.  The 
fibres  from  the  accessory  nucleus  pass  into  the  trapezium,  a  mass  of 
transverse  fibres  lying  in  the  pons  behind  the  pyramidal  fibres.  In 
their  course  through  the  trapezium  some  of  the  fibres  terminate  around 
the  cells  of  the  nucleus  of  the  trapezium,  others  run  into  the  superior 
olive  of  the  same  side,  and  end  there ;  but  most  of  them  cross  the  middle 
line,  and  enter  the  trapezoid  nucleus  and  superior  olive  of  the  opposite 
side,  where  many  of  them  terminate.  Others,  however,  run  through 
those  nuclei  and  pass  into  the  lateral  fillet,  to  end  in  its  nucleus  or  in 
the  posterior  corpora  quadrigemina.  The  path  of  the  fibres  which 
terminate  in  the  nuclei  of  the  trapezium,  superior  olive,  and  lateral 
fillet,  is  continued  by  another  relay  of  fibres,  which  link  them  also  to 
the  posterior  corpora  quadrigemina.  The  axons  of  the  cells  of  the 
acoustic  tubercle  enter  for  the  most  part  the  sirics  acusticcB,  a  series  of 
prominent  strands  that  run  transversely  across  the  floor  of  the  fourth 
ventricle.  Passing  across  the  raphe,  they  join  the  fibres  from  the 
accessory  nucleus  on  their  way  to  the  superior  olive,  and  accompany 
them  into  the  lateral  fillet,  which  terminates  in  the  grey  matter  of  the 
posterior  corpus  quadrigeminum.  We  must  assume,  from  clinical  and 
experimental  data,  that  the  dorsal  root  is  ultimately  connected  with 
the  first  or  first  and  second  temporo-sphenoidal  convolutions  on  the 
opposite  side.  From  the  posterior  corpora  quadrigemina  the  auditory 
path  to  the  convolutions  seems  to  run  in  the  brachium  to  the  internal 
or  mesial  geniculate  body,  whence  it  is  continued  in  the  posterior 
extremity  of  the  internal  capsule. 

The  fibres  of  the  ventral  root  of  the  eighth  nerve,  better  termed  the 
vestibular  nerve,  after  entering  the  medulla  oblongata,  pass  to  a 
nucleus  called  the  principal  nucleus  of  the  vestibular  division.  Here 
each  bifurcates  into  a  descending  and  an  ascending  branch.  The 
descending  branches  running  down  in  tlie  medulla  terminate  at  dif- 
ferent levels  around  cells  in  the  principal  nucleus,  and  the  grey  matter 
continued  down  from  it  {descending  vestibular  nucleus).  The  ascending 
branches  run  up  on  the  inner  side  of  the  restiform  body  towards  the 
nucleus  of  the  roof  [nucleus  tecti)  in  the  cerebellar  worm.  On  their 
course  they  enter  into  relation  through  their  collaterals  with  the  nuclei 
of  Deiters  and  Bechterew.  The  nucleus  of  Deiters,  as  already  stated, 
sends  fibres  into  the  posterior  longitudinal  bundle.  Through  ascend- 
ing branches  of  these  fibres  a  communication  is  established  with  the 
nuclei  of  the  third  and  sixth  nerves,  and  through  descending  branches 
that  pass  into  the  antero-lateral  descending  tract  of  the  cord  with  the 
anterior   horn   cells.     It   is   obvious   that   through   these   connections 


THE  CRANIAL  NERVES  929 

which  link  the  vestibule  with  the  cerebellum,  the  nuclei  of  the  motor 
nerves  of  the  eyeball  and  the  motor  cells  of  thj  cord,  the  nucleus  of 
Deiters  has  an  important  relation  to  the  co-ordination  of  those  move- 
ments mainly  concerned  in  equilibration.  Nothing  is  known  of  the 
connections  of  the  vestibular  nerve  with  the  cerebrum.  Two  promi- 
nent symptoms  may  be  associated  with  disease  of  the  auditory  nerve — 
{a)  disturbance  or  loss  of  hearing;  {b)  loss  or  impaii-ment  of  equilibration. 

The  ninth  or  glosso-pharyngeal  nerve  comprises  both  sensory  and 
motor  libres — sensory  for  the  posterior  third  of  the  tongue  and  the 
mucous  membrane  of  the  back  of  the  mouth,  motor  for  the  middle 
constrictor  of  the  pharynx  and  the  stylo-pharyngeus.  It  also  conta,ins 
the  nerves  of  taste  for  the  posterior  third  of  tiic  tongue.  The  efferent 
libres  arise  from  a  nucleus  {moior  nucleus  of  the  glosso-pharyngeal)  a 
little  posterior  to  the  facial  nucleus.  The  afferent  fibres  take  origin 
from  unipolar  cells  in  ganglia  of  spinal  type  connected  with  the  nerve 
(ganglion  petrosum  and  ganglion  superius).  Entering  the  medulla, 
oblongata,  the  central  processes  of  these  cells  bifurcate  into  ascending 
and  descending  branches.  Their  peripheral  processes  pursue  their 
course  as  the  axons  of  sensory  fibres  to  the  structures  to  which  the 
nerve  is  distributed.  The  ascending  branches  terminate  in  a  nucleus 
{prmcipal  nucleus  of  the  glosso-pharyngeal)  beneath  the  floor  of  the 
fourth  ventricle.  The  descending  branches,  as  well  as  similar  branches 
from  the  pars  intermedia  of  the  seventh  nerve  and  from  the  afferent 
fibres  of  the  vagus,  form  a  bundle  called  the  fasciculus  solitarius  (some- 
times termed  the  descending  root  of  the  facial,  vagus,  and  glosso-pharyn- 
geal). It  can  be  traced  to  the  lower  boundary  of  the  spinal  bulb. 
Along  the  mesial  border  of  the  fasciculus  solitarius  are  strung  out  the 
somewhat  scattered  nerve-cells  [descending  nucleus  of  facial,  vagus,  ami 
glosso-pharyngeal),  around  which  the  descending  branches  arborize. 
At  its  upper  end  the  grey  matter  of  the  fasciculus  solitarius  is  con- 
tinuous with  the  principal  nuclei  of  the  glosso-pharyngeal  and  vagus. 

The  tenth  nerve,  or  vagus,  also  contains  both  motor  and  sensory 
fibres.  The  efferent  fibres  arise  partly  from  the  nucleus  ambiguus  or 
ventral  nucleus  of  the  vagus,  a  collection  of  large  nerve-cells  situated  in 
the  reticular  formation,  and  extending  from  a  point  a  little  below  the 
facial  nucleus  to  a  point  a  little  above  the  lower  limit  of  the  medulla 
oblongata,  where  it  becomes  continuous  with  the  column  of  cells  from 
which  the  spinal  fibres  of  the  eleventh  nerve  take  origin.  A  second 
nucleus  of  origin  for  efferent  vagus  fibres  is  constituted  by  the  upper 
part  of  the  dorsal  accessory-vagus  nucleus,  a  collection  of  rather  small 
cells  extending  from  a  little  below  the  lower  margin  of  the  pons  to 
nearly  the  level  of  the  first  cervical  nerve. 

The  affei-ent  fibres  of  the  vagus  arise  from  unipolar  cells  in  ganglia 
connected  with  the  nerve  (ganglion  jugulare,  ganglion  nodosum).  In 
tile  medulla  oblongata  they  bifurcate,  like  other  fibres  coming  off  from 
the  cells  of  ganglia  of  spinal  type.  The  ascending  branches,  which  are 
short,  terminate  in  the  upper  sensory  or  principal  nucleus,  and  the 
descending  branches,  which  are  long,  in  the  cells  of  the  fasciculus  soli- 
tarius, just  as  in  the  case  of  the  glosso-pharyngeus. 

The  motor  fibres  of  the  vagus  are  partly  derived  from  the  accessory, 
whose  internal  branch  joins  the  vagus  not  far  from  its  origin.  The 
distribution  of  the  nerve  is  more  extensive  than  that  of  any  other  in 
the  body.  The  oesophagus  receives  both  motor  and  sensory  branches 
from  the  oesophageal  plexus.  I'he  pharyngeal  branch  of  the  vagus  is 
the  chief  motor  nerve  of  the  pharynx  and  soft  palate  (including  the 
tensor  palati).  The  superior  laryngeal  branch  is  the  nerve  of  common 
sensation  for  the  larynx  abo\e  the  vocal  cords,  and  the  motor  nerve 

59 


930  THE  CENTRAL  NERVOUS  SYSTEM 

of  the  crico-thyroid  muscle.  The  inferior  or  recurrent  laryngeal  sup- 
plies the  rest  of  the  laryngeal  muscles,  and  tlie  sensory  fibres  for  the 
mucous  membrane  of  the  trachea  and  the  larynx  below  the  glottis. 
The  superior  laryngeal  contains  afferent  fibres,  stimulation  of  which 
gives  rise  to  coughing,  slows  respiration,  or  stops  it  in  expiration. 
Reflex  movements  of  deglutition  are  also  caused.  The  vagus  supplies 
the  lungs  both  with  motor  and  sensory  filaments  through  the  pulmonary 
plexus.  The  motor  fibres  when  stimulated  cause  constriction  of  the 
bronchi;  excitation  of  the  afferent  fibres  causes  reflex  changes  in  the 
rate  or  depth  of  respiration.  The  cardiac  branches  contain  inhibitory 
fibres  probably  derived  from  the  spinal  accessory,  and  depressor  fibres 
which  pass  up  in  the  vagus  trunk  (dog),  or  as  a  separate  nerve  to  join 
the  vagus  or  its  superior  laryngeal  branch  or  both  (rabbit).  The  gastric 
and  intestinal  branches  contain  both  motor  and  sensory  nerves  for  the 
stomach  and  intestines.  The  sensory  are  probably  large  medullated 
fibres  (7  /*  to  9  m).  The  afferent  vagus  fibres  from  the  stomach  carry 
up  impulses  v/hich  excite  the  action  of  vomiting.  Lesions  of  the  vagus, 
its  nuclei  of  origin,  or  its  branches,  are  associated  with  many  interest- 
ing forms  of  paralysis  and  other  symptoms.  Paralysis  of  the  pharynx 
is  generally  caused  by  disease  of  the  nucleus  in  tlie  medulla.  From  its 
anatomical  relation  to  the  nuclei  of  the  glosso-pharj'-ngeal  and  hypo- 
glossal, it  will  be  easily  understood  that  these  nerves  are  often  involved 
in  localized  central  lesions  along  with  the  vagus.  But  the  fact  that  in 
progressive  bulbar  palsy  (glosso-labio-laryngeal  paralysis) — a  condition 
characterized  by  progressive  paralysis  and  atrophy  of  the  muscles  of 
the  tongue,  lips,  larynx,  and  pharynx — the  orbicularis  oris  and  other 
muscles  of  the  mouth  and  chin  are  paralyzed,  while  the  rest  of  the 
muscles  supplied  by  the  facial  remain  intact,  might  seem  to  indicate 
that  in  system  diseases  it  is  not  so  much  anatomical  groups  of  nerve- 
cells  which  are  liable  to  simultaneous  degeneration  and  failure,  as 
physiological  groups  normally  associated  in  particular  functions.  Such 
functional  groups  of  cells,  occupied  with  the  same  kinds  of  labour  at 
the  same  times  and  under  the  same  conditions,  might  be  supposed  to 
take  on  a  similar  bias  or  tendency  to  degeneration — a  tendency  not 
indicated,  it  may  be,  by  any  structural  peculiarity,  but  traced  deep  in 
the  molecular  activity  of  the  cells.  There  is  no  foundation  for  the 
view  that  the  lips  are  involved  in  progressive  bulbar  palsy  because  the 
fibres  of  the  facial  which  supply  them  arise  from  the  hypoglossal 
nucleus,  any  more  than  for  the  idea  that  the  upper  part  of  the  face 
escapes  becau.se  its  motor  fibres,  wliile  reaching  it  in  the  seventh  nerve, 
really  arise  from  the  oculo-motor  nucleus  (Bruce).  Difficulty  in  swal- 
lowing is  the  chief  symptom  of  pharyngeal  paralysis.  The  sjanptoms 
of  laryngeal  paralysis  have  been  already  described  under  '  Voice  ' 
(p.  316).  Tachycardia,  or  a  permanent  increase  in  the  rate  of  the 
heart,  has  been  stated  to  occur  in  certain  cases  of  paralysis  of  the 
vagus,  caused  by  disease  or  accidental  interference;  and  a  persistent 
slowing  of  the  respiration  has  been  occasionally  attributed  to  the  same 
cause.  But  it  is  difficult  to  reconcile  many  of  these  cases  with  experi- 
mental results,  for  in  most  of  them  the  lesion  only  involved  one  vagus; 
and  in  animals  section  of  one  vagus  has  no  permanent  effect  on  the 
rate  of  the  heart  or  of  the  respiratory  movements. 

Destruction  of  the  nerve  near  its  origin  has  been  sometimes  found 
associated  with  disappearance  of  the  food-appetites,  hunger  and  thirst, 
and  it  has  been  assumed  that  this  was  due  to  loss  of  afferent  impulses 
from  the  stomach.  But  clinical  testimony  is  by  no  means  unanimous 
on  this  puint,  and  experiments  on  animals  show  that  other  factors  are 
involved  in  these  sensations  (see  Chapter  XVIII.). 


FUNCTIONS  OF  THE  BRAIN  931 

The  eleventh  or  spinal-accessory  nerve  contains  only  efferent  fibres. 
The  cells  of  origin  of  its  spinal  portion  lie  in  the  lateral  horn  of  the 
cord,  from  about  the  level  of  the  first  to  the  fifth  or  sixtJx  cervical 
nerves.  The  bulbar  portion,  sometimes  called  the  bulbar  accessory, 
arises  from  the  lower  two-thirds  of  the  dorsal  accessory-vagus  nucleus, 
from  about  the  level  of  the  first  cervical  nerve  up  to  the  level  of  the 
tip  of  the  calamus  scriptorius.  The  accessory  portion  of  the  nucleus 
lies  behind  and  to  the  side  of — i.e.,  dorso-lateral  to — the  central  canal; 
the  upper  or  vagus  portion  is  more  laterally  placed  in  the  floor  of  the 
fourth  ventricle.  Soon  after  the  junction  of  its  bulbar  and  spinal 
portions,  the  nerve  divides  into  two  branches,  an  internal  and  an 
external.  The  external  branch,  containing  the  spinal  fibres,  passes  out 
to  supply  the  trapezius  and  sterno-mastoid  muscles  with  motor  fibres. 
The  internal  branch,  containing  the  bulbar  fibres,  passes  bodily  into 
the  vagus. 

The  twelfth  or  hypoglossal  nerve  is  exclusively  an  efferent  nerve. 
Its  nucleus  of  origin  is  an  elongated  collection  of  large  nerve-cells  ex- 
tending throughout  approximately  the  lower  two-thirds  of  the  bulb 
close  to  the  median  line  and  parallel  to  it.  It  contains  the  motor 
supply  of  the  intrinsic  and  extrinsic  muscles  of  the  tongue  and  of  the 
thyro-  and  genio-hyoid.  Paralysis  of  it  causes  deficient  movement  of 
the  corresponding  half  of  the  tongue.  When  the  tongue  is  put  out,  it 
deviates  towards  the  paralyzed  side,  being  pushed  over  by  the  un- 
paralyzed  genio-hycglossus  of  the  opposite  side,  which  is  thrown  into 
action  in  protruding  the  tongue. 

Section  X. — Functions  of  the  Central  Nervous  System  — 

(2)  The  Brain. 

The  paths  by  which  the  various  parts  of  the  central  nervous 
system  are  connected  with  each  other  and  with  the  periphery  have 
been  already  described,  and  we  have  completed  the  examination  of 
the  functions  of  the  spinal  cord  and  medulla  oblongata.  The 
events  that  take  place  in  the  upper  part  of  the  central  nervous 
stem  and  in  the  cortex  of  the  cerebellum  and  cerebrum  now  claim 
our  attention. 

From  very  early  times  the  brain  has  been  popularly  believed  to  be 
the  seat  of  all  that  we  mean  by  consciousness — sensation,  ideation, 
emotion,  volition.  And  he  who  loves  to  trace  the  roots  of  things  back 
into  the  past  may  see,  if  he  choose,  running  through  the  whole  texture 
of  the  older  speculations  a  belief  that  the  brain  does  not  act  as  a  whole, 
but  is  divided  into  mechanisms,  each  with  its  special  work — a  fore- 
shadowing, often  in  grotesque  outlines,  of  the  doctrine  of  localization 
so  widely  held  to-day.  But  until  comparatively  recent  times,  cerebral 
physiology  remained  a  kind  of  scientific  terra  incognita ;  and  no  notable 
additions  were  made  for  a  thousand  years  to  the  doctrines  of  Galen. 
Even  to-day  the  utmost  limit  of  our  knowledge  is  reached  when  in 
certain  cases  we  have  connected  a  particular  movement  or  sensation 
with  a  more  or  less  sharply-defined  anatomical  area.  How  the  cere- 
bral processes  that  lead  to  sensations  and  movements,  to  emotions  and 
intellectual  acts,  arise  and  die  out;  what  molecular  changes  are  asso- 
ciated with  them;  above  all,  how  the  molecular  changes  are  translated 
into  consciousness — how,  for  example,  it  is  that  a  series  of  nerve- 
impulses  from  the  optic  radiation  flickering  across  the  labyrinth  of  the 


932  THE  CENTRAL  NERVOUS  SYSTEM 

occipital  cortex  sliould  light  up  there  a  visual  sensation — these  are 
questions  tc  wliich  we  can  as  yet  give  no  answer,  and  the  answers  to 
some  of  which  must  for  ever  remain  hidden  from  us. 

Functions  of  the  Upper  Part  of  the  Central  Stem  and  Basal  Ganglia. 

— Tlie  function  of  tlie  pons  is  .sufficiently  indicated  by  its  name.  The 
grey  matter  so  plentifully  scattered,  especially  in  its  ventral  portion, 
may  exercise  a  not  unimportant  influence  on  the  impulses  that  traverse 
it.  But  on  the  whole  its  main  office  is  to  provide  a  bridge  along  which 
impulses  may  travel  between  other  portions  of  the  nervous  system. 
We  have  already  seen  that  many  of  its  transverse  fibres  arising  from 
the  cells  of  the  pontine  grey  matter,  and  then  crossing  the  middle  line 
to  the  opposite  middle  peduncle,  arc  the  cerebellar  segments  of  com- 
missural arcs  connecting  the  cerebral  with  the  opposite  cerebellar 
hemispheres.  The  cerebral  segments  of  these  arcs  are  the  cortico- 
pontine fibres  originating  in  the  prefrontal,  temporal,  and  occipital 
portions  of  the  cerebral  cortex,  and  passing  through  the  corona  radiata, 
internal  capsule,  and  crura  cerebri,  to  end  in  the  nuclei-pontis.  Many 
fibres  and  collaterals  of  the  pyramidal  tract  also  terminate  here.  On 
the  dorsal  aspect  of  the  pons  in  the  floor  of  the  fourth  ventricle  are  the 
nuclei  of  origin  (or  reception)  of  the  fifth,  sixth,  and  seventh  cranial 
nerves.  Various  reflex  centres  are  situated  in  this  region — e.g.,  that 
for  the  closure  of  the  eyelids,  when  the  conjunctiva  is  stimulated. 

The  posterior  corpora  qiiadrigemina  and  internal  geniculate  bodies  are 
connected  with  the  cochlear  division  of  the  auditory  nerves,  and  form 
important  stations  on  the  auditory  path  to  the  cortex. 

The  anterior  corpora  quudrigemina  and  the  lateral  corpora  geniculata 
are  connected  with  the  optic  tracts.  Their  development  is  arrested 
after  extirpation  of  the  eyeball  in  young  animals,  and  they  may  there- 
fore be  assumed  to  be  concerned  in  vision,  although  the  size  of  their 
homologues,  the  optic  lobes  or  corpora  bigemina,  in  animals  below  the 
rank  of  mammals  (birds,  reptiles,  amphibians),  does  not  seem  to  be 
related  to  the  development  of  the  organs  of  sight.  Proteus  and  the 
Hag-fish,  e.g.,  have  large  optic  lobes,  rudimentary  eyes  and  optic  tracts. 
The  optic  nerve,  the  anterior  corpus  quadrigeminum,  the  nucleus  of  the 
oculo-motor  nerve  in  the  wall  of  the  Sjdvian  aqueduct,  and' the  fibres 
which  it  carries  to  the  iris,  form  a  reflex  arc  for  the  contraction  of  the 
pupil  to  light,  as  represented  in  Fig.  370,  p.  923. 

The  functions  of  the  optic  thalami  have  not  been  fully  defined  either 
by  experiment  or  pathological  observation,  except  in  so  far  as  they  can 
be  deduced  from  their  connections.  Lying  as  they  do  in  the  isthmus 
of  the  brain,  begirt  by  the  great  motor  and  sensory  paths,  it  is  to  be 
expected  that  lesions  of  the  thalami  should  affect  also  the  internal 
capsule,  and  give  rise  to  the  symptoms  of  motor  and  sensory  paralysis. 
But  it  is  questionable^ whether  any  definite  defect  of  motor  power  or 
common  sensation  has  ever  been  unequivocally  associated  with  a  lesion 
restricted  to  the  thalami.  The  most  constant  features  of  the  so-called 
thalamic  syndrome  (or  symptom-complex)  are  partial  loss  of  sensibility, 
especially  to  tactile  impressions,  and  of  the  muscular  sense  on  the 
opposite  side,  with  some  degree  of  inco-ordination  and  disorder,  though 
little,  if  any,  actual  paralysis  of  voluntary  movements.  These  phe- 
nomena are  accounted  for  by  the  extensive  connections  of  the  thalami. 
Each  of  the  thalamic  nuclei  is  linked  with  a  definite  cortical  region  in 
such  a  way  that  destruction  of  the  cortical  area  in  young  animals  or 
human  beings  leads  to  degeneration  of  the  corresponding  nucleus. 
Some  of  the  fibres  connecting  the  cortex  (and  the  corpus  striatum) 
with  the  thalamus  end  in  the  thalamic  grey  matter,  and  are  therefore 
efiferent  with  respect  to  the  cortex  (corticofugal).     It  is,  however,  the 


FUNCTIONS  OF  THE  BRAIN  933 

afferent  paths  to  the  cortex  with  which  the  thalami  are  specially  related 
as  centres  of  relay.  The  fibres  of  the  upper  fillet  carrying  afferent  im- 
pulses up  from  the  opposite  posterior  column  of  the  cord  to  the  cere- 
brum end  in  the  grey  matter  of  the  thalamus,  as  docs  the  central  path 
of  the  afferent  fibres  of  the  opposite  fifth  nerve.  The  posterior  portion 
of  the  thalamus,  or  pulvinar,  forms  part  of  the  central  visual  apparatus; 
for  (rt)  it  is  found  to  be  undeveloped  in  animals  from  which  the  eyeballs 
have  been  removed  soon  after  birth ;  (b)  a  portion  of  the  optic  tract  is 
certainly  connected  with  it;  (c)  in  some  cases  of  atrophy  of  the  occipital 
cortex,  which,  as  we  shall  see,  is  undoubtedly  a  central  area  for  visual 
sensations,  atrophy  of  the  pulvinar  has  also  been  noticed;  {d)  a  lesion 
of  the  pulvinar  may  give  rise  to  hemianopia  (p.  923). 

Haemorrhage  into  the  caudate  cr  lenticular  nucleus  of  the  corpus 
striatum  often  causes  hemiplegia,  but  this  is  frequently  due  to  implica- 
tion of  the  internal  capsule.  It  is  said,  however,  that  lesions  presumably 
confined  to  the  lenticular  nucleus  cause  paralj'^sis  or  paresis  of  the  limbs 
or  face,  which  is  less  severe  than  that  produced  by  lesions  in  the  internal 
capsule.  Experimental  lesions  in  dogs  and  rabbits  are  stated  to  be 
followed  by  disturbances  of  the  heat-regulating  mechanism  and  rise  of 
temperature. 

Certain  structures  belonging  to  the  primary  fore-brain  which  have 
now  lost  some  or  all  of  their  functional  importance  may  nevertheless  be 
mentioned  as  milestones  in  the  march  of  development.  The  pineal 
body  is  made  up  of  the  vestiges  of  the  unpaired  mesial  eye  of  such 
animals  as  the  ancient  labyrinthodonts,  which  resembled  the  eye  of 
invertebrates  in  having  the  retinal  rods  directed  towards  the  cavity 
instead  of  towards  the  circumference  of  the  eyeball.  In  many  living 
forms,  especially  in  certain  lizards,  this  pineal  or  parietal  eye  is  found 
in  a  more  perfect  condition,  though  covered  by  a  thin  membrane.  The 
ganglia  habennlcB,  two  small  collections  of  nerve-cells,  one  of  which  is 
situated  at  the  posterior  part  of  each  thalamus,  are  supposed  by  some 
authorities  to  represent  the  optic  ganglia  of  this  cyclopean  eye.  They 
are  less  prominent  in  man  than  in  many  of  the  lower  animals.  The 
infu-ndibidum  is  probably  what  remains  cf  the  gullet  of  the  ancestors 
of  the  vertebrates.  The  pituitary  body  is  in  a  different  category.  It 
is  now  known  that,  far  from  being  a  useless  vestigial  remnant,  it  has  a 
highly  important  function  (p.  667).  It  consists  of  two  portions,  the 
anterior  lobe,  or  hypophysis,  derived  from  the  buccal  cavity,  the  pos- 
terior lobe,  or  infundibular  body,  from  the  primary  fore-brain. 

Functions  of  the  Cerebellum. — The  elaborate  pattern  of  the  arbor 
vitae,  the  appearance  given  by  the  branched  laminae  in  a  section 
of  the  cerebellum,  excited  the  speculation  of  the  old  anatomists. 
A  structure  so  mar\'ellous  must  be  matched,  they  thought,  with 
functions  as  unique.  At  a  time  when  the  discoveries  of  Galvani 
and  Volta  were  fresh,  and  the  world  ran  mad  on  electricity,  the 
hypothesis  of  Rolando,  that  '  nerve-force  '  was  generated  by  the 
lamellae  of  the  cerebellum  as  electrical  energy  is  generated  by  the 
plates  of  the  voltaic  pile,  ridiculous  as  it  now  appears,  was  not 
unnatural.  The  speculation  of  Gall,  who  connected  the  cerebellum 
with  the  development  of  sexual  emotions  and  the  action  of  the 
generative  mechanisms,  was  based  on  no  fact.  It  has  been  definitely 
disproved  by  the  observations  of  Luciani,  who  found  that  a  bitch 
deprived  of  its  cerebellum  showed  all  the  phenomena  of  heat  or 


934 


THE  CENTRAL  NERVOUS  SYSTEM 


'  nit,'  was  impregnated,  whelped  at  full  term  in  an  entirely  normal 
manner,  and  manifested  the  maternal  instincts  in  their  full  intensity. 
Flourens  put  foru'ardthe  doctrine  that  the  cerebellum  is  an  organ 
concerned  in  the  co-ordination  of  movements,  and  especially  the 
maintenance  of  equilibrium,  supporting  his  conclusions  by  an 
elaborate  series  of  experiments.  Notwithstanding  the  very  large 
amount  of  experimental  and  clinical  study  which  has  been  devoted 
to  the  cerebellum  since  the  time  of  Flourens,  our  actual  knowledge 


Fig.  373- — Cerebellar  Cortex:  Section  in  Direc- 
tion ol  Lamina  (Cajal).  a,  Purkinje's  cell; 
b,  granule  cell  in  inner  layer;  c,  dendrite  of 
a  granule  cell;  d,  axon  of  a  granule  passing 
into  the  molecular  layer,  where  it  bifur- 
cates into  two  fine  longitudinal  branches 
(Golgi's  method). 


I'ig-  374  — Cerel^ellar  Cortex  : 
Section  across  a  Lamina 
(Cajal).  a,  Purkinje's  cell; 
the  numerous  dots  in  the 
molecular  layer  represent 
cross-sections  of  the  bifur- 
cated axons  of  the  granule 
cells  (Golgi's  method). 


of  its  functions  had  not  until  recently  greatly  advanced  beyond  the 
point  then  reached.  Some  of  the  more  modern  authorities  restrict 
its  influence  entirely  to  the  actions  on  which  equilibration  depends ; 
others  extend  it  to  all  volitional  movements.  Luciani  looks  upon 
it  as  '  an  organ  which  by  processes  that  do  not  awaken  conscious- 
ness exerts  a  continual  strengthening  (reinforcing)  action  upon  the 
activity  of  all  other  nerve-centres.'  Sherrington  conceives  of  the 
cerebellum  as  the  head  ganglion  of  the  proprio-ceptive  system — 
i.e.,  of  the  system  of  neurons  whose  receptors  he  not  on  the  surface. 


r UNCTIONS  Ol-   Tin:  BRAIN  935 

bill  in  the  ckcpcr  parts  of  the  body  (labyrinth  of  car,  muscles, 
tendons,  joints,  viscera,  etc.)  (p.  914)-     After  removal  of  the  whole 
cerebellum  (in  the  dog  or  monkey),  there  is  at  first  rigidity  and  tonic 
spasm  of  cerl;).in  muscles,  which  contribute  to  the  difficulty  of  co- 
ordinating their   movements.     When   this  stage   has  passed,    the 
muscles  all  over  the  body,  but  especially  those  of  the  loins  and  hind- 
limbs,  and  those  which  fix  the  head,  are  weaker  than  normal  (as- 
thenia), are  deficient  in  tone  (atonia),  and  contract  with  a  peculiar 
want  of  steadiness  (Luciani).     When  one  lateral  half  of  the  cere- 
bellum is  removed,  the  symptoms  affect  especially  the  muscles  on 
the  same  side.     In  extensive  lesions  of  the  cerebellum  in  man  what 
has  been  noticed  is  a  marked  in;d)ility  to  maintain  the  upright 
posture,  giddiness,  a  staggering  gait,  twitching  movements  of  the 
eyes  (nystagmus),  tremor  accompanying  voluntary  movements — 
in  a  word,  a  general  breakdown  of  the  co-ordinating  machinery 
(asynergy  or  asynergia),  and  especially  of  the  part  of  it  concerned 
in  the  movements  necessary  for  locomotion,  and  for  the  maintenance 
of  the  equilibrium  of  the  body— the  so-called  cerebellar  ataxia. 
There  is  no  sensory  paralysis  and  none  of  voluntary  movement 
such  as  lesions  of  the  cerebral  cortex  produce,  nor  is  there  any 
psychical  disturbance.     In  cases  of  congenital  defect  of  the  cere- 
bellum, the  power  of  walking,  and  even  of  standing,  may  be  late  in 
being  acquired,  and  imperfect.     But  it  is  remarkable  what  great 
deficiencies  in  the  cerebellar  substance  are  often  compensated  for 
when  established  early  in  life,  so  that  even  cases  of  marked  atrophy 
or  lack  of  development  have  sometimes  been  recognized  for  the 
first  time  at  the  necropsy. 

The  connections  of  the  cerebellum  with  other  parts  of  the  central 
nervous  system  and  with  the  periphery  corroborate  the  direct 
results  of  experiment.  For,  in  addition  to  the  visual  impressions, 
the  most  important  afferent  impulses  concerned  in  equilibration  are 
those  from  the  semicircular  canals  and  vestibule  of  the  internal  ear, 
the  muscles,  tendons,  joints,  etc.,  and  certain  portions  of  the  skin, 
such  as  that  of  the  soles  of  the  feet.  And  the  cerebellum,  as  we  have 
seen  (p.  885),  is  linked  with  all  of  these,  and  has  besides  an  extensive 
crossed  connection  through  the  middle  and  superior  peduncles  with 
the  opposite  cerebral  hemisphere.  The  importance  and  extent  of 
this  crossed  connection  with  the  great  brain  is  illustrated  by  the  facts 
that  in  disease  atrophy  or  deficient  development  of  one  cerebellar 
hemisphere  is  associated  with  a  similar  condition  of  the  opposite 
cerebral  hemisphere,  and  that  a  lesion  in  one-half  of  the  cerebellum 
affects  chiefly  the  co-ordination  of  the  movements  of  the  same  side 
of  the  body— that  is  to  say,  of  the  side  connected  with  the  opposite 
cerebral  hemisphere. 

We  do  not  as  yet  know  the  full  significance  of  this  extraordinarily 
free  communication  of  the  grey  matter  of  the  cerebellum  with  every 
part  of  the  central  nervous  svstem.     But  it  is  evident  that  by  the  broad 


936 


THE  CENTRAL  NERVOUS  SYSTEM 


highway  of  the  rcstiform  body,  or  the  cross-country  routes  from  cere- 
bral cortex  to  cerebellum,  impulses  may  reach  it  from  every  quarter; 
while  impulses  passing  out  from  it  along  its  peduncles  may  influence 
the  motor  discharge  either  indirectly  through  the  Rolandic  cortex  and 
the  pyramidal  tract,  or  more  directly  through  the  antero-lateral  de- 
scending spinal  path  that  brings  it  into  relation  with  the  nuclei  of 
origin  of  the  motor  nerves.  It  is  an  organ  so  connected  that  is  suited 
to  take  cognizance  of  the  multitudes  of  afferent  impressions  concerned 
in  the  co-ordination  of  movements  and  the  maintenance  of  equilibrium, 
and  to  regulate  the  outflow  of  efferent  impulses  in  correspondence  with 
the  inflow  of  aitcrcnt. 

Sherrington  points  out  that  all  the  modern  theories  of  cerebellar 
function  harmonize  with  his  conception  of  the  cerebellum  as  the  head 
ganglion  of  the  proprio-ceptive  system  (p.  934).  The  most  influential 
of  the  proprJo-ceptivc  organs  being  the  labynnth,  the  central  organ  of 
the  whole  proprio-ceptive  mechanism  is  built  up  over  the  central  con- 
nections of  the  labyrinth.  Thither  converge  connecting  (internuncial) 
paths  from  the  central  endings  of  proprio-ceptive  neurons  in  all  seg- 
ments of  the  body  (from  joints,  muscles,  tendons,  ligaments,  viscera, 
etc.).  Thus  a  central  organ  is  developed,  which  varies  in  size  and 
complexity  in 
different  kinds  of 
animals  accord- 
ing to  the  com- 
plexity of  their 
habitual  move- 
ments. 


Fig-  375- — The  Semicircular  Ca-ials  (Diagrammatic)  (after 
Ewald).  H,  horizontal  or  external;  S,  superior;  P,  pos- 
terior. The  two  horizontal  canals  lie  in  the  same  plane. 
The  plane  of  the  superior  vertical  canal  of  one  side  is 
parallel  to  the  plane  of  the  posterior  vertical  canal  of  the 
opposite  side. 


Afferent  Im- 
pulses concerned 
in  Equilibration 
and  Orientation. 
— This  is  a  con- 
venient place  to 
consider  a  little 
more  in  detail 
the   nature  and 

peripheral  sources  of  some  of  the  most  important  afferent  impressions 
concerned  in  equilibration  and  orientation. 

(i)  Afferent  Impulses  from  the  Semicircular  Canals. — The  semi- 
circular canals  are  three  in  number,  and  lie  nearly  in  three  mutually 
rectangular  planes:  the  external  canal  in  the  horizontal  plane,  the 
superior  canal  in  a  vertical  longitudinal  plane,  and  the  posterior  canal 
in  a  vertical  transverse  plane.  Each  canal  bulges  out  at  one  end  into 
a  swelling,  or  am])ulla,  which  opens  into  the  utricular  division  of  the 
vestibule  (Figs,  375,  455).  The  other  extremities  of  the  superior  and 
posterior  canals  join  together,  and  have  a  common  aperture  into  the 
utricle,  but  the  undilatcd  end  of  the  external  or  horizontal  canal  opens 
separately.  The  utricle  and  the  semicircular  canals  are  thus  connected 
by  five  distinct  orifices.  The  greater  part  of  the  internal  surface  of 
the  membranous  canals,  utricle  and  saccule,  is  lined  by  a  single  layer 
of  flattened  epithelium.  But  at  or.e  part  of  each  ampulla  projects  a 
transverse  ridge,  the  crista  acustica,  covered  not  with  squamous,  but 
with  long  columnar  epithelium.      Hair-like  processes  (auditory  hairs) 


FUNCTIONS  OF  THE  BRAIN 


937 


arc  borne  by  some  of  the  columnar  cells,  between  which  lie  more 
elongated  fibrc-likc  supporting  cells.  The  hairs  project  into  a  mucus- 
like mass,  sometimes  containing  otoconia,  or  crystals  of  calcium  car- 
bonate. The  ampullae,  like  the  rest  of  the  membranous  labyrinth,  is 
filled  with  a  watery  fluid  called  endolymph.  The  utricle  and  saccule 
have  each  a  somewhat  similar  but  broader  elevation,  the  macula 
acustica,  covered  with  epithelium  and  hair-cells  of  the  same  character, 
and  the  hairs  project  into  a  similar  mass  in  which  otoconia  are  con- 
stantly present.  In  some  animals,  as  fishes,  the  calcareous  matter  in 
the  utricle  and  saccule  forms  masses  of  considerable  size  {otoliths). 
Fibres  of  the  auditory  nerve  end  in  arborizations  around  the  bodies 
of  the  hair-cells  of  the  macular  and  cristse  acusticse.  We  have  already 
seen  that  it  is  the  ventral  or  vestibular  division  of  the  nerve  which  is 
especially  related  to  the  vestibule  (p.  927). 

There  is  very  strong  evidLUce  that  the  semicircular  canals  are  con- 
cerned, not  in  hearing,  but  in  equilibration.  A  pigeon  from  which 
the  membranous  canals  have  been  removed  still  hears  perfectly 
well  so  long  as  the  cochlea  is  intact,  but  exhibits  the  most  profound 
disturbance  of  equilibrium.  If 
the  horizontal  canal  is  destroyed 
or  divided,  the  pigeon  moves  its 
head  continually  from  side  to  side 
around  a  vertical  axis  ;  if  the 
superior  canal  is  divided,  the 
head  moves  up  and  down  around 
a  horizontal  axis.  The  power  of 
co-ordination  of  movements  is 
diminished,  but  not  to  the  same 
extent  in  all  kinds  of  animals. 
Thrown  into  the  air,  the  pigeon  is 
helpless ;  it  cannot  fly ;  but  a  goose 
with  divided  semicircular  canals 
can  still  swim.  The  condition  is 
only  temporary,  even  when  the 
injury  involves  the  three  canals 
on  one  side ;  but  if  the  canals  on 
both  sides  are  destroyed,  recovery  Fig.  376.  —Dog  Twenty -two  Months 
is  tardy,  and  often  incomplete.  p^^-r't,"'  "**'  ''''""'"' 
In  mammals  the  loss  of  co-ordina- 
tion is  less  than  in  birds,  although  at  first  the  animal  is  unable  to 
walk  propcrlv,  easily  falls  over  to  the  injured  side,  and  goes  con- 
tinually in  a  circle  turning  towards  the  side  of  the  lesion.  Move- 
ments of  the  eyes,  the  direction  of  which  depends  on  the  canal 
destroyed,  take  to  a  large  extent  the  place  of  movements  of 
the  head.  Torsion  of  the  head  towards  the  side  of  the  injury  is, 
however,  pronounced  and  permanent  (\Mlson  and  Pike^  (Fig.  376). 
Speaking  generally,  the  eyes  are  deviated  to  the  side  of  the  lesion, 
and  exhibit  the  phenomenon  of  nystagmus. 


938  THE  CENTRAL  NERVOUS  SYSTEM 

I'his  is  composed  of  two  phases,  a  slow  movement  towar.ls  the  injured 
side  and  a  quick  jerk  back  towards  the  uninjured  side.  The  nystag- 
mus is  synchronous  in  both  eyes,  and  is  constantly  present  for  some 
clays  after  the  operation.  There  is  reason  to  believe  that  the  slow 
deviation  is  due  to  excitation  arising  in  the  labyrinth  and  conveyed 
through  the  vestibular  nuclei  to  the  oculomotor  nuclei  by  way  of  the 
posterior  longitudinal  bundle.  The  slow  movement  can  still  be  ob- 
tained after  removal  of  the  cerebral  cortex.  The  quick  return  jerk  is 
different  in  its  origin,  since  it  is  abolished  by  the  removal  of  the  cere- 
bral hemisphere  on  the  side  to  which  the  eyes  are  moved  in  the  slow 
deviation — i.e.,  the  side  of  the  cerebrum  from  which  the  efferent  im- 
pulses concerned  in  pulling  the  eyes  back  to  the  primary  position  of 
equilibrium  arise. 

In  speaking  of  the  postural  reflexes  it  was  stated  that  evidence 
had  been  obtained  of  the  widespread  influence  of  the  labyrinth  on 
the  tonus  of  the  skeletal  muscles.  The  effects  on  the  postural  tonus 
of  the  limb  muscles  were  separated  into  two  components,  one  due 
to  the  labyrinth  directly,  and  the  other  to  impulses  passing  along 
the  afferent  nerves  of  the  neck  muscles  whose  postural  tonus  is 
itself  affected  from  the  labyrinth.  These  phenomena  have  been 
demonstrated  especially  b}^  Magnus  and  his  pupils,  in  mammals 
like  the  rabbit,  cat,  and  dog,  and  to  a  certain  extent  in  man.  They 
studied  the  effects  of  excitation  of  the  labyrinth  as  well  as  the 
effects  of  its  extirpation.  To  excite  the  labyrinth  they  emploj^ed 
such  '  adequate  '  stimuli  as  are  generated  when  the  position  of  the 
head  is  altered  with  reference  to  the  vertical.  Without  going  into  the 
details  of  this  elaborate  work,  it  may  be  said  that  it  has  placed  in 
a  clear  light  the  manner  in  which  the  posture  of  the  head  and  of 
the  neck  reacts  upon  the  postural  contractions  of  the  limbs.  The 
strange  attitudes  so  often  seen  after  injury  or  disease  of  the  laby- 
rinth are  to  a  great  extent  the  consequences  of  the  abnormal 
postures  assumed  by  the  neck. 

In  the  frog,  in  which  no  direct  influence  of  destruction  of  the  labyrinth 
on  the  tonus  of  the  extremities  has  been  established,  the  effects  of  the 
altered  neck  posture  on  the  postural  tonus  of  the  limbs  have  also  been 
clearly  demonstrated.  On  the  injured  side  the  extremities,  especially 
the  anterior  limb,  arc  flexed  and  adducted,  the  extremities  of  the  other 
side  extended  and  abducted;  the  head  and  vertebral  column  are  ro- 
tated to  the  injured  side  (Ewald).  All  that  is  necessary  to  abolish  the 
difference  in  the  posture  of  the  limbs  on  the  two  sides  is  to  divide  the 
posterior    roots    of    the    spinal    nerves    supplying    the    neck    muscles 

(I'ig-  377)- 

The  effects  of  destructive  lesions  of  the  labyrinth  have  their 
counterpart  in  the  phenomena  caused  by  stimulation ;  excitation  of  a 
posterior  canal,  for  example,  in  the  pigeon  causes  movements  of  the 
head  from  side  to  side. 

Lee's  results  in  fishes  are,  on  the  whole,  of  similar  tenor.  Mechan- 
ical stimulation  of  the  ampullfe  in  the  dogfish,  by  pressing  on  them 
with  a  blunt  needle,  calls  forth  characteristic  movements  of  the 


FUNCTIONS  or  THE  BRAIN  gjg 

eyes  and  fins,  and  electrical  stimulation  of  the  auditory  nerve 
causes  movements  compounded  of  the  separate  movements  obtained 
by  stimulation  of  the  ampullae  one  by  one.  Lee  concludes  that  the 
semicircular  canals  are  the  sense-organs  for  dynamical  equilibrium 
{i.e.,  equilibrium  of  an  animal  in  motion),  and  the  utricle  and  saccule 
for  statical  equilibrium  {i.e.,  equilibrium  of  an  animal  at  rest). 

The  evidence  from  all  sources  points  strongly  to  the  conclusion 
that  afferent  impulses  are  actually  set  up  in  the  fibres  of  the  auditory 
nerve,  through  the  hair-cells,  by  alterations  of  picssure  or  by  stream- 
ing movements  of  the  cndolymph  when  the  position  of  the  head  is 
changed.  Rotation  of  the  head  to  the  right  may  be  supposed  to 
cause  the  cndolymph  in  the  right  external  canal,  in  virtue  of  its 
inertia,  to  lag  behind  the  movement,  and  to  press  upon  the  anterior 
surface  of  the  ampulla.  The  disorders  of  movement  after  lesions  of 
the  canals  may  be  explained  as  the  result  of  the  withdrawal  of 
certain  of  these  afferent  impulses,  and  the  consequent  overthrow  of 


Fig-  377- — '^>  ^'^^^  after  Extirpation  of  the  Left  Labyrinth,  showing  the  Difference 
in  the  Posture  of  the  Limbs  on  the  Two  Sides.  B,  the  Same  Frog  after  Section 
of  the  Posterior  Roots  of  the  Second  Pair  of  Spinal  Nerves.  The  head  and 
vertebral  column  remain  rotated  toward  the  side  of  the  lesion,  but  the  legs  are 
now  held  symmetrically. 

that  equipoise  of  excitation  necessary  for  the  maintenance  of  equi- 
librium. An  experiment  of  Kreidl  on  a  crustacean  (palaemon)  has 
made  it  probable  that  the  otoliths  by  their  weight  may  mechani- 
cally affect  the  hair-cells,  and  so  increase  their  sensitiveness  to 
changes  of  position.  This  animal  has  the  peculiarity  that  in  moult- 
ing the  inner  lining  of  the  otocysts,  in  which  the  otoliths  lie  and 
which  open  to  the  exterior,  are  shed  along  mth  the  otoliths.  When 
moulting  is  over,  the  animal  by  means  of  its  claws  conveys  fine 
sand  grains  into  the  otocysts,  where  they  function  as  otoliths. 
Kreidl  placed  the  animal  after  moulting  upon  finely  powdered  iron, 


940  THE  CENTRAL  NERVOUS  SYSTEM 

some  of  wliich  was  conveyed  into  the  otocyst  instead  of  sand.  It 
was  now  found  possible  to  obtain  definite  reactions  from  the  animal 
in  the  presence  of  a  magnet,  which,  of  course,  tended  to  attract  the 
ferruginous  otoliths,  and  so  to  alter  their  position  with  reference 
to  the  hairs.  The  way  in  wliich  the  animal  changed  its  position  in 
response  to  the  magnet  could  be  satisfactorily  accounted  for  on  the 
hypothesis  that  normally  the  contact  of  the  otoliths  with  the  hairs 
is  altered  under  the  influence  of  gravity  when  such  changes  of  posi- 
tion occur.  Even  in  man  there  is  evidence  of  the  existence  of  some 
mechanism  not  depending  on  the  muscular  sense  or  on  impressions 
passing  up  the  channels  of  ordinary  or  special  sensation,  by  which 
orientation  (the  determination  of  the  position  of  tlie  body  in  space) 
is  rendered  possible.  For  a  man  lying  perfectly  still,  witli  eyes  shut, 
on  a  horizontal  table  wliich  is  made  to  rotate  uniformly,  can  not 
only  judge  whether,  but  also  in  what  direction,  and  approximately 
through  what  angle,  he  is  moved.  The  phenomena  of  pathology 
afford  weighty  additional  testimony  in  favour  of  the  equilibratory 
function  of  the  semicircular  canals.  For  many  cases  of  vertigo  are 
associated  with  changes  in  the  internal  ear  (Meniere's  disease). 
And  while  nearly  every  normal  individual  becomes  dizzy  when 
rapidly  rotated,  35  per  cent,  of  deaf-mutes  are  entirely  unaffected 
(James),  and  the  proportion  seems  to  be  much  higher  among  con- 
genital deaf-mutes.  Kreidl  and  Bruck,  too,  have  found  that  ab- 
normalities of  locomotion  and  equilibration  are  much  more  common 
in  deaf-and-dumb  children  than  in  others.  Now,  in  these  cases 
the  defect  is  usually  in  the  internal  ear. 

Summary. — We  must  conclude,  then,  that  the  co-ordination  of 
muscular  movements  necessary  for  equilibrium  is  achieved  in  some 
centre  or  centres  to  which  afferent  impulses  pass  from  the  internal  ear 
by  the  vestibular  branch  of  the  auditory  nerve,  and  from  ivhich  efferent 
impulses  pass  out  to  the  muscles.  If  this  centre  or  one  of  these  centres 
is  situated  in  the  cerebellum,  the  efferent  path  is,  as  already  suggested, 
partly  an  indirect  one  {perhaps  by  commissural  fibres  to  the  Rolandic 
area,  arid  then  out  along  the  Pyramidal  tract),  or  more  probably  to 
lower  centres,  which  control  such  massive  co-ordinated  movements  as 
those  concerned  in  walking  and  the  maintenance  of  the  normal  attitude, 
and  thence  out  along  certain  tracts  that  connect  the  thalamus  to  the 
spinal  cord  (/>.  88b). 

The  influence  of  the  labyrinth  on  the  eye  nio\ements  through  its 
connection  with  the  oculomotor  nuclei  in  the  mid-brain  has  been 
previously  mentioned  as  a  factor  in  the  phenomena  whicii  follow 
its  destruction  or  stimulation.  It  would,  however,  be  erroneous  to 
assume  that  either  the  cerebellum  or  the  labyrinth  is  essential  to  the 
crude  maintenance  of  that  postural  muscular  tonus  which  is  the  reflex 
foundation  of  the  act  of  standing,  l-'or  in  the  dog  and  cat  the  posture 
persists  after  removal  of  the  fore-brain,  the  mid-brain  back  to  the 


FUNCTIONS  01-    THE  BRAIN  94I 

hinder  edge  of  the  posterior  corpora  quadrigemina  and  the  labyrinth, 
being  supported  partly  through  spinal  centres  and  partly  through 
prc-spinal  centres  mainly  in  the  region  of  the  pons,  but  partly  in  the 
bulb  (Sherrington) .  But  it  is  none  the  less  true  that  the  act  of  standing 
is  aided  and  regulated  in  important  xvays  by  centres  in  the  mid-brain 
and  cerebellum  through  afferent  impulses  originating  in  the  labyrinth 
and  elsexi'hcre — e.g.,  in  the  muscles. 

Ewald  has  made  an  observation  which  illustrates  the  peculiar 
relation  of  the  semicircular  canals  to  the  muscular  system — namely, 
that  the  labyrinth  (in  rabbits),  influences  the  course  of  rigor  mortis 
in  the  striped  muscles.  Rigor  does  not  come  on  so  soon  on  the  side 
from  which  tlic  labyrinth  has  been  removed. 

(2)  Afferent  Impressions  from  the  Muscles.— Muscles  are  richly 
supplied  with  afferent  fibres,  for  about  half  of  the  fibres  in  the  nerves 
of  skeletal  muscles  degenerate  after  section  of  the  posterior  roots 
beyond  the  ganglia  (Sherrington).  Various  kinds  of  impressions 
may  pass  up  these  nerves :  («)  Impressions  giving  rise  to  pain,  as  in 
muscular  cramp  and  in  experimental  excitation  of  even  the  finest 
muscular  ner\'e-filament ;  {b)  impulses  causing  a  rise  of  blood-pres- 
sure ;  (c)  impulses  which  are  not  associated  with  a  distinct  impres- 
sion in  consciousness,  but  which  enable  us  to  localize  the  position 
of  the  limbs,  head,  eyes,  and  other  parts  of  the  body;  (d)  impulses 
which  inform  us  as  to  the  extent  arid  force  of  muscular  contraction, 
and  seem  to  underlie  the  so-called  muscular  sense.  It  is  the  last 
two  kinds — if,  indeed,  they  are  distinct — which  must  be  concerned 
in  equilibration.  In  locomotor  ataxia  such  impressions  are  blocked 
by  degeneration  in  a  part  of  the  afferent  path  (p.  915),  and  disorders 
of  equilibrium  are  the  result. 

(3)  Afferent  Impressions  from  the  Skin. — Of  the  various  kinds  of 
impulses  that  arise  in  the  nerve-endings  of  the  skin,  only  those  of 
touch  and  pressure  seem  to  be  concerned  in  the  maintenance  of 
equilibrium.  When  the  soles  of  the  feet  are  rendered  insensitive  by 
local  anaesthesia  or  by  cold,  and  the  person  is  directed  to  close  his 
eyes,  he  staggers  and  sways  from  side  to  side.  The  disturbance  of 
equilibrium  in  locomotor  ataxia  must  be  partly  attributed  to  the 
loss  of  these  tactile  sensations,  for  numbness  of  the  feet  is  a  frequent 
symptom,  and  the  patient  asserts  that  he  does  not  feel  the  ground. 
An  interesting  illustration  of  the  importance  of  afferent  impubcs 
from  the  skin  in  the  maintenance  of  equihbrium  is  afforded  by  the 
behaviour  of  a  frog  deprived  of  its  cerebral  hemispheres.  Such  a 
frog  will  balance  itself  on  the  edge  of  a  board  like  a  normal  animal, 
but  if  the  skin  be  removed  from  the  hind-legs,  it  will  fall  like  a  lo^'. 

Localization  of  Function  in  the  Cerebellum. — In  birds  and  lower 
vertebrates  the  cerebellum  is  only  represented  by  the  worm.  Yet  in 
many  of  these  animals  the  same  characteristic  disturbances  follow  its 
removal  as  in  the  higher  animals  where  the  cerebellar  hemispheres  have 
become   so   prominent.     Indeed,   it  was   mainly  on   the   pigeon   that 


942 


THE  CENTRAL  NERVOUS  SYSTEM 


Flourens  made  his  classical  experiments.  At  first  the  pigeon  can 
neither  fly  nor  feed  itself.  When  it  attempts  to  walk,  extensor  spasms 
of  the  legs  come  on,  and  it  falls,  wildly  struggling  and  apparently 
panic-stricken,  to  the  ground.  The  power  of  flight  is  soon  regained, 
but  for  a  long  time  the  animal  is  unable  to  perch,  the  legs  and  talons 
stiffening  in  rigid  extension  as  it  attempts  to  alight. 

In  the  higher  animals  stimulation  of  certain  parts  of  the  worm  and 
lateral  lobe  causes  conjugate  movements  of  the  eyes  towards  the  same 
side,  both  eyes  being  turned  to  the  right— eg-.,  when  the  cerebellum  is 
stimulated  to  the  right  of  the  middle  line.  Inhibition  of  movement 
can  also  be  elicited  from  the  organ.     Excitation  of  the  cerebellar  cortex 

for    some    distance 

-..        /      LcK        \  Ls 


Lans 


outwartls  from  the 
line  of  junction  of 
the  superior  worm 
with  the  lateral  lobe 
in  animals  which 
exhibit  tonic  con- 
traction of  extensor 
muscles  after  ex- 
cision of  the  cere- 
bral hemispheres 
(decerebrate  rigid- 
ity or  acerebral 
tonus,  as  it  is  called) 
causes  immediate 
relaxation  of  the 
rigid  muscles  of  the 
neck,  tail,  and  espe- 
cially the  anterior 
limb,  particularly 
on  the  same  side. 
The  relaxation  of 
the  extensors  may 
be  accompanied  by 
contraction  of  the 
antagonistic  flexors 
— for  example,  relaxation  of  the  triceps  and  contraction  of  the  biceps 
(Horsley  and  Lowenthal).  But  this  can  scarcely  be  considered  a  re- 
action specific  to  the  cerebellum.  For  Sherrington,  who  finds  that 
the  tonus  or  spasm  is  largely  due  to  centripetal  impulses  coming  from 
the  rigid  limb,  has  been  able  to  inhibit  it  by  stimulation  of  various 
other  regions,  including  the  portion  of  the  cerebral  cortex  in  front  of 
the  fissure  of  Rolando  (p.  955). 

The  confusion  which  so  long  reigned  in  regard  to  cerebellar 
localization  has  in  great  measure  been  cleared  up  by  recent  physio- 
logical work  following  on  a  more  accurate  anatomical  mapping  of  the 
lobes  and  lobules  of  the  cerebellum  in  accordance  with  their  genetic 
relations  (Elliott  Smith,  Bolk)  (Figs.  378,  379).  The  classical  descrip- 
tion of  the  mammalian  cerebellum  as  consisting  of  a  median  lobe  or 
vermis  and  two  hemispheres  has  been  abandoned. by  the  modern 
investigators  in  this  field.  They  divide  the  organ  into  two  chief 
lobes,  an  anterior  and  a  posterior,  separated  by  the  deep  and  constant 
primary  fissure. 


Fig.  378. — Scheme  of  Dog's  Cerebellum  (Dorsal  View),  ac- 
cording to  the  Anatomical  Dixision  of  Bolk  (after  van 
Rynberk).  La,  lobus  anterior,  which  is  separated  from 
the  larger  posterior  lobe  by  the  deep  primary  fissure 
(sulcus  priniarius),  Spr,  Ls,  lobulus  simplex;  Si,  sulcus 
intercruralis;  C^,  crus  primum;  C^,  crus  secundum; 
L.ans,  lobulus  ansiformis;  Lp,  lobulus  paramedianus; 
Lmp,  lobulus  medianus  posterior;  Fv,  formatio  vermi- 
cularis  (pars  tonsillaris);  Sp,  sulcus  paramedianus. 


FUNCTIONS  OF  THE  BRAIN 


943 


Followiiif,'  tliis  scheme,  van  Rynberk  has  obtained  satisfactory 
evidence  of  hjcahzation  of  function.  Thus  the  loljuhis  simplex  con- 
stitutes a  centre  for  tlie  neck  muscles,  and  the  elimination  of  its 
influence  by  excision  leads  to  movements  of  the  head  (so-called  head 
nystagmus).  The  anterior  extremity  is  represented  by  a  centre  in 
the  crus  primum,  and  the  posterior  extremity  by  a  centre  in  the  cms 
secundum,  of  the  ansiform  lobule  of  its  own  side,  and  injury  in  the 
region  of  these  centres  is  associated  with  abnormal  movements  of  the 
corresponding  fore  and  hind  foot  respectively.  Extirpation  of  a 
lobulus  paramedianus  causes  rolling  movements  of  the  body  around 
its  long  axis  or  bending  of  the  body  to  one  side,  and  this  centre  is 
connected  with  the  muscles  of  the  trunk.  A  general  scheme  of  the 
localizations  in  the  mammalian  cerebellum  is  given  in  Fig.  379. 


Ftacc 


Fig.  oyg. — Bolk's  Scheme  of  the  Mammalian  Cerebellum.     On  the  right  half,  certain 
localizations  are  indicated  (Mills  after  Von  Bechterew). 

It  must  be  remarked  that  the  areas  connected  with  the  co- 
ordination (synergia)  of  the  muscles  concerned  in  particular  move- 
ments cannot  be  so  sharply  localized  on  the  surface  of  the  cere- 
bellum as  the  areas  connected  with  the  discharge  of  the  movements 
can  be  localized  on  the  surface  of  the  cerebrum.  It  is  stili  an  open 
question  whether  in  the  function  of  these  centres  only  the  cortex 
of  the  lobules  is  concerned,  or  in  addition  the  corresponding  por- 
tions of  the  central  nuclei  of  the  eerebellum.  These  observations 
are  supported  by  other  facts.  For  example,  microscopical  studies 
have  shown  that  definite  regions  of  the  cerebellar  cortex  are  especially 
connected  with  definite  levels  of  the  spinal  cord.  Further,  the 
lobulation  of  the  cerebellum  in  mammals  keeps  pace  with  the  in- 
crease in  complexity  of  the  voluntary  motor  apparatus  of  the  whole 
body,  and  the  variations  in  the  degree  of  development  of  definite 
lobules  are  related  to  the  variations  in  the  anatomical  and  physio- 


944 


THE  CENTRAL  NERVOUS  SYSTEM 


logical  development  of  the  corresponding  groups  of  muscles.  All 
this  fits  in  well  with  the  idea  that  the  cerebellum  is  a  great  reflex 
mechanism  standing  in  intimate  relation  on  the  one  hand  to  numer- 
ous afferent  paths  (skin,  muscles,  labyrinth,  etc.),  and  on  the  other 

to  the  voluntary  muscles.  It  is 
the  precise  nature  of  the  influence 
exerted  by  it  upon  the  latter 
which  is  in  doubt,  whether  an 
augmenting  sthenic  influence,  as 
Luciani  supposes,  or  a  co-ordinat- 
ing influence,  asFlourens  assumed, 
or  a  combination  of  these. 

Progress  has  recently  been  made 
in  utilizing  the  results  of  experi- 
mental and  clinical  study  of  the 
cerebellum  for  the  localization  of 
circumscribed  cerebellar  lesions  in 
man  (Barany). 

The  centres  for  the  limbs  are 
situated  in  the  cortex  of  the  hemi- 
spheres, those  for  the  right  ex- 
tremities in  the  right  semilunar 


Fig.  380. — Localizations  on  the  Infero- 
latcral  Aspect  of  the  Human  Cere- 
bellum (Barany).  X  ,  is  a  centre  for 
the  tonus  of  the  muscles  abducting 
the  right  arm  ;  O,  a  centre  for  the 
tonus  of  the  muscles  concerned  in 
adduction   of   the  right   hand  ;  +  ,  a 

centre  for  the  tonus  of  the  muscles    (superior  and  inferior)  and  digas- 

adducting  the  right  arm;  ±,  a  centre    t^ic    lobuleS  ;     thoSC    for    the    left 


for  the  tonus  of  the  muscles  adducting 
the  right  hip.  N.V,  N.VI,  N.VIl, 
N.IX,  N.XII,  are  cranial  nerves. 


extremities  in  the  corresponding 
positions  on  the  left  cerebellar 
hemisphere. 

Forced  Movements.— Wc  have  incidentally  mentioned  that  in  fishes 
mjuncs  to  the  semicircular  canals  may  give  rise  to  movements  which 
seem  to  be  beyond  the  control  of  the  animal,  and  which  have  conse- 
quently received  the  name  of 
'  forced  movements.'  It  may 
be  added  that  when  the  in- 
ternal ear  of  a  Necturus  (one 
of  the  tailed  amphibia)  is 
destroyed  on  one  side,  rapid 
movements  of  rotation  around 
a  longitvidinal  axis  arc  ob- 
served. The  animal  spins 
round  and  round  apparently 
without  voluntary  control, 
purpose,  or  fatigue.  The  di- 
rection of  rotation  is  towards 
the  side  of  the  lesion,  the 
observer  being  supposed  to 
look  down  upon  the  animal  as 
it  lies  in  its  normal  position. 
After  a  time  it  becomes  quiescent;  but  the  forced  movements  can  be 
again  produced  by  pinching  or  exciting  it  in  other  ways.  Similar 
rolling  movements,  and  in  the  same  direction,  have  been  observed  in 


Fig.  381 — Localizations  on  Posterior  Aspect 
of  Human  Cerebellum  (Barany).  '^,  a  centre 
for  the  tonus  of  the  muscles  concerned  in 
the  movements  of  the  right  arm  downwards; 
X  ,  same  as  in  Fig.  380. 


FUNCTIONS  OF  THE  DRAIN  945 

niainnials  after  extirpation  of  one  labyrinth.  They  arc  elicited  with 
special  eas?  in  the  rabbit.  In  this  animal  it  has  been  shown  by  study- 
ing the  movements  by  the  aid  of  the  cinematograph  that  the  rolling 
movements  are  really  movements  of  progression  (running  and  spring- 
ing), which,  on  account  of  the  changes  in  the  position  of  the  head  and 
neck,  and  in  the  tonus  of  the  muscles,  lead  to  a  spiral  rotation  of  the 
body,  in  which  the  forward  movement  is  small  in  proportion  to  the 
rotation. 

In  man,  too,  during  the  passage  of  a  galvanic  current  through  the 
head  by  electrodes  applied  just  behind  the  ears,  a  tendency  to  move 
the  head  towards  the  anode  is  experienced.  The  person  may  resist 
the  tendency;  but  if  the  current  be  strong  enough  his  resistance  will  be 
overcome ;  he  will  execute  a  forced  movement.  When  the  head  turns 
towards  the  anode  the  eyes  move  in  the  same  direction,  and  then  under- 
go jerking  movements  towards  the  kathode.  There  is  at  the  same 
time  a  feeling  of  vertigo.  Complex  as  such  an  experiment  is,  involving 
as  it  docs  stimulation  of  so  many  structures  within  the  cranium,  there 
is  reason  to  believe  that  it  is  the  excitation  of  the  semicircular  canals,  or 
their  cerebellar  connections,  that  is  responsible  for  these  forced  move- 
ments. For  when  the  experiment  is  performed  on  a  pigeon,  forced 
movements  are  caused  so  long  as  the  membranous  canals  are  intact, 
but  not  after  they  have  been  destroyed  (Ewald).  The  observation  of 
Rawitz,  that  the  peculiar  rotatory  movements  of  the  so-called  Japanese 
dancing  mice  are  associated  with  marked  anatomical  peculiarities  in 
the  labyrinth,  is  another  fact  in  favour  of  the  connection  of  the  canals 
with  the  maintenance  of  equilibrium  and  the  sense  of  rotation.  So  is 
the  relation  between  the  degree  of  development  of  the  canals  in  different 
species  of  birds  and  the  degree  of  agility  in  the  co-ordination  of  then 
movements  (Laudenbach). 

But  forced  movements  may  also  follow  injuries  (especially  unilateral) 
to  many  portions  of  the  brain — e.g.,  the  pons,  crus  cerebri,  posterior 
corpora  quadrigemina,  corpus  striatum,  even  the  cerebral  cortex,  and 
above  all  the  cerebellum.  The  movements  are  of  the  most  various 
kinds.  The  animal  may  run  round  and  round  in  a  circle  (circus  move- 
ment) ;  or,  with  the  tip  of  its  tail  as  centre  and  the  length  of  its  body 
as  radius,  it  may  describe  a  circle  with  its  head,  as  the  hand  of  a  clock 
does  (clock-hand  movement) ;  or  it  may  rush  forward,  turning  end- 
less somersaults  as  it  goes.  Intervals  of  rest  alternate  with  paroxysms 
of  excitement,  and  the  latter  may  be  brought  on  by  stimulation.  In 
man  forced  movements  associated  with  vertigo  have  been  sometimes 
seen  in  cases  of  tumour  of  the  cerebellum — e.g.,  involuntary  rotation 
of  the  body  in  tumour  of  the  middle  peduncle.  No  entirely  satisfac- 
tory explanation  of  these  forced  movements  has  been  given.  They  are 
evidently  connected  with  disturbance  of  the  mechanism  of  co-ordina- 
tion, leading  to  a  loss  of  proportion  in  the  amount  of  the  motor  dis- 
charge to  muscles  or  groups  of  muscles  accu.stomed  to  act  together  in 
executing  definite  movements.  For  instance,  in  circus  movements  the 
muscles  of  the  outer  side  of  the  body  contract  more  powerfully  than 
those  of  the  inner  side,  and  the  animal  is  therefore  constrained  to  trace 
a  circle  instead  of  a  straight  line,  the  excess  of  contraction  on  the  outer 
side  being  analogous  to  the  acceleration  along  the  radius  in  the  case 
of  a  point  moving  in  a  circle. 

In  connection  with  the  consideration  of  the  mechanism  of  equilibra- 
tion,  a  short  account  of  the  muscular  actions  concerned  in  the  main- 
tenance of  the  erect  posture  so  characteristic  of  man,  and  of  those 
concerned  in  locomotion,  is  subjoined  here: 

Standing. — In  the  upright  posture  the  body  is  supported  chiefly  by 

60 


946  THE  CENTRAL  NERVOUS  SYSTEM 

non-muscular  structures,  the  bones  and  ligaments.  But  muscles  also 
play  an  essential  part,  for  it  is  only  peculiarly-gifted  individuals,  like 
sorne  of  the  fishermen  of  the  North  Sea,  who  can  go  to  sleep  on  their 
feet,  and  a  dead  body  cannot  be  made  to  stand  erect.  The  condition 
of  equilibrium  is  that  the  perpendicular  dropped  from  the  centre  of 
gi-avity  to  the  ground  should  fall  within  the  base  of  support — that  is, 
within  the  area  enclosed  by  the  outer  borders  of  the  feet  and  lines 
joining  the  toes  and  heels  respectively.  The  centre  of  gravity  alters 
its  position  with  the  position  of  the  body,  which  tends  to  fall  whenever 
the  perpendicular  cuts  the  ground  beyond  the  base  of  support. 

In  the  comfortable  and  natural  erect  position  tlic  centre  of  gravity 
of  the  head  is  a  little  in  front  of  the  vertical  plane  passing  through  the 
occipital  condjdcs,  and  as  much  as  4  centimetres  in  front  of  the  vertical 
plane  passing  through  the  ankle-joints.  A  certain  degree  of  contrac- 
tion of  the  muscles  of  the  nape  of  the  neck  is  required  to  balance  it. 
When  these  muscles  are  relaxed,  as  in  sleep,  the  head  must  fall  forward, 
and  this  is  the  reason  why  Homer  or  any  lesser  individual  nods.  In 
animals  which  go  upon  all-fours  none  of  the  weight  of  the  head  bears 
directly  upon  the  occipito-atloid  articulation;  its  support  by  muscular 
action  alone  would  be  an  intolerable  fatigue,  and  the  ligamentum 
nuchae  is  specially  strengthened  to  hold  it  up. 

The  vertebral  column  is  kept  erect  by  the  ligaments  and  muscles 
of  the  back.  The  centre  of  gravity  of  the  trunk  lies  almost  vertically 
over  the  horizontal  line  joining  the  two  acetabula,  but  the  centre  of 
gravity  of  the  whole  body  is  about  the  level  of  the  third  sacral  vertebra, 
and  a  little  more  than  4  centimetres  in  front  of  the  vertical  plane 
passing  through  the  ankle-joints.  E(iuilibrium  is  maintained  by  con- 
traction of  the  muscles  of  the  back  and  of  the  legs.  By  means  of  the 
muscular  sense,  and  the  tactile  sensations  set  up  by  the  pressure  of  the 
.soles  on  the  ground,  alterations  in  the  position  of  the  centre  of  gravity, 
and  consequent  deviations  of  the  perpendicular  passing  through  it, 
are  detected,  and  adjustment  of  the  amount  of  contraction  of  this  or 
the  other  muscular  group  is  promptly  made. 

In  standing  at  '  attention  '  the  heels  are  close  together,  the  legs  and 
back  straightened  to  the  utmost,  and  the  head  erect;  the  weight  falls 
equally  upon  both  legs,  but  the  advantage  may  be  more  than  counter- 
balanced by  the  muscular  exertion  associated  with  this  more  orna- 
mental than  useful  position.  In  '  standing  at  case,'  practically  the 
wliolc  weight  is  supported  by  one  leg,  the  ]jerpcndicular  from  the 
centre  of  gravity  passing  through  the  knee  and  ankle-joint.  The 
centre  of  gravity  is  brought  o\  er  the  supporting  leg  by  llcxure  of  the 
body  to  the  corresponding  side,  and  comparatively  little  muscular 
effort  is  required.  The  other  foot  rests  lightly  on  the  ground,  the 
weight  of  the  leg  itself  being  almost  balanced  by  the  atmospheric 
pressure  acting  upon  the  air-tight  and  air-free  cavity  of  the  hip-joint. 
The  light  touch  of  this  foot  varies  slightly  from  time  to  time,  so  as  to 
maintain  equilibrium. 

When  the  head  or  arms  are  moved,  or  the  body  swaj-ed,  the  centre 
of  gravity  is  correspondingly  displaced,  and  it  is  by  such  movements 
that  tight-rope  dancers  continue  to  keep  the  perpendicular  passing 
through  it  always  within  the  narrow  base  of  support. 

In  sitting,  the  base  of  support  is  larger  than  in  standing,  and  the 
equilibrium  therefore  more  stable.  The  easiest  posture  in  sitting 
without  support  to  the  back  or  feet  is  that  in  which  the  perpendicular 
from  the  centre  of  gravity  passes  through  the  horizontal  line  joining 
the  two  tubcra  ischii. 

Locomotion. — In  walking,  the  legs  are  alternately  swung  forward 


FUNCTIONS  OF  THE  BRAIN  947 

and  rested  on  the  ground,  With  most  persons  the  swinging  foot  tirst 
strikes  the  ground  by  the  heel;  then  the  sole  comes  down,  tlie  heel 
rises,  the  leg  is  extended,  and,  with  a  parting  pusli  from  the  toe,  the 
leg  again  swings  free.  By  this  manoeuvre  the  body  is  raised  vertically, 
tilted  to  the  opposite  side,  and  also  pushed  in  advance. 

The  forward  swing  of  the  leg  is  only  slightly,  if  at  all,  due  to  mus- 
cular action;  it  is  more  like  the  oscillation  of  a  pendnlum  displaced 
behind  its  position  of  equilibrium,  and  swinging  through  that  position, 
and  in  front  of  it,  under  the  influence  of  gravity.  For  this  reason  the 
natural  pace  of  a  tall  man  is  longer  and  slower  than  that  of  a  short 
man;  but  it  may  be  modified  by  voluntary  effort,  as  when  a  rank  of 
soldiers  of  different  height  keeps  step.  The  lateral  swing  of  the  body 
is  illustrated  bj'  the  everyday  experience  that  two  persons  knock 
against  each  other  when  they  try  to  walk  close  together  without 
keeping  step.  In  step  both  swing  their  bodies  to  the  same  side  at 
the  same  moment,  and  there  is  no  jarring.  Even  in  the  fastest  walk- 
ing on  le\el  ground  there  is  a  short  time  during  whi<  h  both  feet  touch 
the  ground  together,  the  one  leg  not  beginning  its  swing  until  the 
other  foot  has  begun  to  be  set  down.  In  running,  on  the  other  hand, 
there  is  an  interval  during  which  the  body  is  completely  in  the  air, 
while  in  walldng  uphill  or  in  carrying  a  load  the  one  foot  is  not  raised 
until  the  other  has  been  firmly  planted. 

Functions  of  the  Cerebral  Cortex.— When  an  animal,  Hke  a  frog, 
is  deprived  of  its  cerebral  hemispheres,  the  power  of  automatic 
voluntary  movement  appears  to  be  definitively  and  entirely  lost. 
The  animal,  as  soon  as  the  effects  of  the  anaesthetic  and  the  shock 
of  the  operation  have  passed  away,  draws  up  its  legs,  erects  its  head, 
and  assumes  the  characteristic  position  of  the  normal  frog  at  rest. 
So  close  maybe  the  resemblance,  that  if  all  external  signs  of  the  opera- 
tion have  been  concealed,  it  may  not  be  possible  for  a  casual  ob- 
server to  tell  merely  bj^  inspection  which  is  the  intact  and  which  the 
'  brainless  '  frog.  The  latter  will  jump  if  it  be  touched  or  othenvise 
stimulated.  It  will  croak  if  its  flanks  be  stroked  or  gently  squeezed 
together.  It  will  swim  if  thrown  into  water.  If  placed  on  its  back, 
it  will  promptly  recover  its  normal  position.  But  it  will  do  all 
theve  things  as  a  machine  would  do  them,  without  purpose,  without 
regard  to  its  environment,  with  a  kind  of  '  fatal  '  regularity. 
Every  time  it  is  stimulated  it  will  jump,  every  time  its  flanks  are 
squeezed  it  will  croak,  and,  in  the  absence  of  all  stimulation,  it  will 
sit  still  till  it  withers  to  a  mummy,  even  by  the  side  of  the  water 
that  might  for  a  while  preserve  it. 

A  Necturus,  without  its  cerebral  hemispheres,  will,  like  the  frog, 
refuse  to  lie  on  its  back.  On  stimulation  it  move's  its  feet  or  tail, 
or  its  whole  body;  but  if  not  interfered  with,  it  lies  for  an  indefinite 
time  in  the  same  position.  Its  giUs  are  seen  to  execute  rhythmic 
movements,  which  never  stop,  and  rarely  slacken,  except  for  an 
instant,  when  some  part  of  the  skin,  particularly  in  the  region  of 
the  head,  is  mechanically  or  electrically  stimulated.  The  normal 
Necturus,  on  the  other  hand,  hes  for  long  periods  with  its  gills  at 


948  THE  CENTRAL  NERVOUS  SYSTEM 

perfect  rest,  and  w  Ijcn  stimulated,  moves  for  a  considerable  distance. 
Alter  a  time — two  months  or  more — it  is  true  the  brainless  frog, 
if  it  be  kept  alive,  as  may  be  done  by  careful  attention,  will  recover 
a  certain  portion  of  the  powers  which  it  has  lost  by  removal  of  the 
cerebral  hemispheres;  and,  indeed,  the  longer  it  lives,  the  nearer  it 
approximates  to  the  condition  of  a  normal  frog.  A  brainless  frog 
has  been  seen  to  catch  flies  and  to  bury  itself  as  winter  drew  on. 
A  fish  even  three  days  after  the  destruction  of  its  cerebrum  has  been 
seen  to  dart  upon  a  worm,  seize  it  before  it  had  time  to  sink  to  the 
bottom  of  the  aquarium,  and  swallow  it.  Even  in  the  pigeon  the 
loss  of  the  hemispheres,  which  at  first  induces  a  state  of  profound 
and  seemingly  permanent  lethargy,  is  to  a  great  extent  compensated 
for,  as  time  passes  on,  by  the  unfolding  in  the  lower  centres  of 
capabilities  previously  dormant  or  suppressed.  A  brainless  pigeon 
has  been  known  to  come  at  the  whistle  of  the  attendant  and  follow 
him  through  the  whole  house. 

In  the  mammal  the  removal  of  the  whole  or  the  greater  part  of 
the  cerebral  hemispheres  at  a  single  operation  is  uniformly  and 
speedily  fatal;  even  rabbits  or  rats,  which  bear  the  operation  best, 
survive  but  a  few  hours.  During  those  hours  they  manifest 
phenomena  similar  to  those  observed  in  the  bird  and  the  frog.  In 
the  dog  the  entire  cortex  has  been  removed  piecemeal  by  successive 
operations.  In  this  case,  of  course,  the  change  in  the  condition  of 
the  animal  is  more  gradually  produced,  and  an  opportunity  is 
afforded  for  a  certain  recovery  of  function  in  the  intervals  between 
the  operations.  On  the  whole,  however,  as  might  be  expected, 
from  its  greater  intellectual  development,  recovery  is  more  imperfect 
in  the  dog  than  in  the  bird,  much  more  imperfect  than  in  the  frog. 
But  even  in  the  dog  wonderful  resources  Ue  hidden  in  the  grey 
matter  of  the  central  neural  axis,  and  are  called  forth  by  degrees 
to  replace  the  lost  powers  of  the  cerebral  cortex.  It  is  true  that  a 
brainless  dog  is  a  less  efficient  animal  than  a  brainless  fish,  or  even 
than  a  brainless  frog;  but  in  favourable  cases,  even  in  the  dog,  the 
mo\ements  of  walking  may  still  be  carried  out  with  tolerable  pre- 
cision in  the  absence  of  the  cerebral  hemispheres.  The  animal  can 
swallow  food  pushed  well  back  into  the  mouth,  although  it  cannot 
feed  itself.  Stupid  and  listless  as  it  is  compared  with  the  normal 
dog,  it  seems  to  be  by  no  means  devoid  of  the  power  of  experiencing 
sensations  as  the  result  of  impressions  from  without,  or  of  carrying 
on  mental  operations  of  a  low  intellectual  grade.  Goltz  had  a  dog 
which  lived  more  than  a  year  and  a  half  practically  without  its 
cerebral  hemispheres,  and  another  which  lived  thirteen  weeks. 
He  believes  that  they  had  lost  understanding,  reflection,  and 
memor}',  but  not  sensation,  special  or  general,  nor  emotions  and 
voluntary  power.  Their  condition  may  be  best  described  as  one  of 
general  imbecility.     Hunger  and  thirst  are  present.     They  experi- 


FUNCTIONS  OF  THE  BRAIN  949 

enco  sitisfaction  when  fed,  become  angry  when  attacked,  see  a  very 
brit'ht  light,  avoid  obstacles,  hear  loud  sounds,  such  as  those  pro- 
duct d  by  a  fog-horn,  and  can  be  awakened  by  them.  They  are  not 
completely  deprived  of  sensations  of  taste  and  touch.  But  it  ought 
to  be  remembered  that  the  interpretation  of  the  objective  signs  of 
sensation  in  animals  is  beset  with  difficulties;  and  although  every- 
body admits  the  accuracy  of  Goltz's  description  of  what  is  to  be 
seen,  his  interpretation  of  the  facts  has  been  severely  criticized, 
particularly  by  H.  Munk. 

Difficult  as  it  is  to  keep  dogs  alive  after  removal  of  the  greater 
part  of  the  cerebrum,  the  problem  is  far  more  difficult  in  monkeys. 
In  some  recent  experiments,  however,  in  which  the  hemispheres 
were  removed  by  two  successive  operations  from  Macaque  monkeys, 
one  of  the  animals  survived  for  as  long  as  twenty-six  days  the  ex- 
cision of  the  second  hemisphere,  and  others  lived  a  week.  The 
movements  of  the  extremities  were  much  affected.  The  animals 
seemed  to  be  in  a  sleepy  condition  with  the  eyelids  closed,  and  most 
of  them  made  no  movements  which  could  be  interpreted  as  voluntary 
movements  during  tlie  first  days  after  loss  of  the  second  hemisphere. 
Sounds  caused  the  appropriate  reflex  movements  of  the  ears.  The 
pupil  was  constricted  by  light.  The  animals  cried  in  the  usual 
manner  when  subjected  to  painful  stimuli,  but  the  ordinary  facial 
accompaniments  of  pain  were  absent. 

In  man  the  destruction  of  considerable  masses  of  brain-substance, 
particularly  if  gradual,  is  not  necessarily  fatal.  How  great  a  loss 
is  compatible  with  life  cannot  be  exactly  stated.  It  depends  to  a 
large  extent  on  the  position  of  the  lesion.  But  it  is  possible  that 
one  cerebral  hemisphere  may  be  rendered  functionally  useless 
without  immediately  putting  a  term  to  existence.  In  the  foetus, 
however,  no  portion  of  the  great  brain  is  absolutely  indispensable  for 
life  and  movement.  An  anencephalous  foetus  (in  whicli  the  brain  has 
remained  undeveloped)  may  be  bom  alive,  and  live  for  a  short  time. 

We  see,  then,  that  homologous  organs  are  not  necessarily,  nor 
indeed  usually,  of  the  same  physiological  value  in  different  kinds  of 
animals.  A  loss  which  perhaps  hardly  narrows  the  range  of  the 
psychical,  and  certainly  restricts  only  to  a  slight  extent  the  phj'sical 
powers  of  a  fish,  impairs  in  a  marked  degree  the  voluntary  move- 
ments of  a  dog,  still  more  those  of  a  monkey,  in  addition  to  cutting 
off  from  it  a  great  part  of  its  intellectual  life,  and  is  in  man  incom- 
patible with  life  altogether.  It  would  be  easy,  however,  to  exag- 
gerate the  difference  in  the  importance  of  the  cerebrum  to  the  higher 
and  the  lower  animals.  After  all,  it  remains  a  striking  fact  that 
monkeys  and  dogs  can  live  in  the  absence  of  the  cerebral  hemispheres, 
and  to  the  remnant  of  the  central  nervous  system  which  enables  such 
highly  organized  animals  to  support  life  must  still  be  regarded  as  a 
very  wonderful  and  complex  mechanism.  Perhaps,  indeed,  it  is 
not  too  much  to  say  that  the  real  lesson  of  these  experiments  on  the 


950 


THE  CENTRAL  NERVOUS  SYSTEM 


extirpation  of  the  cerebrum  is  not  so  much  tlie  supreme  importance 
of  tlie  h('misi)hcrcs  of  the  great  brain  in  the  l)iglicr  animals  as  the 
manifold  and  fundamental  functions  which  still  reside  in  the  basal 
ganglia.  The  cerebral  cortex  seems  to  have  taken  over  and  exten- 
sively developed  and  adapted  some  of  those  primitive  powers  of 
lower  portions  of  the  nervous  axis,  but  without  depriving  the  older 
formations  of  the  capacity  for  reassuming  them  in  some  degree  when 
the  cortex  has  been  destro3'ed. 

The  results  of  the  removal  of  the  entire  cerebral  hemispheres  help 
us  to  fix  their  position  as  a  whole  in  the  physiological  hierarchy.  A 
more  minute  analysis  shows  us  that  the  cerebral  cortex  itself  is  not 
homogeneous  in  function,  that  certain  regions  of  it  have  been  set 

aside  for  special   labours. 


:,C.//, 


Our  knowledge  of  this 
localization  of  function  in 
tlie  cerebral  cortex  has  been 
derived  partly  from  clinical, 
coupled  with  pathological 
observations  on  man,  and 
partly  from  the  results  of 
the  removal  or  stimulation 
of  definite  areas  in  animals. 
In  addition,  the  study  of 
tlie  development  of  the 
myehn  sheath,  and  especi- 
ally in  recent  years  the 
minute  study  of  the  hist- 
ology of  the  various  regions, 
lia\e  aided  materially  in 
niapi)ing  out  the  cortex. 

It  is  a  fact  which  might 
appear  strange  and  almost 
inexplicable  did  the  history 
of  science  not  constantly 
present  us  with  the  Hke,  that 
fifty  years  ago  the  universal 
opinion  among  physiologists, 
,,    ^  ^,  ,      ,  .        .     ,  pathologists,  and  physicians 

was  that  the  cerebral  cortex  is  mexcitable  to  artificial  stimuli  that 
no  visible  response  can  be  obtained  from  it.  The  great  names  of 
Flourens  and  iMagendie  stood  sponsors  for  this  error,  and  repressed 
research.  In  1870,  however,  Ilitzig  and  Fritsch  showed  that  not  only 
was  It  possible  to  elicit  muscular  contractions  by  stimulation  of  the 
cortex  of  the  brain  in  the  dog  with  voltaic  currents,  but  that  the 
excitable  area  occupied  a  definite  region  in  the  neighbourhood  of  the 
crucial  sulcus  or  sulcus  centralis,  which  runs  out  over  the  convexity  of 
the  hemispheres  nearly  at  right  angles  to  the  longitudinal  fissure  In 
this  region  they  were  further  able  to  isolate  several  distinct  areas 
stimulation  of  which  was  followed  by  movements  respectively  of  the 
head,    face,   neck,   hind-leg,   and   fore-leg   (Fig.   382).     This  was  the 


Fig.  382. — Motor  Areas  of  Dog's  Brain,  n,  neck ; 
/./.,  fore-limb;  h.L,  hind-liinb;  /,  tail;/,  face; 
C.S.,  crucial  sulcus;  e.m.,  eye  movements;  p, 
dilatation  of  the  pupil  in  both  eyes,  but  espe- 
cially in  the  opposite  eye.  All  the  areas  are 
marked  in  the  figure  only  on  the  left  side 
except  the  eye  areas,  whose  position,  to  avoid 
confusion,  is  indicated  on  the  right  hemi- 
sphere. 


FUNCTIONS  OF  THE  BRAIN 


95» 


starting-point  of  a  long  series  of  researches  by  Ferrier,  Munk,  Horsley, 
Soliafer,  Heidcnhain,  and  many  others,  on  the  brains  of  monkeys  as 
well  as  dogs — researches  which  liavc  formed  the  basis  of  an  exact 
cortical  localization  in  the  brain  of  man,  and  have  enriched  surgery 
with  a  new  province.  In  these  later  experiments  the  interrupted  cur- 
rent from  an  induction  machine  has  been  found  the  most  suitable  form 
of  stimulus  (see  Practical  Exercises,  p.  looi),  especially  when  one  elec- 
trode only  is  placed  on  the  cortex  and  the  other  on  some  indifferent 
part  of  the  body — e.g.,  in  the  rectum  (unipolar  stimulation),  a  pro- 
cedure which  permits  of  finer 


localization  than  when  both 
electrodes  are  applied  to  the 
brain  (bipolar  stimulation). 

'  Motor  '  Areas.* — These 
have  been  localized 
with  great  care  (both  by 
stiiniilation  and  by  removal 
of  portions  of  the  cortex) 
in  the  brains  of  the  higher 
apes  (gorilla,  orang,  and 
chimpanzee)  by  Sherrington 
and  Griinbaum,  and  there 
can  be  no  doubt  that  the 
results,  in  their  general 
outlines  at  least,  can  be 
applied  to  the  human  brain. 
These  observers  employed 
the  so-called  unipolar 
method  of  stimulation. 

The  '  motor  '  region  in- 
cludes the  whole  length  of 
and  the  whole  of  the  free 
width  of  the  precentral 
or  ascending  frontal  con- 
volution, and  dips  down  to 
the  bottom  of  the  central 
sulcus  (fissure  of  Rolando 
in  man),  but  does  not 
extend  behind  the  sulcus.  It  extends  also  into  the  depth  of  all  the 
fissures,  so  that  the  hidden  part  of  the  excitable  area  probably 
equals,  perhaps  exceeds,  the  part  which  is  free  on  the  surface  of  the 
hemisphere.     The  anterior  limit  of  the  '  motor '  field  is  not  quite 

*  Since  the  so-called  '  motor  '  area,  as  is  now  well  known,  is  really  sensori- 
motor, and  a  region  having  to  do  purely  with  the  discharge  of  motor  impulses 
does  not  exist,  it  would  be  better  to  call  it  the  sensori-motor,  or,  follo\\'ing 
Bastian's  suggestion,  the  kinaesthetic  area.  Probably,  however,  the  altera- 
tion of  a  term  so  long  sanctioned  by  custom  in  physiological  writings  would 
lead  to  confusion.  Accordingly,  in  what  follow^s  the  word  'mjtor'  will  be 
retained,  but  to  show  that  it  is  used  in  a  special  sense  it  will  be  enclosed  in 
quotation  marks. 


F'g-  383. — Dog's  Brain  with  Lesion.  A  portion 
of  the  cortex  indicated  by  the  shaded  area 
was  destroyed  by  cauterization.  The  symp- 
toms were  complete  blindness  of  the  opposite 
eye  (in  this  case  the  right);  weakness  of  the 
muscles  of  the  limbs  and  of  the  neck  on  the 
right  side;  slight  weakness  of  the  limbs  on  the 
left  side.  When  the  animal  walked,  there  was 
a  tendency  to  turn  to  the  left  in  a  circle.  In 
eating  or  drinking,  the  head  was  turned  to  the 
left,  so  that  the  mouth  was  oblique,  and  the 
right  angle  of  the  mouth  was  lower  than  the 
left.  The  tail  movements  were  normal,  and 
there  was  no  deviation  of  the  tail  to  one  side. 


952 


THE  CENTRAL  NERVOUS  SYSTEM 


sharp,  but  sliadis  off  soincvvliat  gradually  into  inexcitable  cortex. 
The  sulci  in  this  region  cannot  be  considered  to  represent  physio- 
logical boundaries,  and  they  vary  so  much  in  these  higher  brains, 
that  they  can  easily  prove  fallacious  landmarks.  On  the  mesial 
surface  of  the  hemispliere  the  '  motor  '  area  does  not  extend  quite 
to  the  calloso-marginal  fissure. 

Within  this  area  are  localized  movements  of  the  leg  and  arm  and 
their  various  joints,  of  the  head,  face,  mouth,  tongue,  ear,  nostril, 
and  vocal  cords,  of  the  neck,  chest,  and  abdominal  wall,  of  the  pelvic 
floor,  and  the  anal  and  vaginal  orifices. 

Anus  $  vayina.. 
^oes  ^  SaUt 

Anhl^e 
Kne^ 

"^.^^^ 

Shouider 
Eihqv/ 
WrlsC 

Fin£er3 

(f  thumb ,.__ 


Abdomen 

Cheat 


Ofjd.W. 


Opening 
ofj&w. 


Sulcus  cerUraUa. 


Voca.i  '; 

cords.     fiaaiictiCion 


CSS.<f«/. 


Fig.  384. 


-'  Motor  '  Area  of  Cortex  of  Chirtapanzee  (Griinbaum  and  Sherrington). 
Lateral  aspect  of  the  hemisphere. 


The  arrangement  of  the  various  regions  follows  very  closely  the 
order  of  the  cranio-spinal  nerves,  which  supply  them,  but  the  organs 
whose  nerves  come  off  lowest  down  arc  represented  highest  up  in 
the  '  motor  '  area.  Figs.  3.'^4,  385  will  make  this  clear.  In  the  frontal 
region,  isolated  from  the  motor  '  area  by  a  strait  of  inexcitable 
cortex,  lies  an  area  the  stimulation  of  which  causes  conjugate  devia- 
tion of  the  eyes.  But  the  reaction  differs  from  that  obtained  on 
excitation  of  the  '  motor '  area  proper  in  front  of  the  Rolandic  fissure. 

It  is  to  be  particularly  noted  (i)  that  within  the  larger  areas,  such 
as  those  of  the  arm  and  leg,  smaller  foci  can  be  mapped  off  which 
are  related  to  movements  of  the  separate  joints — thus,  in  the  leg 
area,  the  hip,  knee,  and  ankle-joints,  and  the  great  toe,  are  repre- 


FUNCTIONS  OF  THE  BRAIN 


953 


sented  by  separate  and  special  centres;  (2)  that  stimulation  of  any 
one  of  these  areas  leads,  not  to  contraction  of  individual  muscles, 
but  to  contraction  of  muscular  groups  which  have  to  do  with  the 
execution  of  definite  movements. 


Sul<:  calloso 
marg- 

Stiic.pariito 
uccip 


StUc  Central       ^^"■'^^^^g'^'^ 

Sulc  prccenCr.mary 


SuJbc.calcarin 


CS  S  del. 


Fig, 


385. — 'Motor'  Area  on  Mesial  Surface  of  Hemisphere:  Brain  of  a  Cliimpanzee 
{Troglodytes  Niger)  (Griiubaum  and  Sherrington).  Left  hemisphere:  mesial  sur- 
face. The  extent  of  the  '  motor  '  area  on  the  free  surface  of  the  hemisphere  is 
indicated  by  the  black  stippling.  On  the  stippled  area  '  LEG  '  indicates  that 
the  movements  of  the  lower  limb  are  represented  in  all  the  regions  of  the  '  motor  ' 
area  visible  from  this  aspect.  The  muiuter  subdivisions  m  this  area  overlap 
each  other  so  much  that  no  attempt  is  made  to  distinguish  them  in  the  diagram. 
'  Anus  and  vagina  '  indicates  the  position  from  which  perineal  movements  can 
be  primarily  elicited.  Sulc.  central.  =  central  fissure;  Sulc.  calcarin.  =  calcarine 
fissure;  Stilc.  parieto  occ/^.  =parieto-occipital fissure;  Sm/c.  calloso  warg.^calloso- 
marginal  fissure;  Sttlc.  precentr.  niarg.  =  precentral  marginal  fissure.  The  single 
italic  letters  mark  spots  whence,  occasionally  and  irregularly,  movements  of  the 
toot  and  leg  (//),  of  the  shoulder  and  chest  (s),  and  of  the  thumb  and  fingers  [h), 
have  been  evoked  by  strong  faradization.  The  shaded  area  marked  'EYES' 
indicates  a  field  of  free  surface  of  cortex  which,  imder  faradization,  yields  con- 
jugate movements  of  the  eyeballs.  The  conditions  under  which  these  reactions 
are  obtained  separates  them  from  those  characterizing  the  '  motor  '  area. 

Th^  Stability  of  the  Reactions  obtained  by  Stimulating  Cortical  Points. 

— The  question  whether  stimulation  of  a  '  motor '  area,  or  point  invariably 
causes  the  same  movements,  when  it  causes  any  movements  at  all,  has 
been  recently  investigated  by  Graham  Brown  and  Sherrington.  They 
observed  the  contractions  of  two  isolated  antagonistic  muscles  acting 
on  the  elbow-joint  (in  monkeys)  after  elimination  of  all  the  other 
muscles  of  the  arm  and  shoulder  by  section  of  their  '  motor '  nerves,  when 
a  point  on  the  area  of  the  cortex  in  which  the  movements  of  the  elbow 
are  represented  was  excited  by  the  unipolar  method.  They  find  that 
a  cortical  point  which  has  given  flexion  at  the  elbow,  sometimes  on 


954  THE  CENTRAL  NERVOUS  SYbThM 

investigation  the  next  day,  may  give  the  opposite  result  of  extension  oi 
the  elbow.  Even  within  shopt  intervals  reversal  of  the  reaction  elicited 
from  one  and  the  same  point  may  be  seen.  They  do  not  question  at  all 
the  general  regularity  of  the  results  which  such  cortical  points  give 
when  investigated  by  suitable  methods  after  sufficient  intervals  of  rest, 
and  on  which  the  current  statements  as  to  the  reactions  elicited  from 
the  various  '  motor  '  areas  arc  based.  But  they  see  in  the  influence  of 
transient  excitation  either  of  the  point  itsek  or  of  other  more  distant 
points  in  modifying  or  reversing  the  reaction  an  indication  that  one 
of  the  functions  of  the  cortex  may  be  the  carrying  out  of  such  phe- 
nomena of  reversal,  a  function  which  may  play  some  part  in  the 
co-ordination  of  voluntary  movements.  In  this  connection  it  may  be 
remarked  that  a  phenomenon  analogous  to  the  '  facilitation  '  already 
described  for  the  reflex  arc  is  also  exhibited  by  the  motor  cortex. 
If  a  motor  reaction — e.g.,  the  movement  of  flexion  at  the  elbow,  as 
studied  in  a  pair  of  isolated  antagonistic  muscles  in  monkeys,  is  elicited 
by  stimulation  of  the  appropriate  cortical  area,  and  a  second  cortical 
stimulation  is  made  to  follow  the  first,  the  reaction  evoked  by  the 
second  stimulus  is  greater  than  that  following  the  first,  providccl  that 
the  interval  of  time  between  the  two  is  not  too  long.  If  the  first  stimu- 
lus is  so  chosen  that  it  is  just  below  the  strength  necessary  to  evoke  a 
movement,  a  second  or  third  stimulus,  which  also  by  itself  would  fail 
to  cause  a  reaction,  may  do  so.  Not  only  so,  but  stimulation  of  one 
cortical  point,  say  in  the  area  which  gives  flexion  of  the  elbow,  may 
raise  the  excitability  of  neighbouring  points  in  that  area  (so-called 
'  secondary  facilitation  '),  so  that  a  stimulus  which  previously  did  not 
ehcit  the  flexion  movement  from  these  points  may  now  do  so. 

Inhibition  from  the  Cortex. — Contraction  is  not  the  only  effect  on 
the  muscles  which  can  be  elicited  by  stimulating  the  cortex.  Cor- 
tical inhibition  of  tonus  and  of  active  contraction  is  just  as  char- 
acteristic, though  not  so  obvious  a  result.  There  is  abundant  evi- 
dence of  reciprocal  innervation  of  volitional  movements  from  the 
cortex.  When,  e.g.,  the  part  of  the  arm  area  whicli  presides  over 
extension  of  the  elbow  is  stimulated  (in  the  monkey),  it  can  be  shown 
that  the  biceps  relaxes  as  the  triceps  contracts.  In  like  manner, 
stimulation  of  the  appropriate  part  of  the  leg  area  will  cause  along 
with  contraction  of  the  extensors  of  the  hip  relaxation  of  such  flexors 
as  the  psoasiliacns  and  the  tensor  fascia  femoris.  Such  observations 
are  most  easily  made  when,  in  a  certain  stage  of  narcosis,  the  limbs, 
instead  of  hanging  limp,  assume  a  position  of  tonic  flexion,  especially 
at  the  elbow  and  hip.  Under  other  conditions  the  position  of  tonic 
extension  of  a  joint  may  be  assumed,  and  then  it  can  be  shown  that 
excitation  of  the  appropriate  focus  for  flexion  of  that  joifit  will 
cause  simultaneous  contraction  of  the  flexors  and  relaxation  of  the 
extensors. 

The  observer  cannot  fail  to  be  struck  with  the  general  resem- 
blance between  these  cortical  reactions  and  their  co-ordination  and 
the  co-ordinated  bulbo-spinal  reflex  movements  previously  studied. 
There  are,  however,  certain  differences  which  place  the  cortical 
reactions  upon  a  higher  level.  One  of  the  most  important  is  the 
part  played  by  visual,  auditory,  and  pure  '  touch  '  stimuli  in  eliciting 


FUNCTIONS  OF  THE  BRAIN  955 

cortical  motor  responses — e.g.,  '  the  closure  of  the  hand,  pricking 
of  the  ear,  opening  of  the  eyes,  and  turning  of  the  head  in  the 
direction  of  the  gaze  '  (Shernngton).  The  facility  of  response  to 
stimuli  acting  from  a  distance  tiirough  the  distance-receptors,  such 
as  those  of  tlie  retina  and  labyrinth,  is  one  of  the  great  characteristics 
of  the  cerebrum  as  an  organ  concerned  in  movements,  and  helps 
to  place  tlie  '  motor  '  cortex  at  the  helm,  since  these  distance- 
receptors  control  more  than  others  the  skeletal  musculature  as  a 
whole.  Spinal  reflex  movements  are  mainly  such  as  are  elicited 
by  harmful  (nocuous)  stimuli  (protective  reflexes),  or  through  the 
sexual  skin  nerves,  or  from  the  visceral  afferent  fibres,  or  such  as 
are  concerned  in  the  chief  movements  of  locomotion. 

Decerebrate  Rigidity  is  a  phenomenon  closely  related  to  the  in- 
hibitory function  of  the  cerebral  cortex.  It  is  a  condition  of  pro- 
longed s])asm  of  certain  groups  of  skeletal  muscles  (especially  the 
retractor  muscles  of  the  head  and  neck,  the  elevators  of  the  jaw 
and  tail,  and  the  extensors  of  the  elbow,  knee,  shoulder,  and  hip), 
supervening  on  removal  of  the  cerebral  hemispheres  by  transection 
anywhere  in  the  mid-brain  or  in  the  posterior  part  of  the  thalamus, 
and  favoured  by  suspending  the  animal  in  the  vertical  posture. 
If  the  afferent  roots  belonging  to  one  of  the  rigid  limbs  are  severed, 
it  at  once  becomes  flaccid,  while  the  other  limbs  remain  rigid.  The 
tonus  is  therefore  reflex  through  the  local  afferent  nerves,  and,  to 
be  more  precise,  through  those  that  supply  the  deep  structures 
(joints,  muscles,  etc.).  The  centre  must  be  situated  somewhere 
between  cerebrum  and  spinal  bulb,  since  section  of  the  bulb 
abolishes  the  rigidity.  It  is  not  apparently  in  the  cerebellum.  It 
is  noteworthy  that  the  muscles  mainly  involved  in  decerebrate 
rigidity  are  those  which  are  much  more  easily  inhibited  than  excited 
from  the  '  motor  '  cortex,  and  also  in  the  local  spinal  reflexes.  After 
removal  of  the  cerebrum,  the  mechanism  which  maintains  their 
tonic  contraction  has  free  play.  Sherrington  points  out  that  this 
mechanism  sustains  the  steady  muscular  tension  necessary  to  pre- 
serve against  the  force  of  gravity  the  attitude  or  posture  of  the  body. 
According  to  him,  decerebrate  rigidity  is  simply  'reflex  standing.' 
When  the  transient  spinal  reflex  or  the  transient  cortical  effect 
breaks  in  upon  this  tonic  contraction — e.g.,  in  locomotion — ^inhibi- 
tion of  the  contracted  extensors  accompanies  contraction  of  the 
flexors  (see  also  p.  942). 

Removal  of  a  single  '  motor  '  region  leads  to  paralysis  of  the 
corresponding  limb,  or  part  of  a  limb,  on  the  opposite  side.  For 
example,  after  extirpation  of  the  hand  area  the  hand  is  for  a  few 
days  practically  useless  and  apparently  powerless.  In  a  few  weeks, 
however,  it  recovers  remarkably,  so  that  it  is  once  more  used  in 
climbing  or  in  conveying  food  to  the  mouth.  It  is  an  important 
question  in  what  way  this  recovery  is  brought  about.     If  the  whole 


956 


THE  CENTRAL  NERVOUS  SYSTEM 


of  the  corresponding  area  in  the  opposite  hemisphere  is  now  re- 
moved, a  similar  paralysis  occurs  in  the  other  hand,  but  the  hand 
whose  '  motor  '  area  was  first  extirpated  remains  entirely  unaffected 
by  the  second  lesion.  On  the  contrary,  the  first  hand  is  used  more 
freely  and  more  adroitly  than  before  the  second  operation,  probably 
because  the  animal  needs  to  use  it  more.  The  second  hand  recovers 
eventually,  like  the  first.  If  when  this  has  taken  place  the  remain- 
ing part  of  the  arm  area  from  which  the  hand  area  was  first  excised 
be  removed,  neither  hand  is  apparently  affected,  although  there  is 
severe  paralysis  of  the  shoulder  and  slighter  paralysis  of  the  elbow 
on  the  side  opposite  to  the  lesion,  which  is  again  largely  recovered 
from.  The  recovery  of  the  hand  movement  cannot  therefore  be 
attributed  to  the  taking  on  of  the  function  of  the  corresponding 


Fig.  386. — Cerebral  Cortex  Man  (seen  from  Above).  The  front  of  the  brain  is  towards 
the  left.  The  dotted  line  shows  the  position  of  the  fissure  of  Rolando,  as  fixed 
by  Thane's  rule  (p.  963). 

'  motor  '  area  either  by  the  opposite  hand  area  or  by  the  adjacent 
'  motor '  cortex  of  the  same  hemisphere.  According  to  some 
authorities,  the  recovery  is  due  to  the  representation  of  the  upper 
limb  in  the  post-central  gyrus  (ascending  parietal  convolution  in 
man)  acting  through  fibres  that  descend  from  this  g>Tus  to  the 
optic  thalamus,  and  thence  through  the  rubro-spinal  tract,  which 
runs  to  the  spinal  cord  (p.  8^-7). 

Removal  of  the  whole  of  the  '  motor  '  cortex  of  one  hemisphere, 
in  such  animals  as  this  operation  has  been  performed  on,  causes 
paralysis  of  movement  on  the  opposite  side  of  the  body.  The 
paralysis  is  less  marked  in  the  case  of  bilateral  muscles  that  habitu- 
alh'  act  together  than  in  the  case  of  those  which  ordinarily  act  alone. 
Thus  the  muscles  of  respiration  and  the  muscles  of  the  trunk  in 


FUNCTIONS  OF  THE  BRAIN  957 

general  are,  although  perhaps  weakened,  never  completely  para- 
lyzed. This  is  an  indication  that  each  member  of  such  functional 
pairs  of  muscles  is  innervated  from  both  hemispheres;  and  this 
physiological  deduction  is  supported  by  the  anatomical  fact  already 
referred  to,  that  after  removal  of  the  '  motor  '  cortex,  or  injury  to 
the  pyramidal  tracts  in  the  internal  capsule  or  crus,  some  degener- 
ated fibres  (homolateial  fibres)  are  found  in  the  crossed  pyramidal 
tract  on  the  side  of  the  lesion  (p.  875)- 

In  the  dog  after  a  time  the  paralysis  may  more  or  less  completely 
disappear.     In  the  monkey  restoration  is  less  complete. 

Some  interesting  observations  have  been  made  on  a  monkey, 
which  was  carefully  watched  for  eleven  years  after  the  removal  by 
two  operations  of  the  cortex  of  the  greater  portion  of  the  frontal 
and  parietal  lobes  on  the  left  side.  The  character  of  the  animal 
which  had  been  studied  for  months  before  the  operations,  was  en- 
tirely unaffected.  All  its  traits  remained  unaltered.  There  was  no 
loss  of  memory  or  intelHgence.  On  the  other  hand,  disturbances 
of  movement  on  tlie  right  side  were  very  noticeable  up  till  its  death. 
It  learned  again  to  use  the  right  limbs  in  locomotion ;  but,  although 
they  were  not  markedly  weaker  than  those  of  the  left  side,  their 
movements  had  a  certain  clumsiness,  which  was  associated  with  a 
permanent  diminution  in  the  sensibility  of  the  skin  of  these  limbs. 
^Muscular  sensibility  was  also  lessened.  In  acts  requiring  the  use  only 
of  one  hand,  the  right  was  never  willingly  employed,  and  it  evidently 
cost  the  animal  a  great  effort  to  use  it  in  such  movements,  but  by 
special  training  it  learnt  again  to  give  the  right  hand  when  asked 
for  it,  and  to  make  use  of  it  for  other  purposes.  The  movements 
with  which  the  '  motor  '  areas  are  concerned  are  essentially  skilled 
movements,  and  we  may  suppose  that  it  is  more  difficult  for  a 
monkey  to  educate  again  a  centre  for  such  complex  and  elaborate 
mancEuvres  as  are  performed  by  its  hand  than  for  a  dog  to  regain 
normal  control  of  the  comparatively  simple  movements  of  its  paw. 
In  man  in  cases  of  hemiplegia,  when  the  patient  lives  for  some  time, 
a  certain  amount  of  recovery  usually  takes  place,  especially  in  young 
persons,  in  the  paralyzed  leg,  but  much  less  in  the  paralyzed  arm. 

In  the  lower  monkeys  the  '  motor  '  area  was  formerly  stated  to 
extend  behind  the  sulcus  centralis  into  what  in  man  would  be  called 
the  ascending  parietal  convolution  (post-central  gyrus),  and  also  to 
be  more  extensively  represented  on  the  mesial  surface  of  the  hemi- 
sphere than  in  the  higher  apes.  Such  observations,  however,  require 
to  be  reinterpreted  in  view  of  the  results  of  Sherrington  and  Griin- 
baum,  especially  as  they  were  carried  out  by  the  bipolar  method  of 
stimulation,  with  both  electrodes  on  the  cortex.  This  method  does 
not  admit  of  such  strict  locahzation  of  the  stimulus  as  the  unipolai 
method.     The   most  recent  work  with  the  unipolar  method  has 


958  THE  CENTRAL  NERVOUS  SYSTEM 

indicated  that  in  the  lower  apes  also  excitation  of  the  gyrus  post- 
centralis  does  not  cause  movements  (C.  and  O.  Vogt). 

It  is  in  the  light  of  the  results  obtained  in  monkeys,  and  by  the 
aid  of  histological,  embry ©logical,  clinical,  and  pathological  ob- 
servations, that  the  '  motor  '  areas  in  man  have  to  a  great  extent 
been  mapped  out. 

'Jhe  histological  differentiation  of  the  various  cortical  regions  recently 
demonstrated  by  Brodmann  and  by  Campbell  are  of  especial  interest 
(Figs.  387-391).  It  has  long  been  customary  to  divide  the  cortex  into 
layers,  although  the  number  and  the  boundaries  of  these  layers  are 
somewhat  arbitrarily  fixed.  Brodmann  distinguishes  six  layers:  (i)  A 
zonal  or  peripheral  layer,  containing  many  nerve-fibres  and  neuroglia 
cells,  but  few  nerve-cells;  (2)  a  layer  containing  '  granules  '  and  small 
pyramidal  cells  {external  granular  layer) ;  (3)  a  layer  of  medium  and 
large  pyramidal  cells  {pyramidal  layer);    (4)  a  laj'cr  of  small  irregular 


iirr-- 


\. 


^:U. 


Pig.  387. — Ctll-Lamination  of  Gyrus  Postcentralis  (Campbell).  A,  just  behind 
upper  end  cf  fissure  of  Rolando;  B,  from  the  posterior  edge  of  the  gyrus  (inter- 
mediate postcentral  area  of  Campbell). 

cells  {internal  granular  or  stellate  layer) ;  (3)- a  'ganglionic'  layer,  con- 
taining the  largest  pyramidal  cells  ideep  large  pyramids);  (6)  a  layer 
{lamina  miilliformis)  of  spindle-shaped  or  polymorphous  cells.  These 
layers  vary  in  their  structural  details,  and  especially  in  their  relative 
devcloi>mcnt  in  animals  of  different  rank  in  the  mammalian  scale,  in 
one  and  the  same  animal  at  diflercnt  periods  in  its  embryonic  and 
extra-uterine  growth,  and  also  in  different  parts  of  the  cortex  in  an 
adult  animal  of  given  species.  The.  region  in  front  of  the  central 
sulcus  (fissure  of  Rolando),  e.g.,  is  characterized  by  the  presence  of  the 
giant  pyramids  of  Betz,  which  give  origin  to  the  pyramidal  fibres 
going  to  the  trunk  and  limbs  (Fig.  388).     More  than  forty  years  ago 


FUNCTIONS  OF  THE  BRAIN 


950 


Bctz.when  first  describing  these  large  pyramidal  cells,  suggested  thatthey 
were  related  to  some  motor  function,  and  this  view  was  a  few  years  later 
more  clearly  developed  by  Lewis,  the  real  pioneer  in  cortical  localization 
by  the  histological  method.  He  mapped  out  the  motor  area  in  man 
by  this  method,  and  his  results  differ  surprisingly  little  from  those  of 
Campbell  obtained  by  a  much  more  elaborate  technique.  He  pointed 
out  that  areas  containing  the  giant  pyramids  corresponded  with  a 
number  of  the  areas  defined  as  motor  areas  by  the  experimental 
physiologists  by  means  of  electrical  excitation.  Definite  proof  of 
the  connection  of  the  Betz  cells  with  the  pyramidal  fibres  was  not 
obtained  till  much  later.  Some  of  the  facts  which  have  established 
such  a  connection  are  alluded  to  on  a  previous  page  (p.  S73).  Other 
characters  than  the  size,  shape   and   distribution   of  the   nerve    cells 


<r 


.■  y 


V    b' 


:v. 


.^1 


Fig-  3S8 — Cell-Lamination  of  Gyrus 
Preccntralis  (Campb-U).  From  the 
portion  of  the  gyrus  immediately 
in  front  of  the  central  sulcus  (Camp- 
bell's precentral  area  in  Figs.  390, 
391)- 


Fif-  389. — Cell-Lamination  of  Gyrus 
Precentralis  (Campbell).  From  an- 
terior part  of  the  gyrus  (Campbell's 
intermediate  precentral  area  in  Figs. 
390,  391)' 


have  also  proved  of  value  in  differentiating  histologically  the  various 
regions  of  the  cortex — for  example,  the  differences  in  the  diameter 
and  the  number  of  the  medullated  nerve  fibres  which  run  verti- 
cally into  and  out  of  the  grey  matter.  Although  the  method  has 
yielded  valuable  and  suggestive  results,  it  would  be  misleading  to 
state  that  the  agreement  with  the  experimental  and  pathological 
findings  is  anything  more  than  a  general  one.  Discrepancies  in 
detail  are  not  lacking,  and  this  might  be  expected.  Histological  dif- 
ferences, after  all,  are  only  rough  criteria  for  the  differentiation  of 
function. 

Although  the  results  are  less  definite,  the  work  of  Flechsig  on  the 
time  of  development  of  the  medullary  sheath  of  the  fibres  in  the  various 
cerebral  convolutions  has  also  contributed  to  our  knowledge  of  localiza- 


96o 


THE  CENTRAL  NERVOUS  SYSTEM 


tvo-ptydua 


Te*P»" 


Fig.  390. — Structurally  DLSerentiated  Cortical  Area?  (Campbell).     External  surface 
of  hemisphere  (human  brain). 


Vino- 


Fig.  391. — Structurally  Differentiated  Cortical  Areas  fCan>jl»iI;      Mesial  surface  of 
hemispheie  (humar*  brain). 


FUNCTIONS  OF  THE  BRAIN 


961 


tion  in  the  cortex.  In  the  dev^elopment  of  a  neuron  four  stages  can  be 
distinguished :  (i)  Oils  witliout  processes;  [z)  the  appearance  of  pro- 
cesses, first  tlie  axon  and  tiien  the  dendrites;  (3)  the  formation  of  col- 


Fig.  3<52. — Flechsig's  Developmental  Zones  (after  Flechsig).  Outer  surface  of  human 
cerebral  hemisphere.  Primary  zones  (i-io),  darkly  shaded;  intermediate  zones 
(11-31),  less  deeply  shaded;  terminal  zones  {32-36),  unshaded. 

laterals;   (4)   myelination  or  the  formation  of  the  medullary  sheath 
(Fig.  3J3.  P-  854). 

Myelination  occurs  in  the  cerebral  convolutions  in  a  regular  order. 
In  some  areas  the  fibres  miy  be  meduUated  three  months  before  birth, 


Fig.  393- — Flechsig's  Developmental  Zones  (after  Flechsig).     Inner  surface  of  human 
cerebral  hemisphere. 

in  others  not  till  six  months  later.  For  instance,  the  Rolandic  and 
olfactor}'-  regions,  the  calcarine  portion  of  the  occipital  lobe  associated 
with  vision,  and  the  portion  of  the  temporal  lobe  associated  with 
hearing,  are  plentifully  provided  with  meduUated  fibres  a  short  time 
after  birth,  at  any  rate  before  the  first  month,  whereas  the  remaining 
regions  of  the  cortex  are  completely,  or  almost  completely,  free  from 


<j^i  THE  CENTRAL  NERVOUS  SYSTEM 

such  fibres.     In  this  way  Flechsig  has  distinguished  thirty-six  cortical 
fields   (Figs.   392,  393).   which  he  divides  according    to   the  time  of  ^ 
myehnation  into  three  groups: 

1.  Primary  fields,  ten  in  number,  which  are  well  provided  with  mye- 
linated fibres  at  birth.  They  include  the  cortical  centres  for  the 
various  sensations  and  also  the  '  motor  '  area.  They  are  connected 
especially  with  the  so-called  projection  fibres.  Thus,  the  cutaneous 
and  muscular  sense  is  assumed  to  be  represented  in  field  i,  the  sense 
of  smell  in  field  2,  of  vision  in  4,  and  of  hearing  in  5.  From  field  i 
arise  the  fibres  of  the  pyramidal  tract,  chiefly  from  the  ascending 
frontal  convolution,  while  the  sensory  fibres  from  the  skin  and  muscles 
end  mainly  in  the  ascending  parietal.  This  is  an  illustration  of  what 
Flechsig  considers  a  general  rule  for  these  primary  fields — viz.,  that 
each  primordial  sensory  region  is  connected  both  with  an  afferent 
(cortici-petal)  and  witli  an  efferent  (cortici-fugal)  tract.  From  the 
visual  area  (4),  e.g.,  arises  a  tract  which  proceeds  mainly  to  the  anterior 
corpus  quadrigeminum. 

2.  Terminal  fields  (32  to  36  in  the  figures)  which  become  myelinated 
late,  the  process  not  beginning  until  at  least  a  month  after  birth. 

3.  Intermediate  fields  (11  to  31)  which  become  myelinated  earlier 
than  the  terminal,  but  later  than  the  primary.  They  and  the  terminal 
fields  constitute  par  excellence  association  centres,  which  furnish  fibres 
(association  fibres)  connecting  the  centres  represented  in  the  primary 
fields — e.g.,  such  fibres  as  must  be  continually  conveying  impressions 
from  the  visual  centre  to  the  '  motor '  cortex  when  the  hand  is  sketching 
a  landscape.  It  may  also  be  considered  a  function  of  these  association 
centres  to  store  up  the  memories  of  previous  sense  impressions.  Flech- 
sig divides  the  association  centres  represented  in  the  terminal  fields 
into — (i)  The  great  anterior  association  centre  in  the  frontal  lobe  in 
front  of  the  '  motor  '  area;  (2)  the  great  posterior  association  centre  in 
the  parieto-temporal  region;  (3)  the  smaller  middle  or  insular  associa- 
tion centre,  which  coincides  with  the  island  of  Reil.  an  area  which, 
according  to  Sherrington  and  Griinbaum,  is  totally  '  inexcitable  '  as 
regards  the  production  of  movement  in  the  anthropoid  apes.  These 
association  centres  are  foci,  from  which  issue  and  to  which  come  the 
long  association  paths.  The  reader  must  bear  in  mind  that  Flechsig's 
conclusions  as  to  the  functions  of  his  very  numerous  areas  are  in  niany 
cases  hypothetical,  and  can  only  be  accepted  when  corroborated  by 
other  methods.  We  are  far  from  being  able  at  present  to  subdivide 
the  functions  of  the  cortex  so  minutely  as  is  suggested  by  his  map. 

Clinical  and  Pathological  Observations  in  man  agree,  upon  the 
whole,  with  wonderful  precision  with  the  results  of  experiments  on 
animals;  and,  indeed,  before  any  experimental  proof  of  the  minute 
and  elaborate  subdivision  of  the  cortex  had  been  obtained,  Broca 
had  already,  from  the  phenomena  of  the  sick-bed  and  the  post- 
mortem room,  located  a  centre  for  speech  in  the  left  inferior  frontal 
convolution  (but  see  p.  971),  and  Hughlings  Jackson  had  associated 
pathological  lesions  of  the  Rolandic  area  with  certain  cases  of  epi- 
leptiform convulsions. 

An  extensive  haemorrhage  involving  the  Rolandic  area  of  the 
cerebral  cortex,  or  an  embolus  blocking  the  middle  cerebral  artery, 
causes  paralysis  of  the  opposite  side  of  the  body.  An  embolus  of  a 
branch  of  the  middle  cerebral  artery  causes  paralysis  of  the  muscles. 


FUNCTIONS  Of  THE  BRAIN  963 

or  rather  movements,  represente'd  in  the  area  supphed  by  it.  A 
tumour  causes  symptoms  of  irritation,  motor  or  sensory — convul- 
sions beginning  in,  or  sensations  referred  to,  the  parts  represented 
in  the  regions  on  which  it  presses.  In  connection  with  the  locahza- 
tion  of  lesions  in  the  '  motor'  area  of  the  cortex,  and  operative 
interference  for  their  cure,  the  cortex  has  been  frequently  stimulated 
in  man.  There  is  no  doubt  that  the  '  motor  '  region  corresponds 
closely  in  position  to  that  of  the  higher  apes.  It  does  not  include 
the  postcentral  gyrus,  for  stimulation  of  this  convolution  with  such 
strengths  of  current  as  are  permissible  evokes  no  movements,  while 
movements  are  readily  elicited  from  the  precentral  gyrus  (Horsley, 
etc.).  In  exposing  the  '  motor  '  region,  or  any  particular  part  of  it, 
the  exact  position  of  the  fissure  of  Rolando  becomes  important;  and 
Thane  has  given  the  following  simple  method  for  fixing  it:  The 
point  midway  between  the  point  of  the  nose  and  the  occipital  pro- 
tuberance is  fixed  by  measuring  the  distance  with  a  tape.  The 
upper  end  of  the  fissure  of  Rolando  lies  half  an  inch  bebind  this 
middle  point.  The  fissure  makes  an  angle  of  67°  with  the  longi- 
tudinal fissure  (Fig.  386).  The  minor  fissures  are  so  inconstant  as 
to  afford  no  safe  guidance  in  the  locahzation  of  a  given  area.  This 
must  be  delimited  by  stimulation. 

Sensory  Functions  of  the  Rolandic  Area. — There  are  many  proofs 
that  the  '  motor  '  region  is  not  a  purely  motor,  but  a  sensori-motor, 
or  kincBsthetic,  area.  Histological  and  embryological  studies  on  the 
course  of  the  sensory  paths,  as  already  pointed  out,  support  this 
conclusion.  It  has  also  been  mentioned  that,  according  to  Goltz's 
observations  (p.  948),  removal  of  the  Rolandic  cortex  causes  defects 
of  sensation  as  well  as  of  movement.  In  man,  in  connection  with 
operations  on  the  brain,  still  better  evidence  has  been  obtained. 
In  two  cases  Gushing  was  able  to  elicit  tactile  sensations  by  electrical 
stimulation  of  the  gyrus  postcentralis  (ascending  parietal  convolu- 
tion), and  the  sense  of  muscular  movement  by  electrical  stimulation 
of  the  gyrus  precentralis.  In  a  very  careful  study  of  a  case  in  which 
he  removed  the  upper  limb  area  of  the  right  hemisphere  in  a  boy 
for  violent  convulsive  movements  of  the  whole  of  the  left  arm, 
Horsley  came  to  the  conclusion  that  the  precentral  gyrus  in  man 
is  the  seat  of  representation  of  (i)  slight  tactile  sensation  (after  the 
operation  appreciation  of  the  lightest  tactile  stimuli  was  lost); 
(2)  topognosis — i.e.,  appreciation  of  the  localization  in  space  of  the 
point  touched;  (3)  muscular  sense;  (4)  stereognosis,  or  the  power  of 
recognizing  the  form  of  objects  touched  and  handled;  (5)  pain — 
e.g.,  that  caused  by  a  pin-prick;  (6)  volitional  movement.  The 
postcentral  gyrus  in  man  appears  to  be  the  seat  of  a  similar  sensory 
representation,  but  as  its  relation  to  the  efferent  impulses  concerned 
in  volitional  movements  is  less  decided  than  that  of  the  precentral 
gyrus,  so  its  relation  to  afferent  impulses,  both  from  the  skin  and  the 


964  THE  CENTRAL  NERVOUS  SYSTEM 

deeper  structures,  is  better  markfid.  From  the  tield  of  experiment 
further  evidence  of  the  sensori-motor  nature  of  the  '  motor  '  region 
is  forthcoming. 

(i)  It  has  been  found  that  if  the  posterior  roots  of  the  nerves 
supplying  one  of  the  Hmbs  be  cut  in  a  monkey,  all  the  most  delicate 
and  skilled  movements  of  the  limb  are  either  greatly  impaired  or 
totally  abolished  (Mott  and  Sherrington).  The  limb  is  not  used  for 
progression  or  for  climbing,  but  hangs  limp,  and  apparently  help- 
less, by  the  side  of  the  animal.  That  this  condition  is  not  due  to 
any  loss  of  functional  power  by  the  peripheral  portion  of  the  motor 
path  may  be  assumed,  since  the  anterior  roots  remain  intact.  That 
it  is  not  due  to  any  want  of  capacity  on  the  part  of  the  '  motor  ' 
centres  to  discharge  impulses  when  stimulated  may  be  shown  by 
exciting  the  cortical  area  of  the  limb — either  electrically  or  by 
inducing  epileptic  convulsions  by  intravenous  injection  of  absinthe 
— when  movements  of  the  affected  limb  take  place  just  as  readily 
as  movements  of  the  sound  limb.  The  cause  of  the  impairment  of 
voluntary  motion,  then,  can  only  be  the  loss  of  the  afferent  impulses 
which  normally  pass  up  to  the  brain,  and  presumably  to  the  '  motor 
cortex.  When  only  one  sensory  nerve-root  is  cut,  no  defect  of  move- 
ment can  be  seen;  and  this  is  evidently  in  accordance  \sith  the  fact 
previously  mentioned  (p.  891),  that  complete  anjesthesia  of  even  the 
smallest  patch  of  skin  is  never  caused  by  section  of  a  single  posterior 
root.  And  that  it  is  the  loss  of  impulses  from  the  skin  which  plays 
the  chief  part  is  shown  by  the  fact  that  after  division  of  the  posterior 
roots  supplying  the  muscles  of  the  hand  or  foot,  which  only  partially 
interferes  with  the  sensory  supply  of  the  skin,  joints,  sheaths  of 
tendons,  etc.,  movement  is  unimpaired;  while  section  of  the  nerve- 
roots  supplying  the  skin,  those  of  the  muscles  being  left  intact,  causes 
extreme  loss  of  motor  power. 

(2)  If  a  strength  of  stimulus  be  sought  which  will  just  fail  to 
cause  contraction  of  the  muscular  group  related  to  a  given  motor 
area,  and  a  sensory  nerve,  or,  better,  a  sensory  surface  (best  of  all, 
the  skin  over  the  corresponding  muscles),  be  now  stimulated,  con- 
traction may  occur — that  is  to  say,  the  excitability  of  the  motor 
centres  may  be  increased.  This  shows  that  the  '  motor  '  region  is 
en  rapport  not  only  with  efferent,  but  also  with  afferent  fibres,  that 
it  receives  impulses  as  well  as  discharges  them. 

The  same  experiment  is  a  proof  that  the  results  of  excitation  of  the 
motor  cortex  are  due  to  stimulation  of  the  grey  matter,  and  not,  as 
might  be  objected,  of  the  white  fibres  of  the  corona  radiata.  It  is 
undoubtedly  possible  to  excite  these  fibres  by  electrodes  directly 
applied  to  the  motor  cortex,  but  in  the  latter  case  the  current  has  to 
be  made  stronger  than  is  sufficient  to  excite  the  grey  matter  alone. 
Further  evidence  is  afforded  by  the  following  facts:  [a)  The  '  period 
of  delay  ' — that  is,  the  period  which  elapses  between  stimulation  and 
contraction — is  greater  by  nearly  50  per  cent,  when  the  cortex  is  stimu- 


FUNCTIONS  OF  THE  ISRAIN 


965 


latcd  tlum  when  the  white  hbres  are  directly  excited.  (6)  Morphine 
greatly  increases  the  period  of  delay  for  stimluation  of  the  cortex,  and 
at  the  same  time  renders  the  resulting  contractions  more  prolonged 
than  normal,  wliile  the  results  of  direct  stimulation  01  the  white  fibres 
are  much  less,  if  at  all,  affected,  (c)  Stimulation  of  the  grey  matter, 
when  separated  from  the  subjacent  white  matter  by  the  knife,  but  left 
in  position,  is  without  effect  unless  the  strength  of  stimulus  be  increased, 
although  twigs  of  the  current  ought,  of  course,  to  pass  into  the  corona 
radiata  as  easily  as  before. 
Perfectly  definite    movements  LI"  RF 

can.  however,  be  excited  or 
inhibited  by  stimulating  de- 
finite spots  in  the  corona  radi- 
ata, and  even  in  the  internal 
capsule.  This  simply  means 
that  in  these  positions  the 
fibres  representing  these  move- 
ments are  not  yet  intermingled 
with  fibres  representing  other 
movements. 

Sensory  Areas — ^Visual  Cen- 
tres.— In  the  occpital  lobe  in 
animals  an  area  of  consider- 
able extent  has  been  found, 
destruction  of  which  causes 
hemianopia  (p.  923).  Thus, 
if  the  right  occipital  cortex  is 
destroyed,  the  right  halves 
of  the  two  retinae  are  para- 
lyzed, and  the  left  half  of  the 
field  of  vision  is  a  blank. 
There  is  conjugate  deviation 
of  the  head  and  eyes  to  the 
5ame  side  as  the  lesion — in 
other  words,  the  animal  turns 
its  head  and  eyes  to  the  right. 
Destruction  of  this  region  on 
both  sides  causes  complete 
blindness.  When  the  same 
region  is  stimulated,  the  eyes 
and  head  are  turned  to  the 
left — that  is,  there  is  conju- 


Fig.  394. — Diagram  oi  Relations  of  Occipital 
Cortex  to  the  Retinae.  RO,  LO,  right  and 
left  occipital  cortex;  RE,  LE,  right  and  left 
retina;  C,  optic  chiasma;  RF,  LF,  right  and 
left  visual  fields.  The  continuous  lines 
passing  back  from  the  retinae  to  the  occi- 
pital cortex  represent  the  crossed,  the 
broken  lines  the  uncrossed,  fibres  of  the 
optic  nerves  and  tracts.  For  the  sake  of 
simplicity  the  intermediate  stations  on  the 
visual  path  in  the  anterior  corpora  quadri- 
gemina,  lateral  geniculate  bodies,  and  pul- 
vinar  are  not  represented  in  the  diagram. 
For  these  connections,  see  Fig.  370,  p.  923 


gate  deviation  to  the  opposite 
side.  In  the  higher  monkeys  the  eye  movements  can  be  elicited  only 
from  the  extreme  posterior  apex  of  the  occipital  lobe  and  from  its 
calcarine  region,  and  then  not  easily.  The  movements  differ  from 
those  produced  by  stimulation  of  the  area  for  eye  movements  in  the 
frontal  lobe.  They  are  not  so  certain,  their  latent  period  is  longer, 
and  a  stronger  stimulus  is  required  to  evoke  them.     It  cannot  be 


966  THE  CENTRAL  MERVOUS  SYSTEM 

doubted  tliat  the  occipital  region  is  concerned  in  vision,  and  it  is  a 
very  natural  suggestion  that  the  movements  are  the  result  of  visual 
sensations  in  the  excited  occipital  cortex.  The  right  occipital  lobe 
is  concerned  with  vision  in  the  right  halves  of  the  two  retina  (Figs. 
370  and  3_)4)-  Now,  under  normal  conditions,  a  visual  image  would 
be  cast  on  the  two  right  retinal  halves  by  an  object  placed  towards 
the  left  of  the  field.  The  movements  of  the  head  and  eyes  to  the 
left  may  therefore  be  plausibly  explained  as  an  attempt  to  look  at, 
and  a  rotation  towards,  the  supposed  object. 

The  pathological  evidence  is  very  clear  that  disease  of  the  occipital 
lobe,  especially  of  the  cuneus,  a  triangular  area  on  its  mesial  surface, 
causes  hemianopia  in  man.  A  limited  lesion  may  even  be  associated 
with  an  incomplete  hemianopia,  and  cases  have  been  recorded  in  which 
colour  hemianopia  (blindness  of  the  corresponding  halves  of  the  two 
retinae  for  coloured  objects)  co-existed  with  normal  vision  for  white 
light.  The  precise  limits  of  the  occipital  visual  area  are  still  disputed. 
It  probably  occupies,  in  addition  to  the  cuneus,  the  lingual  lobule  and 
a  portion  of  the  external  aspect  of  the  occipital  lobe.  The  question  of 
the  projection  of  the  retina  upon  the  visual  cortex — i.e.,  the  question 
whether  each  retinal  area  is  represented  in  a  definite  cortical  area — 
has  given  rise  to  much  debate.  The  representation  of  the  fovea  cen- 
tralis, the  area  of  most  distinct  vision,  has  aroused  especial  interest. 
It  has  been  asserted  that  a  circumscribed  area  in  the  region  of  the  cal- 
carine  fissure  is  the  centre  for  the  fovea  (Henschen).  But  it  is  totally 
opposed  to  this  view  that  extensive  lesions  of  the  occipital  cortex,  even 
on  both  sides,  do  not,  except  in  rare  cases,  cause  total  blindness  in  the 
foveal  region,  although  peripheral  vision  is  destroyed.  On  the  other 
hand,  in  no  case  has  a  purely  cortical  lesion  been  found  associated  with 
blindness  confined  to  the  fovea  (Monakow).  The  fibres  of  the  optic 
radiation  which  are  on  the  path  from  the  fovea  are  accordingly  dis- 
tributed diffusely  to  the  visual  cortex.  Sometimes  dimness  of  vision  in 
the  whole  of  the  opposite  eye  (crossed  amblyopia),  and  not  hemianopia, 
is  caused  by  a  lesion  of  the  occipital  cortex.  It  seems  impossible  to 
explain  this  and  other  facts  without  postulating  the  existence  of  more 
than  one  visual  centre;  and  it  has  been  supposed  that  in  the  angular 
gyrus  and  the  neighbouring  region  a  higher  visual  centre  exists  which 
is  connected  with  the  lower  occipital  centres  for  the  two  halves  of  the 
opposite  e^-e.  Thus,  the  right  angular  gyrus  would  be  in  connection 
with  the  part  of  the  right  occipital  cortex  which  has  to  do  with  vision 
in  the  nasal  half  of  the  left  eye,  and  with  the  part  of  the  left  occipital 
cortex  which  has  to  do  with  vision  in  the  temporal  half  of  that  eye. 
This  higher  centre,  which  perhaps  functions  as  a  storehouse  of  visual 
memories,  probably  corresponds  to  the  structurally  differentiated  area 
(visuo-psychic  area  of  Campbell),  as  the  lower  centre  corresponds  to 
his  structurally  differentiated  visuo-sensory  area  (Figs.  391,  392)- 

Auditory  Centre. — On  the  outer  surface  of  the  temporo-sphenoidal 
lobe,  mainly  in  the  first  temporal  convolution,  lies  an  area  asso- 
ciated with  the  sense  of  hearing.  Stimulation  in  the  region  of  the 
hrst  temporal  convolution  may  cause  the  animal  to  prick  up  its  ears 
on  the  opposite  side.  Destruction  of  this  area  on  both  sides  is 
followed  by  complete  and  irremediable  loss  of  hearing.  If  it  is 
destroyed  only  on  one  side,  there  is  partial  deafness  of  the  opposite 


FUNCTIONS  OF  THE  BRAIN 


967 


ear,  and  also  to  sonic  extent  of  the  ear  on  the  same  side.  This  is 
grathuiHy  recovered  from.  If  it  is  destroyed  on  the  left  side  there 
is  also  tlie  pecuHar  condition  called  '  word-deafness,'  which  will  be 
referred  to  directly  (p.  972).  In  deaf-mutes  the  first  temporal 
convolution  may  be  atrophied.  There  is  evidence  that  the  posterior 
corpora  quadrigemina  and  the  mesial  geniculate  body  form  an  in- 
ferior relay  on  the  route  between  the  fibres  of  the  auditory  nerve 
and  the  temporal  cortex.  There  are  indications  that  within  the 
auditory  area  so-called  '  musical  centres  '  exist — that  is,  an  orderly 


SYLVIA 
FISSURE 

Fig.    395. — Lateral  View  oi  Left  Hemisphere  with  Sensory  Areas:  Man. 
of  the  brain  is  towards  the  left. 


The  front 


arrangement  of  the  cell-bodies  of  the  neurons  that  have  to  do  with 
the  perception  of  pitch,  so  that  a  limited  lesion  may  cause  deafness 
to  notes  of  a  particular  pitch  when  it  is  situated  on  one  part  of  the 
area,  and  deafness  to  notes  of  a  different  pitch  when  it  is  situated 
elsewhere  (Larionow). 

Centre  for  Smell. — As  to  the  position  of  the  centre  for  smell,  direct 
experiment  on  animals  cannot  teach  us  much,  for  if  the  outward 
tokens  of  visual  and  auditory  sensations  are  dubious  and  fluctuating, 
still  more  is  this  the  case  with  the  signs  of  sensations  of  smell.      A 


968 


THE  CENTRAL  NERVOUS  SYSTEM 


further  source  of  fallacy  is  the  fact  that  other  sensations  tlian  those 
of  smell  are  caused  by  stimulation  of  the  mucous  membrane  of  the 
nose.  Substances  like  ammonia,  for  example,  affect  entirely  the 
endings  of  the  trigeminus,  which  is  the  nerve  of  common  sensation 
for  the  nostrils.  Pathological  and  clinical  evidence  would  be  of  great 
value,  but  it  is  as  yet  scanty,  and  of  itself  indecisive.  Some  cases 
of  epilepsy  have  been  reported  in  which  the  attack  was  heralded  by 
smells  for  which  there  was  no  objective  cause.  At  necropsy  the  un- 
cinate gyrus  was  found  diseased.  So  far  as  it  goes,  such  evidence 
supports  the  view  derived  from  the  anatomical  connections  of  the 
olfactory  tracts,  that  the  centre  for  smell  is  situated  in  the  uncinate 
gyrus  on  the  mesial  aspect  of  the  temporal  lobe,  for  the  olfactory 
track  may  be  traced  into  this  region.  In  animals  with  a  very  acute 
sense  of  smell,  this  gyrus  is  magnified  into  a  veritable  lobe,  called 
from  its  shape  the  pyriform  lobe;  from  its  supposed  function,  the 


Fig.  396. 


-Sensory  Areas  of  Mesial  Surface  of  Human  Brain.    The  front  of  the  brain 
is  towards  the  right. 


rhinencephalon.  The  centre  for  taste  is  supposed  to  be  situated  in 
the  same  region  as  the  centre  for  smell  (in  the  hippocampal  convolu- 
tion posterior  to  the  uncinate  gyrus). 

Ordinary  and  Tactile  Sensations,  including  the  muscular  sense, 
have  been  located  in  the  Rolandic  area  (p.  963) ;  and  there  are  good 
grounds  for  believing  that  afferent  fibres  from  the  joints,  the  muscles 
and  their  accessory  structures  and  the  skin  terminate  here  in  arboriza- 
tions which  come  into  contact  either  with  the  motor  pyramidal 
cells,  or  with  intermediate  cells  which  link  them  to  the  pysamidal 
cells. 

Our  knowledge  of  the  localization  of  this  group  of  sensations  is  still 
unsatisfactory,  largely  because  it  has  hitherto  lx>en  necessary  to  rely 
almost  exclusively  upon  extirpation  experiments,  and  it  is  difficult 
to  determine  in  animals  the  existence  of  a  local  defect  of  sensation  due 
to  a  limited  cortical  lesion.  .\  promising  new  method,  the  application 
of  strychnine  to  limited  regions  of  the  cortex,  seems  likely  to  aid  in 
illuminating  this  dark  corner  of  cerebral  physiology  (de  Barenne). 
Changes  in  cutaneous  and  deep  sensibility  of  the  fore-lnnbs  of  the  cat 


FUNCTIONS  01-   Till-:  lih'AlN 


969 


arc  produced— c.i7..  by  applying  stryclininc  to  a  zone  including  the 
gyrus  signu.idcus  anterior,  the  frontal  part  of  the  gyrus  siginoueus 
posterior,  the  frontal  part  of  the  gvrus  suprasylvius  and  the  iniddlc 
third  of  the  gyrus  cctosylvius  anterior.  The  zone  for  the  head  almost 
completely  overlaps  the  fore-limb  zone.  The  zone  for  the  hind-limb 
occupies  the  frontal  half  of  the  gvrus  marginalis. 

As  regards  the  cutaneous  sensibilitv  localized  in  these  zones,  both 
sides  of  the  body  seem  to  be  represented  in  the  cortex  of  one  hemi- 
sphere, but  the  opposite  side  the  most.  The  disturbances  of  deep 
sensibility  caused  by  the  application  of  strychnine  to  the  cortex  of  one 
hemisphere  are  confined  to  the  bones,  tendons,  and  muscles  of  the 
opposite  side  of  the  body.     The  remainder  of  the  region  of  the  cortex 


\,aiiiv^J^'^- 


lag  con.  o.f 

C/i"os£eflL 
Sy  nx^xXo-n-uiXoLo  qy 

Fig.  397. — Zones  for  Cutaneous  and  Deep  Sensibility  on  the  Convexity  of  the  Left 
Cerebral  Hemisphere  of  the  Cat  (Dusser  de  Barenne).     The  chief  gyri  and  sulci 
are  indicated,     s.cr.,  Crucial  sulcus;  F.S.,  fissure  of  Sylvius;  a,  the  'compensa- 
tory ansate  fissure '  of  Campbell. 

which  responds  to  strychnine  by  sensory  changes  is  called  by  de 
Barenne,  the  zone  of  '  crossed  symptomatology,'  because  the  altered 
or  increased  sensitivity  of  the  skin  is  manifested  in  the  fore-limb  of  the 
same  side,  and  the  hind-limb  of  the  opposite  side.  He  suggests  that 
the  sensory  mechanism  in  this  area  may  be  related  to  the  movements 
of  progression.  In  so  far  as  these  sensory  zones  overlap  the  motor  area 
a  common  sensori-motor  cortical  zone  may  be  said  to  exist. 

Aphasia. — Words  are,  at  bottom,  arbitrarv  signs  by  which  certain 
ideas  are  expressed.  The  power  of  intelligent  communication  by  spoken 
or  written  language  may  be  lost:  (i)  by  paralysis  of  the  muscles  of 
articulation  or  the  muscles  which  guide"  the  pen;  (2)  by  inability  to 
hear  or  sec  the  spoken  or  written  word — i.e.,  by  deafness" or  blindness; 
(3)  by  inability  to  comprehend  the  meaning  of  spoken  or  written  lan- 
guage, although  sensations  of  hearing  and  sight  mav  not  be  abolished 


97<»  THE  CENTRAL  NERVOUS  SYSTEM 

— that  is  to  say,  by  inability  to  interpret  the  auditory  or  visual  symb  )ls 
by  which  ideas  are  conveyed;  (4)  by  inability  to  clothe  ideas  in  words, 
althougli  the  words  may  be  present  in  the  patient's  consciousness,  and 
the  ideas  conveyed  by  speech  or  writing  may  be  comprehended. 
Neither  (i)  nor  {2)  is  considered  to  constitute  the  condition  of  aphasia; 
(3)  represents  what  is  called  amnesia,  or  sensory  aphasia  :  (4)  is  aphasia 
in  the  ordinary  restricted  sense,  or  motor  aphasia. 

Motor  aphasia  may  be  divided  into  two  varieties — subcortical  or  pure 
motor  aphasia,  and  cortical,  or  Broca's  aphasia.  In  t^e  subcortical 
type  the  patient  understands  speech  and  writing  perfectly,  and  is  able 
to  write  normally;  but  he  cannot  speak  spontaneously  or  read  aloud, 
or  repeat  words  when  requested  to  do  so.  He  may  know  quite  well 
what  to  reply  in  answer  to  a  question,  but  the  words  necessary  to 
express  his  meaning  do  not  come  to  him.  In  Broca's  type  of  aphasia, 
which  is  the  most  common,  the  patient  may  understand  spoken 
and  written  words — often  imperfectly,  it  is  true — but  he  is  unable  to 
speak  spontaneously,  to  repeat  words  spoken  to  him,  and  to  read  aloud. 
Unlike  the  person  suffering  from  the  subcortical  type  of  motor  aphasia,  he 
has  difficulty  in  reading  by  the  eye  without  articulation,  and  in  writing 
spontaneously  or  to  dictation.  There  is  often  or  always  some  intellectual 
deficiency.  The  gradations  in  the  loss  of  the  expressive  factor  in  speech 
may  be  infinite.  A  patient  may  sometimes  sing  a  song  without  a  single 
slip  in  words  or  measure,  and  yet  be  unable  to  speak  or  write  it.  In  a 
case  recorded  by  Larionow  an  aphasic  could  speak  only  one  syllable, 
'  tan,'  but  could  sing  the  '  Marseillaise.'  In  certain  cases  the  change 
is  confined  to  loso  of  the  power  of  spontaneous  speech,  and  the  patient 
may  be  able  to  read  intelligently.  Sometimes  he  can  express  his  ideas 
in  speech,  but  not  in  writing  (agraphia).  Sometimes  the  loss  is  restricted 
to  certain  sets  of  ideas.  For  example,  a  boy  was  injured  by  falling  on 
his  head.  Typical  symptoms  of  motor  aphasia  developed,  but  the 
power  of  dealing  with  ideas  of  number  was  not  interfered  with,  and 
the  boy  continued  to  learn  arithmetic  as  if  nothing  had  happened. 
Proper  names  and  nouns  are  more  easily  lost  than  adjectives  and  verbs. 
Motor  aphasia  is  generally  accompanied  by  paralysis,  frequently 
transient,  of  voluntary  movement  on  the  right  side,  sometimes  amount- 
ing to  complete  hemiplegia,  but  more  often  involving  the  right  arm  alone. 
This  association  is  generally  explained  by  the  proximity  of  the  inlerior 
frontal  convolution  to  the  motor  area  of  the  arm,  and  their  common 
blood-supply.  It  has  already  been  stated  that  since  Broca  it  has  been 
generally  assumed  that  in  most  persons  the  inferior  frontal  convolution 
on  the  left  side  is  concerned  in  the  expression  of  ideas  in  spoken  or 
written  language.  It  is  even  said  that  oratorical  powers  have  been 
found  associated  with  marked  development  of  this  convolution  (as  in  the 
case  of  Gambetta,  the  French  statesman).  It  is  the  cortical  or  Broca's 
type  of  motor  aphasia  which  has  been  supposed  to  be  associated  with  a 
lesion  in  the  left  inferior  frontal  convolution.  The  portion  of  the  con- 
volution concerned  is  the  posterior  extremity,  where  it  borders  on  the 
fissure  of  Sylvius,  and  it  either  completely  coincides  with  or  largely 
overlaps  the  centre  for  the  movements  of  the  tongue,  lips,  and  larynx 
concerned  in  articulation.  The  failure,  however,  does  not  lie  in  the 
articulatory  mechanism.  The  patient  uses  the  same  muscles  of  articu- 
lation, without  any  marked  impairment  of  function,  for  chewing  and 
swallowing  his  food.  It  is  only  when  the  corresponding  area  in  the 
right  inferior  frontal  convolution,  or  the  path  from  it  to  the  internal 
capsule,  is  also  destroyed,  that  articulation  is  greatly  and  permanently 
interfered  with. 

The  question  obviously  presents  itself  whj''  it  is  that  motor  aphasia  is 


FUNCTIONS  OF  THE  BRAIN  971 

commonly  due  to  a  lesion  in  the  left  hemisphere  alone.  The  answer  to 
this  question  is  supposed  to  be  partly  supplied  by  the  important  and 
curious  observation  that  in  left-handed  individuals  damage  to  the  right 
inferior  frontal  convolution  may  cause  aphasia.  In  the  right-handed 
man  the  motor  areas  of  the  left  hemisphere  may  be  supposed  to  be  more 
highly  educated  than  those  of  the  right  hemisphere.  The  movements 
of  the  right  side  which  they  initiate  or  control  are  stronger  and  more 
delicate  and  precise  than  those  of  the  left  side.  It  is  only  necessary  to 
assume  that  this  processs  of  specialization,  of  selective  training,  has 
been  carried  on  to  a  still  greater  extent  in  the  left  frontal  convolution, 
that  in  most  men  the  speech-centre  there  has  taken  upon  itself  the  whole, 
or  the  greater  part,  of  the  labour  of  clothing  ideas  in  words,  leaving  to 
the  right  centre  only  its  primitive  but  undeveloped  powers.  In  left- 
handed  persons  the  speech-centre  on  the  right  side  may  be  supposed  to 
share  in  the  general  functional  development  of  the  right  hemisphere. 
That  great  capabilities  are  lying  dormant  in  the  right  speech-centre  of 
the  ordinary  right-handed  individual  is  indicated  by  the  fact  that  after 
complete  destruction  of  the  left  inferior  frontal  convolution  the  power 
of  speech  may  be  to  a  considerable  extent,  though  slowly  and  laboriously 
regained;  and  it  is  said  that  this  second  accumulation  may  be  swept 
away,  and  without  remedy,  by  a  second  lesion  in  the  right  inferior  frontal 
convolution.  But  frail  is  the  tenure  of  life  in  a  person  who  has  twice 
suffered  from  such  a  lesion ;  and  we  do  not  know  whether  recovery  might 
not  take  place  to  some  extent  even  after  destruction  of  both  inferior 
frontal  convolutions,  if  the  patient  only  lived  long  enough. 

Recently  ]\Iarie  has  reopened  the  whole  question  of  the  relation  of 
aphasia  to  lesions  of  the  inferior  frontal  convolution.  He  believes  that 
the  so-called  Broca's  area  has  nothing  to  do  with  aphasia  in  the  proper 
sense  of  the  term — i.e.,  it  is  not  a  cortical  area  concerned  in  '  internal ' 
speech  processes,  or  in  which  motor  or  kinaesthetic  '  speech  memories  ' 
are  stored — but  simply  a  '  motor  '  area  for  the  movements  of  articula- 
tion. He  maintains  that  there  is  but  one  form  of  true  aphasia — the 
aphasia  of  Wernicke — which  has  for  its  basis  a  lesion  of  the  so-called 
zone  of  Wernicke  (the  supramarginal  and  angular  gyri,  and  the  posterior 
portions  of  the  first  and  second  temporal  convolutions) .  This,  according 
to  him,  is  the  true  speech-centre.  The  symptom-complex  known  as 
Broca's  aphasia,  which  everybody  admits  to  exist  as  a  distinctly  charac- 
terized clinical  condition,  is  due,  he  says,  to  a  double  lesion.  One  lesion 
causes  aphemia  (loss  of  the  power  of  co-ordinating  the  movements 
needed  in  the  articulation  of  words  without  actual  paralysis  of  the 
muscles),  and  the  other  the  disturbance  of  internal  speech,  and  the 
difficulty  of  reading  and  of  writing,  which  constitute  the  true  aphasia. 
According  to  Marie,  the  lesion  which  causes  the  aphemia  is  not  even 
situated  in  Broca's  convolution,  but  somewhere  in  a  rather  badly  de- 
fined region,  which  he  denominates  the  lenticular  zone,  since  it  includes 
the  lenticular  as  well  as  the  caudate  nucleus,  in  addition  to  the  external 
and  internal  capsules  and  the  cortex  of  the  island  of  Reil.  It  would  be 
out  of  place  to  enter  more  minutely  here  upon  such  controversial 
matters.  The  conclusion  which  emerges  most  definitely  from  the  dis- 
cussion is  that  Broca's  localization  was  based  upon  a  very  narrow 
foundation,  and  must  probably  be  modified. 

It  is  generally  recognized  that  in  almost  all  cases  of  aphasia  in  which 
the  brain  has  been  studied  after  death,  some  lesion  of  association  fibres 
has  been  present,  and  not  merely  a  cortical  lesion.  Interference  with  the 
association  fibres  causes  confusion  in  the  processes  of  association  which 
are  so  important  in  mental  activity',  and  defects  of  intelligence  are  there- 
fore commonly  observed  in  aphsisia. 


972  THK  CENTRAL  NERVOUS  SYSTEM 

A  so-called  temporary'  aphasia  may  occur  without  any  structural 
change  in  the  speech-centre — for  exajnpie,  during  an  attack  of  migraine. 
In  children  it  may  even  be  caused  by  some  comparatively  slight  irrita- 
tion in  the  digestive  tract,  such  as  that  due  to  the  presence  of  a  tape- 
worm. 

In  the  anthropoid  apes  no  evidence  of  the  existence  of  any  '  speech- 
centre,'  even  distantly  foreshadowing  the  human,  has  been  obtained 
by  stimulating  tlic  inferior  frontal  convolution  on  either  side.  No  move- 
ments, and  particularly  no  movements  connected  with  vocalization,  are 
elicited. 

Sensory  Aphasia. — In  typical  motor  aphasia  spoken  and  written 
words  convey  to  the  patient  their  ordinary  meaning.  They  call  up  in 
his  mind  the  usual  sequence  of  ideas,  but  the  chain  is  broken  at  the 
speech-centre,  and  the  outgoing  ideas  cannot  be  clothed  in  words.  The 
expressive  factor  in  speech  is  deranged.  In  sensory-  aphasia  the  percep- 
tive factor  in  speech  is  deranged.  In  ordinary  sensory  aphasia  [Wer- 
nicke's, or  cortical  sensory  aphasia)  the  patient  cannot  understand 
spoken  or  written  language,  but,  far  from  being  unable  to  speak,  he 
often  babbles  incessantly.  He  may  string  together  a  series  of  words, 
each  correctly  articulated,  but  having  no  meaning,  or  may  utter  a  jargon 
not  composed  of  known  words  at  all.  Instead  of  the  words  which  he 
desires  to  use  to  express  his  meaning,  he  may  use  others  having  a 
similar  sound  {paraphasia).  Damage  to  two  regions  of  the  brain  has 
been  found  associated  with  this  condition:  (i)  the  middle  part  of  the 
first  and  second  temporal  convolutions,  (2)  inferior  parietal  convolu- 
tions and  the  angular  g>'rus  in  the  neighbourhood  of  the  occipital  visual 
centre.  When  the  temporal  region  is  alone  affected,  it  is  the  spoken 
word  that  is  missed,  the  written  that  is  understood  {word-deafness). 
When,  as  occasionally  happens,  the  lesion  is  confined  to  the  occipital 
region,  spoken  language  is  perfectly  understood,  written  language  not 
at  all  {word-blindness) .  It  is  the  left  hemisphere  wh'ch  is  affected  in 
right-handed  persons,  the  right  hemisphere  in  left-handed  persons. 
Sensory,  like  motor  aphasia,  may  exist  in  any  degree  of  completeness, 
from  absolute  word-deafness  or  word-blindness,  in  which  no  spoken  or 
printed  word  calls  up  any  mental  image,  to  a  condition  not  amounting 
to  much  more  than  a  marked  absence  of  mind  or  unusual  obtuseness. 
Motor  and  sensory  aphasia  may  be  present  together.  In  well-marked 
cortical  word-deafness  speech  is  always  interfered  with  to  some  extent. 
In  so-called  pure  word-deafness  (subcortical  sensory  aphasia)  the  patient 
may  be  perfectly  capable  of  rational  speech.  He  may  talk  to  himself 
or  on  a  set  topic  with  fluency  and  sense,  may  write  intelligently,  and 
understand  what  he  reads ;  but  he  may  be  unable  to  understand  a  single 
word  spoken  to  him,  or  to  repeat  words  when  asked  to  do  so. 

Cortical  Epilepsy. — Disturbed  action  of  the  motor  centres  may  take 
the  form  either  of  depression  or  of  increased  excitability.  The  former 
will  be  associated  with  partial  or  complete  paralysis  of  the  movements 
represented  in  the  area,  the  latter  by  abnormally  intense  or  prolonged 
discharge  leading  to  the  condition  called  cortical  epilepsy — that  is. 
epileptic  attacks  associated  with  cortical  lesions.  Among  these  are  the 
cases  of  so-called  Jacksonian  epilepsy — a  condition  characterized  by  the 
fact  that  the  seizure  does  not  begin  by  general,  but  by  local,  convulsions. 
They  may  remain  confined  to  a  single  limb,  or  to  one  side  of  the  face,  or 
to  one  side  of  the  body.  So  long  as  the  convulsions  are  not  general, 
consciousness  need  not  be  lost.  Or  a  seizure  beginning  as  Jacksonian 
may  spread  so  as  to  involve  the  whole  body,  in  which  case  the  symptoms 
become  identical  with  those  of  ordinary  ep'lep.«^y,  including  the  loss  of 
consciousness.     It  has  been  found  possible  in  some  cases  to  localize  the 


FrSCTIONS  OF  THE  BRATN  973 

position  of  the  lesion  from  the  part  of  the  body  in  which  the  lit,  or  the 
aura  (the  sensation  or  group  of  sensations  peculiar  to  each  case,  which 
precedes  and  announces  the  ati:ack)  begins.  For  example,  if  the  con- 
vulsions commence  with  a  twitching  of  the  right  thumb  and  extend  over 
the  arm,  or  if  the  aura  consists  of  sensations  beginning  in  the  thumb, 
there  is  a  strong  presumption  that  the  seat  of  the  lesion  is  the  part  of  the 
arm-area  known  as  the  '  thumb-centre  '  in  the  left  cerebral  hemisphere. 
It  is  the  seat  of  the  convulsion  at  its  commencement,  not  the  regions  to 
which  it  may  afterwards  spread,  that  is  important  in  diagnosing  the 
position  of  the  lesion.  For  just  as  strong  or  long-continued  electrical 
stimulation  of  a  given  '  centre  '  of  the  '  motor  '  cortex  may  give  rise  to 
contractions  of  muscles  associated  with  other  '  centres,'  so  the  excita- 
tion set  up  by  localized  disease  may  spread  far  and  wide  from  its 
original  focus,  involving  area  after  area  of  the  '  motor  '  region  first  in 
the  one  hemisphere  and  then  in  the  other.  The  part  of  the  body  to 
which  a  sensory  aura  is  referred  is  as  significant  an  indication  of  the 
seat  of  the  discharging  lesion  as  is  the  part  of  the  body  which  first  begins 
to  twitch.  This  is  one  of  the  proofs  that  the  '  motor  '  region  is  not  a 
purely  motor  area.  Disturbed  action  of  the  sensory  areas  on  the  cortex 
may,  as  in  the  case  of  the  motor  regions,  take  the  form  either  of  de- 
ficiency or  of  excitation.  Excitation  expresses  itself  by  hallucinations, 
the  person  having  the  impression  of  a  sight,  a  sound,  a  smell  or  taste,  or 
one  or  other  of  the  cutaneous  sensations  in  the  absence  of  the  related 
objects. 

Seat  of  Intellectual  Processes — ^Association  Areas. — When  we 
have  deducted  from  the  cortex  of  the  hemisphere  the  vi^hole  Rolandic 
region  and  the  sensory  centres,  there  still  remains  a  large  territory 
unaccounted  for.  Considerable  portions  of  the  occipital,  parietal, 
and  temporal  lobes,  nearly  the  whole  of  the  island  of  Reil  and  the 
greater  part  of  the  frontal  lobe  anterior  to  the  ascending  frontal 
convolution  are  '  silent  areas,'  and  respond  to  stimulation  by  neither 
motor  nor  sensory  sign.  They  correspond  to  the  association 
centres  previously  referred  to.  They  are  connected  with  the 
sensory  and  motor  areas  and  with  each  other,  but  are  not  directly 
connected  by  projection  fibres  with  the  lower  parts  of  the  central 
nervous  system,  as  the  motor  area,  for  example,  is  by  the  pyramidal 
path.  By  a  process  of  exclusion  it  has  been  supposed  that,  in  addi- 
tion to,  or  partly  in  virtue  of,  their  associative  function,  they  are 
the  seat  of  intellectual  and  psychical  operations.  It  is  supposed 
that  the  sensations  aroused  in  the  various  sensory  areas  by  the 
impulses  received  from  the  sense  organs  are  linked  in  the  associa- 
tion areas  into  complex  perceptions.  For  instance,  when  an 
orange  is  taken  into  the  hand,  the  visual  sensation  of  a  yellow  body, 
the  tactile  sensation  of  a  smooth  round  body,  and  perhaps  the 
olfactory  sensation  characteristic  of  an  orange,  are  collected  from 
the  sensor}^  areas,  connected  and  combined,  or  synthesized  in  an 
association  area  to  the  concept  of  an  orange.  Somewhere  in  the 
association  areas  it  is  to  be  supposed  is  stored  the  memory  of  past 
experiences.  The  intellectual  function  has  been  more  particularh' 
assigned  to  the  frontal  lobes,  and  with  great  probability,  although 


974  THF.   CENTRAL  NERVOUS  SYSTEM 

we  have  little  real  knowledge  to  guide  us  to  a  decision.  Extensive 
destruction  and'  loss  of  substance  of  the  prefrontal  region  may 
sometimes  occur  without  any  marked  symptoms.  But  usually 
there  is  restriction  of  mental  power,  or  it  may  be  loss  of  moral 
restraint.  Thus  in  the  famous  '  American  crowbar  case,'  an  iron 
bar  completely  transfixed  the  left  frontal  lobe  of  a  man  engaged 
in  blasting.  Although  stunned  for  the  moment,  he  was  able  in 
an  hour  to  climb  a  long  flight  of  stairs,  and  to  answer  the  inquiries 
of  the  surgeon.  Finally,  he  recovered,  and  lived  for  nearly  thirteen 
years  without  either  sensory  or  motor  deficiency,  except  that  he 
suffered  occasionally^  from  epileptic  convulsions.  But  his  intellect 
was  impaired;  he  became  fitful  and  vacillating,  profane  in  his 
language  and  inefficient  in  his  work,  although  previously  decent  in 
conversation  and  a  diligent  and  capable  workman. 

Flechsig  supposes  that  his  great  anterior  association  centre  in  the 
frontal  lobe  is  concerned  in  the  retention  of  the  memory  of  all  conscious 
bodily  experiences,  especially  those  connected  with  voluntary  acts. 
The  great  posterior  association  centre  he  imagines  to  be  engaged  in  the 
formation  and  collection  of  ideas  of  external  objects  and  of  the  '  word 
pictures  '  which  represent  them,  and  with  the  preparation  of  speech  in 
respect  of  the  thoughts  to  be  expresseji  and  the  form  of  expression,  the 
office  of  the  Broca's  area  (but  see  p.  971)  being  to  execute  the  mechanical 
part  of  the  process  by  transforming  these  thoughts  into  actual  spoken 
words.  This  posterior  association  centre  may  be  looked  upon  as  the 
seat  of  intellect  in  the  narrower  sense,  as  the  anterior  is  of  will  and  feeling. 

The  experiments  of  Franz  on  the  relation  of  the  cerebral  association 
areas,  and  especially  the  frontal  area,  to  certain  acquired  habits  are  of 
interest.  Cats  were  allowed  to  acquire  certain  habits  involving  simple 
mental  processes,  and  then  it  was  seen  how  these  were  affected  by 
cortical  lesions.  After  bilateral  extirpation  of  the  frontal  lobes  (the 
area  anterior  to  the  crucial  sulcus)  newly-formed,  but  not  long-standing, 
habits  are  lost.  This  cannot  be  due  to  shock,  since  other  brain  lesions 
are  not  followed  by  loss  of  the  habits.  Extirpation  of  one  frontal  area 
usually  causes  a  partial  loss  of  newly-acquired  habits,  or,  rather,  a  slow- 
ing of  the  association  process  leading  to  unusual  delay  in  the  execution 
of  the  movements  connected  with  the  habit.  Habits  once  lost  after 
removal  of  the  frontal  lobes  may  be  releamed. 

The  influence  of  psychical  events  upon  bodily  functions  is  well  known 
and  has  been  more  than  once  illustrated  in  preceding  pages.  The  con- 
verse question  of  the  influence  of  bodily  states  upon  psychical  e\•ent^ 
has  also  been  raised,  especially  in  connection  with  the  genesis  of  emotion. 
Some  psychologists  assume  that  the  bodily  changes  associated  with  such 
emotions  as  grief,  fear,  rage,  or  love,  are  not  evoked  as  a  consequence  ol 
the  emotions,  but  that  the  bodily  changes  follow  directly  the  perception 
of  the  exciting  fact — e.g.,  a  spectacle  which  causes  fear  or  rage,  '  and 
that  our  feeling  of  the  same  changes  as  they  occur  is  the  ernotion  ' 
(James).  Sherrington,  however,  has  shown  that  in  dogs  in  which,  by 
transection  of  the  vagi  and  the  spinal  cord,  all  sensation  of  viscera,  skin, 
and  muscles  behind  the  level  of  the  shoulder  was  eliminated,  no  obvious 
emotional  defect  was  caused.  Notwithstanding  the  immense  abridg- 
ment of  the  field  of  sensation,  anger,  joy,  fear,  disgust  (as  on  being 
offered  dog's  flesh,  which  most  dogs  refuse  to  eat),  were  as  marked  as 
ever,  and  were  evoked  by  the  same  objects  as  before  the  operation 


FUNCTIONS  OF  THE  BRAIN  975 

When  the  afferent  field  is  still  more  restricted,  as  in  the  head  of  a  dog 
grafted  on  the  circulation  of  another  dog  by  anastomosis  of  the  blood- 
vessels, with  precautions  to  avoid  interruption  of  the  blood-flow,  not 
only  docs  the  respiratory  centre  continue  to  discharge  itself  with  a 
regular  rhythm,  but  cortical  volitional  movements  persist  (Guthrie, 
Pike,  and  Stewart),  and,  so  far  as  can  be  judged,  sense  perception, 
emotional,  and  even  intellectual,  processes  continue.  In  one  case  the 
picture  represented  by  the  engrafted  head  was  essentially  the  same  as 
that  presented  by  the  head  of  the  '  host  '  for  over  two  hours.  In  a 
transplanted  head  from  a  younger  dog  in  which  the  circulation  had 
been  interrupted  for  twenty-nine  minutes,  a  remarkable  return  of 
cerebral  function  was  observed  (Guthrie). 

Conditioned  or  Conditional  Reflexes. — This  is  perhaps  the  place  to 
refer  briefly  to  certain  phases  of  brain  function  which  have  been  illus- 
trated by  the  work  of  Pawlow,  already  alluded  to  in  Chapter  VI,  on 
the  so-called  psychical  secretions.  This  study  has  led  him  to  formulate 
some  novel  views  of  the  higher  nervous  activities.  He  has  shown,  for 
instance,  that  if  food  is  presented  to  an  animal,  and  at  the  same  time 
the  skin  of  the  foot  i^:  stimulated  electrically,  the  psychical  secretion 
of  saliva,  which  the  mere  sight  or  smell  of  the  food  brings  about,  be- 
comes, when  the  experiment  has  been  repeated  for  a  sufficient  number 
of  times,  associated  with  the  electrical  stimulus.  It  is  then  no  longer 
necessary  to  offer  the  food  in  order  to  elicit  the  secretion ;  all  that  is  re- 
quired is  to  stimulate  the  foot.  Even  the  nature  of  the  stimulus  may 
be  altered,  cutting  or  burning  the  foot  being  substituted  for  the  electri- 
cal excitation ;  the  secretion  is  still  obtained.  Pawlow  has  termed  such 
reactions  conditioned  or  conditional  reflexes,  because,  unlike  the 
ordinary  spinal  and  bulbar  reflexes  which  are  always  obtainable  and 
are  therefore  spoken  of  as  unconditioned  reflexes,  the  conditioned  re- 
flexes depend  upon  the  establishment  of  certain  conditions,  such  as  the 
associated  influence  of  some  stimulation  of  the  sense  organs  or  of  psy- 
chical excitation.  He  concludes  from  his  extensive  studies  on  this 
subject  that  an  important  function  of  the  central  nervous  system,  and 
especially  of  the  cerebrum,  in  addition  to  its  power  of  integrating  or 
correlating  nerve  impulses,  is  that  of  dispersing  impulses,  producing  new 
types  of  activity  and  new  reflexes. 

Localization  of  Function  in  the  Central  Nervous  System. — Let 
us  now  consider  a  little  more  closely  the  real  meaning  of  this 
localization  of  function.  Scattered  all  over  the  grey  matter  of 
the  primitive  neural  axis,  and,  as  we  have  seen,  over  the  grey  mantle 
of  the  brain  as  well,  are  numerous  '  centres  '  which  seem  to  be 
related  in  a  special  way  to  special  mechanisms,  sensory,  secretory, 
or  motor.  The  question  may  fitly  be  asked  whether  those  centres 
are  really  distinct  from  each  other  in  quality  of  structure  or  action, 
or  whether  they  owe  their  peculiar  properties  solely  to  differences 
in  situation  and  anatomical  connection.  It  is  clear  at  the  outset 
that  the  nature  of  the  work  in  which  a  centre  is  engaged  must  be 
largely  determined  by  its  connections.  The  kind  of  activity  which 
goes  on  in  the  vaso-motor  centre  in  the  bulb,  for  example,  may 
in  no  essential  respect  differ  from  that  which  goes  on  in  the  respira- 
tory centre.  The  calibre  of  the  bloodvessels  will  alter  in  response 
to  a  change  of  activity  in  the  one  because  it  is  anatomically  con- 


q76  TUl'-   Cr.MTKAL  NERVOUS  SYSTEM 

nected  with  the  muscular  coat  of  the  bloodvessels.  Tiie  rate  or 
depth  of  the  respiratory  movements  will  alter  in  response  to  a  change 
of  activity  in  the  other,  because  it  is  connected  witli  muscles  which 
can  act  u})()n  the  chest-walls. 

Experiments  on  the  anastomosis  of  nerves  afford  a  very  interest- 
ing illustration  of  the  (kti-rniining  influence  of  their  peripheral  con- 
nections on  the  function  of  nerve-fibres.  It  has,  in  fact,  been 
shown  that  the  central  end  of  any  efferent  somatic  fibre — i.e.,  any 
fibre  running  from  the  central  nervous  system  and  ending  in 
striated  muscle — can  make  functional  connection  with  the  peri- 
pheral end  of  any  other  efferent  fibre  of  the  same  class,  whatever 
be  the  normal  actions  produced  by  the  two  fibres.  Advantage  has 
been  taken  of  this  in  surgery.  For  instance,  in  a  case  of  severe 
facial  (motor)  tic  the  facial  nerve  was  divided,  and  its  peripheral 
end  united  with  a  portion  of  the  fibres  of  the  spinal  accessory.  The 
voluntary  movements  of  the  face,  after  regeneration  had  occurred, 
were  normally  carried  out  through  impulses  descending  the  spinal 
accessory.  In  cases  of  local  paralysis,  due  to  destruction  of  anterior 
horn-cclis  (anterior  poliomyelitis),  restoration  of  movement  has  also 
been  obtained  by  connecting  the  motor  nerve  of  the  paralyzed  muscles 
to  a  portion  of  a  nerve  coming  off  from  an  uninjured  region  of  the 
cord.     But  the  possibilities  of  this  procedure  have  been  exaggerated 

By  such  operations  it  has  been  possible  to  transpose  motor  areas 
on  the  cerebral  cortex  associated  with  the  flexion  and  extension 
of  a  particular  joint,  so  that  the  part  of  the  cortex  which  originally 
caused  flexion  after  the  nerve  anastomosis  causes  extension,  and 
vice  versa.  When  the  nerves  supplying  a  group  of  muscles  of  the 
dog's  fore-limb  are  eliminated,  the  nerves  of  the  antagonistic  group 
may  be  used  to  supply  both  groups,  and  co-ordinated  movements 
may  be  restored,  although  this  does  not  occur  so  rapidly  as  when 
the  nerves  supplying  the  two  groups  are  simply  cut  and  cross- 
sutured  (Kennedy).  However,  the  limitations  of  this  method 
ought  to  be  recognized.  Before  any  anastomosis  of  nerves  can  be 
made,  good  fibres  must  first  be  destroyed.  Under  favourable  cir- 
cumstances these  may  all  regenerate  and  find  their  way  to  the  struc- 
tures they  are  intended  to  innervate.  When  regeneration  is  com- 
plete, the  number  of  fibres  capable  of  functioning  will  at  best  be  the 
same  as  before  the  operation,  and  may  easily  be  considerably  less. 
The  benefit,  whatever  it  is,  will  be  associated  solely  with  the  re- 
distribution of  the  fibres.  There  is  reason  to  think  that  the  closer 
to  the  cell  of  origin  a  nerve  is  injured  or  divided,  the  less  is  the  chance 
of  restoration,  and  Feiss  has  found  that  after  lesions  in  the  cord 
or  the  spinal  roots  neither  the  anatomical  pattern  of  the  affected 
nerves  nor  their  functional  power  is  much  affected  by  subsequent 
nerve  anastomosis. 

The  central  end  of  any  efferent  somatic  fibre  can  also  make 


FVXcTioxs  or  Tin-  /5/?.i/.v  077 

functional  union  with  tlic  peripheral  end  of  any  of  the  efferent  fibres 
which  run  from  the  central  nervous  system  and  end  in  ganglion 
cells  (pre-ganglionic  fibres),  and  the  central  end  of  any  pre-gan- 
glionic  fibre  can  do  the  same  with  the  peripheral  end  of  any  efferent 
somatic  fibre  (Langley  and  Anderson).  For  instance,  Langley 
divided  (in  cats)  the  vagus  nerve  and  the  cervical  sympathetic. 
The  peripheral  end  of  the  former  degenerated,  of  course,  below  the 
section,  and  the  peripheral  (cephalic)  end  of  the  latter  degenerated 
above  the  section,  up  to  the  terminations  of  its  axons  in  the 
supsrior  cervical  ganglion.  The  central  end  of  the  cut  vagus  was 
subsequently  sutured  to  the  peripheral  end  of  the  cut  sympathetic. 
After  a  time  the  vagus-fibres  grew  along  the  course  of  the  degener- 
ated sympathetic  up  to  the  ganglion,  where  some  of  them  formed 
arborizations  around  the  ganglion  cells.  It  was  now  found  that 
stimulation  of  the  vagus  produced  the  effects  usually  caused  by 
stimulation  of  the  cervical  sympathetic — for  example,  dilatation 
of  the  pupil  and  constriction  of  the  bloodvessels  of  the  head  and 
neck.  From  these  experiments  it  follows  that  the  functions  of  the 
various  groups  of  fibres  in  the  cervical  sympathetic  do  not  depend 
on  anything  pecuHar  to  the  fibres;  any  fibre  which  can  make  con- 
nection with  one  of  the  ganglion  cells  that  send  axons  to  the 
dilator  muscle  of  the  iris  will,  when  stimulated,  act  as  a  pupillo- 
dilator  fibre,  just  as  well  as  a  cervical  sympathetic  fibre.  Other 
instances  of  the  same  law  have  already  been  given  in  connection 
with  the  regeneration  of  nerves  (p.  800). 

Functional  union  does  not  take  place  between  efferent  somatic 
fibres  (or  pre-ganglionic  fibres)  and  post-ganglionic  fibres — i.e., 
fibres  arising  in  peripheral  ganglia,  and  ending  in  smooth  muscle 
and  glandular  tissue;  e.g.,  the  cervical  s3-mpathetic  after  excision 
of  the  superior  cervical  ganglion  does  not  unite  with  the  fibres 
leaving  the  anterior  end  of  the  ganghon  in  such  a  way  that  stimula- 
tion of  it  can  produce  any  of  the  effects  normally  produced  through 
these  fibres.  No  proof  has  been  given  that  afferent  fibres  can  unite 
with  efferent  fibres  or  efferent  with  afferent. 

Afferent  fibres  of  one  nerve  can  unite  with  afferent  fibres  of 
another  nerve,  but  there  is  not  sufficient  evidence  to  show  whether 
fibres  concerned  in  one  sensation  can  unite  with  fibres  concerned 
in  another. 

The  localization  of  function  in  the  cerebral  cortex  has  been  likened  to 
the  localization  of  industries  in  the  multiplex  commercial  life  of  the 
modem  world.  The  barbarian  household  in  which  cloth  is  woven  and 
worked  into  garments;  sandals,  or  moccasins  cobbled  together;  rough 
pottery  baked  in  the  kitchen  fire,  and  all  the  rude  furniture  of  the  lodge 
fashioned  by  the  hands  which  built  it,  and  which  rest  beneath  its  roof  at 
night — this  state  of  things  where  centralization  has  not  yet  begun,  it 
has  been  said,  is  a  picture  of  what  goes  on  in  the  undeveloped  brains  of 
the  frog,  the  pigeon,  and  the  rabbit.  The  '  diffusion  '  of  industries 
which  is  characteristic  of  a  primitive  state  has  given  place  among  the 

62 


978  THE  CKSTRAL  NERVOUS  SYSTEM 

most  highly  civilized  men  to  extreme  centralization  and  concentra- 
tion. Manchester  spins  cotton  and  Liverpool  ships  it.  Chicago  handles 
wheat  and  pork  that  ha\'e  been  produced  on  the  prairies  of  Alinnesota 
and  Illinois.  Amsterdam  cuts  diamonds.  Munich  brews  beer.  Lyons 
weaves  silk.  New  York  and  London  are  centres  of  finance.  This,  it  is 
said,  is  the  picture  of  the  highly  specialized  brain  of  a  monkey  or  a  man. 
But  ingenious  and  alluring  though  such  analogies  are,  they  do  not  rest 
upon  a  sufficient  basis  of  fact.  Indeed,  the  more  deeply  the  structure 
and  function  of  the  central  nervous  system  are  studied,  the  more  clearly 
does  its  essential  solidarity  appear,  the  more  clearly  does  it  emerge  as  an 
organized  co-ordinated  system,  not  an  aggregate  of  separate  mechanisms 
jumbled  together  for  convenience  of  storage  in  the  protected  cranio- 
spinal cavity. 

It  has  never  been  shown — nor  is  it  likely  that  the  proof  will  soon  be 
forthcoming — that  there  is  any  difference  whatever  in  the  physical, 
chemical,  or  psychical  processes  which  go  on  in  the  various  centres  of 
the  '  motor  '  cortex.  It  may  be  supposed,  indeed,  that  the  so-called 
sensory  areas  of  the  cortex  differ  more  widely  in  their  internal  activity 
from  the  '  motor  '  areas  than  the  latter  do  among  themselves,  and  that 
the  activity  of  the  anterior  portion  of  the  brain,  the  portion  which  has 
been  credited  par  excellence  with  pyschical  functions,  differs  in  kind,  not 
merely  in  degree,  from  that  of  all  the  rest.  But,  as  we  have  just  seen, 
even  the  '  motor  '  areas  have  sensory  functions.  A  cast-iron  physiology 
may  explain  this  by  the  assumption  of  '  sensory  '  as  well  as  '  motor  ' 
cells  in  the  Rolandic  area,  and  may  find  support  for  such  an  assumption 
in  the  well-known  fact  that  the  large  pyramidal  cells  whose  axons  form 
the  pyramidal  tract  make  up  but  a  small  proportion  of  the  total  number 
of  pyramidal  cells  in  this  region,  which,  besides,  contains  numerous  cells 
of  Golgis  second  type  (p.  856)-  And  although  it  may  be  true  that  the 
tactile  sensations  constituting  the  so-called  body-sense  are  represented 
mainly  not  in  the  motor  region  itself,  but  in  the  adjacent  gyrus  post- 
centralis  posterior,  to  the  Rolandic  fissure  (p.  951),  there  is  nothing  to 
contradict  the  supposition  that  the  discharge  of  energy-  from  the  most 
circumscribed  motor  area  or  element  may  be  accomi>anied  with  con- 
sciousness. And,  indeed,  some  writers  have  supposed  that  such  a 
consciousness  of,  or  even  conscious  measurement  of,  the  discharge 
from  the  '  motor  '  areas  is  the  basis  of  the  muscular  sense  (Bain, 
Wundt). 

So  far,  at  least,  as  the  '  motor  '  region  and  the  grey  matter  imme- 
diately around  the  neural  canal  are  concerned,  the  analogy  of  an 
electrical  switch-board  connected  with  machines  of  various  kinds  might 
be  more  correct.  Touch  one  key  or  another,  and  an  engine  is  set  in 
motion  to  grind  corn,  or  to  saw  wood,  or  to  light  a  town.  The  difference 
in  result  lies  not  in  any  difference  of  material  or  workmanship  in  the 
switches,  but  solely  in  the  difference  in  their  connections. 

Grey  matter  in  the  upper  part  of  the  precentral  convolution  is  excited, 
?.nd  the  muscles  of  the  leg  contract.  Grey  matter  on  the  lower  part  of 
the  convolution  is  excited,  and  there  are  movements  of  the  face  and 
mouth.  Grey  matter  in  the  medulla  oblongata  is  excited,  and  the 
salivary  glands  pour  forth  a  thin,  watery  fluid,  poor  in  proteins,  and 
containing  an  amylolytic  ferment.  Another  portion  of  grey  (?)  matter 
in  the  medulla  is  thrown  into  activity,  and  the  pancreatic  ducts 
become  flushed  with  a  thicker  secretion,  relatively  rich  in  proteins  and  in 
ferments  which  act  on  proteins,  starch,  and  fat.  Here,  too,  there  is  a 
variety  in  result  according  as  one  or  another  nervous  switch  is  closed ; 
here,  too,  the  variety  is  due.  not  to  essential  differences  in  the  structure 
of  the  acti\  ity  or  the  nervous  centres,  but  to  their  connection,  by  nervous 


FUNCTIONS  OF  THE  BRAIN  970 

paths,  with  pcripchral  organs  ol  different  kinds.  There  is,  indeed,  a 
specialization,  a  localization,  of  function,  but  the  localization  is  at  the 
peripherv',  the  specialization  is  in  the  peripheral  organs. 

It  may  be  asked  whether,  if  this  is  the  case  for  the  peripheral  organs 
of  efferent  nerves,  the  converse  does  not  hold  true  for  the  afferent  nerves 
— in  other  words,  whether  the  localization  here  is  not  at  the  centre.  And 
that  there  is  in  some  degree  a  central  localization  of  sensation  may  be 
considered  proved  by  the  well-known  clinical  fact,  already  referred  to, 
that  sensations  of  various  kinds  may  be  produced  by  pathological 
changes  in  the  cortex.  For  example,  a  tumour  involving  the  upper  part 
of  the  temporal  lobe  may  give  rise  to  epileptiform  convulsions  preceded 
by  an  auditory  aura,  a  sound,  it  may  be,  resembling  the  ringing  of  bells; 
a  tumour  involving  the  occipital  region  may  cause  a  visual  aura,  and  so 
on.  Central  sensory  localization  is  the  fundamental  idea  of  the  old 
doctrine  of  the  specific  energy  of  nerves,  which,  in  modem  phraseology, 
expresses  the  fact  that  excitation  of  the  central  end  of  a  sensory  nerve 
by  various  kinds  of  stimuli  causes  always — or  at  least  very  often — the 
particular  kind  of  sensation  appropriate  to  the  nerve.  The  observation 
so  frequently  made  in  surgery  before  the  days  of  anaesthetics,  that  when 
the  optic  nerve  was  cut  in  removing  the  eyeball  the  patient  experienced 
the  sensation  of  a  flash  of  light,  *  was  long  looked  upon  as  the  strongest 
prop  of  the  law  of  specfic  energy,  and  well  illustrates  the  meaning  of  the 
term.  Here  a  mechanical  excitation  of  the  optic  fibres  in  their  course 
gives  rise  to  the  same  sensation  as  excitation  of  the  retina  by  the 
natural  or  homologous  or  adequate  stimulus  of  light.  Since  a  similar 
mechanical  stimulus  applied  to  the  auditory  nerve  gives  rise  to  a  sensa- 
tion of  sound,  and,  applied  to  the  trigeminal  nerve,  to  a  sensation  of  pain, 
many  physiologists  have  assumed  that  the  impulses  set  up  in  the 
auditory  nerve  when  sound  impinges  on  the  tympanic  membrane  do  not 
differ  essentially  from  those  set  up  in  the  optic  nerve  when  a  ray  of  light 
falls  upon  the  retina,  or  from  those  set  up  in  the  fifth  nerve  by  the  irri- 
tation of  a  carious  tooth,  or  from  those  set  up  in  certain  fibres  of  the 
cutaneous  nerves  when  a  warm  body  comes  in  contact  with  the  skin. 
Since  the  results  in  consciousness  are  very  different,  this  assumption  has 
necessitated  the  further  conclusion  that  somewhere  or  other  in  the 
central  nervous  system  there  exist  organs  that  are  differently  affected 
by  the  same  kinds  of  afferent  impulses — in  other  words,  that  senson,' 
localization  is  at  the  centre.  On  this  view,  the  viscual  areas  in  the  cortex 
respond  to  all  kinds  of  stimuli  by  visual  sensations ;  the  auditory  areas 
by  sensations  of  sound,  and  so  on. 

But  while  it  cannot  be  doubted  that  special  sensory  regions  exist  in 
the  grey  matter  of  the  brain,  where  the  afferent  paths  concerned  in  the 
different  kinds  of  sensation  end,  it  has  not  been  proved  that  the  nerve- 
impulses  which  travel  up  the  various  paths  are  absolutely  similar  until 
they  have  reached  the  centres,  and  there  suddenly  become,  or  produce, 
sensations  absolutely  different.  There  is,  indeed,  evidence  of  a  certain 
amount  of  sensory  specialization  at  the  periphery.  For  example,  when 
an  ordinary  nerve-trunk  is  touched,  the  resultant  sensation  is  not  one 
of  touch.  If  there  is  any  sensation  at  all,  it  is  one  of  pain.  Heating 
or  cooling  a  naked  nerve-trunk  gives  rise  to  no  sensations  of  tempera- 
ture. When  the  ulnar  nerve  is  artificially  cooled  at  the  elbow,  the  first 
effect  is  severe  pain  in  the  parts  of  the  hand  supplied  by  the  nerve.  The 
pain  disappears  somewhat  abruptly  as  cooling  goes  on,  and  is  succeeded 
by  gradual  loss  of  all  sensation  in  the  ulnar  area  of  the  hand ;  but  the 
cooling  of  the  nerve-trunk  does  not  give  rise  to  any  sensation  of  cold 
(Weir  Mitchell).     Stimulation  of  the  receptors  or  end -organs  is  normally 

*  It  is  said  that  this  is  not  always  the  cas«. 


986  THE  CENTRAL  NERVOUS  SYSTEM 

essential  in  order  that  sensations  of  touch  and  temperature  should  be 
experienced,  .\lthough  as  previously  stated,  one  great  function  of 
the  receptor  is  to  lower  the  threshold  of  the  adequate  stimulus, 
and  thus  to  render  the  afferent  neuron  more  easily  excited  by  an 
adequate  stimulus  than  by  any  other,  it  may  also  serve  to  impress  a 
particular  rhythm  or  other  character  upon  the  nerve  impulse,  so  that  the 
afferent  impulses  may  be  to  some  extent  differentiated  before  they  reach 
their  centres.  One  reason,  then,  why  excitation  of  the  temporal  cortex 
by  impulses  falling  into  it  along  the  auditory  nerve-fibres  causes  a  sensa- 
tion different  from  that  caused  by  impulses  reaching  the  occipital  cortex 
through  the  fibres  of  the  optic  nerve  may  be  a  difference  in  the  nature  of 
the  impulses.  If  this  were  the  only  reason,  it  would  follow  that  were  it 
possible  to  physiologically  connect  the  fibres  of  the  optic  radiation  with 
the  temporal  cortex,  and  those  of  the  temporal  radiation  with  the 
occipital  cortex,  sights  and  sounds  would  still  be  perceived  and  dis- 
criminated in  a  norr.ial  manner,  although  now  the  integrity  of  the 
occipital  lobe  would  be  bound  up  with  the  perception  of  sound,  the 
integrity  of  the  temporal  lobe  with  visual  sensation.  This  state  of 
affairs  would  correspond  to  complete  specialization  for  sensation  in  the 
peripheral  organs,  complete  absence  of  specialization  in  the  centres.  On 
the  other  hand,  it  is  conceivable  that,  after  such  an  ideal  experiment, 
sound-waves  falling  on  the  auditors^  apparatus  might  cause  visual 
sensations,  and  luminous  impressions  falling  on  the  retina  sensations  of 
sound.  This  would  correspond  to  complete  specialization  of  sensation 
in  the  centres,  complete  absence  of  specialization  at  the  periphery.  A 
third  possibility  would  be  that  the  '  tran.sposed  '  centres,  responding  at 
first  feebly  or  not  at  all  to  the  new  impulses,  might,  by  slow  degrees, 
become  more  and  more  excitable  to  them.  This  would  correspond  to  a 
peripheral  specialization,  combined  with  a  tendency  to  development  oi 
central  specialization.  And,  indeed,  it  is  not  easy  to  conceive  in  what 
way,  except  as  the  result  of  differences  in  the  nature  of  impulses  coming 
from  the  periphery',  specialization  of  sensor^^  areas  in  the  central  nervous 
system  could  have  at  first  arisen. 

Degree  of  Localization  in  Different  Animals. — Before  leaving  this 
subject,  two  points  ought  to  be  made  clear:  (i)  The  degree  of 
localization  of  function  in  the  cortex  goes  hand  in  hand  with  the 
general  development  of  the  brain.  In  man  and  the  monkej-,  the 
motor  localization  is  more  elaborate  than  in  the  dog — that  is  to 
say,  a  greater  number  of  movements  can  be  associated  with  definite 
cortical  areas.  In  the  rabbit,  whose  '  motor  '  centres  have  been 
particularly  studied  in  recent  years  by  Mann  and  ]\Ii]ls,  localization 
is  still  less  advanced  than  in  the  dog.  Towards  the  bottom  of  the 
mammalian  group  certain  '  motor  '  areas  can  still  be  demonstrated, 
though  they  are  rather  ill-defined,  for  instance  in  the  hedgehog 
(Mann),  opossum  (Cunningham),  and  ornithorhynchus  (Martin). 
In  general  the  movements  of  the  anterior  limb  are  easier  to  obtain 
than  those  of  the  posterior.  In  birds  Mills  found  no  evidence  of  the 
existence  of  any  '  motor  '  centres. 

(2)  Areas  of  the  same  name  (homologous  areas)  in  different  groups 
of  animals  do  not  necessarily  have  the  same  function — that  is,  in 
the  case  of  the  '  motor  '  areas,  are  not  necessarily  associated  with 
the  same  movements.     Taking  the  position  of  the  centre  for  the 


FUNCTIONS  or  Till-:  BRAIN  981 

orbicularis  oculi  as  a  test,  Ziehen  has  come  to  tJie  conclusion  that 
in  the  anthropoid  apes  and  in  man  this  centre  has  been  pushed 
forward  by  the  encroachment  of  the  centres  behind  it,  and  especially 
of  the  visual  centre,  the  arm  centre,  and  the  speech  centre,  which 
have  undergone  a  great  functional  development. 

Acquisition  of  Co-ordination  of  Voluntary  Movements. — The  co-ordina- 
tion of  movements  has  already  been  alhidcd  to  in  connection  with  the 
spinal  reflexes.  No  fundamental  distinction  can  be  drawn  between  the 
co-ordination  of  reflex  and  of  voluntary  movements,  but  the  conscious 
and  often  long-continued  efforts  necessary  to  acquire  mastery  over  the 
latter  lends  to  their  co-ordination  a  special  interest.  The  new-born  child 
brings  with  it  into  the  world  a  certain  endowment  of  co-ordinative 
powers;  it  has  inherited,  for  example,  from  a  long  line  of  mammalian 
ancestors  the  power  of  performing  those  movements  of  the  cheeks,  lips, 
and  tongue,  on  which  sucking  depends;  perhaps  from  a  long,  though 
somewhat  shadowy,  race  of  arboreal  ancestors  the  power  of  clinging 
with  hands  and  feet,  and  thus  suspending  itself  in  the  air.  Many  move- 
ments, such  as  walking  and  the  co-ordinated  muscular  contractions 
involved  in  standing,  and  even  in  sitting,  which,  once  acquired,  appear 
so  natural  and  spontaneous,  have  to  be  learnt  by  painful  effort  in  the 
hard  school  of  (infantile)  experience,  and  this  despite  the  fact  that  in 
these  movements  the  \-oluntarv  co-ordination  mechanism  makes  use  to 
a  great  extent  of  a  motor  machinery  already  existing  in  the  cord  and 
capable  of  discharging  well  co-ordinated  reflexes.*  In  addition  to  such 
fundamental  movements,  most  people  consciously  learn,  and  are 
willing  to  confess  that  they  have  learnt,  to  execute  a  considerable 
number  of  co-ordinated  movements  with  the  arms,  and  especially  with 
the  fingers.  Some  part  even  of  the  extreme  dexterity  of  jaws,  tongue, 
and  teeth  displayed  by  a  hungry  school-boy,  in  a  minor  degree,  perhaps, 
by  a  hungry  mouse,  is  the  result  of  the  much  practice,  entailing  at  first 
some  conscious  effort,  which  maketh  perfect.  The  exquisite  co-ordina- 
tion of  the  muscles  of  the  eyeball,  which  we  shall  afterwards  have  to 
speak  of,  and  the  no  less  wonderful  balance  of  eft'ort  and  resistance,  of 
power  put  forth  and  work  to  be  done,  of  which  we  have  already  had 
glimpses  in  studying  the  mechanism  of  voice  and  speech,  become  to  a 
s^reat  extent  the  common  property  of  all  fully-developed  persons.  But 
the  technique  of  the  finished  singer  or  musician,  of  the  swordsman  or 
acrobat,  and  even  the  operative  skill  of  the  surgeon,  are  in  large  part  the 
outcome  of  a  special  and  acquired  agility  of  mind  or  bod  ■,  in  virtue  of 
w^hich  highly-complicated  co-ordinated  movements  are  promptly  deter- 
mined on  and  immediately  executed. 

With  such  special  and  elaborate  movements  it  is  impossible  to  occupy 
ourselves  in  a  book  like  this.     Their  number  may  be  almost  indefinitely 

*  The  question,  how  much  is  '  learned  '  in  an  act  such  as  walking,  and 
how  much  is  already  present  at  birth  in  the  form  of  a  co-ordinated  mechanism 
in  the  nervous  system,  is  not  easy  to  answer,  and  indeed  the  answer  may  be 
different  for  different  animals.  It  has  been  shown  that  even  the  unborn 
foetus  of  the  cat,  when  shelled  out  of  the  uterus  into  saline  solution  without 
interference  with  the  circulation  through  the  umbihcal  cord,  can  be  made  to 
execute  unmistakable  movements  of  progression  under  the  influence  of 
asphyxia,  produced  by  pressure  upon  the  cord.  It  may  also  execute  such 
movements  spontaneously.  Graham  Brown,  to  whom  we  owe  these  facts, 
concludes  thai  the  co-ordination  of  the  mechanism  concerned  in  walking  is 
already  developed  during  intra-uterine  life,  and  is  not  '  learned'  after  birth. 


0R2  THE  CENTRAL  NERVOUS  SYSTEM 

extended,  and  their  nature  almost  infinitely  varied,  by  the  needs  and 
training  of  special  trades  and  professions,  it  will  be  sufficient  for  our 
purpose  to  sketch  in  a  few  words  the  mechanism  of  one  or  two  of  the 
most  common  and  fundamental  co-ordinations  of  muscular  effort, 
passing  over  the  rest  with  the  general  statement  that  the  more  refined 
and  complex  movements  are  in  general  brought  about,  not  by  the  abrupt 
contraction  of  crude  anatomical  groups  of  muscles,  but  by  the  contrac- 
tion of  portions  of  muscles,  perhaps  even  single  fibres  or  small  bundles 
of  fibres,  while  the  rest  remain  relaxed.  The  excitation  may  gradually 
wax  and  wane  as  the  different  stages  of  the  movement  require.  Antago- 
nistic muscles  may  be  called  into  play  to  balance  and  tone  down  a  con- 
traction which  might  otherwise  be  too  abrupt. 

Many  interesting  illustrations  of  this  process  of  '  give  and  take  ' 
between  opposing  muscles  have  been  reported,  especially  by  Sherring- 
ton. Some  have  been  already  alluded  to  in  discussing  reflex  move- 
ments (p.  903).  One  or  two  additional  observations  may  be  given  here. 
In  the  cortex  cerebri,  as  we  shall  see  (pp.  95 1,  965),  there  is  an  area  in 
the  frontal  region,  and  another  in  the  occipital  region,  stimulation  of 
which  gives  rise  to  conjugate  deviation  of  the  eyes — that  is,  rotation  of 
both  eyes — to  the  opposite  side.  Sherrington  divided  the  third  and 
fourth  cranial  nerves  in  monkeys — say  on  the  left  side.  The  externai 
rectus,  which  is  supplied  by  the  sixth  nerve,  caused  now  by  its  unopposed 
contraction  external  squint  of  the  left  eye.  When  either  of  the  cortical 
areas  referred  to,  or  even  the  subjacent  portion  of  the  corona  radiata, 
was  stimulated  on  the  left  side,  both  eyes  moved  towards  the  right,  the 
left  eye,  however,  only  reaching  the  middle  line— that  is,  the  position  in 
which  it  looked  straight  forward.  The  same  thing  was  observed  when 
the  animal,  after  complete  recovery  from  the  operation,  was  caused  to 
voluntarily  turn  its  eyes  to  the  right  by  the  sight  of  food.  Here  an 
inhibitory  influence  must  have  descended  the  fibres  of  the  abducens,  the 
only  nervous  path  connected  with  the  extrinsic  muscles  of  the  left  eye, 
and  the  relaxation  of  the  left  externa)  rectus  must  have  kept  accurate 
step  with  the  contraction  of  the  right  internal  rectus.  Hering  has  made 
an  exhaustive  analysis  of  the  co-ordinated  movements  concerned  in 
opening  and  closing  the  hand  in  monkeys.  These  movements  can  be 
produced  by  stimulation  of  the  cortex  or  the  internal  capsule,  but  not 
by  stimulation  of  the  anterior  spinal  roots.  When  the  hand  is  opened 
the  muscles  that  open  it  are  excited,  and  those  which  close  it  are  in- 
hibited from  the  cortex. 

Reaction  Time. — Just  as  in  a  reflex  act  a  certain  measureable 
time  (reflex  time)  is  taken  up  by  the  changes  that  occur  in  the  lower 
nervous  centres,  so  we  may  assume  that  in  all  psychical  processes 
the  element  of  time  is  involved.  And,  indeed,  when  the  interval 
that  elapses  between  the  application  of  a  stimulus  and  the  signal 
which  announces  that  it  has  been  felt  {reaction  time)  is  measured, 
it  is  found  that  for  the  cerebral  processes  associated  with  the  per- 
ception of  the  simplest  sensation  and  the  production  of  the  simplest 
voluntary  contraction  it  is  longer  than  the  time  which  the  spinal 
centres  require  for  the  elaboration  of  even  complex  and  co-ordinated 
reflex  movements.  Suppose,  e.g.,  that  the  stimulus  is  an  induction 
shock  applied  to  a  given  point  of  the  skin,  and  that  the  signal  is  the 
closing  of  the  circuit  of  an  electro-magnet,  then,  if  both  events  are 


FATIGUE  AND  SLEEP— HYPXOSIS  9S3 

automatically  recorded  on  a  revolving  drum,  the  interval  can  be 
readily  determined.  It  is  evident  that  this  includes,  not  only  the 
time  actually  consumed  in  the  central  processes,  but  also  the  time 
required  for  the  afferent  impulse  to  reach  the  brain,  and  the  efferent 
impulse  the  hand,  along  with  the  latent  period  of  the  muscles.  The 
time  taken  up  in  these  three  events  can  be  approximately  calculated, 
and  when  it  is  subtracted,  the  remainder  represents  the  reduced  or 
corrected  reaction  time — that  is,  the  interval  actually  spent  in  the 
centres  themselves.  This  is  by  no  means  a  constant.  It  is  in- 
fluenced not  only  by  the  degree  of  complexity  of  the  psychical  acts 
involved,  and  the  mental  attitude  of  the  person  (whether  he  expects 
the  stimulus  or  is  taken  by  surprise,  whether  he  has  to  choose 
between  several  possible  kinds  of  stimuli  and  respond  to  only  one, 
etc.),  but  it  varies  also  for  different  kinds  of  sensation,  for  the  same 
sensation  at  different  times,  and,  as  is  recognized  in  the  personal 
equation  of  astronomers,  in  different  individuals.  For  sensations 
of  touch  and  pain  it  may  be  taken  as  one-ninth  to  one-fifth,  for 
hearing  one-eighth  to  one-sixth,  and  for  sight  one-eighth  to  one- 
fifth  of  a  second.  So  that  the  proverbial  quickness  of  thought  is 
by  no  means  great,  even  in  comparison  with  that  of  such  a  gross 
process  as  the  contraction  of  a  muscle  (one-tenth  of  a  second). 
Nor  is  it  the  case  that  the  man  '  of  quick  apprehension  '  has  always 
a  short  reaction  time,  or  the  dullard  always  a  long  one,  although  in 
all  kinds  of  persons  practice  will  reduce  it. 


Section  XI. — Fatigue  and  Sleep — Hypnosis. 

Sleep  and  Fatigue. — Certain  gland-cells,  certain  muscular  fibres, 
and  the  epithelial  cells  of  ciliated  membranes,  never  rest,  and 
perhaps  hardly  ever  even  slacken  their  activity.  But  in  most 
organs  periods  of  action  alternate  at  more  or  less  frequent  inter- 
vals with  periods  of  relative  repose.  In  all  the  higher  animals 
the  central  nervous  system  enters  once  at  least  in  the  twenty-four 
hours  into  the  condition  of  rest  which  we  call  sleep.  What  the 
cause  of  this  regular  periodicity  is  we  do  not  know.  It  is 
accompanied  by  changes  in  the  microscopical  appearance  of  the 
nerve-cells.  Thus,  Hodge  found  differences  between  the  cells  of 
certain  portions  of  the  cerebral  cortex  in  birds,  and  of  certain 
ganglia  in  the  honey-bee  after  a  long  day  of  work  and  after  a 
night's  rest.  Mann,  Lugaro,  and  other  observ^ers,  found  similar 
dift'erences  in  the  cells  of  the  cerebral  cortex  and  the  anterior 
horn,  and  Dolley  in  the  Purkinje's  cells  of  the  cerebellum  in 
dogs  fatigued  by  muscular  exercise  as  compared  with  rested  dogs 
(Fig.  398). 


9^4 


THE  CF.XTRAL  NERVOJrS  SYSTEM 


According  to  Dolloy,  tlicrc  is,  as  a  result  of  coiuimied  activity',  at 
first  a  steady  increase  of  the  basic  chromatic  material.  This  increase 
affects  first  the  extra-nuclear  chromatin,  the  Nissl  substance,  which, 
according  to  the  most  modern  view,  is  really  nuclear  substance  distri- 
buted through  the  cytoplasm  and  functions  as  such  (C.oldschmidt). 
The  size  and  number  of  the  granules  are  increased,  and  some  of  the 
chromatic  material  is  diffused  throughout  the  cyto})lasm,  as  indicated 
by  diffuse  staining.  Then  the  intranuclear  chromatin  also  undergoes 
an  increase,  and  the  size  of  the  cell  is  increased  too.  In  moderate 
activity  the  change  goes  no  farther.  At  this  stage  the  cell  is  hyper- 
chromatic — i.e.,  as  compared  with  a  normal  resting  cell  it  contains  an 


ei 


Pig  3gg — Effect  of  Fatigue  on  Nerve-Cells  (Barker,  after  Mann).  Two  motor 
cells  from  kunbar  cord  of  dog  fixed  in  sublimate  and  stained  with  toluidiu 
blue,  a,  from  rested  dog;  i,  pale  nucleus;  2,  dark  Nissl  spindles ;  3,  bundles 
of  nerve'  fibriW.  b,  from  fatigued  dog;  4,  dark  shrivelled  nucleus;  5,  pale 
spindles. 

excess  of  chromatin.  The  production  of  chromatin  ha\ing  reached  the 
maximum  of  whicli  the  nucleus  is  capable,  and  functional  activity, 
which  entails  the  using  up  of  the  extranuclear  chromatin,  still  continu- 
ing, the  total  chromatin  content  begins  t(j  diminish,  first  in  the  nucleus, 
through  the  passage  of  its  chromatin  into  the  cytoplasm  to  recruit  the 
Nissl  substance,  then  in  the  cytoplasm  as  well.  Accompanying  the 
disappearance  of  the  chromatic  material  there  is  diminution  in  the  size 
of  both  cell  and  nucleus,  but  especially  of  the  nucleus,  so  that  the  normal 
j)roportion  between  volume  of  celland  volume  of  nucleus  (nucleus- 
plasma  relation  of  Hertwig)  is  disturl)cd  in  favour  of  the  cytoplasm. 
Both  cell  and  nucleus  become  irregular  in  outline  or  crenated.     Later 


FATTGVF.  AND  SLEEP— HVrSOSTS  983 

on,  and,  it  would  seem,  rallier  abniptly,  swelling  of  the  nucleus  and, 
after  sonic  time,  of  the  cytoplasm  occurs.  This  is  due  to  oedema, 
and  may  be  taken  to  indicate  an  upset  of  their  normal  osmotic  relations. 
The  earlier  occurrence  of  a>dema  in  the  nucleus  leads  to  another  change 
in  the  nucleus-plasma  relation,  which  is  now  disturbed  in  favour  of  the 
nucleus.  In  the  measure  in  which  fatigue  progresses  the  extranuclear 
chromatic  material  continues  U->  be  used  up,  and,  in  spite  of  its  replenish- 
ment from  the  nucleus,  it  almost  or  entirely  vanishes  from  the  cyto- 
plasm. Then  follows  what  is  perhaps  a  '  last  effort  '  on  the  part  of  the 
nucleus  to  supply  the  cytoplasm,  in  the  form  of  a  discharge  of  chro- 
matic substance,  which"  first  masses  itself  around  the  outside  of  the 
nuclear  membrane,  and  tliencc  gradually  diffuses  into  the  cytoplasm. 
With  the  using  up  of  this  supply  all  the  basic  chromatic  material  of 
the  cell,  except  that  in  the  karyosome  (nucleolus) ,  is  exhausted.  Finally, 
this  too  is  yielded  up  to  the  cytoplasm,  and  with  its  consumption  there 
remains  a  totally  exhausted  cell,  devoid  of  basic  chromatin  and  incap- 
able of  recuperation. 

According  to  Pugnet,  even  in  extreme  fatigue,  as  when  dogs  were 
caused  to  run  forty  to  nearly  sixty  miles  in  a  special  apparatus,  the 
changes  varied  greatly  in  degree  in  different  cortical  cells,  from  mere 
diminution  of  the  chromatic  substance  to  complete  disappearance  of  it. 
and  such  disintegration  of  the  cell  as  must  have  precluded  its  recovery, 
had  the  animal  been  allowed  to  live.  Many,  and  indeed  most,  of  the 
cortical  cells  were  quite  unaffected.  Histological  alterations  may  also 
be  caused  in  sympathetic  ganglion  cells  by  prolonged  artificial  stimula- 
tion of  the  nerves  connected  with  the  ganglia.  Experiments  on  fatigue 
changes  in  the  cells  of  the  spinal  ganglia  after  electrical  excitation  of  the 
posterior  root-fibres  are  less  decisive,  some  observers  having  obtained 
positive,  others  negative,  results  (p.  913). 

Theories  of  the  Causation  of  Sleep. — (i)  Some  have  suggested  that  sleep 
is  induced  by  the  using  up  of  substances  necessary  for  the  functional 
activity  of  the  neurons — e.g.,  the  stored -up  or  intramolecular  oxygen — 
or  by  the  action  of  the  waste  products  of  the  tissues,  and  especially  lactic 
acid,  when  they  accumulate  beyond  a  certain  amount  in  the  blood,  or  in 
the  nervous  elements  themselves. 

(2)  Others  have  looked  for  an  explanation  to  vascular  changes  in  the 
brain,  but  so  far  are  the  possible  causes  of  such  changes  from  being 
understood,  that  it  is  even  yet  a  question  whether  in  sleep  the  brain  is 
congested  or  anaemic.  Certain  writers  have  settled  this  question  by  the 
summary  statement  that  when  the  brain  rests  the  quantity  of  blood  in 
it  must  be  supposed  to  be  diminished,  as  in  other  resting  organs.  But 
this  is  a  fallacious  argument.  For  when  the  whole  body  rests,  as  it  does 
in  sleep,  it  has  as  much  blood  in  it  as  when  it  works ;  in  sleep,  therefore, 
if  some  resting  organs  have  less  blood  than  in  waking  life,  other  resting 
organs  must  have  more ;  and  it  is  the  province  of  experiment  to  decide 
which  are  congested  and  which  anaemic.  In  coma,  a  pathological  con- 
dition which  in  some  respects  has  analogies  to  profound  and  long- 
continued  sleep,  the  brain  is  congested,  and  the  proper  elements  of  the 
nervous  tissue  presumably  compressed.  And  artificial  pressure  (applied 
by  means  of  a  distensible  bag  introduced  through  a  trephine  hole  into 
the  cranial  cavity)  may  cause  not  only  unconsciousness,  but  absolute 
anaesthesia.  But  it  is  possible  that  this  artificial  increase  of  intra- 
cranial pressure  may  produce  its  effects  by  rendering  the  brain  anaemic, 
and  it  has  been  actually  observed  that  the  retinal  vessels,  as  seen  with 
the  ophthalmoscope,  and  the  vessels  of  the  pia  mater  exposed  to  direct 
observation  in  man  by  disease  of  the  bones  of  the  skull,  or  in  animals  by 
operation,  shrink  during  sleep.     Statements  to  the  contrary  may  be  due 


986  THE  CENTRAL  NERVOUS  SYSTEM 

to  neglecting  the  influence  of  difference  of  position  in  tHc  sleeping  and 
waking  states.  In  sleeping  children  the  fontanelle  sinks  in,  an  indica- 
tion that  the  intracranial  pressure  is  reduced.  Observations  witli  the 
plethysmograph  have  shown  that  the  arm  swells  in  sleep,  and  shrinks 
when  the  sleeper  awakes,  or  even  when  lie  is  subjected  to  sensorj^  stimuli 
not  sufficient  to  arouse  him — e.g.,  a  tune  played  by  a  musical-box 
(Howell).  The  tone  of  the  vaso-motor  centre  is  therefore  diminished, 
and  the  arterial  pressure  falls  during  sleep.  But  a  fall  of  general  arterial 
pressure  is  usually  accompanied  by  a  diminution  of  the  quantity  of 
blood  passing  through  the  brain.  So  that  the  balance  of  evidence  is  in 
favour  of  the  view  that  sleep  is  associated  iviih  a  certain  degree  of  cerebral 
auamia. 

As  to  the  nature  of  the  relation  between  the  two  conditions,  it  has 
been  suggested  that  the  anaemia  is  produced  by  fatigue  of  the  vaso- 
motor centre,  which  causes  it  to  relax  its  grip  upon  the  periplieral  blood- 
vessels, and  that  the  condition  of  the  cortical  ner\c-cells  which  we  call 
sleep  is  directly  produced  by  the  lack  of  blood.  But  there  does  not 
appear  to  be  any  good  reason  for  believing  that  the  vaso-motor  centre 
is  more  susceptible  of  fatigue  than  the  higher  cerebral  centres.  On  the 
contrary',  it  is  probable  that  the  bulbar  centres  are  less  delicately 
organized  and  more  resistant  than  the  higher  centres.  In  any  case,  if 
the  cerebral  nerve-cells  '  go  to  sleep  '  because  their  blood-supply  is 
diminished,  ought  we  not  to  look  for  a  similar  cause  for  diminished 
activity  of  the  vaso-motor  centre  ?  Or  if  the  answer  is  made  that  the 
activity'  of  the  vaso-motor  cells  is  directly  lessened  by  fatigue,  or  by  the 
cessation  of  external  stimuli,  why  should  not  this  be  the  case  also  for  the 
cortical  cells  ?  It  can  be  shoxs-n  by  means  of  the  sphygmomanometer 
(p.  114)  that  the  fall  of  arterial  pressure  is  not  essentially  connected  with 
sleep,  but  is  produced  by  the  bodily  rest  and  waiTnth  which  accompany 
it.  Further,  even  a  great  diminution  in  the  supply  of  blood  going  to  the 
brain  is  not  necessarily  followed  by  sleep.  For  example,  both  carotid.'; 
and  both  vertebral  arteries  may  frequently  be  tied  in  dogs  at  the  same 
time  without  producing  any  symptoms,  the  anastomosis  of  the  superior 
intercostal  arteries  with  the  aiiterior  spinal  artery  providing  a  sufficient 
channel  for  the  blood  absolutely  required  by  the'brain.  Monkeys  after 
ligation  of  both  carotids  may  be  most  alert  and  active.  To  produce 
sopor  in  animals  the  cortical  "circulation  must  be  reduced  almost  to  the 
vanishing-point,  and  to  a  far  greater  degree  than  e\er  occurs  in  sleep 
(Hill).  We  must,  therefore,  conclude  that  although  sleep  is  normally 
associated  with  some  anesmia  of  the  hrain,  it  is  not  directly  caused  by  it. 
The  cortical  centres  go  to  sleep  because  they  are  '  tired,'  or  because  the 
stimuli  which  usually  excite  them  have  ceased,  and  not  because  their 
blood-supply  is  diminished. 

(3)  The  idea  that  the  dendrites  are  contractile,  and  by  pulling  them- 
selves in,  and  thus  breaking  certain  nervous  chains,  cause  sleep,  is  a 
mere  theon.-,  unsupported  by  any  real  evidence.  The  same  is  true  of 
the  notion  that  the  fibrils  of  "the  neuroglia  insinuate  themselves  into  the 
'  joints,'  by  which  one  neuron  comes  into  contact  with  another,  and, 
acting  as  insulating  material,  block  the  nerve-impulses. 

In  general,  the  depth  of  sleep,  as  measured  by  the  intensity  of  sound 
needed  to  awaken  the  sleeper,  increases  rapidly  in  the  first  hour,  falls 
abruptly  in  the  second,  and  then  slowly  creeps  down  to  its  minimum, 
which  it  reaches  just  before  the  person  awakens.  As  to  the  amount  of 
sleep  required,  no  precise  rules  can  be  laid  down.  It  varies  with  age, 
occupation,  and  perhaps  climate.  An  infant,  whose  main  business  is  to 
grow,  spends,  or  ought  to  spend,  if  mothers  were  wise  and  feeding-bottles 
clean,  the  greater  part  of  its  time  in  sleep.     The  man,  whose  main 


FATIGUE  AND  SLEEP—HYPNOSIS  987 

business  it  is  to  work  witli  his  hands  or  brain,  requires  his  full  tale  of 
eight  liours'  sleep,  but  not  usually  more.  The  dry  and  exliilarating  air 
of  some  of  the  inland  portions  of  North  America,  and  perhaps  the  plains 
of  Victoria  and  New  South  Wales,  incites,  and  possibly  enables  a  new- 
comer to  live  for  a  considerable  period  with  less  than  his  ordinary 
amount  of  sleep.  Idiosyncrasy,  and  perhaps  to  a  still  greater  extent 
"habit,  have  also  a  marked  influence.  The  great  Napoleon,  in  his 
heyday,  never  slept  more  than  four  or  five  hours  in  the  twenty-four. 
Five  or  six  hours  or  less  was  the  usual  allowance  of  Frederick  of  Prussia 
throughout  the  greater  part  of  his  long  and  active  life. 

Hypnosis  is  a  condition  in  some  respects  allied  to  natural  slumber; 
but  instead  of  the  activity  of  the  whole  brain — or  perhaps  we  should 
rather  say,  the  whole  activity  of  the  brain — being  in  abeyance,  the 
susceptibility  to  external  impressions  remains  as  great  as  in  waking  life, 
or  may  be  even  increased,  while  the  critical  faculty,  which  normally 
sits  in  judgment  on  them,  is  lulled  to  sleep.  The  condition  can  be 
induced  in  many  ways — by  asking  the  subject  to  look  fixedly  at  a  bright 
object,  by  closing  his  eyes,  by  occupying  his  attention,  by  a  sudden  loud 
sound  or  a  flash  of  light,  etc.  The  essential  condition  is  that  the  person 
should  have  the  idea  of  going  to  sleep,  and  that  he  should  surrender  his 
will  to  the  operator.  In  the  hypnotic  condition  the  subject  is  extremely 
open  to  suggestions  made  by  the  operator  with  whom  he  is  en  rapport. 
He  adopts  and  acts  upon  them  without  criticism.  If,  for  example,  the 
hypnotizer  raises  the  subject's  arm  above  his  head,  and  suggests  that  he 
cannot  bring  it  dowTi  again,  it  stays  fixed  in  that  position  for  a  long  time 
without  any  appearance  of  fatigue;  or  the  whole  body  may  be  thrown, 
on  a  mere  hint,  into  some  unnatural  pose,  in  which  it  remains  rigid 
as  a  statue.  Suggested  hemiplegia  or  hemianaesthesia,  or  paralysis  of 
motion  and  sensation  together  or  apart  in  limited  areas,  can  also  be 
realized ;  and  surgical  operations  have  been  actually  performed  on 
hypnotized  persons  without  any  appearance  of  suffering.  If,  on  the 
other  hand,  the  operator  suggests  that  the  subject  is  undergoing  intense 
pain,  he  will  instantly  take  his  cue,  writhing  his  body,  pressing  his  hands 
upon  his  head  or  breast,  and  in  all  respects  behaving  as  if  the  suggestion 
were  in  accord  with  the  facts.  If  he  is  told  that  he  is  blind  or  deaf,  he 
will  act  as  if  this  were  the  case.  If  it  is  suggested  that  a  person  actually' 
present  is  in  Timbuctoo.  the  subject  will  entirely  ignore  him,  will  leave 
him  out  if  told  to  count  the  persons  in  the  room,  or  try  to  walk  through 
him  if  asked  to  move  in  that  direction.  What  is  even  more  curious  is 
that  the  organic  functions  of  the  body  are  also  liable  to  be  influenced  by 
suggestion.  A  postage-stamp  was  placed  on  the  skin  of  a  hypnotized 
person,  and  it  was  suggested  that  it  would  raise  a  blister.  Next  day  a 
blister  was  actually  found  beneath  it.  The  letter  K,  embroidered  on  a 
piece  of  cloth,  was  suggested  to  be  red-hot.  The  left  shoulder  was  then 
'  branded  '  with  it,  and  on  the  right  shoulder  appeared  a  facsimile  of  the 
K  as  if  burnt  with  a  hot  iron.  The  secretions  can  be  increased  or 
diminished,  subcutaneous  haemorrhages,  veritable  stigmata,*  can  be 
caused,  and  many  of  the  '  miracles  '  of  Lourdes  and  other  shrines,  ancient 
and  modem,  repeated  or  surpassed  by  the  aid  of  hypnotic  suggestion. 
Hypnotism  has  also  been  practically  employed  in  the  treatment  of 
various  diseases,  and  particularly  in  functional  derangements  of  the 

*  I.e.,  bleeding  spots  on  the  skin  generally  corresponding  to  the  wounds 
of  Christ.  In  the  well-known  case  of  Louise  Latour,  which  excited  great 
interest  in  France  in  1868,  blisters  first  appeared;  they  burst,  and  then  there 
was  bleeding  from  the  true  skin.  The  probable  explanation  is  that  she  con- 
centrated her  attention  on  these  parts  of  her  body  and  so  influenced  them, 
perhaps  by  causing  congestion  through  the  vaso-motor  centre. 


q88 


THE  CENTRAL  NERVOUS  SYSTEM 


nervous  system.  But  care  and  judgment  are  necessary'  on  the  part  of 
the  operator,  and  although  as  a  rule  there  is  no  difficulty  in  putting  an 
end  to  the  condition  by  a  suitable  suggestion,  it  is  said  that  in  rare 
instances  grave  mischances  have  occurred .  There  seems  to  be  no  ground 
for  the  opinion  that  women  are  more  easily  hypnotized  than  men.  Out 
of  more  than  a  thousand  persons,  Liebault  found  only  seventeen  abso- 
lutely refractory. 


Section  XII. — Size  of  Brain  and  Intelligence — Circulation 
IN  and  Resuscitation  of  Central  Nervous  System  after 
Anemia — Chemistry  of  Nervous  Activity — Cerebro-spinal 
Fluid. 

Relation  of  Size  of  Brain  to  Intelligence. — While  it  is  the  case 

that  some  men  of  great  ability  have  liad  remarkably  heavy  and 
richly  convoluted  brains,  it  would  seem  that  in  general  neither  great 
size  nor  any  other  obvious  anatomical  peculiarity  of  the  cerebrum 
is  constantly  associated  vi^ith  exceptional  intellectual  power.  In 
the  animal  kingdom,  as  a  whole,  there  is  undoubtedly  some  relation 
between  the  status  of  a  group  and  the  average  brain  development 
within  the  group.  But  that  this  is  a  relation  which  is  complicated 
by  other  circumstances  than  the  mere  degree  of  intelligence  is 
sufficiently  shown  by  the  fact  that  a  mouse  has  more  brain,  in  pro- 
portion to  its  size,  than  a  man,  and  thirteen  times  more  than  a  horse ; 
while  both  in  the  rabbit  and  sheep  the  ratio  of  brain-weight  to  body- 
weight  is  nearly  twice  as  great  as  in  the  horse,  in  the  dog  only  half 
as  great  as  in  the  cat,  and  not  very  much  more  than  in  the  donkey. 
The  following  tables,  too,  which  illustrate  the  weight  of  the  brain 
in  man  at  different  ages,  show  that,  although  we  might  give  '  the 
infant  phenomenon  '  an  anatomical  basis,  we  should  greatly  over- 
rate the  intellectual  acuteness  of  the  average  baby  if  we  were  to 
measure  it  by  the  ratio  of  brain  to  body-weight  alone. 


Age. 

Brain-weight. 

Age. 

Brain-weight. 

I  year 

885  grm. 

8 

years 

1,045  grm. 

2  years 

909       .- 

10 

•  > 

1. 315     .. 

3       .. 

1,071       ,, 

II 

1,168     ,, 

4       ., 

1,099      .. 

12 

1.286     ., 

5 

1,033       .. 

13 

1.505     .. 

6       ,, 

1. 147       .. 

14 

1-336     ,. 

7       .. 

1,201       ,, 

15 

1,414     •. 

— BiSCHOFF. 

Brain-weight — 

Brain-weight — 

Brain-weighl- 

Brain-weight— 

Age. 
10-19 

Men. 

Women. 

Age. 

Men. 

Women. 

. .  1,411  grm. 

. .    1,219  grm. 

50 

-59 

..  1,389  grm 

.   ..   1,239  grm. 

20-29 

..   1,419      .. 

.  .     1,260       ,, 

60 

-69 

. .  1,292     ,, 

..     1,219       ,. 

30-39 

..   1,424      .. 

.  .     1,272       ,, 

70 

-79 

..  1,254    .. 

..     1,129       ,. 

40-49 

.  .   1,406      ,, 

.  .     1,272       ,, 

80- 

-90 

. .  1,303   .. 

898       .. 
— HUSCHKE. 

THE  CEREBRAL  CIRCULATION  fjho 

In  sumo  small  l)ir(.l^  \.\w  ratio  is  as  high  as  i  :  12,  in  large  birds 
as  low  as  i  :  i,2ou ;  in  certain  fishes  a  gramme  of  brain  has  to  serve 
for  over  5  kilos  of  body.  As  a  rule,  especially  within  a  given  species, 
the  brain  is  proportionally  of  greater  size  in  small  than  in  large 
animals.  It  is  to  be  supposed  that  quality  as  well  as  quantity  of 
brain  substance  is  a  potent  factor  in  determining  the  degree  of 
mental  capacity. 

The  Cerebral  Circulation. — The  arrangement  of  the  cerebral  blood- 
vessels has  certain  peculiarities  which  it  is  of  importance  to  remember 
in  connection  with  the  study  of  the  diseases  of  the  brain,  many  of  which 
are  caused  by  lesions  in  the  vascular  system — haemorrhage,  or  embolism. 
I'our  great  arterial  trunks  carry  blood  to  the  brain,  two  internal  carotids 
and  two  vertebrals.  The  vertebrals  unite  at  the  base  of  the  skull  to 
form  the  single  mesial  basilar  artery,  which,  running  forward  in  a  groove 
in  the  occipital  bone,  splits  into  the  two  posterior  cerebral  arteries. 
Each  carotid,  passing  in  through  the  carotid  foramen,  divides  into  a 
middle  and  an  anterior  cerebral  artery;  the  latter  runs  forward  in  the 
great  longitudinal  fissure,  the  former  lies  in  the  fissure  of  Sylvius.  A 
communicating  branch  joins  the  middle  and  posterior  cerebrals  on  each 
side,  and  a  short  loop  connects  the  two  anterior  cerebrals  in  front.  In 
this  way  a  hexagon  is  formed  at  the  base  of  the  brain,  the  so-called 
circle  of  Willis.  While  the  anastomosis  between  the  large  arteries  is 
thus  very  free,  the  opposite  is  true  of  their  branches.  All  the  arteries 
in  the  substance  of  the  brain  and  cord  are  '  end-arteries  ' — that  is  to 
say,  each  terminates  within  its  area  of  distribution  without  sending 
communicating  branches  to  make  junction  with  its  neighbours.  The 
consequence  of  these  two  anatomical  facts  is:  (i)  that  interference  with 
the  blood-supply  of  the  brain  between  the  heart  and  the  circle  of  Willis 
does  not  readily  produce  symptoms  of  cerebral  aneemia;  (2)  that  the 
blocking  of  any  of  the  arteries  which  arise  from  the  circle  or  any  of  their 
branches  leads  to  destruction  of  the  area  supplied  by  it.  Nearly  all 
dogs  recover  after  ligation  in  one  operation  of  both  carotids  and  both 
vertebral  arteries.  In  monkeys  both  carotids  may,  as  a  rule,  be  safely 
tied,  and  one  carotid  in  man.  If,  in  addition  to  the  two  carotids,  one 
vertebral  be  ligated  at  the  same  time  in  the  monkey,  sopor  results,  and 
this  is  generally  followed  by  extensor  rigidity,  coma,  and  death  in 
twenty-four  hours.  In  one  case  a  monkev  survived  this  triple  ligation, 
but  became  demented.  The  motor  paralysis  and  rigidity  were  much 
greater  than  in  the  dog.  In  the  condition  of  partial  anaemia  the  cortex 
is  more  excitable  than  normal,  but  the  excitability  disappears  at  once 
when  the  anaemia  is  rendered  complete  (Hill). 

The  basal  ganglia  are  fed  by  twigs  from  the  circle  of  Willis  and  the 
beginning  of  the  posterior,  middle,  and  anterior  cerebral  arteries.  Of 
these  the  most  important  are  the  lenticulo-striate  and  lenticulo-optic 
branches  of  the  middle  cerebral,  which  are  given  off  near  its  origin,  and 
run  through  the  lenticular  nucleus  into  the  internal  capsule,  and  thence 
to  the  caudate  nucleus  and  optic  thalamus  respectivel3^  The  chief  part 
of  the  blood  from  the  circle  of  Willis  is  carried  by  the  three  great  cerebral 
arteries  over  the  cortex  of  the  brain.  The  white  matter,  with  the 
exception  of  that  in  the  immediate  neighbourhood  of  the  basal  ganglia, 
is  nourished  by  straight  arteries  which  penetrate  the  cortex.  The 
middle  cerebral  supplies  the  whole  of  the  parietal  as  well  as  that  portion 
of  the  frontal  lobe  which  lies  immediately  in  front  of  the  fissure  of 
Rolando  and  the  upper  part  of  the  temporal  lobe.     The  rest  of  the 


990  THE  CENTRAL  NERVOUS  SYSTEM 

frontal  lobe  is  supplied  by  the  anterior  cerebral,  and  the  occipital  lobe, 
with  the  lower  part  of  the  temporal  lobe,  by  the  posterior  cerebral. 
The  medulla  oblongata,  cerebellum,  and  pons  are  fed  from  the  vertc- 
brals  and  the  basilar  artery-  before  the  circle  of  Willis  has  been  formed. 

Resuscitation  of  the  Central  Nervous  System  after  Total  Anaemia. 
— Complete  temporary  anaemia  of  the  brain  and  upper  cervical 
cord  can  be  produced  in  most  cats  by  passing  temporary  ligatures 
around  the  innominate  artery  and  left  subclavian  proximal  to 
the  origin  of  the  vertebral  artery.  Artificial  respiration  is  main- 
tained through  a  tube  passed  through  the  glottis.  The  eye  reflexes 
disappear  very  quickly,  and  a  period  of  high  blood-pressure  imme- 
diately follows  the  occlusion.  A  fall  of  pressure  succeeds,  due  to 
vagus  inhibition  of  the  heart,  and  this  is  followed  by  a  second  rise 
after  the  vagus  centre  succumbs  to  the  anaemia.  Respiration  stops 
temporarily  (in  twenty  to  sixty  seconds)  after  occlusion;  then 
follows  a  series  of  strong  gasps,  and  finally  cessation  of  all  respiratory 
movements.  The  blood-pressure  slowly  falls  to  a  level  which  is  then 
maintained  approximately  constant  for  the  remainder  of  the  occlu- 
sion period.  The  anterior  part  of  the  cord  and  the  encephalon  lose 
all  function ;  no  reflexes  can  be  elicited  from  this  part  of  the  central 
nervous  system.  The  intra-ocular  tension  is  much  reduced,  and  the 
cornea  is  characteristically  wrinkled. 

When  the  cerebral  circulation  is  restored  by  releasing  the  vessels, 
the  general  arterial  pressure  soon  begins  to  rise  if  the  period  of 
occlusion  has  not  overstepped  the  limit  of  successful  cardio-vascular 
resuscitation.  The  respiration  returns  suddenly,  the  time  of 
return  depending  on  the  length  of  the  occlusion  and  on  other  factors. 
The  respiratory  rate,  at  first  slow,  soon  becomes  normal,  and  then 
more  rapid  than  normal.  The  eye-reflexes  reappear  more  gradu- 
ally; the  intra-ocular  tension  increases,  and  the  shrunken  cornea 
becomes  smooth  and  hard.  The  anterior  part  of  the  cord  recovers 
its  functions  gradually;  the  reflexes  connected  with  it  return,  first 
the  homonymous,  then  the  crossed.  A  short  period  of  quiet  follows ; 
then  spasms  of  the  skeletal  muscles  appear,  gradually  increase  in 
severity  and  extent,  and  terminate  in  (a)  death,  (J)  partial,  or 
(c)  complete  recovery.  In  partial  recovery,  disturbances  of  loco- 
motion, such  as  walking  in  a  circle,  paralysis,  apparent  dementia 
or  loss  of  intelligence,  and  loss  of  sight  or  hearing,  may  be  observed. 
Voluntary  movements  of  the  head,  neck,  shoulders,  and  fore-limbs 
have  been  seen  eight  minutes  after  release  from  an  occlusion  of  six 
minutes.  Blindness  has  been  observed  without  loss  of  the  pupillary 
light  reflex.  In  this  case  the  visual  cortex  would  seem  to  have 
suffered  more  than  the  lower  centres,  an  illustration  of  a  general 
rule.  Complete  recoverv  is  rare  after  total  anaemia  lasting  as  much 
as  fifteen  minutes,  and  has  not  been  observed  after  an  anaemia  of 
twenty  minutes.     Ten  to  fifteen  minutes  of  total  anaemia  represent 


CHEMISTRY  OF  NERVOUS  ACTIVITY  Q^l 

the  limit  beyond  which  recovery  of  the  brain,  and  therefore  successful 
resuscitation  of  the  animal,  cannot  be  expected. 

Chemistryof  Nervous  Activity.- -Of  this  we  are  practically  ignorant. 
The  percentage  composition  of  the  sohds  and  the  percentage  of 
water  in  the  brains  of  three  persons  of  different  ages  are  ex- 
hibited in  the  following  table  (W.  Koch) : 


Child  6  Weeks 
(Brain  640  Grms.). 

Child  2  Years 
(Brain  1,100  Grms.). 

Adult  19  \'ears 
(Brain  1,670  Grms.).       j 

Whole  Uraiii. 

Grey. 

White. 

Whole 
Brain.* 

Grey. 

White. 

Whole 
Brain,  t 

37-1 

6-7 
4-1 

27-3 
12-7 

0-3 
117 

1  Proteins 

1  Extractives     . . 

Ash 

Lecithins      and 
kephalins     .  . 

Cerebrins 

Lipoid  S  as  SO4 

Cholestcrint 

46-6 
I2'0 

8-3 

24-2 
69 

O-I 

1-9 

48-4 
lO-O 

5-8 

247 
8-6 
o-i 

2-4 

31-9 
5-9 
3-2 

26-3 
17-2 

0-5 
15.0 

40-1 
8-0 

4-5 
25-5 

12-9 

0-3 
87 

47-1 

9-5 
5-9 

237 
8-8 

O-I 

4-9 

27-1 

3-9 

2-4 

3I-0 
1 6-6 

0-5 
18.5 

Water  .  . 

8878 

84-49 

76-45 

80-47 

83-17 

69-67 

76-42 

The  next  table  shows  the  variations  in  the  content  of  water, 
soHds,  and  protein  in  different  parts  of  the  nervous  system  (Halli- 
burton) : 


Water. 

Solids. 

Percentage  of  Pro- 
teins in  Solids. 

Cerebral  grey  matter 
Cerebral  white  matter 
Cerebellum 
"  Spinal  cord  as  a  whole     . 
Cervical  cord 
Dorsal  cord 
Lumbar  cord 
Sciatic  nerves 

• 

83-5 
69-9 

79-8 
71-6 

72-5 
69-8 
72-6 
65-1 

16-5 
30-1 

20-2 
28-4 

27-5 
30-2 
27-4 

34-9 

51 

33 
42 
31 
31 

28 

33 
29 

The  grey  matter  of  the  cerebrum  in  the  adult  contains  8i  to 
86  per  cent,  of  water,  the  white  matter  68  to  72  per  cent.,  the 
brain  as  a  whole  81  per  cent.,  the  spinal  cord  68  to  76  per  cent., 
and  the  peripheral  nerves  57  to  64  per  cent.  In  the  foetus  more 
water  is  present  (92  per  cent,  in  the  grey  and  87  per  cent,  in  the 
white  matter). 

The  superior  richness  of  the  grey  matter  in  proteins  and  the 
preponderance  of  water  in  it  are  the  chief  chemical  peculiarities 
which  distinguish  it  from  the  white  matter.  That  it  should  have 
*  CalculatL'd.  t  Calculated  by  difference. 


,j()2  Tin:  CESTRAL  MiRVOUS  SYSTLM 

a  high  pidtiin  content  is  easily  understood,  for  tlie  protoplasmic 
structures,  the  nerve-ccUs,  are  situated  in  the  grey  matter.  But 
that  the  most  important  functions  should  have  their  seat  in  a  tissue 
containing  only  14  to  19  per  cent,  of  solids  is  surprising,  and  should 
warn  us  that  the  water  is  no  less  significant  a  constituent  of  living 
matter  than  the  solids,  and  that  it  is  not  the  mass  of  the  solid 
substances  in  a  tissue  wliich  is  the  essential  thing,  but  the  whole 
colloid  complex,  which  cannot  be  constituted  without  the  water. 

Fresh  nervous  tissues  are  alkaline  to  Utmus,  but  become  acid 
soon  after  death.  No  change  of  reaction  has  been  detected  during 
activity. 

That  o.xygen  is  used  up  during  cerebral  activity  is  certain,  and 
when  the  brain  is  coloured  with  methylene  blue,  b\-  injecting  it 
into  the  circulation,  any  spot  of  it  which  is  stimulated  loses  the 
blue  colour,  the  pigment  being  reduced.  But  if  the  animal  is  so 
deeply  narcotized  that  it  does  not  respond  to  stimulation,  the  change 
of  colour  does  not  occur. 

ChoUn  (p.  366),  a  substance  which  can  be  derived  from  lecithin, 
is  believed  to  represent  one  of  the  waste  products  of  nervous  activity. 
Exceedingly  small  traces  of  it  are  present  in  normal  cerebro-spinal 
fluid,  and  in  certain  diseased  conditions  of  the  brain,  as  in  general 
paralysis,  the  quantity  is  said  to  be  notably  increased,  indicating 
an  increased  decomposition  of  lecithin.  The  fatty  acid  constituent 
of  lecithin  is  liberated  in  degenerating  nerve,  giving  rise  to  the 
reaction  with  osmic  acid  (p.  797).  Some  writers  assert  that  this 
increase  in  the  cholin  can  be  used  as  a  test  to  distinguish  organic 
nervous  disease  from  that  which  is  purely  functional.  But  the 
matter  is  in  dispute. 

Cerebro-spinal  Fluid. — The  cerebro-spinal  fluid,  which  fills  the 
ventricles  of  the  brain  and  the  central  canal  of  the  cord,  is  con- 
tinuous with  that  contained  in  the  subarachnoid  space  through  the 
foramen  of  Magendie,  an  opening  in  the  piece  of  pia  mater  that  helps 
to  roof  in  the  fourth  ventricle.  It  is  secreted  in  part  by  the  cubical 
cells  covering  the  choroid  plexus,  a  fold  of  pia  mater  which  i)rojects 
into  each  lateral  ventricle.  Extracts  of  choroid  plexus,  when  in- 
jected intravenously,  increase  the  rate  of  secretion. 

This  action  is  dependent  upon  the  presence  of  sonu'  sul^stance  in 
the  choroid  plexus,  wliich,  however,  is  not  a  specific  product  of  the 
activity  of  the  plexus,  since  extracts  of  the  brain  produce  the  same 
efifect.  It  may  therefore  be  some  product  of  the  metabolism  of  the 
brain  which  passes  to  the  choroid  plexus  and  stimulates  secretion 
by  the  epithelium.  The  substance  is  removed  from  the  fluid  by 
filtration  through  a  Chamberland  filter,  and  is  therefore  probably 
of  high  molecular  weight.  It  is  probable  that  variations  in  the  rate 
of  secretion  of  the  cerebro-spinal  fluid  In'  the  choroid  plexus  are  more 
infiuential  in  governing  the  intracranial  pressure  than  variations  in 


C  EREB  RO-SPINA  L  l-I.  UID 


995 


the  arterial  and  venous  pressures.  The  idea  that  the  cranial  contents 
constitute  a  fixed  quantity,  without  the  power  of  contraction  or 
expansion,  can  no  longer  be  maintained  (Dixon  and  Halliburton). 
A  graphic  record  of  the  rate  of  secretion  of  the  cerebro-spinal  fluid 
in  the  dog  may  be  obtained  by  inserting  a  hollow  needle  through  the 
occipito-atlantoid  ligament  into  the  great  subarachnoid  cistern, 
and  allowing  the  liquid  to  fall  upon  a  drop-counter  writing  on  a 
drum  (Mg.  J()<)).  It  is  not  always  possible,  ho\ve\'er,  to  be  certain 
by  this  method  that  the  rate  at  which  the  fluid  escapes  represents 


"\  ■....^-^■ 


Fig.  399. — Influence  of  Extract  of  the  Posterior  Lobe  of  the  Pituitary  upon  the  Flow 
of  Cerebro-Spinal  Fluid  through  a  Hollow  Needle  inserted  into  the  Cisterna 
Magna  through  the  Occipito-Atlantoid  Ligament  in  a  Dog.  The  animal  was 
anaesthetized  by  a  constant  method,  insufflation  of  ether  into  the  trachea.  The 
uppermost  curve  is  respiration;  the  next,  drops  of  cerebro-spinal  fluid;  the  next, 
arterial  blood  pressure;  the  fourth,  signal  line  showing  the  point  at  which  50  mg. 
of  a  dried  extract  of  posterior  lobe  was  injected  into  a  vein.  The  signal  line  is 
also  the  zero  of  blood  pressure.  The  bottom  trace  is  the  time  in  seconds  {Weed 
and  Gushing). 

accurately  the  rate  at  which  it  is  formed.  A  more  exact  method 
appears  to  be  the  introduction  of  the  needle  into  the  third  ventricle 
(Fig.  400). 

Cerebro-spinal  fluid  can  easily  be  obtained  in  man  by  lumbar 
puncture  with  a  hypodermic  needle  sufficiently  long  to  enter  the 
subarachnoid  space  in  the  spinal  canal.  The  point  usually  selected 
for  the  puncture  is  between  the  fourth  and  fifth  lumbar  vertebrae. 
The  normal  pressure  of  the  fluid  is  such  that  it  trickles  out  by  drops, 
but  in  disease  it  is  sometimes  so  high  that  it  spurts  out  in  a  steady 
stream.  An  examination  of  the  fluid.  especiaUy  for  leucocytes  or 
bacteria,  is  of  great  diagnostic  value  in  certain  conditions.  Nor- 
mally it  is  a  thin,  clear,  watery  fluid,  faintly  alkaline  in  reaction 

63 


994 


THE  CENTRAL  NERVOUS  SYSTEM 


to  litmus,  and  with  a  specific  ;,'ravity  of  about  1004  to  1007.  It 
contains  tin-  ordinan-  salts,  but  more  potassium  than  sodium,  unhkc 
other  bodv  fluids;  a  ver\'  small  amount  of  protein  (globulin)  — 
usually  about  01  per  cent. — and  a  little  dextrose  (Xawratzki). 
Its  composition  is  e\idently  different  from  that  of  ordinan,'  lymph. 
Only  a  few  Ivmphocvtes  are  present  in  health,  but  in  some  diseases 
(as  in  general  paralysis  of  the  insane,  tabes,  and  cerebro-spinal 
syphilis)  a  marked  increase  occurs.  In  acute  cerebro-spinal  menin- 
gitis numerous  polymorphonuclear  leucocytes  are  found,  which  are 
absent  from  the  normal  fluid. 

The  depression  of  the  freezing-point  (A)  usually  lies  between 
060°  and  0-65°  C.  In  a  case  of  hydrocephalus  it  was  065°  C. 
Normally,  cerebro-spinal  fluid  is  somewhat  hypertonic  to  the  blood- 


Fig.  400. — Sagittal  Section  of  Dog's  Skull.  ?h' Aving  the  Needle  introduced  into  Third 
Ventricle  to  tap  Cerebro-Spinal  Fluid  (Weed  and  Cashing). 

serum.  In  injury  of  the  cribriform  plate  of  the  ethmoid  bone  and 
also  in  some  cases  where  there  is  no  traumatic  injury,  the  fluid 
escapes  from  the  nose,  and  the  rate  of  its  formation  can  thus  be 
ascertained.  In  one  case  it  was  found  to  be  as  much  as  2  c.c.  to 
nearly  4  c.c.  in  ten  minutes. 


PRACTIC.\I.  EXERCISES  OX  CHAPTER   XVT. 

I.  Section  and  Stimulation  of  the  Spinal  Nerve-Roots  in  the  Frog.  — (a) 
Select  a  large  fn.g  [a.  bull- frog,  il  possible  Pith  the  brain.  Fasten 
the  frog,  belly  down,  on  a  plate  of  cork.  Make  an  incision  in  the  middle 
line  over  the  spinous  processes  of  the  lowest  three  or  four  vertebrae, 
separate  the  muscles  frtmi  the  vertebra!  arches,  and  with  strong  scissors 
o  jen  the  spinal  canal,  taking  care  not  to  injure  the  cord  by  passing  the 
bla-lc  of  the  scissors  too  deeply.     Extend  the  opening  upwards  till  tvvo 


PRACTICAL  EXERCISES  995 

or  three  posterior  roots  come  into  view.  Pass  fine  silk  ligatures  under 
two  of  them,  tic,  and  divide  one  root  central  to  the  ligature,  the  other 
peripheral  to  it.  Stimulate  the  central  end,  and  reflex  movements  will 
occur.  Stimulate  the  peripheral  end;  no  effect  is  produced.  Now  cut 
away  the  expo.sed  posterior  roots  and  isolate  and  ligature  two  of  the 
anterior  roots,  which  arc  smaller  than  the  posterior.  Stimulate  the 
central  end  of  one  :  there  is  no  effect.  Stimulation  of  the  peripheral  end 
of  the  other  causes  contractions  of  the  corresponding  muscles. 

[b)  Stimulation  of  the  roots  may  be  repeated  on  the  mammal,  using 
the  dog  employed  for  the  experiment  on  the  motor  areas  (p.  100 1); 
Place  lue  auiiiial,  belly  down,  and  insert  a  good-sized  block  of  wood 
between  it  and  the  board  at  the  level  of  the  lumbar  vertebra;  of  the 
spine.  Divide  the  skin  and  muscles  on  either  side  of  this  region  till  the 
laminae  of  the  vertebrae  are  exposed.  Snip  through  them  with  strong 
forceps,  and  open  the  spinal  canal,  exposing  a  length  of  cord  correspond- 
ing to  three  or  four  vertebrae.     Ligate  and  stimulate  the  roots  as  in  {a). 

2.  Reflex  Action  in  the  '  Spinal  '  Frog. — Pith  the  brain  of  a  frog, 
destroying  it  down  to  the  posterior  third  of  the  medulla  oblongata, 
(i)  Note  the  position  of  the  limbs  immediately  after  the  operation,  and 
again  thirty  to  fortj-  minutes  later.  Its  hind-legs  possess  tone,  and  are 
drawn  up  against  the  flanks.  The  animal  can  still  execute  certain 
co-ordinated  movements — e.g.,  pulling  away  its  leg  if  a  toe  is  pinched. 
The  power  of  maintaining  equilibrium  is  lost.  If  placed  on  its  back,  it 
lies  there.  When  thrown  into  water  it  sinks  usually  without  any 
attempt  at  swimming.  Verify  the  following  facts,  using  mechanical 
stimulation  (pinching  the  toes  or  skin  of  the  leg) :  (a)  If  the  stimulus 
provokes  muscular  movements  only  on  one  side  of  the  body,  this  is 
usually  on  the  same  side  as  the  stimulated  point,  {b)  When  the  stimulus 
causes  reflex  moA-ements  on  both  sides  of  the  body,  the  stronger  con- 
tractions are  on  the  side  to  which  the  stimulus  was  applied. 

Determine  whether  it  is  easier  to  obtain  movement  of  a  portion  of  the 
body  innervated  from  a  region  of  the  cord  above  the  level  of  the  stimu- 
lated nerv^es  or  below  that  level. 

(2)  With  electrical  stimuli  (using  a  coil  arranged  for  single  shocks  de- 
termine if  reflex  movements  are  elicited  by  a  single  induced  shock  ap- 
plied to  the  skin.  Verify  the  fact  that  a  series  of  shocks  is  more  efficient, 
the  effects  of  the  separate  stimuli  being  summated  in  the  reflex  centres. 

(3)  To  test  the  effect  of  thermal  stimuli,  dip  the  leg  into  a  beaker  of 
warm  water.  Vary  the  temperature  of  the  water,  using  a  series  of 
beakers  with  water  at  io°C.,  I5°C.,  20°C.,  etc.,  above  the  temperature  of 
the  room.  Place  the  leg  for  a  moment  in  each,  and  determine  which  is  the 
most  efficient  stimulus.  Immediately  on  withdrawing  the  leg  from  each 
of  the  hot-water  beakers  immerse  it  in  a  beaker  of  water  at  room  tem- 
perature. Finally,  dip  the  leg  into  a  beaker  of  cold  water,  and  heat  it 
gradually  to  a  temperature  at  which  a  reflex  was  previously  obtained. 
Probably  it  will  not  be  elicited  by  the  gradual  warming. 

(4)  '  Purposive  '  Movements. — Touch  the  skin  of  one  thigh  with  blot- 
ting-paper soaked  in  strong  acetic  acid.  The  leg  is  drawn  up,  and  the 
foot  moved  as  if  to  get  rid  of  the  irritant.  If  the  leg  is  held,  the  other 
is  brought  into  action.     Immerse  the  frog  in  water  to  wash  away  the  acid . 

(5)  Spread  {Irradiation)  of  Reflexes. — Gently  stimulate  a  toe  or  a  small 
spot  on  the  flank  with  weak  induction  shocks  or  weak  mechanical 
stimuli,  and  note  the  reflex  effect  obtained.  Then  go  on  gradually 
increasing  the  strength  of  stimulation  without  increasing  the  area  of 
the  field  stimulated,  and  observe  the  extent  and  order  of  spread  of  the 
reflex  movements. 

3.  Reflex  Time. — Pass  a  hook  through  the  jaws.     Holding  the  frog  by 


996  THE  CENTRAL  NERVOUS  SYSTEM 

the  hook,  dip  one  leg  into  a  dilute  solution  of  sulphuric  acid  (02  to 
05  per  cent),  and  note  with  the  stop-watch  the  interval  which  elapses 
before  the  frog  draws  up  its  leg  (Tiirck's  method  of  determining  the 
reflex  time).     Wasli  the  acid  off  with  water. 

Determine  how  the  reflex  time  varies  with  the  strength  of  the  stimulus. 
This  can  be  done  by  using  various  strengths  of  acid.  The  reflex  time 
will  be  shorter  the  stronger  the  stimulus  up  to  a  certain  point.  Compare 
the  reflex  time  of  movements  on  the  same  side  of  the  body  as  the  point 
pf  application  of  tin-  stimulus  and  on  the  opposite  side. 

4.  Inhibition  of  the  Reflexes. — (i)  Destroy  the  cerebrum  of  a  frog. 
Dip  one  leg  into  dilute  sulphuric  acid  as  in  3,  and  estimate  the  reflex 
time.  Then  apply  a  crystal  of  common  salt  to  the  upper  part  of  the 
spinal  cord.  If  the  opening  made  for  pithing  the  frog  is  not  large  enough 
to  enable  the  cord  to  be  clearly  seen,  enlarge  it.  Again  dip  the  leg  in 
the  dilute  acid.  It  will  either  not  be  drawn  up  at  all,  or  the  interval  will 
be  distinctly  longer  than  before. 

(2)  Expose  the  viscera,  including  the  heart,  taking  care  not  to  injure 
the  cardiac  nerves.  Tap  the  intestines  sharply  with  the  handle  of  a 
scalpel  many  times  in  succession.     The  heart  is  inhibited. 

(3)  Tie  strings  tightly  around  both  fore-legs  of  a  normal  frog.  Place 
the  animal  on  its  back;  it  does  not  turn  over.  The  hind-legs  may  be 
pulled  about  in  various  ways  without  the  frog  turning  over  into  its 
normal  position.  The  reactions  concerned  in  the  maintenance  of 
equilibrium  are  inhibited.  Remove  the  strings.  The  animal  cannot 
be  made  to  lie  on  its  back  except  by  force. 

5.  Spinal  Cord  and  Muscular  Tonus. — Destroy  the  brain  of  a  frog. 
Isolate  the  gastrocnemius,  and  cut  away  the  bone  below  the  knee. 
Isolate  the  sciatic  nerve  without  injuring  it.  Remove  the  muscles  from 
the  femur,  cut  the  bone  and  fix  it  in  a  clamp  for  graphic  recording. 
Connect  the  tendon  with  a  lever,  weighted  with  5  to  10  grammes.  Take 
a  base  line.  Destroy  the  spinal  cord,  or  cut  the  sciatic  and  again  take 
a  base  line.     The  Jength  of  the  muscle  is  slightly  altered. 

6.  Spinal  Cord  and  Tonus  of  the  Bloodvessels. — Destroy  the  brain  of 
a  frog.  Arrange  the  web  of  the  foot  on  the  stage  of  a  microscope,  and 
note  the  calibre  of  the  bloodvessels  in  the  field.  Destroy  the  cord,  and 
observe  the  change  in  their  calibre.     They  will  dilate. 

7.  Action  of  Strychnine. — Pith  a  frog  (brain  only).  Inject  into  one  of 
the  lymph-sacs  thice  or  four  drops  of  a  o'l  per  cent,  solution  of  strych- 
nine. In  a  few  minutes  general  spasms  come  on,  which  have  inter- 
missions, but  are  excited  by  the  slightest  stimulus.  The  extensor 
muscles  of  the  trunk  and  limbs  overcome  the  flexors.  Destroy  the 
spinal  cord;  the  spasms  at  once  cease,  and  cannot  again  be  excited. 

8.  Mammalian  Spinal  Preparation  (Sherrington).* — Deeply  anaes- 
thetize a  cat  with  ether.  Insert  a  cannula  into  the  trachea  (p.  202),  and 
continue  the  anaesthesia  through  this.  Expose  and  ligate  both  common 
carotids.  Make  a  transverse  incision  through  the  skin  over  the  occiput, 
and  extend  it  laterally  behind  the  ears.  Pull  back  the  skin  so  as  to 
exf)Ose  the  neck  muscles  at  the  level  of  the  axis  vertebra.     Feel  for  the 

•  A  similar  preparation  can  be  used  for  certain  experiments  on  the  circu- 
lation (Crile,  Guthrie).  For  these,  as  well  as  for  the  study  of  many  reflexes, 
a  good  preparation  is  obtained  by  occlusion  of  the  cerebral  blood-supply  in  cats 
(without  decapitation).  Even  a  human  "spinal  preparation'  is  capable  of 
executing  reflex  movements,  llie  Turkomans  are  stated  to  have  decapitated 
their  prisoners  and  immediately  placed  on  the  neck  a  hot  metal  plate,  which 
sealed  up  the  cut  vessels.  The  (reflex)  movements,  which  are  described  as  very 
lively  were  then  watched  with  an  interest,  it  is  to  be  supposed,  not  wholly 
scientific. 


PRACTICAL  EXERCISES  997 

ends  of  the  transverse  processes  of  the  atlas,  and  divide  tlic  muscles 
down  to  the  bone  just  behind  these  processes.  Now  start  artificial 
respiration  (p.  202),  or  sooner  if  necessary-  Notch  the  spinous  process 
of  the  axis  with  bone  forceps.  Pass  a  strong  thick  hgature  by  a  sharp- 
ended  aneurism  needle  close  under  the  body  of  the  axis,  and  tic  it  tightly 
in  the  groove  left  by  the  incis-on  behind  the  transverse  processes  of  the 
atlas  and  the  notch  made  in  the  spinous  process  of  the  axis.  This  com- 
presses the  vertebral  arteries  where  they  pass  from  transverse  process 
of  axis  to  transverse  process  of  atlas.  Pass  a  second  strong  ligature 
under  the  trachea  at  the  level  of  the  cricoid  cartilage  and  include  in  it 
the  whole  neck,  except  the  trachea,  but  at  present  only  tie  a  single  loop 
on  it.  Now  decapitate  the  animal  with  a  large  knife  (an  amputating 
knife)  passed  from  the  ventral  aspect  of  the  neck  through  the  occipito- 
atlantal  space,  severing  the  cord  just  behind  its  junction  with  the  bulb. 
At  the  moment  of  decapitation  tighten  the  ligature  round  the  neck  and 
complete  the  Itnot.  Destroy  the  head.  If  there  is  oozing  of  blood  from 
the  vertebral  canal,  arrest  it  by  raising  the  neck  somewhat  above  the 
level  of  the  body.  The  carcass  must  be  kept  warm  by  placing  it  on  a 
metal  box  or  table  containing  hot  water,  and  the  air  used  for  artificial 
respiration  must  also  be  warmed,  as  by  passing  it  through  a  coil  of 
rubber  tubing  immersed  in  a  water-bath  which  is  kept  hot.  Stitch  the 
skin-flaps  together  so  as  to  cover  the  cut  end  of  the  spinal  cord  and  the 
other  structures  cut  in  decapitation.  By  this  procedure  the  spinal  cord 
is  usually  severed  about  4  millimetres  behind  the  point  of  the  calamus 
scriptorius.  Although  the  blood-pressure  remains  low,  reflexes  employ- 
ing the  skeletal  muscles  can  be  fairly  well  elicited  for  hours.  Study  on 
the  preparation  the  reflexes  described  in  the  text  (pp.  Qoi,  904) — e.g.,  the 
flexion  reflex  of  the  hind  and  fore  limb,  as  elicited  from  the  skin,  or  one 
of  the  afferent  nerves  of  the  limb — the  crossed  extension  reflex  of  hind 
and  fore  limb,  the  scratch  reflex. 

(i)  Scratch  Reflex. — -(a)  Evoke  the  reflex  by  rubbing  the  skin  of  the 
neck  behind  the  pinna.  The  scratching  movements  are  in  the  hind-leg 
of  the  same  side.  Record  them  on  a  drum,  on  which  is  also  written  a 
time-tracing  in  seconds.  The  record  can  be  obtained  by  tying  a  piece 
of  tape,  not  too  tightly,  round  the  foot,  leg,  or  thigh,  and  connecting 
this  by  a  thread  with  a  lever.  The  thread  is  passed  over  a  pulley  below 
the  lever,  so  that  its  pull  may  be  exerted  at  right  angles  to  the  axis  of 
rotation  of  the  lever.  The  lever  is  attached  to  a  light  spring  or  a  rubber 
band,  which  is  stretched  when  it  moves  in  one  direction,  and  in  recoiling 
brings  it  back  again  to  its  position  of  rest  at  the  end  of  the  contraction. 
If  the  reflex  is  not  easily  evoked,  it  can  be  facilitated  by  producing  a 
slight  degree  of  asphyxia  by  temporarily  clamping  the  respiration  tube. 
Some  time  must  elapse  after  the  decapitation  before  a  fair  scratch  reflex 
can  be  expected.     It  is  usually  sufficiently  well  marked  within  an  hour. 

{b)  WTiile  the  reflex  is  occurring,  stimulate  w^th  an  interrupted  current 
the  central  stump  of  the  popliteal  nerve  of  the  opposite  hind-limb. 
The  scratch  reflex  may  be  cut  short  by  inhibition.  Also,  during  the 
stimulation  of  this  nerve  the  reflex  may  be  incapable  of  being  elicited 
till  the  excitation  of  the  inhibitory  afferent  nerve  is  stopped. 

(2)  Flexion  Reflex.— {a)  Stimulate  with  a  weak  interrupted  current 
the  skin  of  some  part  of  the  hind-limb — say  one  of  the  toes.  The  flexion 
reflex  of  the  hind-limb  on  the  same  side  may  be  evoked — i.e.,  a  flexion 
movement  at  the  knee,  hip,  and  ankle.  Record  the  movements  of  one 
of  the  joints  or  of  flexor  muscles  after  severing  them  from  their  insertion. 

(6)  Stimulate  with  a  weak  interrupted  (faradic)  current  the  central 
stump  of  one  of  the  nerves  of  a  hind-limb — say  the  peroneal  nerve. 
The  flexion  reflex  of  the  same  limb  may  be  elicited.    Record  the  move- 


998  I  HI-:  CENTRAL  NERVOUS  SYSTEM    . 

merits.  Now  produce  temporary  asphyxia  by  clampinq;  the  respiration 
tube,  and  repeat  the  stinuilation  at  half-minute  intervals.  The  reflex 
will  be  increased  by  the  asphyxia.  Do  not  interrupt  the  respiration  for 
more  than  two  or  three  minutes,  and  immcchatciy  start  it  if  the  heart, 
which  can  be  felt  through  the  chest,  begins  to  weaken. 

(3)  Ehcit  the  knee-jerk,  as  described  in  the  text  (p.  90.}).  It  is 
generally  exaggerated. 

(4)  By  the  unipolar  method  (p.  031)  stimulate  with  a  i)oint  electrode 
one  lateral  half  of  the  cross-section  of  the  cervical  cord  exposed  in 
decapitation.  The  large  electrode  is  placed  on  a  shaved  part  of  a  fore- 
arm. Various  effects  may  be  eUcited  according  to  the  point  of  the 
cross-section  stimulated — e.g.,  stepping  and  scratch  movements  of  the 
hind-limbs.  Other  facts  mentioned  in  the  text  in  regard  to  spinal 
reflexes  can  l)e  verified  on  this  ]irrparation. 

q.  Decerebrate  Cat  Preparation  (Miller  and  Sherrington). — This 
preparation,  which  must  be  made  by  the  demonstrator,  differs  from 
the  spinal  preparation  described  in  8,  in  that  the  plane  of  the  section 
is  considerably  higher,  passing  through  the  posterior  part  of  the  mid- 
brain '  entering  the  posterior  colliculi  (posterior  corpora  quadrigemina) 
near  their  hinder  end  and  emerging  about  a  millimetre  anterior  to  the 
front  edge  of  the  pons.'  Many  reactions  can  be  conveniently  studied 
on  this  preparation,  some  of  which  cannot  be  oV)taincd  with  t:he  spinal 
preparation.  The  respiratory  movements  usually  go  on  without  inter- 
ruption, and  reflexes  whose  centres  are  situated  in  the  bulb,  such  as 
the  swallowing  reflex,  can  be  elicited.  The  circulation  is  well  main- 
tained, and  the  preparation  can  be  used  for  a  number  of  the  experi- 
ments given  after  Chapters  III.  and  IV. 

Under  deep  anaesthesia  (chloroform  and  ether),  the  carotids  are 
temporarily  clamped  opposite  the  uppermost  tracheal  cartilage,  and 
the  cat  is  then  placed  on  the  decerebrator  (Fig.  401)  in  the  prone  posi- 
tion, with  its  neck  on  the  upper  edge  of  the  neck-block. 

The  interparietal  suture  is  exposed  by  an  incision  through  the  scalp 
from  beyond  the  coronal  in  front  to  the  lambdoid  ridge  and  supraocci- 
pital  protuberance  behind.  A  distance  of  30  millimetres  is  then 
measured  off  from  the  coronal  suture  backward  along  the  interparietal 
and  the  point  is  marked  by  notching  the  longitudinal  median  ridge  of 
bone.  The  head  is  placed  between  the  prongs  of  the  yoke  with  the 
tongue-guard  of  the  yoke-plate  inside  the  mouth  above  the  tongue, 
which  it  protects.  The  chin  lies  in  the  hollow  of  the  yoke  under  the 
yoke-plate,  the  lower  canines  covered  by  the  plate.  The  pelvis  lies 
on  the  pelvic  platform,  P,  the  hind  limbs  hanging  freely.  The  head 
is  pushed  down,  the  tongue  guard  in  the  mouth,  until  the  embayed  end 
of  the  yoke-plate  on  either  side  of  the  tongue-guard  meets  the  anterior 
edge  of  the  coronoid  process  of  the  lower  jaw.  The  hook  attached 
to  the  leather  cord  is  fixed  in  a  loop  of  string  previously  tied  trans- 
versely through  the  upper  lip,  and  the  snout  is  drawn  firmly  down  by 
the  cord,  securing  the  head  in  position.  The  cord  is  fastened  to  a 
cleet  on  the  under  surface  of  the  neck-block.  The  nose-piece  is  now 
slid  up  so  as  to  engage  and  support  in  its  notch  the  apex  of  the  muzzle, 
and  is  fixed  by  the  screw-clamp.  A  knife  consisting  of  a  planing-blade 
mounted  in  a  wooden  handle  is  used  for  the  decercbration.* 

*  The  blade  is  12-5  centimetres  wide,  9  centimetres  high,  and  4  millimetres 
thick.  It  is  bevelled  on  one  face,  the  bevelled  edge  being  2  centimetres  deep. 
The  cutting  edge  docs  net  extend  the  whole  width  of  the  blade,  but  stops  short 
at  1-5  centimetres  from  each  lateral  edge.  The  mid-width  of  the  blade  is 
m;irked  bv  an  engraved  line  on  thr  front  of  the  knife. 


PRACTICAL  EXERClSr-:S  90^ 

The  operator,  standinfj;  on  the  loll  side  of  the  animal,  applies  the  mid- 
point of  the  siiarp  edge  of  the  blade,  bevelled  side  forward,  to  the 
point  notchefl  in  the  interparietal  ridge,  the  width  of  the  blade  being 
kept  truly  at  right  angles  to  the  median  plane  of  the  head.  The  knife 
thus  held  in  the  left  hand  is  kept  vertical,  or  nearly  so,  and  is  directed 
so  that  the  plane  of  the  blade  if  continued  downward  through  the 


Fig.  401. — Cat  Decerebrator  (Miller  and  Sherrington).  N,  wooden  neck-block, 
mounted  firmly  on  a  strong  base-board.  N  is  inclined  at  22°  to  the  vertical 
and  supported  by  two  stout  wooden  props  meeting  it  somewhat  below  its  top 
at  an  angle  of  44°.  The  top  edge  of  the  neck-block  (cut  at  right  angles  to  the 
face  of  the  block)  is  therefore  at  an  angle  of  22°  to  the  horizontal.  V,  yoke  a 
Y-shaped  fork  of  wood  with  one  of  the  prongs  projecting  6  centimetres  beyond 
the  top  of  the  neck-block,  the  other  prong  truncated  nearly  to  its  base.  A 
Y-shaped  steel  plate  (the  yoke-plate)  is  screwed  to  Y.  It  is  shaped  somewhat 
like  the  wooden  yoke,  but  its  two  side  prongs  are  of  equal  length,  and  between 
them  projects  a  shorter  prong,  T.  the  tongue-guard.  S  is  a  T-shaped  wooden 
nose-piece,  adjustably  attached  to  the  front  of  the  steel-covered  yoke.  In  the 
upper  boi-der  of  the  cross-piece  of  the  T,  is  a  V-shaped  notch.  A  slot  in  the  stem 
of  the  T  allows  the  T-block  to  be  slid  up  or  down  on  the  fteel  yoke-plate,  and 
it  can  be  fixed  at  any  position  by  a  thumb-screw.  C,  a  leather  cord  passing 
through  a  hole  piercing  neck-block,  yoke  and  yoke-plate.  The  top  end  of  the 
cord,  issuing  from  the  hole  in  the  mid-line  of  the  yoke-plate,  carries  a  short 
strong  hook.  The  point  of  the  notch  in  the  nose-piece  slides  up  to  and  slightly 
beyond  this  hole.  P,  a  light  single-pillared  platform,  somewhat  saddle-shaped 
at  the  top,  which  can  be  slid  on  the  baseboard  nearer  to  or  farther  from  the 
neck-block. 

head  would  meet  a  horizontal  line  engraved  on  the  side-prongs  of  the 
yoke-plate.  This  line  is  at  the  level  of  the  free  end  of  the  tongue- 
guard.  A  light  blow  is  then  struck  with  a  mallet  on  the  top  of  the 
handle  of  the  knife,  sufficient  to  engage  the  edge  in  the  skull  in  the 
proper  direction — i.e.,  toward  the  horizontal  line  on  the  metal  plate. 
Then  with  a  couple  of  heavier  blows  the  head  is  severed  in  the  desired 
plane, 


looo  THE  CESTRAL  NERVOUS  SYSTEM 

The  ]ircparation  is  then  removed  from  the  apparatus,  the  neck  being 
hcUl  laterally  behind  the  wings  of  the  atlas  to  control  the  vertebral 
arteries.  It  is  placed  on  the  experiment  table  with  the  neck  well  raised 
by  a  string  passed  through  the  skin  over  the  occiput,  to  restrain  any 
haemorrhage.  Some  cotton  is  packed  across  the  cut  surface  of  the  mid- 
brain. Bleeding  soon  ceases,  and  in  two  or  three  minutes  one  carotid 
can  be  undamped,  arteries  in  the  masseteric  regions  being  tied  if  neces- 
sary. In  two  minutes  more  the  clamp  can  be  removed  from  the  other 
carotid. 

TO.  With  the  preparation  described  in  q,  study  the  swallowing  reflex, 
evoked — e.g.,  by  the  application  of  water  by  drops  to  the  pre-epiglotti- 
dcan  sinus  between  the  base  of  the  tf)nguc  and  the  epiglottis,  or  by 
allowing  water  to  drop  into  the  pharynx.  Dilute  alcohol  (one  part  of 
ethyl  alcohol  added  to  four  parts  of  water)  is  even  more  effective 
than  water;  oil  much  less  effective. 

II.  Reflex  Postural  Tonus  (Decerebrate  Rigidity). — Study  the  dis- 
tribution of  the  tonus  in  the  decerebrate  cat  prepared  as  in  g  —e.g., 
in  the  extensor  muscle  of  the  knee  (the  vasto-crureus),  the  gastrocne- 
mius, semimembranosus,  triceps,  supraspinatus,  etc.  Isolate  the  knee 
extensor  by  paralvzing  all  the  other  muscles  of  both  hind  limbs  by  nerve 
section.  The  vasto-crurcus  still  maintains  its  postural  reflex  contrac- 
tion. To  observe  the  right  vasto-crureus  place  the  animal  on  its  left 
side.  Begin  with  the  knee  nearly  at  full  extension  and  determine  what 
weight,  attached  to  the  tibia  and  pulling  it  backward  by  a  cord  fastened 
over  a  pulley — i.e.,  tending  to  flex  the  knee — is  just  counteracted  by 
the  postural  action  of  the  muscle.  Now  forcibly  flex  the  knee  nearly 
to  the  full,  bending  it  steadily  and  not  too  quickly,  so  that  thc^  move- 
ment occupies  a  couple  of  seconds.  Apart  from  a  slight  partial  return 
towards  extension,  and  this  not  always,  the  limb  remains  in  the  new- 
position.  Although  the  length  of  the  vasto-crureus  is  now  greater 
than  before,  the  weight  needed  to  counterbalance  its  pull  is  practically 
the  same.  That  is  to  say,  the  muscle  has  assumed  a  new  postural 
length  wnthout  any  sensible  change  of  tension.  This  is  the  so-called 
'  lengthening  reaction  '  of  the  posturally  contracted  muscle.  The 
'  shortening  reaction  '  can  be  obtained  by  repeating  the  observations 
in  the  reverse  order — i.e.,  starting  with  the  knee  in  nearly  full  flexion 
(Sherrington » . 

12.  Reflexes  in  Man.  —  Study  systematically  on  a  fellow-student 
and  on  youi^elf  the  chief  reflexes  described  in  the  text  (p.  914), 
especially — 

The  Knee-jerk. — (i)  Elicit  the  jerk  in  the  usual  way  by  striking  the 
ligamentum  patellae  and  observe  its  height.  Then  cause  the  patient  to 
make  a  strong  voluntary  movement  (squeezing  the  hands  together  or 
clenching  the  jaws)  at  the  moment  when  the  tendon  is  struck,  and  note 
whether  the  height  is  increased  by  '  reinforcement.' 

(2)  Attach  a  suitable  recording  apparatus  to  the  foot  of  a  person 
sitting  with  his  legs  over  the  edge  of  a  table,  and  record  the  jerks 
elicited  by  taps  made  as  uniform  in  strength  as  possible.  A  small 
hammer  worked  by  an  electro-magnet  or  a  spring  might  be  employed 
for  this  purpose.  Compare  the  records  obtained  when  the  jerk  is 
elicited  while  the  person  is  squeezing  his  hands  together  with  those 
previously  obtained.  The  influence  of  mental  activity,  especially  of  ex- 
citement or  irritation  (opportunities  of  studying  such  physical  states 
occasionally  ofter  themselves  in  physiological  "laboratories)  in  increasing 
the  height  of  the  knec-jork  may  also  be  verified  (Lombard). 

13.  Excision  of  Cerebral  Hemispheres  in  the  Frog  (Fig.  402). — 
Anaesthetize  a  frog  lightly  by  putting  it  under  a  bell-jar  or  tumbler 


PRA  C  TIC  A  L  l-XERCISHS 


with  a  small  piece  of  cotton-wool  soaked  in  ether.    Put  very  little  ether 
on  the  cotton,  and  leave  the  frog  only  a  very  short  time  under  the 

bell-jar.       Ihcn,  holding  it  in  a  cloth,  make  an 

incision  through  the  skin  over  the  skull  in  the 

mesial    line.     With  scissors  open  the  cranium 

about  the  position  of  a  line  drawn  at  a  tangent 

to  the  posterior  borders  of  the  two  tympanic 

membranes.     Remove  the  roof  of  the  skull  in 

front  o{  this  line  with   forceps,  scoop  out  the 

cerebral  hemispheres,  eind   sew  up  the  wound. 

As  soon  as  the  animal  has  recovered  from  the 

ether,  the  phenomena  described  at  p.  947  should 

be  verified.     The  frog  will  swim  w^hen  thrown 

into  water,  will   refuse  to  lie  on  its  back,  and 

will  not  fall  if  the   board  on  which  it    lies    be 

gradually    slanted.       Let    the    frog   live    for    a 

day,   keeping  it  in  a  moist  atmosphere ;   then 

expose   the   brain  again,   determine   the   reflex 

time   by  Tiirck's   method  ;    apply  a  crystal  of 

common  salt  to  the  optic  lobes,  and  repeat  the 

observation.      The    reflex    movements  will    be 

completely  inhibited  or  delayed.     Remove  the 

salt,    wash    with    physiologi'^.al    salt    solution, 

excise    the    optic   lobes,  and  see  whether  the 

frog  will  now  swim. 

14.  Excision  of  the  Cerebral  Hemispheres  in 

a  Pigeon. — l-'eed  a  pigeon  for  two  or  three  days 

on  drj^  food,  etherize  it  by  holding  a  piece  of 

cotton-wool  sprinkled  with  ether  over  its  beak, 

or  inject  into   the    rectum    |    gramme    chloral 

hydrate.     The   pigeon  being  wrapped   up  in  a 

cloth,  and  the  head  held  steady  by  an  assis- 
tant, the  feathers  are  clipped  off  the  head,  an 

incision  made  in  the  middle  line   through  the 

skin,  and   the  flaps  reflected   so  as   to  expose 

the  skull.    Cut  through  the  bones  with  scissors, 

and  make  a  sufficiently  large  opening  to  bring  the  cerebral  hemispheres 
into  view.  They  are  now  rapidly  divided  from  the  corpora  bigemina 
and  lifted  out  with  the  handle  of  a  scalpel.  The  bleeding  is  very  free,  but 
may  be  partially  controlled  by  stuffing  the  cavity  with  the  vegetable 
fibre  known  as  Pengavar  Djambi,  which  should  be  removed  in  a  few 
minutes,  the  wound  cleansed  with  iodoform  gauze  wrung  out  of  physio- 
logical salt  solution  at  50°  C,  and  sewed  up.  Study  the  phenomena 
described  on  p.  948. 

15-  Stimulation  of  the  Motor  Areas  in  the  Dog. — (a)  Study  a  hardened 
brain  of  a  dog,  noting  especially  the  crucial  sulcus  (Fig.  382,  p.  950),  the 
convolutions  in  relation  to  it,  and  the  areas  mapped  out  around  it  by 
Hitzig  and  Fritsch  and  others,  (b)  Inject  morphine  under  the  skin  of 
a  dog.  Set  up  an  induction-coil  arranged  for  tetanus,  with  a  single 
Daniell  in  the  primary  circuit.  Connect  a  pair  of  fine  but  not  sharp- 
pointed  electrodes  through  a  short-circuiting  key  with  the  secondary. 
Fasten  the  dog  on  the  holder,  belly  down ,  and  put  a  large  pad  under  the 
neck  to  support  the  head.  Clip  the  hair  over  the  scalp.  Feel  for  the 
condyles  of  the  lower  jaw,  and  join  them  bj-  a  string  across  the  top  of  the 
head.  Connect  the  outer  canthi  of  the  eyes  by  another  thread.  The 
crucial  sulcus  lies  a  little  behind  the  mid-point  between  these  two  lines. 
Now  give  the  dog  ether,  make  a  mesial  incision  through  the  skin  down 


Fig.  402. — Brain  of  Frog 
(after  Steiner).  «,  cere- 
bral hemispheres  ;  h, 
position  of  optic  thala- 
mi;  c,  optic  lobes;  d, 
cerebellum;  e,  medulla 
oblonptata  ;  .4,  upper 
end  of  spinal  cord. 


roo2  THE  CENTRAL  NERVOUS  SYSTEM 

to  the  bone,  and  reflect  the  flaps  on  either  side.  Detach  as  murh  of  the 
temporal  muscle  from  the  bone  as  is  necessary  to  get  room  for  two 
trephine  holes,  the  internal  borders  of  which  must  be  not  less  than 
^  inch  from  the  middle  line,  so  as  to  avoid  wounding  the  longitudinal 
sinus.  Carefully  work  the  trephine  through  the  skull,  taking  care  not 
to  press  heavily  on  it  at  the  last.  Raise  up  the  two  pieces  of  bone  with 
forceps,  connect  the  holes  with  bone  forceps,  and  enlarge  the  opening  as 
much  as  may  be  necessary  to  reach  all  the  '  motor  '  areas.  At  this 
stage  only  enough  ether  should  be  given  to  prevent  suffering.  Now 
unbind  the  hind-  and  fore-limbs  on  the  side  opposite  to  that  on  which 
the  brain  has  been  exposed,  apply  blunt  electrodes  successively  to  the 
areas  for  the  fore-  and  hind-limbs,  and  stimulate.*  The  '  unipolar  ' 
method  of  stimulation  (p.  951)  may  also  be  employed.  Contraction  of 
the  corresponding  groups  of  muscles  will  be  seen  if  the  narcosis  is  not 
too  deep.  Movements  of  the  head,  neck,  and  eyelids  may  also  be  calhd 
forth  by  stimulating  the  '  motor  '  areas  for  these  regions.  Stimulation 
in  front  of  the  crucial  sulcus  may  also  cause  great  dilatation  of  the  pupil, 
the  iris  almost  disappearing.  The  dilatation  takes  place  most  promptly 
and  is  greatest  on  the  opposite  side,  but  the  pupil  on  the  same  side  is 
also  widened.  Even  after  section  of  both  vago-sympathetic  nerves  in 
the  neck,  a  slow  and  slight  dilatation,  greatest  perhaps  on  the  same  side, 
mav  be  caused  by  cortical  stimulation.  Repeat  the  whole  experiment 
on  the  opposite  side  of  the  brain.  In  the  course  of  his  observations  the 
student  will  perhaps  have  the  opportunity  of  seeing  general  epileptiform 
convulsions  set  up  by  a  localized  excitation.  They  begin  in  the  group 
of  muscles  represented  in  the  portion  of  the  cortex  directly  stimulated. 
After  the  convulsions  have  been  sufficiently  studied,  they  should  be 
again  induced,  and  the  stimulated  '  motor  '  area  rapidly  excised  during 
their  course.  In  some  cases  this  will  be  followed  by  immediate  cessation 
of  the  spasms,  {c)  The  same  animal  can  be  used  for  stimulation  of  the 
spinal  nerve-roots,  as  described  in  Experiment  i  (p.  995). 

•  it  is  not  necessary  to  remove  the  dura  mater. 


CHAPTER  XVII 

THE  AUTONOMIC  NERVOUS  SYSTEM  (THE   SYMPATHETIC 
AND  ALLIED  NERVES) 

The  efferent  fibres  of  the  body  can  be  divided  into  two  classes: 
(i)  Those  which  supply  multinuclear  striated  muscle  (skeletal 
muscle);  (2)  those  which  supply  other  structures  (smooth  muscle, 
heart  muscle,  glands).  The  second  group  is  called  '  autonomic,' 
to  indicate  that  it  possesses  a  certain  independence  of  the  central 
nervous  system,  although  this  independence  is  far  from  absolute. 
The  autonomic  fibres  arise  from  four  regions  of  the  central  nervous 
system  :  (i)  The  mid-brain;  (2)  the  bulb;  (3)  the  thoracic  and  upper 
lumbar  cord;  (4)  the  sacral  portion  of  the  cord.  All  autonomic 
fibres  after  issuing  from  the  central  nervous  system  end  sooner  or 
later  by  forming  synapses  around  nerve-cells  of  sympathetic  type, 
by  whose  axons  the  path  is  continued  to  the  peripheral  distribution. 
The  autonomic  path  accordingly  comprises  two  neurons,  the  fibre 
which  arises  from  the  brain  or  cord  being  termed  the  '  pregang- 
lionic,' and  that  which  arises  from  the  sympathetic  ganglion  the 
'  postganglionic  '  fibre. 

The  autonomic  fibres  originating  in  the  mid-brain  emerge  in  the 
oculo-motor  nerve,  and  form  synapses  with  cells  in  the  ciliary 
ganglion,  which  in  turn  send  fibres  to  the  ciliary  muscle  and  the 
constrictor  muscle  of  the  iris  (pp.  923, 1024),  The  bulbar  autonomic 
fibres  emerge  in  the  seventh,  ninth,  and  tenth  cranial  nerves.  Those 
in  the  vagus  include  inhibitory  fibres  for  the  heart  muscle,  motor  and 
inhibitory  fibres  for  the  smooth  muscle  of  the  alimentary  canal  from 
the  oesophagus  to  the  descending  colon,  and  for  the  muscles  of  the 
trachea  and  lungs,  and  secretory  fibres  for  the  gastric  glands  and 
the  pancreas.  The  sympathetic  ganglion  cells  with  which  these 
preganglionic  fibres  form  synapses  have  not  always  been  definitely 
located,  but  lie  near  or  in  the  tissue  supplied  (p.  181).  The  auto- 
nomic fibres  in  the  seventh  and  ninth  nerves  supply  the  mucous 
membranes  of  the  mouth  and  nose  with  vaso-dilator  and  secretory 
fibres.  The  preganglionic  portion  of  the  path  terminates  in  such 
ganglia  as  the  submaxillary  and  subhngual  (p.  391)  and  the  spheno- 
palatine and  otic  ganglia. 

1003 


I004 


THE  AUTONOMIC  NERVOUS  SYSTEM 


\Mief- 
'  Brain 


'  £u/6 


The  part  of  the  autonomic  system  which  originates  in  the  middle 
region  of  the  spinal  cord  (in  the  cat  from  the  first  thoracic  to  the 
fourth  or  fifth  lumbar  nerves)  is  the  sympathetic  proper.  The 
course  of  the  fibres  has  already  been  described  in  connection  with 
the  vaso-motor  nerves  (p.  i8i).  Among  the  fibres  may  be  men- 
tioned the  dilators  of  the  pupil,  the  augmentors 
of  the  heart,  motor  (viscero-motor)  and  inhibi- 
tory fibres  for  the  smooth  muscle  of  the  alimen- 
tarv  canal,  sweat-secretory,  pilo-motor  and  vaso- 
constrictor fibres.  The  preganglionic  fibres  issue 
from  the  cord  in  the  anterior  roots,  and  leave 
the  corresponding  spinal  nerve  in  the  white 
ramus  communicans,  which  connects  it  with  the 
corresponding  ganglion  of  the  lateral  sympa- 
thetic chain.  A  fibre  may  either  end  in  this 
ganglion  by  forming  a  synapse,  or  it  may  run  up 
or  down  in  the  chain  for  some  distance  before 
terminating.  Some  of  the  preganglionic  fibres, 
particularly  the  vaso-constrictors  for  the  ab- 
dominal and  pelvic  viscera,  do  not  end  in  the 
lateral  chain  at  all,  but,  issuing  from  it  still  as 
medullated  fibres,  terminate  in  one  of  the  pre- 
vertebral ganglia — e.g.,  coeliac  ganglion,  inferior 
mesenteric  ganglion — from  which  postganglionic 
fibres  proceed  to  the  viscera,  as  previously 
described  (p.  332).  The  postganglionic  fibres 
arising  from  cells  of  the  lateral  ganglia  return 
as  non- medullated  fibres  in  grey  rami  com- 
municating to  the  spinal  nerves,  and  are  dis- 
tributed with  them  to  the  head,  limbs,  and  the 
superficial  parts  of  the  trunk. 

The  autonomic  fibres  arising  from  the  sacral 
region  of  the  cord  emerge  as  preganglionic  fibres 
in  the  anterior  roots  of  the  second  to  the  fourth 
sacral  nerves,  from  which  they  pass  to  the  pelvic 
nerve  (nervus  erigens)  (pp.  181.  332).  They 
comprise  vaso-dilator  fibres  for  the  rectum,  anus, 
and  external  genitals,  motor  (viscero-motor) 
fibres  for  the  smooth  muscle  of  the  descending 
colon,  rectum,  and  anus,  inhibitory  fibres  for 
the  smooth  muscle  of  the  anus,  and  the 
muscles  of  the  external  genitals,  motor  fibres  for  the  bladder,  etc. 
The  preganglionic  fibres  terminate  by  forming  synapses  with 
sympathetic  ganglion  cells  in  the  pelvic  plexus,  or  in  the  neighbour- 
hood of  the  organs  which  they  supply.  From  these  ganglion  cells 
the  postganglionic  fibres  arise. 


■Sacra  i 


Fig.  403.—  Diagram 
showiag  the  Cen- 
tral Origin  of  the 
Autonomic  Fibres 
(Langley). 


FUNCTIONS  Of  THE  AUTONOMIC  SYSTEM 


1005 


Action  of  Nicotin  and  Adrenalin  on  the  Autonomic  System. — 
The  action  of  nicotin  upon  the  sympathetic  ganghon  cells,  or  the 
link  between  them  and  the  preganglionic  fibres,  which  has  been 
taken  advantage  of  in  tracing  the  course  of  the  autonomic  fibres, 
has  already  been  described  (p.  182).  The  special  relation  of  adrena- 
lin or  epinephrin  to  the  sympathetic,  although  not  to  the  rest  of  the 
autonomic  system,  has  also  been  alluded  to  (p.  655). 

Functions  of  the  Autonomic  System. — The  functions  of  the  auto- 
nomic nerves  are  sufficiently  defined  by  the  enumeration  of  the 
peripheral  organs  with  which  they  are  connected.  It  is  obvious 
that  they  preside  over  functions  for  the  most  part  withdrawn  from 
the  control  of  the  will,  the  so-called  vegetative  functions,  like  the 
heart-beat,  the  tone  of  the  bloodvessels,  the  movements  of  the 
alimentary  canal  and  of  the  uterus,  the  erection  of  the  hairs,  and 
the  secretion  of  sweat.  It  is  no  doubt  advantageous  that  these 
functions  should  be  withdrawn  from  voluntary  control,  and  this 
withdrawal  is,  we  may  assume,  secured  either  by  the  absence  of 
anatomical  connections  betw'een  the  regions  of  the  cortex  connected 
with  voluntary  movements  and  the  ganglion  cells  in  the  cerebro- 
spinal axis  from  which  the  preganglionic  fibres  arise,  or  by  the 
existence  of  a  high  threshold  of  resistance  in  such  paths  as  exist. 
There  is  no  anatomical  or  physiological  reason  why  autonomic 
fibres  should  not  carry  impulses  which  would  elicit  voluntary  move- 
ments were  such  impulses  once  shunted  on  to  an  autonomic  path, 
and  certain  autonomic  fibres  do  innervate  structures  which  are 
under  voluntary  control— <?.^.,  the  fibres  to  the  ciliary  muscle  of 
the  eye  and  those  to  the  urinary  bladder.  The  power  of  voluntarily 
accelerating  the  heart  possessed  by  some  individuals  (p.  172)  is 
a  further  instance  showing  that  the  general  rule  is  broken  by  ex- 
ceptions. 


CHAPTER  XVIII 

THE  SENSES 

Hitherto  we  have  been  considering  from  a  purely  objective  standpoint 
the  organs  that  compose  the  body,  and  their  work.  The  student  has 
been  assumed  to  be  in  the  little  world — the  '  microcosm  ' — of  organiza- 
tion which  he  has  been  studying,  but  not  of  it.  He  has  listened  to  the 
sounds  of  the  heart,  seen  its  contraction,  felt  it  hardening  under  his 
fingers;  but  we  have  not  inquired  as  to  the  meaning  or  the  mechanism 
of  this  hearing,  seeing,  and  feeling.  We  have  now  to  recognize  that  all 
our  knowledge  of  external  things  comes  to  us  by  the  channels  of  the 
senses,  and,  like  the  light  that  falls  through  coloured  windows  on  the  floor 
of  a  church,  is  tinged,  and  perhaps  distorted,  in  the  act  of  reaching  us. 

The  Senses  in  General. — ^The  old  and  orthodox  enumeration  of 
'  the  five  senses  '  of  sight,  hearing,  touch,  taste,  and  smell,  must 
be  augmented  by  at  least  two  more,  the  senses  of  pressure  and 
temperature.  The  so-called  temperature  sensations  are  themselves 
divisible  into  two  groups  of  quite  distinctive  quality,  sensations  of 
warmth  and  sensations  of  cold.  The  power  of  appreciating  the 
amount  of  a  muscular  effort ;  the  power  of  localizing  the  various 
portions  of  the  body  in  space ;  the  sensations  of  pain,  tickling,  itching, 
hunger,  and  thirst;  the  sensations  accompanying  the  generative 
act,  etc.,  can  certainly  be  no  longer  lumped  together  in  the  omnium 
gatherum  of  '  common  sensibility.'  They  are  more  appropriately 
regarded  as  separate  senses  subserved  by  special  nerves,  and 
perhaps  connected  with  definite  centres.  In  the  development  of 
a  simple  sensation  we  may  distinguish  three  stages:  the  stimulation 
of  a  peripheral  end-organ,  the  propagation  of  the  impulses  thus  set 
up  along  an  afferent  nerve,  and  their  reception  and  elaboration  in 
a  central  organ. 

We  do  not  know  in  what  manner  a  series  of  transverse  vibrations  in 
the  ether  when  it  falls  upon  the  eye,  or  a  series  of  longitudinal  vibrations 
in  the  air  when  it  strikes  the  ear,  excites  a  sensation  of  light  or  sound. 
We  can  trace  the  ray  of  light  through  the  refractive  media  of  the  eyeball, 
see  it  focussed  on  the  retina,  lead  off  the  current  of  action  set  up  in  that 
membrane,  which,  doubtless,  gives  token  of  the  passage  of  nervous 
impulses  into  and  up  the  optic  nerve.  We  can  even  follow  the  nervous 
impulses  to  a  definite  portion  of  the  cortex  of  the  occipital  lobe,  and 
determine  that  if  this  is  removed  no  sensation  of  sight  will  result  from 

1 006 


THE  SENSES  IN  GENERAL  1007 

any  excitation  of  retina  or  optic  nerve.  And  it  is  fair  to  conclude  lliat 
in  some  manner  this  part  of  the  cerebral  cortex  is  essential  to  the  pro- 
duction of  visual  sensations.  But  in  wliat  way  the  chemical  or  physical 
processes  in  the  axis-cylinders  or  nerve-cells  are  related  to  the  psychical 
change,  the  interruption  of  the  smooth  and  unregarded  flow  of  conscious- 
ness which  we  call  a  sensation  of  light,  we  do  not  know.  To  our 
reasoning,  and  even  to  our  imagination,  there  is  a  great  gulf  fixed  between 
the  physical  stimulus  and  its  psychical  consequence;  they  seem  incom- 
mensurable quantities;  the  transition  from  light  to  sensation  of  light  is 
certain,  but  unthinkable. 

Each  kind  of  peripheral  end-organ  is  peculiarly  suited  to  respond 
to  a  certain  kind  of  stimulus.  The  law  of  '  adequate  '  or  '  homol- 
ogous '  stimuli  is  an  expression  of  this  fact.  The  '  adequate  ' 
stimuli  of  the  organs  of  special  sense  may  be  divided  into  (1)  vibra- 
tions set  up  at  a  distance  without  the  actual  contact  of  the  object 
— e.g.,  light,  sound,  radiant  heat;  (2)  changes  produced  by  the 
contact  of  the  object — e.g.,  in  the  production  of  sensations  of  taste, 
touch,  pressure,  alteration  of  temperature  (by  conduction).  Mid- 
way between  (i)  and  (2)  lies  the  adequate  stimulus  of  the  olfactory 
end-organs,  which  are  excited  by  material  particles  given  off  from 
the  odoriferous  body  and  borne  by  the  air  into  the  upper  part  of 
the  nostrils. 

The  end-organs  of  the  special  senses  all  agree  in  consisting  essentially 
of  modified  ectodermic  cells,  but  they  occupy  areas  by  no  means  pro- 
portioned to  their  importance  and  to  the  amount  of  information  we 
acquire  through  them.  The  extent  of  surface  which  can  be  affected  by 
light  in  a  man  is  not  more  than  20  sq.  cm. ;  the  endings  of  both  nerves  of 
liearing  taken  together  do  not  at  most  expand  to  more  than  5  sq.  cm.; 
the  olfactony'  portion  of  the  mucous  membrane  of  the  nose  has  an  area  of 
not  more  than  10  sq.  cm.;  the  sensations  of  taste  are  ministered  to  by 
an  area  of  less  than  50  sq.  cm. ;  the  end-organs  of  the  senses  of  pressure, 
touch,  and  temperature  are  distributed  over  a  surface  reckoned  by 
square  metres.  As  the  physiological  status  of  the  sensory  end-organs 
rises,  their  anatomical  distribution  tends  to  shrink.  The  organs  of  com- 
paratively coarse  and  common  sensations  are  widely  spread,  inter- 
mingled with  each  other,  and  seated  in  tissues  whose  primary  function 
may  not  be  sensory  at  all.  Even  the  nerve-endings  of  the  sense  of  taste 
are  not  confined  to  one  definite  and  circumscribed  patch,  but  scattered 
over  the  tongue  and  palate ;  and  both  tongue  and  palate  are  at  least  as 
much  concerned  in  mastication  and  deglutition  as  in  taste.  The 
olfactory  portion  of  the  nasal  mucous  membrane,  although  a  continuous 
area  with  fairly  distinct  boundaries,  is  still  a  part  of  the  general  lining 
of  the  nostril.  The  epithelial  surfaces  which  minister  to  the  supreme 
sensations  of  sight  and  hearing — the  retina  and  the  sensitive  structures 
of  the  cochlea — are  the  most  sequestered  of  all  the  sensory  areas,  as  the 
organs  of  which  they  form  a  part  are,  of  all  the  organs  of  sense,  the  most 
highlv  specialized  in  function,  and  anatomically  the  most  limited.  But 
although  hidden  in  protected  hollows,  they  are  endowed,  either  in  virtue 
of  their  own  movements  or  of  those  of  the  head,  with  the  power  of 
receiving  impressions  from  every  side,  and  their  actual  size  is  thus  in- 
definitely multiplied. 


LOo8  THE  SENSES 


Section  I. — Vision. 


Physical  Introduction. — Physically,  a  ray  of  light  is  a  series  of  dis- 
turbances or  vibrations  in  the  luminiferous  ether,  which  radiates  out 
from  a  luminous  body  in  what  is  practically  a  straight  line.  The  ether 
is  supposed  to  fill  all  space,  including  the  interstices  between  the  mole- 
cules of  matter  and  the  atoms  of  which  those  molecules  are  composed. 
Suppose  a  bar  of  iron  to  be  gradually  heated  in  a  dark  room.  In  the 
cold  iron  the  molecules  are  moving  on  the  average  at  a  relatively  slow 
rate,  and  the  waves  set  up  in  the  ether  by  their  vibrations  are  compara- 
tively long.  Now.  the  long  ethereal  vibrations  do  not  excite  the  retina, 
because  it  is  only  fitted  to  respond  to  the  impact  of  the  shorter  waves ; 
and,  indeed,  the  long  waves  are  largely  absorbed  by  the  water>'  media 
of  the  eye.  As  the  temperature  of  the  iron  bar  is  increased,  the  mole- 
cules begin  to  move  more  quickly,  and  waves  of  smaller  and  smaller 
length,  of  greater  and  greater  frequency,  are  set  up,  until  at  last  some 
of  them  are  just  able  to  stimulate  the  retina,  and  the  iron  begins  to  glow 
a  dull  red.  As  the  heating  goes  on  the  molecules  move  more  quickly 
still,  and,  in  addition  to  waves  which  cause  the  sensation  of  red,  shorter 
waves  that  give  the  sensation  of  yellow  appear.  Finally,  when  a  high 
temperature  has  been  reached,  the  very  shortest  vibrations  which  can 

affect  the  eye  at  all  mingle  with  the  medium 
and  long  waves,  and  the  sensation  is  one  of 
intense  white  light. 

We  have  said  that  a  ray  of  light  travels 

in  a  straight  line,  and  the  direction  of  the 

straight  line  does  not  change  as  long  as  the 

medium  is  homogeneous.     But  when  a  ray 

reaches  the  boundary  of  the  medium  through. 

which  it  is  passing,  a  part  of  it  is  in  general 

turned    back   or   reflected.     If   the    second 

medium  is  transparent  (water  or  glass,  e.g.). 

the  greater  part  of  the  ray  passes  on  through 

it,    a   smaller  portion  is   reflected.     If    the 

404.— Reflection   from  a      second  medium  is  opaque,  the  ray  does  not 

Plane  Mirror.  penetrate  it  for  any  great  distance;  if  it  is 

a  piece  of  polished  metal,  e.g.,   nearly  the 

whole  of  the  light  is  reflected ;  if  it  is  a  layer  of  lampblack,  ver^-  little 

of  the  light  is  reflected,  most  of  it  is  absorbed. 

Reflection. — The  first  law  of  reflection  is  that  the  reflected  ray.  the  ray 
which  falls  upon  the  reflecting  surface  {incident  ray),  and  the  normal  to  the 
surface,  are  in  one  plane.  The  second  law  is  that  the  reflected  ray  makes 
with  the  perpendicular  [normal)  to  the  reflecting  surface  the  same  angle 
as  the  incident  ray.  A  corollary  to  this  is  that  a  ray  perpendicular  to 
the  surface  is  reflected  along  its  own  path. 

Reflection  from  a  Plane  Mirror. — Let  a  ray  of  light  coming  from  the 
point  P  (.Fig.  404)  meet  the  surface  DE  at  B,  making  an  angle  PBA  with 
the  normal  to  the  surface.  The  reflected  ray  BC  will  make  an  equal 
angle  ABC  with  the  normal ;  and  the  eye  at  C  will  see  the  image  of  P 
as  if  it  were  placed  at  P',  the  point  where  the  prolongation  of  BC  cuts 
the  straight  line  drawn  from  P  perpendicular  to  DE.  This  is  the  posi- 
tion of  an  ordinary  looking-glass  image. 

Reflection  from  a  Concave  Spherical  Mirror. — A  spherical  surface  may 
be  supposed  to  be  made  up  of  an  infinite  number  of  infinitely  small  plane 
surfaces.  The  normal  to  each  of  these  plane  surfaces  is  the  radius  of 
the  sphere,  and  the  reflected  ray  makes  with  the  radius  at  the  point  of 


VISION 


too^ 


incidence  the  same  angle  as  the  incident  ray.  Let  D  (Fig.  405)  be  the 
middle  point  of  the  mirror,  and  C  its  centre  of  curvature — i.e.,  the 
centre  of  the  sphere  of  which  it  is  a  segment.  Then  CD  is  the  principal 
axis,  and  any  other  line  through  C  which  cuts  the  mirror  is  a  secondary 
axis.  When  the  mirror  is  a  small  portion  of  a  sphere,  rays  parallel  to 
the  principal  axis  are  focussed  at  the  principal  focus  F  midway  between 
C  and  D;  rays  parallel  to  any  secondary  axis  are  focussed  in  a  point 


405. — Reflectio.i    trom    a    Concave 
Spherical  Mirror. 


Fi,'.  406. — Formation    of  Real  Inverted 
Image  by  a  Concave  Spherical  Mirror. 


lying  on  that  axis ;  and  rays  diverging  from  a  point  on  any  axis  arc 
focussed  in  a  point  on  the  same  axis. 

These  facts  afford  a  simple  construction  for  finding  the  position  of 
the  image  of  an  object  formed  by  a  concave  mirror.  Let  AB  be  the 
object  (Fig.  406).  Then  the  image  of  A  is  the  point  in  which  all  Ta.ys 
proceeding  from  A  and  falling  on  the  mirror,  including  rays  parallel  to 
the  principal  axis,  are  focussed.  But  the  ray  AE,  parallel  to  the  prin- 
cipal axis,  passes  after  reflection  through  the  principal  focus  F,  there- 
fore the  image  of  A  must  lie  on  the  straight  line  EF.  If  any  secondary 
axis  ACD  be  drawn,  the 
image  of  A  must  lie  on 
ACD.  It  must  therefore 
be  the  point  of  intersec- 
tion, a,  of  EF  and  ACD. 
Similarly,  the  image  of  B 
must  be  the  point  of  inter- 
section, b,  of  GF  and  BCH. 
The  image  ab  of  an  object 
AB  farther  from  the  mirror 
than  the  principal  focus 
is  real  and  inverted.  The 
Purkinje -Sanson  image  re- 
flected from  the  concave 
anterior  surface  of  the 
vitreous  humour  (Fig.  421) 
is  an  example. 

After  reflection  from  a  convex  mirror,  rays  of  light  always  diverge,  and 
only  erect,  virtual  images  are  formed — i.e.,  images  which  do  not  really 
exist  in  space,  but  which,  from  the  direction  of  the  rays  of  light  we.  judge 
to  exist.  The  position  of  the  image  of  an  object  AB  (Fig.  407)  niay  be 
found  by  a  construction  similar  to  that  for  reflection  from  a  concave 
mirror.  The  image  of  a  flame  reflected  from  the  anterior  surface  of  the 
cornea  or  lens  is  erect  and  virtual.  It  diminishes  in  size  with  increase 
in  the  curvature  or  convexity'  of  the  reflecting  surface  (Fig.  421). 

Refraction. — A  ray  of  light  passing  from  one  medium  into  another 
has  its  velocity-,  and  consequently  its  direction,  altered.     It  is  said  to 

64 


407. — Formatic  ;i  of  Image  by  a  Convex 
Mirror. 


THE  SENSES 


be  refracted.  The  first  law  of  refraction  is  that  the  refracted  ray  is  in 
the  same  plane  as  the  incident  ray  and  the  nornuil  to  the  surface.  The 
second  law  is  that  the  sine  of  the  angle  of  incidence  has  a  constant  ratio 
(for  any  given  pair  of  media)  to  the  sine  of  the  angle  of  refraction.  The 
angle  of  incidence  is  the  angle  which  the  ray  makes  with  the  normal 
to  the  surface,  separating  the  two  media;  the  angle  of  refraction  is  the 
angle  made  with  the  normal  in  the  second  medium.  This  ratio  is  called 
the  index  of  refraction  between  the  two  media.  For  purposes  of  com- 
parison, the  refractive  index  of  a  substance  is  usually  taken  as  the  ratio 
of  the  sine  of  the  angle  of  incidence  to  the  sine  of  the  angle  of  refraction 
of  a  ray  passing  from  air  into  the  substance. 

When  a  ray  strikes  a  surface  at  right  angles,  it  passes  through  without 
suffering  refraction.  When  a  ray  passes  from  a  less  dense  to  a  denser 
medium  {e.g.,  from  air  to  water),  it  is  bent  towards  the  perpendicular. 


Fi^.  40'. — Refraction  at  a  Plane  Surface 
AB  is  the  incident;  BD,  the  refracted 
ray;  CB,  the  normal  to  the  surface. 
When  the  ray  passes  from  air  into 
another  medium,  the  refractive  index  of 

the  latter  is  the  fraction  - — — . 


Fig.  403. —  Refraction  by  a  Medium 
bounded  by  Parallel  Planes,  P  and 
P'.  The  ray  ABDE  issues  parallel 
to  its  original  direction;  CB,  FD, 
normals  to  P  and  P';  a.  angle  of 
incidence;  B,f,  angles  of  refraction. 


When  it  passes  from  a  more  dense  to  a  less  dense  medium  (as  from 
water  to  air),  it  is  bent  away  from  the  perpendicular. 

When  a  ray  passes  across  a  medium  bounded  by  parallel  planes,  it 
issues  parallel  to  itself;  in  other  words,  it  undergoes  no  refraction 
(Fig.  409). 

Refraction  and  Dispersion  by  a  Prism. — The  beam  of  light  is  bent 
towards  the  normal  N  as  it  ])asses  across  BA  and  away  from  the  normal 
N'  as  it  passes  across  BC  (Fig.  .\io) ;  at  both  surfaces  it  is  bent  towards 
the  base  of  the  prism  AC.  At  the  same  time  the  light  suftcrs  dispersion 
— that  is,  the  rays  of  shorter  wave-length  are  more  refracted  than  those 
of  greater  wave-length.  The  deviation  of  any  given  ray  is  measured  by 
the  angle  which  the  refracted  ray  makes  witli  its  original  direction. 
The  amount  of  dispersion  produced  by  a  prism  is  measured  by  the 
difference  in  the  deviation  of  the  extreme  rays  of  the  spectrum.  The 
dispersion  produced  by  a  given  substance  is  proportional  to  the  differ- 
ence of  its  refractive  indices  for  the  extreme  rnys. 

Refraction  by  a  Biconvex  Lens. — A  straight  line  ABC  passing  tlirough 
the  centres  of  curvature  of  the  two  surfaces  of  the  lens  is  called  the 
principal  axis.      A  point  C  lying  on  the  principal  axis  between  the 


VISION 


loii 


two  centres  of  curvature,  and  possessing  the  property  that  rays  passing 
through  it  do  not  suffer  refraction,  is  called  the  optical  centre  of  the 
lens.  Any  straight  line,  D("E,  passing  through  the  ojHical  centre,  is  a 
secondary  axis.  Rays  of  light  proceeding  from  a  point  in  the  principal 
axis  arc  focussed  in  a  point  on  that  axis.  When  the  rays  proceed  from 
an  infinitely  distant  point  in  the  principal  axis — i.e.,  when  they  are 
parallel  to  it^they  arc  focussed  in  F,  the  principal  focus.  Similarly 
rays  parallel  to,  or 
proceeding  from,  a 
point  in  a  secondary 
axis  are  focussed  in 
a  point  on  that  axis; 
but  if  the  focus  is  to 
be  sharp,  the  angle 
between  the  secon- 
dary and  the  princi- 
pal axis  must  not  be 
so  large  as  is  indi- 
cated in  Fig.  411. 

Formation  of  Im- 
age by  Biconvex  Lens 
(Fig.  412).— Let  AB 
be  the  object;  then 
if  AHD  be  the  path 
of  a  ray  from  A  parallel  to  the  prmcipal  axis,  the  image  of  A  will  be  the 
intersection  of  the  straight  line  DF  and  the  secondary'  axis  passing 
through  A.  Similarly,  the  image  of  B  will  be  the  intersection  of  GF 
and  the  secondary  axis  BC.  Where  AB  is  farther  from  the  lens  than 
the  principal  focus,  the  image  ab  is  real  and  inverted.  This  is  the  case 
with  the  image  of  an  external  object  formed  on  the  retina.  When  the 
object  is  nearer  than  the  principal  focus,  the  image  is  virtual  and  direct. 


Fig.  410.  —Refraction  and  Dispersion  by  a  Prism. 


411. —  Refraction 
Biconvex  Lens. 


—  Formation    of    Image    by 
Biconvex  Leas. 


The  image  formed  by  the  objective  of  a  microscope  when  the  object  is  in 
focus  is  real  and  inverted ;  the  ocular  forms  a  virtual  erect  image  of  this 
real  image. 

Refraction  by  a  Biconcave  Lens  (Fig.  413). — Parallel  rays  are  rendered 
divergent  by  the  lens ;  there  is  no  real  focus ;  but  if  the  rays  are  pro- 
longed backwards  they  meet  ui  the  virtual  focus  F,  from  which  they 
appear  to  come  when  received  by  the  eye  through  the  lens. 

Formation  of  Image  by  Biconcave  Lens  (Fig.  414). — Let  AB  be  the 
object.     Let  AHDI  be  the  path  of  a  ray  from  any  point  A  of  the  object 


I012 


THE  SENSES 


parallel  to  the  principal  axis.  Produce  DI  backwards  (dotted  line); 
it  will  pass  through  the  principal  focus  F.  'J  hrou^h  A  draw  the  second- 
ary axis  AC.  The  image  of  A  must  lie  both  on  A("  and  on  IDh'—i.e.. 
it  must  be  the  intersection,  a.  of  these  straight  lines.  Similarly,  the 
image  of  B  is  b,  the  intersection  of  KGF  and  BC.  The  image  is  virtual 
and  erect. 

Absorption. — No  substance  is  perfectly  transparent;  in  addition  to 
what  is  reflected,  some  light  is  always  absorbed.     In  other  words,  in 


Fig.  4 1 3. —  Refraction  by 
a  Biconcave  Lens. 


Fig.  414. — Formation  of  Image  by  Biconcave  Lens. 


passing  through  a  body  some  of  the  light  is  transformed  into  heat,  a 
portion  of  the  energy  of  the  short,  luminous  waves  going  to  increase  the 
vibrations  of  the  molecules  of  the  medium,  just  as  a  wave  passing  under 
a  row  of  barges  or  fishing-boats  set  them  swinging  and  pitching,  and  so 
imparts  to  them  a  certain  amount  of  energy,  which  is  ultimately  changed 
into  heat  by  friction  against  the  water,  and  against  each  other,  and  by 

the  straining  and  rubbing  of 
the  chains  at  their  points  of 
attachment.  Some  bodies  ab- 
sorb all  the  rays  in  the  pro- 
portion in  which  they  occur  in 
white  hght ;  whether  looked  at 
or  looked  tlu-ough,  they  appear 
colourless  or  white.  Other 
substances  absorb  certain  rays 
by  preference,  and  the  amount 
oi  absorption  is  proportional 
to  the  thickness  of  the  layer. 
The  colours  of  most  natural 
bodies  are  clue  to  this  selective 
absorption.  Even  when  looked 
at  in  reflected  light,  they  are 
seen  by  rays  that  have  pene- 
trated a  certain  way  into  th6 
substance  and  have  then  been 


<o" 


Fig.  415.— Diagram  to  show  Connection  of  Body  reflected;    and,    of    course,    a 
Colour  with  Selective  Absorption.  smaller  number   of  the  rays 

which  the  body  specially  ab- 
sorbs are  reflected  than  of  the  rays  which  it  readily  transmits,  for  more 
of  the  latter  than  of  the  former  reach  any  given  depth.  This  is  called 
'  body  colour' ;  and  such  substances  have  the  same  colour  when  seen  by 
reflected  and  by  transmitted  light.  The  colour  of  haemoglobin  is  due 
to  the  absorption  of  the  violet  and  many  of  the  yellow  and  green  rays, 
as  is  shown  by  the  position  of  the  absorption  bands  in  its  spectrum  (p.  51  )• 
In  Fig.  4 1 5  the  violet  rays  are  represented  as  being  totally  absorbed  before 
passing  through  the  substance.   Some  of  the  green  rays  are  reflected,  some 


VISION 


1013 


transmitted,  some  absorbed.  The  red  rays  are  supposed  to  be  mostly 
reflected  and  transmitted,  only  to  a  slight  extent  absorbed.  The  colour 
of  such  a  substance,  botii  wlun  looked  at  and  when  looked  through, 
would  therefore  be  that  due  to  a  mixture  of  red  light  with  a  smaller 
quantity  of  green.  Then  there  is  another  class  of  substances  which  owe 
their  colour  to  selective  rejection.  Certain  rays  only  are  reflected  from 
their  surface,  and  the  light  transmitted  through  a  thin  layer  is  com- 
plementary to  the  reflected  light— that  is,  the  reflected  and  transmitted 
rays  together  would  make  up  white  light.  These  bodies  have  what  is 
called  '  surface  colour.'  and  include  metals,  various  aniline  dyes,  and 
other  substances. 

Comparative. — Many  invertebrate  animals  possess  rudimentary  sense- 
organs,  by  means  of  which  they  may  receive  certain  luminous  impres- 
sions. It  is  true  that  the  mere  sensation  of  light  is  not  in  itself  sufficient 
for  the  exact  appreciation  of  the  form  and  situation  of  surrounding  objects. 
But  even  the  closure  of  the  eyelids  does  not  prevent  a  person  of  normal 
eyesight  from  distinguishing  differences  in  the  intensity  of  illumination. 


Cornea 


..diiiary  Afusclc 


Fovea ^  CentmlisS. 


-Jclemtc 

---Retina 
Optic  Nen/& 


Fig.  416. — Diagrammatic  Horizontal  Section  of  the  Left  Eye. 

And  it  is  possible  that  many  of  the  humbler  animals  may,  through  the 
pigment  spots  which  are  often  called  eyes,  or  perhaps,  as  in  the  earth- 
worm, by  means  of  end -organs  more  generally  diffused  in  the  skin, 
attain  to  some  such  dim  consciousness  of  light  and  shadow  as  will  enable 
them  to  avoid  an  obstacle  or  an  enemy,  to  seek  the  sunny  side  of  a 
boulder  or  the  obscurity  of  an  overhanghig  ledge  of  rock.  But  the 
indispensable  condition  of  distinct  vision  is  that  an  image  of  each  part 
of  an  object  should  be  formed  upon  a  separate  portion  of  the  receiving 
or  sensitive  surface.  This  condition  is,  to  a  certain  exentt,  fulfilled  by 
the  compound  eyes  of  some  of  the  higher  invertebrates  (insects,  e.g.). 
Here  rays  from  one  point  of  the  object  pass  through  one  of  the  funnel- 
shaped  elements  of  the  compound  eye,  and  rays  from  another  point 


IOI4 


THE  SENSES 


Rod* 


Cones. 


through  another.  Rays  striking  obliquely  on  the  facets  are  stopped 
by  the  opaque  partitions  between  them.  In  the  Cephalopods  we  find 
that  this  compound  type  of  eye  has  already  been  abandoned ;  the  smgle 
system  of  curved  refracting  surfaces  so  characteristic  of  the  vertebrate 
eye  has  made  its  appearance;  and  the  formation  of  a  clean-cut  image 
of  the  object  on  the  retina,  with  the  excitation  of  a  sharply-bounded  area 
of  that  membrane,  follows  as  a  geometrical  consequence  from  the  theor>' 
of  lenses. 

We  have  to  consider  (i)  the  mechanism  by  which  an  image  is 
formed  on  the  retina,  and  (2)  the  events  that  follow  the  formation 
of  such  an  image  and  their  relations  to  the  stimulus  that  calls  them 
forth. 

Structure  of  the  Eye. — The  eye  may  be  described  with  sufficient 
accuracy  as  a  spherical  shell,  transparent  in  front,  but  opaque  over 

the  posterior  five-sixths  of  its 
surface,  and  filled  up  with  a 
series  of  transparent  liquids 
and  solids.  The  sheU  consists 
of  three  layers  concentrically 
arranged,  like  the  coats  of  an 
onion:  (i)  An  external  tough, 
fibrous  coat,  the  sclerotic,  the 
anterior  portion  of  which 
appears  as  the  white  of  the  eye. 
In  front  this  external  layer  is 
completed  by  the  transparent 
cornea.  (2)  A  vascular  layer, 
the  choroid,  which,  in  the  re- 
stricted sense  of  the  term,  ends 
in  front  in  a  series  of  folds  or 
plaits,  the  cilian,-  processes.  The 
choroid  contains  a  greater  or 
smaller  quantity  of  the  black 
pigment  melanin.  The  cilian,- 
processes  abut  on  the  outer 
boundary  of  the  iris,  which 
may  be  looked  upon  as  an 
anterior  continuation  of  the 
choroidal  or  middle  coat  of  the 
eyeball.     Betvveen  the  comeo- 

..  -.  sclerotic  junction  and  the  an- 

Fig.  417.— Diagram   of  Structure  of  Retina     terior  portion  of  the  choroid  is 


(after  Cajal).  H,  layer  of  nerve-fibres;  G, 
layer  of  ganglion  cells;  F,  internal  mole- 
cular layer;  E,  internal  nuclear  layer; 
C,  external  molecular  layer;  B.  external 
nuclear  layer;  external  limiting  membrane  ; 
A ,  laver  of  rods  and  cones. 


interposed  a  ring  of  unstriped 
muscular  fibres,  the  ciliary 
muscle.  (3)  The  inner  or  sen- 
sitive coat,  termed  the  retina 
(Fig.  417).  This  covers  the 
choroid  as  a  delicate  mem- 
brane, extending  to  the  ciliary  processes,  where  it  ends  in  a 
toothed  margin,  the  ora  serrata.  The  optic  nerve  forms  a  kind  of 
stalk  to  which  the  eyeball  is  attached.  Its  point  of  entrance  at 
the  optic  disc  is  a  little  nearer  the  median  line  than  the  antero-posterior 
axis  which  nearlv  passes  through  the  centre  of  a  small  depression, 
the  fovea  centralis,  situated  in  the  middle  of  the  macula  lutea,  or 
yellow    spot.      From    the     optic    disc    ^metimes    called    the    optic 


VISION 


1015 


papilla)  tho  optic  nerve  spreads  over  the  retina  as  a  laj'er  of  non- 
meduUated  fibres,  separated  from  the  interior  of  the  eyeball  only 
by  the  internal  liniitinf,'  nu-nibrane.  'Ihis  so-called  membrane  is  formed 
by  the  expanded  fei-t  of  the  fibres  of  Miiller,  which  run  like  a  scaffolding 
or  framework  through  nearly  the  whole  thickness  of  the  retina,  ter- 
minating at  the  outer  limiting  membrane.  External  to  the  layer  of 
nerve-fibres  is  the  stratum  of  large  ganglion  cells,  whose  axons  they 
are;  next  to  this  the  inner  molecular  layer,  or  inner  synapse  layer, 
made  up  largely  of  the  branching  dendrites  of  these  cells.  The  fifth 
layer  is  the  inner  granular  or  nuclear  layer,  containing  many  fusiform 
(bipolar)  '  granule  '  cells  which  send  out  axons  into  the  fourth,  and 
dendrites  into  the  sixth,  or  outer  molecular  layer,  and  are  thus  con- 
nected with  the  ganglion  cells  of  the  third  layer  on  the  one  hand,  and 
with  the  terminations  of  the  rod  and  cone  fibres  of  the  seventh  or  outer 
nuclear  layer  on  the  other.  The  arborizations  of  the  axons  of  these 
bipolar  cells  are  situate  at  different 
levels  in  the  internal  molecular 
layer.  The  bipolar  cells  connected 
with  the  rod  fibres  send  their  axons 
right  through  the  internal,  mole- 
cular layer  to  arborize  around  the 
bodies  of  the  ganglion  cells,  whereas 
the  axons  of  the  bipolar  cells  con- 
nected with  the  cone  fibres  ramify 
about  the  middle  of  the  layer 
(Fig.  417).  The  seventh  stratum 
receives  its  name  from  the  large 
number  of  nuclei  which  it  contain?. 
These  belong  to  structures  con- 
tinuous with  the  rods  and  cones 
of  the  ninth  layer,  which  is  divided 
from  the  seventh  by  the  exterral 
limiting  membrane.  Each  rod  is 
prolonged  into  the  external  nuckar 
layer  as  a  fine  fibre,  which  has  on 
its  course  a  swelling  containing  a 
nucleus,  and  terminates  (in  mam- 
mals) in  a  fine  knob  in  the  external 
molecular  layer  among  the  den- 
drites of  the  bipolar  cells.  Each 
cone  of  the  rod  and  cone  layer  is 

directly  prolonged  into  a  nucleated  enlargement  in  the  external  nuclear 
layer.  From  this  enlargement  a  fibre  (cone  fibre) ,  of  considerably  greater 
calibre  (in  mammals)  than  the  rod  fibre,  passes  into  the  external  mole- 
cular layer,  where  it  forms  an  arborization,  which  comes  into  relation 
with  the  arborization  of  the  dendrites  of  a  bipolar  cells.  At  the  fovea 
centralis  the  rods  are  entirely  absent,  and  the  other  layers  of  the  retina 
greatly  thinned ;  over  the  optic  disc  neither  rods  nor  cones  are  present. 
The  disc  is  pierced  by  the  retinal  bloodvessels  (Fig.  418). 

External  to  the  rods  and  cones  is  a  sheet  of  pigmented  epithelial  cells 
of  hexagonal  shape,  belonging  to  the  choroid,  but  remaining  attached 
to  the  retina  when  the  latter  is  separated,  and  therefore  often  reckoned 
as  its  most  external  layer. 

A  little  behind  the  cornea  and  anterior  to  the  retina  is  the  lens,  en- 
closed in  a  capsule,  and  attached  to  the  choroid  by  the  suspensory 
ligament,  or  zonule  of  Zinn.  The  iris  hangs  down  in  front  of  the  lens 
like  a  diaphragm,  with  a  central  hole,  the  pupil.     Incorporated  in  the 


Fig.  418. — Retinal  Bloodvessels  (Henle). 
The  arteria  centralis  is  seen  issuing 
from  the  optic  dies  and  branching  over 
the  retina.  The  shaded  area  in  the 
middle  of  the  figure  represents  the 
yellow  spot  with  the  fovea  centralis  in 
its  centre. 


roi6  THE  SENSES 

stroma  or  framework  of  Ihc  iris  arc  two  arrangements  of  smooth  mus- 
cular fibres,  wliich  confer  on  it  the  power  of  adjusting  the  size  of  the 
pupil.  One  of  these — the  sphincter  pupilla} — consists  of  a  well-defined 
band  of  concentric  fibres  surrounding  the  margin  of  the  pupil.  The 
other — the  dilator  pupilla: — is  less  sharply  differentiated.  It  is  repre- 
sented by  radial  bundles  of  elongated,  spindle-shaped  cells  running  in 
from  the  ciliary  border  of  the  iris  towards  the  pupil.  Between  the  iris 
and  the  posterior  surface  of  the  cornea  is  the  anterior  chamber  of  the 
eye.  filled  with  the  aqueous  humour.  Between  the  iris  and  the  anterior 
surface  of  the  lens  lies  the  posterior  chamber,  which  is  rather  a  potenial 
than  an  actual  cavity.  The  space  between  the  lens  and  the  retina  is 
accurately  occupied  by  an  almost  structureless  semi-fluid  mass,  the 
vitreous  humour,  enclosed  by  the  delicate  hyaloid  membrane,  which  in 
front  is  reflected  over  the  folds  of  the  ciliary  processes,  and  blends  with 
the  suspensory  ligament  of  the  lens.  The  attachment  of  the  suspensory 
ligament  is  rendered  firmer  by  the  connection  of  this  part  of  the  hyaloid 
membrane  to  a  circular  fibrous  portion  of  the  vitreous.  Around  the 
edge  of  the  lens  is  left  a  space,  the  canal  of  Petit. 

Chemistry  of  the  Refractive  Media. — Ihe  aqueous  humour  is  a  per- 
fectly colourless,  watery  liquid,  of  slightly  alkaline  reaction  to  litmus. 
The  specific  gravity  is  about  1008,  and  the  total  solids  about  i  per 
cent.  Of  the  solids  the  inorganic  salts  (mainly  sodium  chloride)  con- 
stitute much  the  largest  portion.  A  very  small  amount  of  protein 
(o'Oi  to  0-04  per  cent.)  is  present,  also  a  little  dextrose  (0-05  per  cent.), 
and  minute  traces  of  urea  and  other  substances.  The  liquid  of  the 
vitreous  humour  has  a  very  similar  composition,  except  that  it  contains 
a  mucin-like  body,  hyalomucoid,  to  the  amount  of  o-o6  to  o-i  per  cent. 
A  similar  mucin-like  substance  is  present  in  the  cornea.  The  freezing- 
point  of  both  liquids  is  a  little  lower  than  that  of  blood-serum,  A  being 
ibout  0'6°. 

The  lens  is  far  richer  in  solids  than  the  aqueous  and  vitreous  humours 
with  which  it  is  in  contact  (30  to  35  per  cent  of  solids,  60  to  65  per  cent, 
of  water).  The  salts,  with  small  quantities  of  lecithin  and  cholesterin, 
make  up  about  i  per  cent. ;  the  balance  of  the  solids  consists  of  proteins. 
The  physical  alterations,  with  production  of  turbidity,  which  occur  in 
the  lens,  and  presumably  in  its  proteins,  when  water  enters  or  leaves 
it  in  too  great  amount  through  imbibition  or  osmosis,  are  of  importance 
in  connection  with  the  etiology  of  cataract.  The  anatomical  and 
physiological  integrity  of  its  capsule  is  a  prime  factor  in  the  maintenance 
of  that  high  degree  of  transparency  which  is  necessary  for  the  function 
of  the  lens.  Cataract  can  be  experimentally  induced  by  injuring  the 
capsule.  In  like  manner  the  cornea  is  protected  against  injurious 
changes  in  its  water-content  (normally  about  80  per  cent.)  and  conse- 
quent turbidity  by  the  epithelium,  which  separates  it  from  the  tears, 
and  the  endotlieliuni,  wliich  separates  it  from  the  aqueous  humour. 

Secretion  of  the  Intra-ocular  Liquids. — The  aqueous  humour  is 
secreted  by  the  uveal  epithelium  covering  the  ciliary-  processes,  and 
to  some  extent  by  that  covering  the  iris.  As  it  is  continually  secreted, 
so  it  is  continually  absorbed,  the  absorbed  constituents  finding  their 
w:;v  eventually  into  the  vein  or  venous  sinus  called  the  canal  of  Schlemm 
and  the  bloodvessels  of  the  iris  and  ciliary  processes.  The  source  of 
the  liquid  of  the  vitreous  body  is  also  the  uvea.  While  the  intra-ocular 
liquids  differ  from  ordinary  lymph,  there  is  no  reason  to  doubt  that  they 
are  secretions  which  contribute  to  the  nutrition  of  those  transparent 
.structures  of  the  eye  which  are  not,  and,  on  account  of  their  function, 
cannot  be  supplied  with  bloodvessels.     Their  most  obvious  use  is  tc 


VISION  1017 

maintain  the  proper  intra-ocular  pressure  on  which  the  geometrical 
figure  of  the  eyeball,  and  therefore  its  efficiency  as  an  optical  instrument, 
depend.  1  he  balance  between  secretion  and  absorption  is  accurately 
adjusted  in  health,  but  in  disciise  it  may  be  upset,  as  in  glaucoma,  where 
the  intra-ocuhir  tension  is  so  much  increased  as  to  interfere  with  the 
circulation,  and  injuriously  affect  the  nutrition  and  function  of  the  retina. 
Experimentally,  occlusion  of  all  the  arteries  supplying  the  head  causes 
a  rapid  fall  of  tension,  and  the  cornea  becomes  wrinkled  and  slack  to 
the  touch.  On  restoring  the  circulation  after  not  too  long  an  interval, 
the  tension  gradually  returns  to  normal,  and  then  becomes  markedly 
hypernormal,  even  when  the  general  arterial  pressure  is  still  low.  This 
is  probably  due  to  the  crippling  of  the  elements  which  secrete  and 
absorb  the  intra-ocular  fluids,  or  of  the  capillar^'  walls,  so  that  a  proper 
adjustment  can  no  longer  be  attained,  as  happens  in  a  tissue  rendered 
oeaematous  by  temporary'  ana-mia.  Where  asphyxia  of  the  eyeball  is 
avoided  or  is  brief  the  intra-ocular  pressure  varies  directly  as  the  blood- 
pressure  in  the  ocular  vessels  within  a  wide  range  (Henderson  and  Starling) . 

Retraction  in  the  Eye — Formation  of  the  Retinal  Image. — The 

amount  of  refraction  which  a  ray  of  hght  undergoes  at  a  curved 
surface  depends  upon  two  factors — the  radius  of  curvature  of  the 
surface,  and  the  difference  between  the  refractive  indices  of  the 
media  from  which  the  ray  comes  and  into  which  it  passes.  The 
smaller  the  radius  of  curvature,  and  the  greater  the  difference  ol 
refractive  index,  the  more  is  the  ray  bent  from  its  original  direction. 
A  ray  of  light  passing  into  the  eye  meets  first  the  approximately 
spherical  anterior  surface  of  the  cornea,  covered  with  a  thin  layer 
of  tears.  Since  the  refractive  index  of  the  tears  is  much  greater 
than  that  of  air,  the  ray  is  strongly  refracted  here.  The  anterior 
and  posterior  surfaces  of  the  cornea  being  practically  parallel,  and 
the  refractive  indices  of  the  tears  and  aqueous  humour  being  nearly 
equal,  but  little  refraction  takes  place  in  the  cornea  itself.  At  the 
anterior  and  posterior  surfaces  of  the  lens  the  ray  is  again  refracted, 
since  the  refractive  index  of  the  aqueous  and  vitreous  humours  is 
less  than  that  of  the  lens.  The  following  tables  show  the  radii  of 
curvature  of  the  refracting  surfaces  and  the  refractive  indices  of 
the  dioptric  media,  as  well  as  some  other  data  which  are  of  use  in 
studying  the  problems  of  refraction  in  the  eye  : 

In  accommodation  for 


Far  Vision.         Near  Vision. 

rComea     -        -        -        -    7-8  mm.       7-8  mm. 
Radius  of  curvature  of  J  Anterior  surface  of  lens    -  lO'O     ,,  6*o     ,, 

I, Posterior  surface  of  lens  -     6-o     ,,  5-5     ,, 

Anterior   surface   of    cornea   and    an- 
terior surface  of  lens         .         .         .     2-6     ,,  3-2     ,, 
Anterior  surface    of    cornea    and    pos- 
terior surface  of  lens 
Anterior  and  posterior  surface  of  lens 
.Posterior  surface  of  lens  and  retina 
Antero-posterior  diameter  of  eye  along  the  axis 


Distance 
between 


7-6     ,. 

7-6 

4-0     ., 

4-4 

14-6     ,. 

14-6 

22-2       ,, 

22-2 

loi8 


THE  SENSES 


Refractive  Indices — 

Air i-ooo 

Cornea  -         - ^'377 

Aqueous  humour    -------  i"3365 

Vitreous  humour    -------  1-3365 

Lens  (total  refractive  index)  -----  1-437 

Water    .         -         -         - 1-335 

It  will  be  seen  that  the  refractive  indices  of  the  aqueous  and  vitreous 
humours  are  nearly  the  same  as  that  of  water.  That  of  the  lens 
differs  for  its  various  layers,  the  central  core  having  a  higher  re- 
fractive index  (1-411)  than  the  more  superficial  portions  (1-388). 
Although  such  calculations  are  open  to  error,  it  has  been  computed 
that  the  lens  acts  as  a  homogeneous  lens  of 
the  same  curvatures,  and  with  a  refractive 
index  of  1-437  would  do.  This  is  called  the 
total  refractive  index  of  the  lens..  The 
apparent  paradox  that  it  is  greater  than  the 
refractive  index  even  of  the  core  is  explained 
by  the  consideration  that  the  core  taken  by 
itself  has  a  greater  curvature  than  the  entire 
lens,  and  therefore  causes  a  greater  amount  of 
refraction  in  proportion  to  its  refractive  index. 
The  optical  problems  connected  with  the 
formation  of  the  retinal  image  are  complicated 
by  the  existence  in  the  eye  of  several  media, 
with  different  refractive  indices,  bounded  by 
surfaces  of  different  and,  in  certain  cases,  of 
variable  curvature.  For  many  purposes,  how- 
ever, the  matter  can  be  greatly  simplified,  and 
a  close  enough  approximation  yet  arrived  at, 
by  considering  a  single  homogeneous  medium, 
of  definite  refractive  index,  and  bounded  in 
front  by  a  spherical  surface  of  definite  curva- 
ture, to  replace  the  transparent  solids  and 
The  principal  focus  being  supposed  to  lie 
position   of   the   nodal  point — i.e.,  the  point 

reduced  ' 


Fig.  419. — The  Reduced 
Eye.  S.  the  single 
spherical  refracting 
surface,  2-2  mm.  be- 
hind  the  anterior  sur- 
face of  the  cornea;  N, 
the  nodal  point,  5  mm. 
behind  S  ;  F,  the 
principal  focus  (on  the 
retina),  20  mm.  behind 
S.  The  cornea  and 
lens  are  put  in  in 
dotted  lines  in  the 
position  which  they 
occupy  in  the  normal 
eye. 


liquids   of  the  eye. 

on  the  retina,  the 

through  which  rays  pass  without  refraction — of  such  a 

or  '  schematic  '  or  '  simplified  '  eye,  and  other  constants,  are  shown 

in   the    following  table.     The   single   refracting  surface  would   be 

situated  behind  the  cornea  and  in  front  of  the  lens,  at  a  rather 

smaller  distance  from  the  anterior  surface  of  the  latter  than  from 

the  anterior  surface  of  the  former.     The  nodal  point  would  be  less 

than  half  a  millimetre  in  front  of  the  posterior  surface  of  the  lens 

(Fig.  419).     The  refractive  index  of  the  single  transparent  medium 

would  be  a  little  greater  than  that  of  water. 


VISION  luig 

Reduced  Eye — 

Radius  of  curvature  of  the  single  refracting  surface  -       5-1      mm. 

Index  of  refraction  of  the  single  refracting  medium  -         -        I'iS* 
Antero-posterior    diameter    of    reduced    eye    (distance    of 

principal  focus  from  the  single  refracting  surface)  -     20-0 

Distance    of    the    single    refracting    surface    behind    the 

anterior  surface  of  the  cornea       -         -         -         -         -       2-2 
Distance  of    the   nodal   point  of    the   reduced    eye    from 

|its  anterior  surface         -         -         -         -         -         -         -5'0 

Distance    of    the    nodal    point    from   the   principal  focus 

(retina)  -         -         -         -         -         -         -         -         -         -15-0 

Knowing  the  position  of  the  centre  of  curvature  of  the  single 
ideal  refracting  surface — i.e.,  the  nodal  point  of  the  reduced  eye 
— all  that  is  necessary  in  order  to  determine  the  position  of  the 
image  of  an  object  on  the  retina  is  to  draw  straight  lines  from  its 
circumference  through  the  nodal  point.  Each  of  these  lines  cuts 
the  refracting  surface  at  right  angles,  and  therefore  passes  through 
without  any  devi- 
ation. The  retinal 
image  is  accord- 
ingly inverted  and 
its  size  is  propor- 
tional to  the  solid 
angle  contained 
between  the  lines 

,       ,  Fig.  420.  —  Figure  to  show  how  the  Visual  Angle  and 

boimdary     of     the  sjze  of  Retinal   image  varies  with  the  Distance  of 

object  to  the  nodal  an  Object  of  Given  Size.     P'or  the  distant  position 

DOint    or  the  eaual  °^  ^^  *^^  visual  angle  is  a,  for  the  near  position 

^      ,    '         ,    .       1,  (dotted  lines)  B. 

angle  contamed  by 

the  prolongations  of  the  same  lines  towards  the  retina.  This  angle 
is  called  the  visual  angle,  and  evidently  varies  directly  as  the  size 
of  the  object,  and  inversely  as  its  distance.  Thus  the  visual  angle 
under  which  the  moon  is  seen  is  much  larger  than  that  under  which 
we  view  any  of  the  fixed  stars,  because  the  comparative  nearness  of 
the  earth's  satellite  more  than  makes  up  for  its  relatively  small  size. 

The  dimensions  of  the  retinal  image  of  an  object  are  easily  calculated 

when  the  size  of  the  object  and  its  distance  are  known.     For  let  AB 

in  Fig.  420  represent  one  diameter  of  an  object,  A'B'  the  image  of  this 

diameter,  and  let  AB',  BA',  be  straight  lines  passing  through  the  nodal 

point.     Then  AB  and  A'B'  may  be  considered  as  parallel  lines,  and 

the  triangles  of  which  they  form  the  bases,  and  the  nodal  point  the 

common  apex,  as  similar  triangles.     Accordingly,  if  D  is  the  distance 

of  the   nodal  point  from   A,   and   d  its  distance  from    B',    we   have 

AR      A'B' 
— -=  — — .     Now,  d  may  approximately  be  taken  as  15  mm.     Suppose, 

then,  that  the  size  of  the  moon's  image  on  the  retina  is  required.  Here 
0=238,000  miles,  and  AB  (the  diameter  of  the  moon) ^2,160  miles. 

♦  Or  a  httle  more  than  that  of  the  aqueous  humour. 


1020  THE  SENSES 

-ri  J.    2,i6o       A'B'         ,       ,     I       A'B'    ,  ,  .  ,     .,„-  ,^, 

Thus  we  get  —  „ = ,  or  (say)  — = ,  from  which  A  B    (the 

°      238,000       15  ^    •"  no       15  ^ 

diameter  of  the  retinal  image)  =  — ^,  or  about  1  mm. 

^  '     no  ^ 

A  ship's  mast  120  feet  high,  seen  at  a  distance  of  25  miles,  will  throw 

on    the   retina    an    image    whose    height    is .,  -  x  15    mm.,    i.e., 

°  *  25  miles       -* 

120  feet  I  ,  ^ 

— -n 7—7x15  mm.,  or  x  is  mm.,  equal  to  0*013  mm.,  or 

5,280x25  feet       -^  1,100       -»  T 

13  ^  in  size.     This  is  not  much  larger  than  a  red  blood-corpuscle,  and 

only  four  times  the  diameter  of  a  cone  in  the  fovea  centralis,  where  the 

cones  are  most  slender.     In  this  calculation  the  effect  of  aberration 

(p.  1027)  in  enlarging  the  image  has  been  neglected.     This  effect  is,  of 

course,  proportionately  greater  for  small  and  distant  than  for  large  and 

near  objects;  and  it  is  doubtful  whether  the  smallest  possible  image 

can  be  confined  to  an  area  of  the  retina  of  the  size  of  a  single  cone. 

Accommodation. — A  lens  adjusted  to  focus  upon  a  screen  the 
rays  coming  from  a  luminous  point  at  a  given  distance  will  not  be 
in  the  proper  position  for  focussing  rays  from  a  point  which  is 
nearer  or  more  remote.  Now,  it  is  evident  that  a  normal  eye 
possesses  a  great  range  of  vision.  The  image  of  a  mountain  at  a 
distance  of  30  miles,  and  of  a  printed  page  at  a  distance  of  30  cm., 
can  be  focussed  with  equal  sharpness  upon  the  retina.  In  an 
opera-glass  or  a  telescope  accommodation  is  brought  about  by 
altering  the  relative  position  of  the  lenses ;  in  a  photographic  camera 
and  in  the  eyes  of  fishes  and  cephalopods,  by  altering  the  distance 
between  lens  and  sensitive  surface;  in  the  eye  of  man,  by  altering 
the  curvature,  and  therefore  the  refractive  power  of  the  lens.  That 
the  cornea  is  not  alone  concerned  in  accommodation,  as  was  at  one 
time  widely  held,  is  shown  by  the  fact  that  under  water  the  power 
of  accommodation  is  not  wholly  lost.  Now,  the  refractive  index 
of  the  cornea  being  practically  the  same  as  that  of  water,  no  changes 
of  curvature  in  it  could  affect  refraction  under  these  circumstances. 
That  the  sole  effective  change  is  in  the  lens  can  be  most  easily 
and  decisively  shown  by  studying  the  behaviour  of  the  mirror 
images  of  a  luminous  object  reflected  from  the  bounding  surfaces 
of  the  various  refractive  media  when  the  degree  of  accommodation 
of  the  eye  is  altered.  Three  images  are  clearly  recognized:  the 
brightest  an  erect  virtual  image,  from  the  anterior  (convex)  surface 
of  the  cornea;  an  erect  virtual  image,  larger,  but  less  bright,  from 
the  anterior  (convex)  surface  of  the  lens;  and  a  small  inverted  real 
image  from  the  (concave)  posterior  boundary  of  the  lens  (Purkinje- 
Sanson  images).  The  second  image  is  intermediate  in  position 
between  the  other  two.  It  is  possible  with  special  care  to  make 
out  a  fourth  image;  but  since  it  is  reflected  from  the  posterior 
surface  of  the  cornea,  at  which  only  a  slight  change  in  the  refractive 
index  occurs,  it  is  less  brilliant  than  the  first  three.  When  the  eye 
is  accommodated  for  near  vision,  as  in  focussing  the  ivory  point  of 


VISION 


the  phakoscope  (Practical  Exercises),  the  corneal  image  is  unchanged 
in  size,  brightness,  and  position.  The  middle  image  diminishes 
in  size,  comes  forward,  and  moves  nearer  to  the  corneal  image. 
This  shows  that  the  curvature  of  the  anterior  surface  of  the  lens 
has  been  increased — that  is  to  say,  its  radius  of  curvature  diminished 
— for  the  size  of  the  image  of  an  object  reflected  from  a  convex 
mirror  varies  directly  as  the  radius  of  curvature.  A  slight  change 
takes  place  in  the  image  from  the  posterior  surface  of  the  lens, 
indicating  a  small  increase  of  its  curvature  too.  By  means  of  a 
method  founded  on  the  observation  of  the  changes  in  these  images, 
and  a  special  instrument  called  an  ophthalmometer  which  allows 
of  their  measurement,  Helmholtz 
has  calculated  that  during  maxi- 
mum accommodation,  the  radius 
of  curvature  of  the  anterior  surface 
of  the  lens  is  only  6  mm.,  as  com- 
pared with  10  mm.  when  the  eye 
is  directed  to  a  distant  object  and 
there  is  no  accommodation.  When 
the  lens  has  been  removed  for 
cataract,  fairly  distinct  vision  may 
still  be  obtained  by  compensating 
for  its  loss  by  convex  spectacles 
of  suitable  refractive  power  (lo 
diopters*  for  distant  vision,  and 
15  diopters  for  the  distance  at 
which  a  book  is  usually  held),  but 
no  power  of  accommodation  re- 
mains. The  person  does  indeed 
contract  the  pupil  in  regarding  a 
near  object,  just  as  happens  in  the 
intact  eye;  the  most  divergent 
rays  are  thus  cut  off  and  the  image 
made  somewhat  sharper,  and  there 
may  appear  to  be  some  faculty  of 
accommodation  left.  But  the  loss 
of  the  whole  iris  by  operation  does 
not  affect  accommodation  in  the  least;  the  iris,  therefore,  takes 
no  part  in  it.  That  no  change  in  the  antero-posterior  diameter 
of  the  eyeball,  caused  by  its  deformation  by  the  contraction  of  the 
^extrinsic  muscles,  can  have  any  share  in  accommodation,  as  has 

*  A  diopter  (i  D.)  is  the  unit  of  refractive  power  generally  adopted  in 
measuring  the  strength  of  lenses,  and  corresponds  to  a  lens  of  i  metre  focal 
length.  A  lens  of  2  diopters  (2  D.)  has  a  focal  length  of  h  metre,  a  lens  of 
4  diopters  (4  D.)  a  focal  length  of  \  metre,  and  so  on.  The  diverging  power 
of  concave  lenses  is  similarly  expressed  in  diopters  with  the  negative  sign 
prefixed.  Thus,  a  concave  lens  of  i  metre  focal  length  has  a  strength  of  —  i  D.. 
and  will  just  neutralize  a  convex  lens  of  i  D. 


Fig.  421. — Purkinje  -  Sanson  Images. 
A,  in  the  absence  of  accommoda- 
tion; B,  during  accommodation  for 
a  near  object.  The  upper  pair  of 
circles  enclose  the  images  as  seen 
when  the  light  falls  on  the  eye 
through  a  double  slit  on  a  pair  of 
prisms:  the  lower  pair  show  the 
images  seen  when  the  slit  is  single 
and  triangular  in  shape. 


I022  THE  SENSES 

been  suggested,  is  clearly  proved  by  the  fact  that  atropine,  which 
does  not  affect  the  action  of  these  muscles,  paralyzes  the  mechanism 
of  accommodation.  To  the  consideration  of  that  mechanism  we 
now  turn. 

The  Mechanism  of  Accommodation. — While  everybody  is  agreed 
that  the  main  factor  in  accommodation  is  the  alteration  in  the 
curvature  of  the  lens,  there  is  by  no  means  the  same  unanimity 
as  to  the  manner  in  which  this  is  brought  about.  Helmholtz's 
explanation,  which  has  long  been  the  most  popular,  is  as  follows: 
In  the  unaccommodated  eye  the  suspensory  ligament  and  the 
capsule  of  the  lens  are  tense  and  taut,  the  anterior  surface  of  the 
lens  is  flattened  by  their  pressure,  and  parallel  rays  (or,  what  is  the 
same  thing,  rays  from  a  distant  object)  are  focussed  on  the  retina 
without  any  sense  of  effort.  In  accommodation  for  a  near  object, 
the  meridional  or  antero-posterior  fibres  of  the  ciliary  muscle  by 
their  contraction  pull  forward  the  choroid  and  relax  the  suspensory 
ligament.  The  elasticity  of  the  lens  at  once  causes  it  to  bulge 
forwards  till  it  is  again  checked  by  the  tension  of  the  capsule. 

The  explanation  of  Helmholtz,  although  widely  adopted  in  the  text- 
books, has  not  escaped  question  in  the  archives.  Tscheming  has  put 
forward  the  view  that  when  the  ciliary  muscle  contracts,  the  suspensory 
ligament  is  pulled  backwards  and  outwards.  Its  tension  is  thus  in- 
creased, and  the  soft  external  layers  of  the  lens  are  in  consequence 
moulded  upon  the  harder  nucleus,  so  as  to  increase  the  curvature 
especially  around  the  anterior  pole.  And  Schoen,  reviving  a  similar 
theory  originated  fifty  years  ago  by  Mannhardt,  believes  that  the 
ciliary  muscle,  in  contracting,  exerts  pressure  on  the  anterior  portion 
of  the  lens,  and  so  increases  its  curvature.  He  likens  the  process  to  the 
bulging  of  an  indiarubber  ball  when  it  is  held  in  both  hands  and  com- 
pressed by  the  fingers  a  little  behind  one  of  the  poles.  It  will  be  ob- 
served that  in  both  of  these  theories  the  suspensory  ligament  is  supposed 
to  be  stretched  during  accommodation,  not  relaxed  as  Helmholtz  sup- 
posed. While  they  have  certain  advantages  over  the  theory  of  Helm- 
holtz, particularly  in  taking  account  of  the  presence  of  radial  and  circular 
as  well  as  meridional  fibres  in  the  ciliary  muscle,  they  do  not  agree  so 
well  with  such  experimental  tests  as  have  been  applied,  and  therefore 
Helmholtz's  explanation  must  still  be  regarded  as  the  best. 

It  is  supported  by  the  observation  of  Hess  that  when  the  ciliary 
muscle  has  been  very  strongly  contracted  by  eserinc  the  lens  can  he 
observed  to  move  about  with  each  slight  movement  of  the  eye.  The 
suspensory  ligament  must  therefore  be  slackened  by  the  contraction  of 
the  ciliary  muscle.  ,VVhen  atropine  is  applied  the  movability  of  the 
lens  soon  disappears,  owing  to  paralysis  of  the  ciliary  muscle.  These 
facts  were  first  estabUshed  in  patients  after  iridectomy,  but  ha\e  also 
been  demonstrated  in  the  normal  eye.  Ev^en  under  the  influence  of 
gravity  alone,  without  any  movements  of  the  eye,  the  lens  sinks  about 
i^  to  ^  ram.  in  strong  accommodation.  An  additional  proof  that  the 
suspensory  ligament  is  perfectly  slack  during  accommodation  is  derived 
from  the  result  of  simultaneous  measurements  in  animals  of  the  pressure 
in  the  anterior  chamber  and  in  the  vitreous.  Even  in  strong  accommo- 
dation no  alteration  occurs,  although  even  slight  contact  with  the  outer 
surface  of  the  eyeball  or  contraction  of  the  external  eye  muscles  causes 


VISION  1023 

a  distinct  cflcct.  In  two  cavities  separated  by  a  slack  membrane  no 
differences  of  pressure  would  be  expected. 

Anderson  Stuart  lays  stress  upon  tlie  function  of  those  fibres  of  the 
suspensory  ligament  wliicli  are  attached  to  the  vitreous  body,  and  are 
put  under  tension  by  the  contraction  of  the  ciliary  muscle,  in  anchoring 
tlic  Icus  during  strong  accommodation.  He  believes  that  the  liquid 
contents  of  the  hyaloid  canal  move  from  its  anterior  to  its  posterior  end 
in  accommodation,  and  in  the  opposite  direction  when  accommodation 
is  relaxed,  and  that  this  movement  tends  to  prevent  strains  in  the 
vitreous. 

In  cephalopods  and  fishes,  which  are  normally  short-sighted,  accom- 
modation for  objects  at  a  distance  is  effected  by  a  movement  of  the  lens 
towards  the  retina.  In  the  fish's  eye  this  is  accomplished  by  the  con- 
traction of  a  special  muscle,  the  retractor  lentis.  In  amphibia  and  most 
snakes  the  lens  is  mo\ed  towards  the  cornea  and  away  from  the  retina 
by  changes  of  intra-ocular  pressure  (Beer). 

Innervation  of  the  Ciliary  Muscle  and  the  Muscles  of  the  Iris. — The 
ciliary  muscle  and  the  sphincter  pupilla:  are  supplied  by  autonomic 
fibres  (p.  1004),  reaching  them  through  the  short  ciliary  nerves  arising 
from  the  ciliary  ganglion  (Fig.  422).  The  preganglionic  fibres  take 
origin  from  cells  in  the  anterior  part  of  the  oculo-motor  nucleus  in  the 
mid-brain.  Passing  to  the  orbit  in  the  third  nerve,  they  reach  the 
ciliary  ganglion,  and  end  there  by  forming  synapses  with  some  of  its 
cells.  The  axons  of  these  cells  continue  the  path  as  post-ganglionic 
fibres  in  the  short  ciliary  nerves.  The  dilator  pupillse  is  supplied  by  the 
long  ciliary  nerves  coming  from  the  ophthalmic  branch  of  the  fifth 
nerve. 

The  preganglionic  dilator  fibres  pass  out  by  the  anterior  roots  of  the 
first  three  thoracic  nerves  (dog,  cat,  rabbit),  accompanied  by  vaso- 
constrictor fibres  for  the  iris.  Reaching  the  sympathetic  chain  through 
the  corresponding  rami  communicantes,  they  traverse  the  first  thoracic 
ganglion,  the  annulus  of  Vieussens,  the  inferior  cervical  ganglion,  and 
the  cervical  sympathetic.  They  end  by  arborizing  around  some  of  the 
cells  of  the  superior  cervical  ganglion,  whose  axons  eventually  arrive. at 
the  Gasserian  ganglion,  and  running  along  the  ophthalmic  division  of 
the  trigeminal  to  the  eye,  reach  the  iris  by  its  long  ciliary  branches. 

The  exact  origin  of  the  dilator  path  in  the  brain  has  not  been  defi- 
nitely settled..  Some  place  it  in  the  mid-brain,  others  in  the  bulb. 
There  must  be  at  least  one  neuron  on  the  path  central  to  the  spinal 
neuron  whose  axon  emerges  from  the  cord  as  a  preganglionic  fibre. 
The  lower  cervical  and  upper  thoracic  portion  of  the  spinal  cord  has 
received  the  name  of  the  cilio-spinal  region  from  its  relation  to  the 
pupillo-dilator  fibres.  It  must  not  be  looked  upon  as  a  centre  in  any 
proper  sense  of  the  term,  but  rather  as  the  pathway  by  which  these 
fibres  pass  down  from  the  bulb,  and  where  they  may  accordingly  be 
tapped  by  stimulation. 

Stimulation  of  certain  areas  on  the  cortex  of  the  frontal  lobe  of  the 
cerebrum  (p.  1002)  causes  slight  dilatation  of  the  pupil  even  after  the 
sympathetic  has  been  divided.  This  is  due  to  inhibition  of  the  pupillo- 
constrictor  fibres  in  the  third  nerve. 

Changes  in  the  Pupil  during  Accommodation. — It  has  been  aheady 
mentioned  that  along  with  the  alteration  in  the  curvature  of  the 
lens  a  change  in  the  diameter  of  the  pupil  takes  place  in  accommo- 
dation. When  a  distant  object  is  looked  at,  the  pupil  becomes 
larger;  when  a  near  object  is  looked  at,  it  becomes  smaller.  Narrow- 


I024 


THE  SENSES 


ing  of  the  pupil  is  thus  associated  with  contraction  of  the  ciHary 
muscle,  and  widening  of  the  pupil  witli  its  relaxation. 

This  physiolcgical  correlation  has  its  anatomical  counterpart;  for  the 
third  nerve  supplies  both  the  iris  and  the  ciHary  muscle.  Stimulation 
of  the  nerve  within  the  cranium  causes  contraction  of  the  pupil,  while 
stimulation  of  certain  portions  of  its  nucleus  in  the  floor  of  the  third 
ventricle  and  the  Sylvian  aqueduct  or  of  the  short  ciliary  nerves 
(Fig.  4.22),  which  receive  branches  from  the  third  nerve,  or  of  the 
ganglion  itself,  is  followed  by  that  change  in  the  anterior  surface  of  the 
lens  which  constitutes  accommodaticn  (Hcnscn  and  \'oclckers).  This 
can  be  observed  either  through  a  window  in  the  sclerotic  in  a  dog  or  by 
following  the  movements  of  a  needle  thrust  into  the  eyeball.  Bv 
carefully  localized  stimulation  near  the  junction  of  the  aqueduct  with 


e?c 


Fig.  422. — Scheme  of  Innervation  of  CiUar>' 
and  Iris  Muscles  (after  Schultz).  i.  ciliary 
ganglion;  2.  oculo-motor  nucleus;  3.  spinal  cell, 
from  which  comes  off  the  preganglionic  fibre  on 
the  pupillo-dilator  path,  which  forms  a  synapse 
with  4.  a  cell  in  the  superior  cervical  ganglion. 
The  axon  of  4  is  shown  passing  (as  an  interrupted 
line)  through  the  Gasserian  ganglion  into  the 
ophthalmic  division  (Oph.)  of  the  fifth  nerve,  V. 
aad  thence  in  a  long  ciliary  nerve.  5,  to  the  dilator  of  the  iris.  8.  From  i  axons 
are  shown  passing  by  short  ciliary  nerves  to  the  ciliary  muscle,  6.  and  the  constrictor 
pupillje,  7;  9,  cell  of  origin  (in  mid-brain  ?)  of  fibre  which  constitutes  the  central 
neuron  of  the  pupillo-dilator  path;  10.  optic  nerve;  III.  third  nerve;  V.  fifth  nerve 
with  Gasserian  ganglion. 

the  third  ventricle,  it  is  possible  to  bring  about  the  forward  bulging  of 
the  lens  without  any  change  in  the  iris :  but  the  normal  and  voluntary- 
act  of  accommodation  cannot  be  disjoined  from  the  corresponding 
alterations  in  the  size  of  the  pupil.  Inward  rotation  of  the  eyes  accom- 
panies contraction  of  the  pupil  in  accommodation,  and  the  question 
may  be  raised  whether  the  pupillary-  change  is  associated  with  the  action 
of  the  extrinsic  muscles  of  the  eyeball  which  cause  convergence  or  with 
the  action  of  the  intrinsic  muscles  which  determine  the  changes  in  the 
curvature  of  the  lens.  It  is  usually  considered  to  be  associated  with 
both.  In  any  case,  accual  convergence  is  not  necessary-  for  the  reaction, 
since  it  may  still  be  obtained  on  accommodation  when  convergence  is 
impossible  on  account  of  paralysis  of  the  internal  recti. 


VISION  1025 

Changes  in  the  Pupil  produced  by  Light. — It  is  not  only  by 
accommodation  that  the  size  of  the  pupil  may  be  affected.  In 
the  dark  it  dilates,  at  hrst  rapidly,  then  gradually,  and  it  main- 
tains the  width  it  has  reached  for  several  hours.  This  has  been 
shown  by  taking  photographs  of  the  eye  with  the  magnesium  flash- 
light. In  this  way  the  width  of  the  pupil  is  recorded  before  it  has 
time  to  alter.  Or  a  longer  exposure  to  ultra-violet  light,  which 
affects  the  pupil  but  little,  may  be  employed.  When  ordinary 
light  falls  upon  the  retina  the  pupil  contracts,  and  the  amount  of 
contraction  is  roughly  proportional  to  the  intensity  of  the  light. 
Contraction  of  the  pupil  to  light  is  brought  about  by  a  reflex 
mechanism,  of  which  the  optic  nerve  forms  the  afferent  and  the 
oculo-motor  the  efferent  path,  while  the  centre  is  situated  in  the 
floor  of  the  aqueduct  of  Sylvius.  The  relation  of  this  centre  to 
that  which  controls  the  changes  in  the  pupil  during  accommodation 
has  not  as  yet  been  sufficiently  elucidated;  but  this  we  do  know, 
that  one  of  the  paths  may  be  interrupted  by  disease,  while  the  other 
is  intact.  For  in  tabes  (locomotor  ataxia),  and  in  dementia  para- 
lytica (general  paralysis),  the  light-reflex  sometimes  disappears, 
while  the  constriction  of  the  pupil  in  accommodation  and  conver- 
gence still  takes  place  (Argyll-Robertson  pupil).  Artificial  stimula- 
lion  of  the  optic  nerve  has  the  same  effect  on  the  pupil  as  the 
'  adequate  '  stimulus  of  light;  and  in  many  animals  (including  man), 
though  not  in  those  whose  optic  nerves  completely  decussate,  there 
is  a  consensual  light-reflex — i.e.,  both  pupils  contract  when  one 
retina  or  optic  nerve  is  excited.  This  should  be  remembered  in 
using  the  pupil-reaction  as  a  test  of  the  condition  of  the  retina. 
For  although  the  absence  of  contraction  may  show  that  the  retina 
of  the  eye  on  which  the  light  is  allowed  to  fall  is  insensible  (unless 
there  is  some  physical  hindrance  to  its  passage,  such  as  opacity 
of  the  lens  or  cataract),  the  occurrence  of  contraction  does  not 
exclude  insensibility  of  the  retina  unless  the  other  eye  has  been 
protected  from  the  light. 

Stimulation  of  the  cervical  sympathetic  causes  marked  dilata- 
tion of  the  pupil,  even  when  the  third  nerve  is  excited  at  the  same 
time.  The  pupillo-dilator  fibres  do  not  act  by  constricting  the 
bloodvessels  of  the  iris.  For  dilatation  of  the  pupil  can  be  caused 
in  a  bloodless  animal  by  stimulating  the  sympathetic.  And  even 
when  the  circulation  is  going  on,  a  short  stimulation  of  the  sympa- 
thetic causes  dilatation  of  the  pupil  without  vaso-constriction, 
while  with  longer  excitation  the  dilatation  of  the  pupil  begins  before 
the  narrowing  of  the  bloodvessels.  Nor  does  it  seem  possible  to 
accept  the  view  that  the  sympathetic  fibres  are  inhibitory  for  the 
sphincter  muscle  of  the  iris.  They  act  directly  upon  dilator  muscu- 
lar fibres.  It  has,  indeed,  long  been  known  that  in  the  iris  of  the 
otter  and  of  birds  a  radial  dilator  muscle  exists;  and  it  has  been 

65 


1026  THE  SE>!SES 

shown  by  Langley  and  Anderson  that  in  the  ins  of  the  rabbit,  cat, 
and  dog,  the  presence  of  radially  arranged  contractile  substance, 
different  it  may  be  in  some  respects  from  ordinary  smooth  muscle, 
must  be  assumed.  Both  the  constrictor  and  the  dilator  muscles 
of  the  iris  are  normally  in  a  condition  of  greater  or  less  tonic  con- 
traction, so  that  the  size  of  the  pupil  at  any  given  moment  depends 
on  the  play  of  two  nicely  balanced  forces.  Reflex  dilatation  of  the 
pupil  through  the  sympathetic  fibres  is  caused  in  man  by  painful 
stimulation  of  the  skin,  by  dyspnoea,  by  muscular  exertion,  and 
in  some  individuals  even  by  tickling  of  the  palms.  In  animals  the 
stimulation  of  naked  sensory  nerves  has  the  same  effect.  The  '  start- 
ing of  the  eyeballs  from  their  sockets,'  which  the  records  of  torture  so 
often  note,  is  due  to  a  similar  reflex  excitation  of  the  sympathetic 
fibres  supplying  the  smooth  muscle  of  the  orbits  and  eyelids. 

Action  of  Drugs  on  the  Function  of  the  Intrinsic  Eye  Muscles. — The 

local  application  of  atropine  causes  tempc)rar3'  paralysis  of  accommoda- 
tion and  dilatation  of  the  pupil.  When  the  third  nerve  is  divided,  the 
pupil  dilates;  it  dilates  still  more  when  atropine  is  administered  after 
the  operation.  Dropped  into  one  eye  in  small  quantity,  atropine  only 
produces  a  local  effect ;  the  pupil  of  the  other  eye  remains  of  normal 
size,  or  somewhat  constricted  on  account  of  the  greater  reflex  stimula- 
tion of  its  third  nerve  by  the  greater  quantity  of  light  now  entering  the 
widelv-dilated  pupil  of  the  atropinized  eye.  Even  in  the  excised  eye 
the  effect  of  the  drug  is  the  same.  Introduced  into  the  blood  atropine 
causes  both  pupils  to  dilate.  Its  action  is  to  paralyze  the  endings  of 
the  oculo-motor  fibres  to  the  sphincter  pupillae  and  ciliary  muscle. 
Other  mydriatic,  or  pupil-dilating  drugs,  are  cocaine,  daturine.  and 
hyoscvamine.  Physostigmine  or  eserine.  pilocarpine ,  and  muscarine  are 
the  chief  miotics,  or  pupil-constricting  substances.  They  also  cause 
spasm  of  the  ciliary  muscle,  and  inability^  to  accommodate  for  distant 
objects.  They  act'  by  stimulating  the  structures  (nerve-endings)  (see 
pp.  182,  739)  which  atropine  paralyzes.  The  work  of  the  mydriatics 
can  be  undone  by  the  miotics.  Thus  the  dilatation  produced  by  atro- 
pine is  removed  by  pilocarpine. 

Functions  of  the  Iris. — In  vision  the  iris  performs  two  chief 
functions:  (i)  It  regulates  the  quantity  of  light  allowed  to  fall 
upon  the  retina.  The  larger  the  aperture  of  a  lens,  the  greater  is 
its  collecting  power,  the  more  light  does  it  gather  in  its  focus.  In 
the  eye,  the  area  of  the  pupil  determines  the  breadth  of  the  pencil 
of  light  that  falls  upon  the  lens.  If  this  area  was  invariable,  the 
retina  would  either  be  '  dark  from  excess  of  light  '  in  liright  sunshine, 
or  dark  from  defect  of  light  in  dull  weather  or  at  dusk.  In  ordei 
that  the  iris  may  act  as  an  efficient  diaphragm  it  must  be  pig- 
mented, and  it  is  the  pigment  in  it  which  gives  the  colour  to  the 
normal  eye.  The  vision  of  albinos,  in  whose  eyes  this  pigment  is 
wanting,  is  often,  though  not  invariably,  deficient  in  sharpness. 
There  is  always  intolerance  of  bright  light ;  and  the  same  is  true 
in  the  condition  known  as  irideremia,  or  congenital  absence  or 
defect  of  the  iris. 


VISION 


1027 


(2)  Another,  and  pcrliaps  equally  inii)()iiant,  function  of  tlie  iris 
is  to  cut  off  the  more  divergent  rays  of  a  pencil  of  light  falling  upon 
the  eye,  and  thus  to  increase  the  sharpness  of  the  image.  This 
leads  us  to  the  consideration  of  certain  defects  in  the  dioptric 
arrangements  of  the  eye. 

Defects  of  the  Eye  as  an  Optical  Instrument. — (i)  Spherical  Aberra- 
tion.— It  is  a  property  of  a  sphcrii  ,il  rcl'nictiug  surface  that  rays  of 
liglit  passing  through  the  peripheral  portions  arc  more  strongly  reirai.tcd 
than  rays  passing  near  the  principal  axis.  Hence  a  luminous  point 
is  not  focussed  accurately  in  a  single  ix)int  by  a  spherical  lens ;  the  image 
is  surrounded  by  fainter  circles  of  light,  the  so-called  circles  of  diffusion 
representing  the  rays  which  have  not  yet  come  to  a  focus,  or  having  been 
already  focussed  have  crossed  and  arc  now  diverging.  In  the  eye  this 
spherical  aberration  is  partly  corrected  by  the  interposition  of  the  iris, 
which  cuts  off  the  more  peripheral  rays,  especially  in  accommodation 
for  a  near  object,  when  they  are  most  divergent.  In  addition,  the 
anterior  surfaces  of  the  cornea  and  lens  are  not  segments  of  spheres,  but 
of  ellipsoids,  so  that  the  curvature  diminishes  somewhat  with  the  dis- 
tance from  the  optic  axis, 
and,  therefore,  the  re- 
fracting power  as  we  pass 
away  from  the  axis  does 
not  increase  so  rapidly 
as  it  would  do  if  the 
surfaces  were  truly 
spherical.  Further,  the 
refractive  index  of  the 
peripheral  parts  of  the 
lens  is  less  than  that  of 
its  central  portions. 

(2)  Chromatic  Aberra- 
tion.— All  the  rays  of  the 
spectrum  do  not  travel 
with  the  same  velocity 
through  a  lens,  and  are, 
therefore,  unequally  refracted  by  it,  the  short  violet  rays  being  focussed 
nearer  the  lens  than  the  long  red  rays.  It  was  at  one  time  supposed  that 
this  chromatic  aberration,  as  it  is  called,  is  compensated  in  the  eye;  and 
it  is  said  that  this  mistake  gave  the  first  hint  that  Newton's  dictum  as 
to  the  proportionality  between  deviation  and  dispersion  was  erroneous, 
and  led  to  the  discovery  of  achromatic  lenses.  But  in  reality  the  eye 
is  not  an  achromatic  combination ;  and  the  violet  rays  are  focussed 
about  J  mm.  in  front  of  the  red.  Thus,  in  Fig.  424  the  white  light 
passing  through  the  lens  is  broken  up  into  its  constituents:  the  violet 
focus  is  at  V,  and  the  red  at  R,  behind  it.  A  screen  placed  at  R  would 
show  not  a  point  image,  but  a  central  point  surrounded  by  concentric 
circles  of  the  spectral  colours,  with  violet  outside.  If  the  screen  was 
placed  at  V,  the  centre  would  be  violet  and  the  red  would  be  external. 
For  this  reason  it  is  impossible  to  focus  at  the  same  time  and  with  perfect 
sharpness  objects  of  different  colours;  a  red  light  on  a  railway  track 
appears  nearer  than  a  blue  light,  partly  perhaps  for  the  reason  that  it  is 
necessary  to  accommodate  more  strongly  for  the  red  than  for  the  blue, 
and  we  associate  stronger  accommodation  with  shorter  distance  of  the 
object,  although  other  data  are  also  involved  in  such  a  visual  judgment. 
When  we  look  at  a  white  gas-fiame  through  a  cobalt  glass,  which  allows 
only  red  and  violet  to  pass,  we  see  either  a  red  fiame,  surrounded  by  a 


Fig.  423. — Spherical  Aberration.  Rays  passing 
through  the  more  peripheral  parts  of  a  biconvex 
lens  L  are  brought  to  a  focus  F  nearer  the  lens  than 
F',  the  focus  of  rays  passing  through  the  central 
portions  of  the  lens. 


1028 


THE  SENSES 


violet  ring,  or  a  violet  flame  surrounded  by  a  red  ring,  according  as  we 
focus  for  the  red  or  for  the  viokt  rays.  But  the  dispersive  power  of 
the  eye  is  so  small,  and  the  capacity  of  rapidly  altering  its  accommoda- 
tion so  great,  that  no  practical  inconvenience  results  from  the  lack  of 
achromatism,  which,  however,  may  be  easily  demonstrated  by  looking 
at  a  pattern  such  as  that  in  Fig.  425  at  a  distance  too  small  for  exact 
accommodation. 

It  is  also  reckoned  among  the  optical  imperfections  of  the  eye  (3)  that 
the  curved  surfaces  of  the  cornea  and  lens  do  not  form  a  '  centred  '  system 
— that  is  to  say,  their  apices  and  their  centres  of  curvature  do  not  all 
lie  in  the  same  straight  line;  (4)  that  the  pupil  is  eccentric,  being 
situated  not  exactly  opposite  the  middle  of  the  lens  and  cornea,  but 
nearer  the  nasal  side,  and  that  in  consequence  the  optic  axis,  or  straight 
line  joining  the  centres  of  curvature  of  the  lens  and  cornea,  does  not 
coincide  with  the  visual  axis,  or  straight  line  joining  the  fovea  centralis 
with  the  centre  of  the  pupil,  which  is  also  the  straight  line  joining  the 
centre  of  the  pupil  and  any  point  to  which  the  eye  is  directed  in  \'ision. 
The  angle  between  the  optic  and  visual  axis  is  about  5°  (Fig.  416). 


Fi;^.  424. — ^Chromatic  Aberration.  The  violet 
rays  are  brought  to  a  focus  V  nearer  the  lens 
than  R,  the  focus  of  the  red  rays. 


Fig.  425. — To  show  Dispersion  in 
Eye  (v.  Bezold).  View  the 
figure  from  a  distance  too  small 
for  accommodation.  Approach 
the  eye  towards  it;  the  white 
rings  appear  bluish  owing  to 
circles  of  dispersion  falling  on 
them — i.e.,  circles  of  light  of 
different  colours  due  to  the 
decomposition  of  white  light 
into  its  spectral  constituents  by 
the  media  of  the  eye.  A  little 
closer,  and  the  black  rings  be- 
come white  or  yellowish -white. 


(5)  Muscae  volitantes,  the  curious  bead- 
like or  fibrillar  forms  that  so  often  flit 
in  the  visual  field  when  one  is  looking 
through  a  microscope,  are  the  token  that 
the  refractive  media  of  the  eye  arc  not 
perfectly  transparent  at  all  parts ;  they  seem  to  be  due  to  floating  opacities 
in  the  vitreous  humour,  probably  the  remains  of  the  embr^'onic  cells  from 
which  the  vitreous  body  was  developed.  (6)  Lastly,  it  may  be  men- 
tioned that  slight  irregularities  in  the  curvature  of  the  lens  exist  in  all 
eyes,  so  that  a  point  of  light,  like  a  star  or  a  distant  street-lamp,  is  not 
seen  as  a  point,  but  as  a  point  surrounded  by  rays  (irregular  astigma- 
tism). In  bringing  this  review  of  the  imperfections  of  the  dioptric 
media  of  the  normal  eye  to  a  close,  it  may  be  well  to  explain  that  what 
are  defects  from  the  point  of  view  of  the  student  of  pure  optics  are  not 
necessarily  defects  from  tlie  freer  standpoint  of  the  physiologist,  who 
surveys  the  mechanism  of  vision  as  a  whole,  the  relations  of  its  various 
parts  to  one  another  and  to  the  needs  of  the  organism  it  has  to  serve, 
the  long  series  of  developmental  changes  through  which  it  has  come 
to  be  what  it  is,  and  the  possibilities,  so  far  as  we  can  limit  them,  that 
were  open  to  evolution  in  the  making  of  an  eye.  The  optician  may 
perhaps  assert,  and  with  justice,  that  he  could  easily  have  made  a  better 
lens  than  Nature  has  furnished,  but  the  physiologist  will  not  readily 
admit  that  he  could  have  made  as  good  an  eye. 


VISION 


1029 


While  the  defects  hitherto  mentioned  are  shared  in  greater  or 
less  degree  by  every  normal  eye,  there  are  certain  other  defects 
which  either  occur  in  such  a  comparatively  siriail  numlx-r  of  eyes, 
or  lead  to  such  grave  disturbances  of  vision  when  they  do  occur, 
that  they  must  be  reckoned  as  abnormal  conditi(jns.  In  the  normal 
or  emmetropic  eye,  parallel  rays — and  for  this  purpose  all  rays 
coming  from  an  object  at  a  distance  greater  than  65  metres  may  be 
considered  paralK'l — are  brought  to  a  focus  on  the  retina  without 
any  effort  of  accommodation.  The  distance  at  which  objects  can 
be  distinctly  seen  is  only  limited  by  their  size,  the  clearness  of  the 
atmosphere,  and  the  curvature  of  the  earth;  in  other  words,  the 
punchtm  remotnm,  or  far-point  of  vision,  the  most  distant  point  at 
which  it  is  possible  to  see  with  distinctness,  is  practically  at  an 
infinite  distance.  When  accommodation  is  paralyzed  by  atropine, 
only  remote  objects  can  be  clearly  seen.  On  the  other  hand,  the 
normal  eye,  or,  to  be  more  precise,  the  normal  eye  of  a  middle-aged 


Fig.  426. — Refraction  in  the  (Xormal)  Emmetropic  Eye.  The  image  V  oi  a  distant 
point  P  falls  on  the  retina  when  the  eye  is  not  accommodated.  To  save  space, 
P  is  placed  much  too  near  the  eye  in  Figs.  426,  427. 

adult,  can  be  adjusted  for  an  object  at  a  distance  of  not  more  than 
12  cm.  (or  5  inches).  Nearer  than  this  it  is  not  possible  to  see 
distinctly;  this  point  is  accordingly  called  the  punctuni  proximum 
or  near-point.  The  range  of  accommodation  for  distinct  vision 
in  the  enmietropic  eye  is  from  12  cm.  to  infinity. 

Myopia,  or  short-sightedness,  is  generally  due  to  the  excessive 
length  of  the  antero-posterior  diameter  of  the  eyeball  in  relation 
to  the  converging  power  of  the  cornea  and  the  lens.  Even  in 
the  absence  of  accommodation,  parallel  rays  are  not  focussed  on 
the  retina,  but  in  front  of  it;  and  in  order  that  a  sharp  image  may 
be  formed  on  the  retina  the  object  must  be  so  near  that  the  rays 
proceeding  from  it  to  the  eye  are  sensibly  divergent — that  is  to 
say,  it  must  be  at  least  nearer  than  65  metres — but  as  a  rule  an 
object  at  a  distance  of  more  than  2  to  3  metres  cannot  be  distinctly 
seen.  With  the  strongest  accommodation  the  near-point  may  be 
as  little  as  3  cm.  from  the  eye.     The  range  of  vision  in  the  myopic 


I030 


THE  SENSES 


eye  is  therefore  very  small.  The  defect  may  be  corrected  by  con- 
cave glasses,  which  render  the  rays  more  divergent.  It  is  to  be 
noted  that  many  cases  of  internal  squint  in  children  are  connected 
with  myopia,  the  eyes  necessarily  rotating  inwards  as  they  are  made 
to  fix  an  abnormally  near  object.  The  treatment  both  of  the  squint 
and  the  myopia  in  these  cases  is  the  use  of  concave  spectacles 
(Fig.  427).     Myopia,  although  a  condition  that  shows  a  distinct 


Fig.  427. — Myopic  Eye.  The  image  P'  of  a  distant  point  P  falls  in  front  of  the  retina 
even  without  accommodation.  By  means  of  a  concave  le.is  L  the  image  may  be 
made  to  fall  on  the  retina  (dotted  lines). 

hereditar\'  tendency,  is  rarely  present  at  birth;  the  elongation  of  the 
antero-posterior  diameter  of  the  eyeball  develops  gradually  as  the 
child  grows. 

In  hypermetropia,  or  long-sightedness,  the  eye  is,  as  a  rule,  too 
short  in  relation  to  its  converging  power;  and  with  the  lens  in  the 
position  of  rest,  parallel  rays  would  be  focussed  behind  the  retina. 
Accordingly,  the  hypermetropic  eye  must  accommodate  even  for 


Fig.  428. — Hypermetropic  Eye.  The  image  P'  of  a  point  P  falls  beliind  the  retina 
in  the  unaccommodated  eye.  By  means  of  a  convex  lens  L  it  may  be  focussed 
on  the  retina  without  accommodation  (dotted  lines). 

distant  objects,  while  even  with  maximum  accommodation  an 
object  cannot  be  distinctly  seen  unless  it  is  farther  away  than  the 
near-point  of  the  emmetropic  eye.  The  far-point  of  distinct  vision 
is  at  the  same  distance  as  in  the  emmetropic  eye — viz.,  at  infinity — 
the  near-point  is  farther  from  the  eye.  The  defect  is  corrected  by 
convex  glasses  (Fig.  428).  Hypermetropia,  unlike  myopia,  is 
present  at  birth. 


VISION  1031 

Presbyopia,  or  llie  long-sightedness  of  old  age,  is  not  to  be  con- 
founded with  hypermetropia.  It  is  essentially  due  to  failure  in 
the  power  of  accommodation,  chiefly  through  weakness  of  the 
ciliary  muscle,  but  partly  owing  to  increased  rigidity  and  loss  of 
elasticity  of  the  lens.  Images  of  distant  objects  are  still  formed 
on  the  retina  of  the  unaccommodated  eye  with  perfect  sharpness — 
i.e.,  the  far-point  of  vision  is  not  affected.  But  the  eye  is  unable 
to  accommodate  sufficiently  for  the  rays  diverging  from  an  object 
at  the  ordinary  near-point ;  in  other  words,  the  near-point  is  farther 
away  than  normal.     Convex  glasses  are  again  the  remedy. 

The  near-point  of  distinct  vision  can  be  fixed  in  various  ways — 
among  others,  by  means  of  Scheiner's  experiment  (Practical 
Exercises,  p.  1103).  Two  pin-holes  are  pricked  in  a  card  at  a  dis- 
tance less  than  the  diameter  of  the  pupil.  A  needle  viewed  through 
the  holes  appears  single  when  it  is  accommodated  for,  double  if  it 
is  out  of  focus.  The  near-point  of  vision  is  the  nearest  point  at 
which  the  needle  can  still,  by  the  strongest  effort  of  accommoda- 
tion, be  seen  single. 

Astigmatism. — It  has  been  mentioned  that  slight  differences  of 
curvature  along  different  meridians  of  the  refracting  surfaces  exist 
in  all  eyes.  But  in  some  cases  the  difference  in  two  meridians  at 
right  angles  to  each  other  is  so  great  as  to  amount  to  a  serious 
defect  of  vision.  To  this  condition  the  name  of  '  astigmatism  '  or 
'  regular  astigmatism  '  has  been  given.  It  is  usually  due  to  an 
excess  of  curvature  in  the  vertical  meridians  of  the  cornea,  less  fre- 
quently in  the  horizontal  meridians;  occasionally  the  defect  is  in 
the  lens.  Rays  proceeding  from  a  point  are  not  focussed  in  a  point, 
but  along  two  lines,  a  horizontal  and  a  vertical,  the  horizontal 
linear  focus  being  in  front  of  the  other  when  the  vertical  curvature 
is  too  great,  behind  it  when  the  horizontal  curvature  is  excessive. 
The  two  limbs  of  a  cross  or  the  two  hands  of  a  clock  when  they  are 
at  right  angles  to  each  other  cannot  be  seen  distinctly  at  the  same 
time,  although  they  can  be  successively  focussed.  The  condition 
may  be  corrected  by  glasses  which  are  segments  of  cylinders  cut 
parallel  to  the  axis  (Practical  Exercises,  p.  1105). 

The  Ophthalmoscope. — The  pupil  of  the  normal  eye  is  dark,  and 
the  interior  of  the  eye  invisible,  without  special  means  of  illu- 
minating it.  But  this  is  not  because  all  the  light  that  falls  upon  the 
fundus  is  absorbed  by  the  pigment  of  the  choroid,  for  even  the  pupil 
of  an  albino  appears  dark  when  the  eye  is  covered  by  a  piece  of 
black  cloth  with  a  hole  in  front  of  the  pupil.  The  explanation  is 
as  follows : 

Let  the  rays  from  a  luminous  point,  P,  be  focussed  by  the  lens, 
L,  at  P'  (Fig.  429).  It  is  plain  that  rays  proceeding  from  F  will 
exactlv  retrace  the  path  of  those  from  P  and  be  focussed  at  P. 
Now,  the  eye  receives  rays  from  all  directions,  and,  when  it  is 


1032 


THE  SENSES 


sufficiently  well  illuminated,  sends  rays  out  in  all  directions.  The 
moment,  however,  that  the  observing  eye  is  placed  in  front  of  the 
observed  eye,  the  latter  ceases  to  receive  light  from  the  part  of  the 
field  occupied  by  the  pupil  of  the  former,  and  therefore  ceases  to 
reflect  light  into  it. 

This  difficulty  is  avoided  by  the  use  of  an  ophthalmoscopic 
mirror.     The  original,  and  theoretically  the  most  perfect,  form  of 

such  a  mirror  is  a  plate, 
or  several  superposed 
plates,  of  glass,  from  which 
a  beam  of  light  from  a 
laterally  placed  candle  or 
lamp  is  reflected  into  the 
observed  eye,  and  through 
Fig.  429.  which  the  eye  of  the  ob- 

server looks  (Fig .  430). 
But  the  illumination  thus  obtained  is  comparatively  faint;  and  a 
concave  mirror  is  now  generally  used.  In  the  centre  is  a  small 
hole  or  a  small  unsilvered  portion  of  the  mirror  for  the  observer's 
eye.  In  the  direct  method  of  examination  (Fig.  432),  the  mirror 
is  held  close  to  the  observed  eye,  and  an  erect  virtual  image  of 


I-ig.  430. — Figure  to  illustrate  the  Principle  of  the  Ophthalmoscope.  Rays  of  light 
from  a  point  are  reflected  by  a  glass  plate  M  (several  plates  together  in  Helm- 
holtz's  original  forin)  into  the  observed  eye  E*.  Their  focus  would  fall,  as  shown 
in  the  figure,  at  P,  a  little  behind  the  retina  of  E^.  The  portion  of  the  retina 
AB  is  therefore  illuminated  by  diffusion  circles;  and  the  rays  from  a  point  of 
it  I""  will,  if  El  is  emmetropic  and  unaccommodated,  issue  parallel  from  F.^  and 
be  brought  to  a  focus  at  F*  on  the  retina  of  the  (emmetropic  and  unaccommo- 
dated) observing  eye  E. 

the  fundus  is  seen.  When  the  eye  of  the  observer  and  of  the 
patient  are  both  emmetropic,  and  both  eyes  are  unaccommodated, 
the  rays  of  light  proceeding  from  a  point  of  the  retina  of  the 
observed  eye  are  rendered  parallel  by  its  dioptric  media,  and  are 
again  brought  to  a  focus  on  the  observer's  retina. 

If  the  observed  eye  is  myopic,  the  rays  of  light  coming  from 


VISION 


1033 


a  point  of  the  retina  leave  the  eye,  even  when  it  is  unaccommo- 
datecl,  as  a  convergent  pencil;  and  the  emmetropic  non-accom- 
modated eye  of  the  observer  must  have  a  concave  lens  placed 
before  it  in  order  that  the  fundus  may  be  distinctly  seen. 

When  the  observed  eye  is  hyper- 
metropic, the  rays  emerging  from  the 
unaccommodated  eye  are  divergent, 
and  a  convex  lens,  the  strength  of 
which  is  proportional  to  the  amount 
of  hypermetropia,  must  be  placed 
before  the  observer's  unaccommo- 
dated eye  if  he  is  to  see  the  fundus 
distinctly.  By  accommodating,  the 
observer  can  see  the  fundus  clearly 
without  a  convex  lens. 

By  this  method  errors  of  refraction 
in  the  eye  may  be  detected  and 
measured.  The  observer  must  always 
keep  his  eye  unaccommodated,  and 
if  it  is  not  emmetropic,  he  must 
know  the  amount  of  his  short-  or 
long-sightedness  —  i.e.,  the  strength 
and  sign  of  the  lens  needed  to  correct 
his   defect    of   refraction,    and    must 

allow  for  this  in  calculating  the  defect  of  his  patient.  Non- 
accommodation  of  the  eye  of  the  latter  can  always  be  secured  by 
the  use  of  atropine. 


Fig  43>- 


May's  Electric  Ophthal- 
moscope. 


Fig.  432. — Direct  Method  of  using  the  Ophthalmoscope.  Light  falling  on  the  per- 
forated concave  mirror  M  passes  into  the  observed  eye  E' ;  and,  both  E'  and  the 
observing  eye  E  being  supposed  emmetropic  and  unaccommodated,  an  erect 
virtual  image  of  the  illuminated  retina  of  E'  is  seen  by  E. 

By  the  direct  method  of  ophthalmoscopic  examination,  only  a 
small  portion  of  the  retina  can  be  seen  at  a  time,  and  this  is  highly 
magnified.  A  larger,  though  less  magnified,  view  can  be  got  by 
the  indirect  method.     The  observed  eye  is  illuminated  as  before, 


1034  THE  SENSES 

but  the  mirror  and  the  observer's  eye  are  at  a  greater  distance 
(Fig.  435).  Here  the  rays  from  a  considerable  portion  of  the 
retina  are  brought  to  a  focus  by  a  convex  lens  held  near  the  eye 
of  the  patient,  so  as  to  form  a  real  and  inverted  aerial  image  of  the 


Fig.  433. — Use  of  the  Ophthalmoscope  (Direct  Method)  for  testing  Errors  of  Re- 
fraction in  Myopic  Eye.  Rays  issuing  from  a  point  of  the  retina  of  E',  the 
observed  (myopic  and  unaccommodated)  eye,  pass  out,  not  parallel,  but  con- 
vergent. They  will  therefore  be  focussed  in  front  of  the  retina  of  the  observing 
(unaccommodated)  eye  E  if  the  latter  is  emmetropic.  By  introducing  a  concave 
lens  L  of  suitable  strength,  however,  a  clear  view  of  the  retina  of  E'  will  be 
obtained,  and  the  strength  of  this  lens  is  the  measure  of  the  amount  of  myopia. 

retina.     This  image  is  viewed  by  the  observer  at  his  ordinary  visual 
distance.     It  is  not  necessary  in  this  method  that  the  observed 

eye  should  be  non-accommodated,  although  it  is  convenient  as  in 


Eig.  4.34.  Testing  Errors  of  Refraction  in  Hypermetropic  Eye.  Rays  from  a  point 
of  the  retina  of  E',  the  observed  eye,  issue  divergent,  and  are  focussed  behind 
the  retina  of  the  observing  (unaccommodated  and  emmetropic)  eye  E.  The 
strength  of  the  convex  lens  L,  which  must  be  introduced  in  front  of  E  to  give 
clear  vision  of  the  retina  of  E',  measures  the  degree  of  hypermetropia. 

the  direct  method  to  cause  dilatation  of  the  pupil  by  atropine,  which 
also  relaxes  the  accommodation  (Practical  Exercises,  p.  II08). 

Skiascopy. — To  a  great  extent  the  oplithalmoscopic  method  of 
measuring  errors  of  refraction  has  been  replaced  by  the  more  modern 


VISION 


»035 


method  of  skiascopy  (shadow  test).  It  depends  upon  the  following 
observation:  When  one  throws  light  from  a  little  distance  with  a 
concave  mirror  into  an  observed  eye  and  then  rotates  the  mirror 
slowly  aroimd  the  long  axis  of  the  liandle,  one  sees  that  the  pupil, 
which  at  hrst  was  completely  illuminated,  becomes  dark  from  one 
side  as  if  covered  by  a  shadow.  This  shadow  will  move  in  the  same 
direction  in  which  the  mirror  is  rotated  or  in  the  opposite  direction, 
accorchng  to  whether  the  observer  is  farther  from  the  observed  eye 
than  its  far-point,  or  between  the  eye  and  the  far-point.  If  the 
observer  is  exactly  at  tiie  far-point,  no  direction  of  movement  of 
the  shadow  can  be  made  out,  but  the  pupil  in  its  whole  extent  is 


Fig.  435. — Indirect  Method  of  using  the  Ophthalmoscope.  The  rays  of  light  issuing 
from  E',  the  observed  eye,  are  focussed  by  the  biconvex  lens  L,  and  a  real  inverted 
image  of  a  portion  of  the  retina  of  E',  magnified  four  or  five  times,  is  formed  in 
the  air  between  the  lens  and  the  observing  eye  E.  This  image  is  viewed  by  E 
at  the  ordinary  distance  of  distinct  vision  (10  to  12  inches).  (The  exaggeration 
of  the  size  of  the  mirror  makes  it  appear  as  if  some  of  the  rays  from  the  lamp 
passed  through  the  lens  before  being  reflected  from  the  mirror.  This  would  not 
be  the  case  in  an  actual  observation.) 


either  illuminated  or  altogether  dark.  In  this  way  the  distance 
of  the  far-point  of  a  myopic  eye  can  be  easily  determined  by  a 
metre  rule,  and  from  this  the  degree  of  myopia.  If  the  far-point 
is  either  too  near,  as  in  strong  myopia,  or  too  distant,  as  in  weak 
myopia  and  emmetropia,  or  behind  the  observed  eye,  as  in  hyper- 
metropia,  it  can  be  brought  to  a  convenient  distance  by  interposing 
suitable  lenses.  The  observer  then  determines  the  far-point  exactly 
by  moving  his  eye  nearer  to  or  farther  from  the  observed  eye, 
or,  keeping  his  own  eye  fixed,  by  bringing  the  far-point  of  the 
observed  eye  to  coincide  with  it  by  inserting  lenses  (Practical 
Exercises,  pp.  1109,  iiio). 


1036 


THE  SENSES 


The  phenomenon  depends  upon  the  interruption  wliich  the  liglit  pro- 
ceeding from  the  observed  retina  experiences  first  at  the  margin  of  the 
pupil  of  the  observed  eye,  and  then  at  the  margin  of  the  hole  in  the 
mirror  or  of  the  observer's  pupih  When  the  mirror  is  rotated,  an  illu- 
minated point  of  the  observed  retina  will  move  in  the  opposite  direction 
over  the  retina.*  The  light  proceeding  from  this  point  when  the 
observed  eye  is  emmetropic  is  so  refracted  by  the  lens  and  cornea  that 
it  leaves  the  eye  as  a  bundle  of  parallel  rays  in  the  direction  of  the 
image  of  the  source  of  light  (L')  (Fig.  43^).  If  the  image  of  the  flame 
reflected  by  the  mirror  is  situated  on  the  principal  axis  of  the  observer's 
eye,  and  if  the  pupils  of  observed  and  observer  are  of  equal  size,  all 
the  rays  coming  from  the  observed  retina  will  fall  on  the  observer's 
retina,  and  therefore  the  whole  pupil  of  the  observed  eye  will  appear 
light.  If  the  mirror  is  now  rotated  so  that  the  image  of  the  source  of 
light  moves  away  from  the  principal  axis,  and  the  illuminating  rays  are 
no  longer  in  that  axis,  the  illuminated  point  will  move  in  the  opposite 
direction  from  the  principal  axis,  and  the  light  returning  from  the  pupil 
of  the  observed  eye  will  again  issue  in  the  direction  of  the  image  of  the 


Fig.  436. — Path  of  Rays  in  Skiascopy  (Snellen).  U,  observed  eye;  Be,  eye  of  ob- 
server; Sp,  mirror;  /.,  source  of  light;  /-',  image  of  the  source  of  light;  A,  A', 
principal  axis;  P.  I",  pupils. 

source  of  light.  It  can  then  happen  that  none  of  the  rays  hit  the 
observer's  pupil,  and  the  observed  pupil  will  appear  entirely  dark.  Or 
the  direction  of  the  rays  may  be  such  tliat  a  portion  of  them  enters  the 
observer's  pupil,  the  rest  being  interrupted  by  its  border.  In  this  case 
the  part  of  the  observed  pupil  from  which  rays  enter  the  observer's 
pupil  will  appear  light,  while  the  rest  is  dark.  From  Fig.  436  it  can  be 
seen  that  the  light  part  of  the  observed  pupil  is  on  the  opposite  side  of 
the  principal  axis  from  the  image  of  the  source  of  light.  If,  therefbrc, 
the  image  of  the  source  of  light  moves  to  the  riglit  (by  rotation  of  a 
concave  mirror  to  the  right,  or  rotation  of  a  plane  mirror  to  the  left) 
the  skiascopic  appearance  in  the  observed  pupil  moves  to  the  left — i.e., 
in  the  opposite  direction  to  the  image  of  the  source  of  light. 

If  the  observed  pupil  is  myopic — i.e.,  if  its  far-point  is  between  the 
observer  and  the  observed  eye,  rotation  of  the  mirror  so  far  from  the 
jirincipal  axis  that  only  a  part  of  the  rays  issuing  from  the  observed 
pupil  enter  the  observer's  eye,  will  cause  the  pupil  to  appear  light  only 

•  When  a  concave  mirror  is  rotated  to  the  right,  the  inverted  real  mirror 
image  also  moves  to  the  right,  and  the  illuminated  point  to  the  left.  When 
a  plane  mirror  is  rotated  to  the  right,  the  virtual  mirror  image  moves  to  tho 
left,  and  the  illuminated  point  on  the  retina  therefore  to  the  right. 


VISION 


to37 


on  oaie  side,  and  on  account  of  the  crossing  of  the  rays  this  illuminated 
portion  will  be  on  the  same  side  of  the  principal  axis  as  the  image  ol 
the  source  of  light  (Fig.  437).  When  the  image  of  the  source  of  light  is 
moved  to  the  right  the  light  area  of  the  observed  pupil  will  also  move 
to  the  right — i.e..  with  rotation  of  a  concave  mirror  in  the  same  direction 
as  the  image  of  the  source  of  light,  and  with  rotation  of  a  plane  mirror 
in  the  opposite  direction  (Snellen). 

A  method  of  photographing  the  retina  in  the  living  eye  has  also  been 
employed  as  a  means  of  investigating  the  fundus. 

Single  Vision  with  Both  Eyes — Diplopia. — Scheiner's  experiment  shows 
that  it  is  possible  to  have  double  vision,  or  diplopia,  with  a  single  eye 
when  two  separate  images  of  the  same  object  fall  upon  different  parts 
of  the  retina.  In  vision  with  both  eyes,  or  binocular  vision,  an  image 
of  every  object  looked  at  is,  of  course,  formed  on  each  retina,  and  we 
have  to  inquire  how  it  is  that  as  a  rule  these  images  are  blended  in 
consciousness  so  as  to  produce  the  perception  of  a  single  object;  and 


A- 


Fig-  437-- 


-Path  of  Rays  in  Skiascopy  (Myopic  Eye)  (Snellen).     PR,  far -point  ol 
observed  eye.     The  otber  references  are  as  in  Fig.  436. 


how  it  is  that  under  certain  conditions  this  blending  does  not  take 
place,  and  diplopia  results.  Two  chief  theories  have  been  invoked  in 
the  attempt  to  answer  these  questions:  (i)  the  theory  of  identical 
points,  (2)  the  theory  of  projection. 

In  regard  to  the  second  theory,  we  shall  merely  say  that  it  assumes 
that  in  some  way  or  other  the  retina,  or,  rather,  the  retino-cerebral 
apparatus,  has  the  power  of  appreciating  not  only  the  shape  and  size 
of  an  image,  but  also  the  direction  of  the  rays  of  light  which  form  it, 
and  that  the  position  of  the  object  is  arrived  at  by  a  process  of  mental 
projection  of  the  image  into  space  along  these  directive  lines.  Where 
the  directive  lines  of  the  two  eyes  cut  each  other,  the  two  images  coin- 
cide, and  the  object  is  seen  single  in  the  position  of  the  point  of  inter- 
section.    The  first  theory  we  shall  examine  in  some  detail. 

The  Theory  of  Identical  Points. — This  theory  assumes  that  every 
point  of  one  retina  '  corresponds  '  to  a  definite  point  of  the  other  retina, 
and  that  in  virtue  of  this  correspondence,  either  by  an  inborn  necessity 
or  from  experience,  the  mind  refers  simultaneous  impressions  upon  two 
corresponding  or  identical  points  to  a  single  point  in  external  space. 
If  we  imagine  the  two  retinas  in  the  position  which  the  eyes  occupy 
when  fixing  an  infinitely  distant  object — that  is,  with  the  visual  axes 
parallel — to  be  superposed,  with  fovea  over  fovea,  ever)-'  point  of  the 
one  retina  will  be  covered  by  the  corresponding  point  of  the  other 
retina,  so  that  identical  points  could  be  pricked  through  with  a  needle. 


,oj8  THE  SENSES 

But  since  the  actual  centre  of  the  retina  docs  not  corrcsjKind  with  the 
fovea  centralis  ^Fig.  416J.  but  lies  nearer  tlie  nasal  side,  the  nasal  edge 
of  the  left  retina  will  overlap  the  temporal  edge  of  the  right,  and  the 
nasal  edge  of  the  right  will  overlap  the  temporal  edge  of  the  left;  so 
that  a  part  of  each  retina  has  no  corresponding  points  in  the  other. 

The  adherents  of  this  theorj^  claim,  and  with  justice,  that  a  small 
object  so  situated  that  its  image  must  be  formed  on  corresponding 
points  of  the  two  retinae  does,  as  a  rule,  appear  single,  and,  what  is  even 
more  striking,  that  a  phosphene,  or  luminous  ring  produced  by  pressing 
the  blunt  end  of  a  pencil  or  the  finger-nail  on  a  point  of  the  globe  of  one 
eye  (which  Newton  compared  to  the  circles  on  a  peacock's  tail),  is  not 
doubled  by  pressure  over  the  corresponding  point  of  the  other  eye. 
although  two  circles  are  seen  when  pressure  is  made  upon  points  which 
do  not  correspond.  If  in  rotating  the  eyes  one  eye  is  prevented  by 
pressure  with  the  finger  from  following  the  movement  of  the  other, 
there  is  double  vision.  When  strabismus  or  squinting  is  produced  by 
paralysis  of  the  third  (p.  924)  or  the  sixth  cranial  nerve  (p.  g2t)),  it  is 
accompanied  by  diplopia,  until  in  course  of  time  the  mind  icams  to 
disregard  one  of  the  images.  In  some  cases  of  squint  the  double  images 
are  never  completely  suppressed,  but  a  new  abnormal  form  of  visual 
localization  is  developed,  which,  however,  ver\'  seldom  pemiits  any 
accurate  judgment  of  depth.  In  strabismus  it  is  obvious  that  the  two 
images  of  an  object  cannot  fall  on  corresponding  points. 

But  it  is  also  a  fact  that,  under  certain  conditions,  images  situated 
on  corresponding  points  may  not,  and  that  images  not  situated  on 
corresponding  points  may,  give  rise  to  a  single  impression.  For  ex- 
ample, if  one  of  the  closed  ej'es  be  held  slightly  out  of  its  ordinary' 
position  by  the  finger,  pressure  on  identical  points  of  the  two  eyes  gives 
rise  to  two  separate  phosphenes.  And  some  of  the  phenomena  of  stere- 
oscopic vision  (p.  1039)  show  clearly  that  images  falling  on  points  not 
strictly  corresponding  may  give  a  single  impression;  while  we  do  not 
habitually  see  double,  although  it  is  certain  that  the  images  of  multi- 
tudes of  objects  are  constantly  falling  on  points  of  the  retinae  not  ana- 
tomically '  identical.'* 

The  question  therefore  arises.  How  is  it  that  we  do  not  see  these 
double  images?  This  is  one  of  the  difficulties  of  the  theory-  of  identical 
points.  The  following  is  a  partial  explanation:  (i)  The  images  of 
objects  in  the  portion  of  the  field  most  distinctly  seen — that  is,  the 
portion  in  the  immediate  neighbourhood  of  the  intersection  of  the 
visual  lines,  or  the  part  to  which  the  gaze  is  directed — are  formed  on 
identical  points;  and  by  rapid  movements  the  eyes  fix  successively 
different  parts  of  the  field  of  view.  (2)  Vision  grows  less  distinct  as 
we  pass  out  from  the  centre  of  the  retina,  and  we  are  accustomed  to 
neglect  the  blurred  peripheral  images  in  comparison  with  those  formed 

•  In  every  fixed  position  of  the  eyes,  the  objects  whose  images  fall  on 
corresponding  points  will  be  arranged  on  certain  definite  lines  or  surfaces 
which  varv  with  the  direction  of  the  visual  axis  and  to  which  the  name  of 
horopter,  or  point-horopter,  has  been  gi\cn.  I"or  most  eyes  when  directed 
to  the  horizon — that  is,  with  the  visual  axes  parallel — the  horopter  is  practi- 
callv  the  horizontal  plane  of  the  ground,  so  that  all  objects  within  the  field 
of  vision,  and  resting  on  the  ground,  fall  upon  corresponding  points,  and  are 
seen  single.  When  the  eyes  are  directed  to  a  point  at  such  a  distance  that 
the  lines  of  vision  are  sensibly  convergent,  the  horopter  consists  (i)  of  a 
straight  line  dra^^'n  through  the  fixing-point  and  at  right  angles  to  a  plane 
passing  through  the  fixing-point  and  the  two  visual  lines  (visual  plane) ;  (2)  of 
a  circle  passing  through  the  fixing-point  and  the  nodal  points  of  the  two  eyes 
(the  famous  horopteric  circle  of  Miiller). 


VISION 


16.^0 


on  the  fovea.  (3)  When  the  images  of  an  object  do  not  fall  on  identical 
points,  one  of  the  points  on  which  they  flo  fail  may  be  occupied  with 
the  images  of  other  objects,  some  of  which  may  be  so  boldly  marked 
as  to  enter  into  conflict  with  the  extra  image  and  to  suppress  it. 
(4)  Lastly,  the  physiological  '  identical  po'v.t '  is  not  a  geometrical 
j)oint,  but  an  area  which  increases  in  size  in  xm  more  peripheral  zones 
of  the  retina,  and  can  also  be  increased  by  practice;  and  images  which 
lie  wholly  or  in  chief  part  within  two  corresponding  areas  practically 
coincide. 

Stereoscopic  Vision. — ^Although  the  retinal  image  is  a  projection  of 
external  objects  on  a  surface,  we  perceive  not  only  the  length  and 
breadth,  but  iilso  the  depth  or  solidity  of  the  things  we  look  at.  When 
we  look  directly  at  the  front  of  a  build- 
ing, the  impression  as  to  its  form  is  the 
same  whether  one  or  both  eyes  be  used, 
although  with  a  single  eye  its  distance 
cannot  be  judged  so  accumtely.  But 
when  we  view  the  building  from  such  a 
position  that  one  of  the  corners  is  visible, 
we  obtain  a  more  correct  impression  of 
its  depth  with  the  two  eyes.  This  is 
partly  due  to  the  fact  that  to  fix  points 
at  different  distances  from  the  eyes  the 
visual  lines  must  be  made  to  converge 
more  or  less,  and  of  the  amount  of  this 
convergence  we  are  conscious  through 
the  contraction  of  the  muscles  which 
regulate  it.  But  there  is  another  element 
involved.  When  the  two  eyes  look  at  a 
uniformly -coloured  plane  surface,  the 
retinal  image  is  precisely  the  same  in 
both.  But  when  the  two  eyes  are 
directed  to  a  solid  object  (say  a  book 
lying  on  a  table)  the  picture  formed  on 
the  left  retina  differs  slightly  from  that 
formed  on  the  right,  for  the  left  eye  sees 
more  of  the  left  side  of  the  book,  and 
the  right  eye  more  of  the  right  side. 

That  there  is  a  close  connection  be- 
tween uniformity  of  retinal  images  and 
impression  of  a  plane  surface  on  the  one 
hand,  and  difference  of  retinal  images  and 
impression  of  solidity  on  the  other,  is 
proved  by  the  facts  of  stereoscopy.  It 
is  evident  that  if  an  exact  picture  of  the  solid  object  as  it  is  seen  by 
each  eye  can  be  thrown  on  the  retina,  the  impression  produced  will 
be  the  same,  whether  these  images  are  really  formed  by  the  object 
or  not.  Now,  two  such  pictures  can  be  produced  with  a  near  approach 
to  accuracy  by  photographing  the  object  from  the  point  of  \iew  of 
each  eye.  It  only  remains  to  cast  the  image  of  each  picture  on  the 
corresponding  retina,  while  the  eyes  are  converged  tc  the  same  extent 
as  would  be  the  case  if  they  were  viewing  the  actual  object.  This  is 
accomplished  by  means  of  a  stereoscope  (Fig.  438). 

It  is  found  that  the  resultant  impression  is  that  of  the  solid  object. 
It  is  impossible  to  reconcile  this  with  the  doctrine  of  strictly  identical 
geometrical  points.  A  pair  of  identical  pictures  gives  with  the  stere- 
oscope not  the  impression  of  a  solid,  but  of  a  plane  surface.     If  the 


Fig.  438. — Brewster's  Stereoscope. 
p  and  TT  are  prisms,  with  their  re- 
fracting angles  turned  towards 
each  other.  The  prisms  refract 
the  rays  coming  from  the  points 
c,  7  of  the  pictures  ab  and  a^  so 
that  they  appear  to  come  from  a 
single  point  q.  Similarly,  the 
points  a  and  <t>  appear  to  be  situ- 
ated at/,  and  the  points  b  and  /3, 
at  a. 


ro40  THE  SENSES 

relative  position  of  any  two  points  differs  in  the  two  pictures,  the 
blended  picture  has  a  corresponding  point  in  relief.  So  great  is  the 
delicacy  of  this  test  that  a  good  and  a  bad  banknote  will  not  blend 
under  the  stereoscope  to  a  flat  surface,  and  the  method  may  be  actually 
used  for  the  detection  of  forgery. 

When  the  pictures  are  interchanged  in  the  stereoscope  so  that  the 
image  which  ought  to  be  formed  on  the  right  retina  falls  on  the  left,  and 
that  which  is  intended  for  the  left  eye  falls  on  the  right,  what  were 
projections  before  become  hollows,  and  what  were  hollows  stand  out 
in  relief.  The  pseudoscope  of  Wheatstone  is  an  arrangement  by  which 
each  eye  sees  an  object  by  reflection,  so  that  the  images  which  would  be 
formed  on  the  two  retinae,  if  the  object  were  looked  at  directly,  are  inter- 
changed, with  the  same  reversal  of  our  judgments  of  relief. 

Visual  Judgments.^ — We  say  judgments  of  relief;  for  what  we  call 
seeing  is  essentially  an  act  that  involves  intellectual  processes.  As  the 
retina  is  anatomically  and  developmentally  a  projection  of  the  brain 
pushed  out  to  catch  the  waves  of  light  which  beat  in  upon  the  organism 
from  every  side,  so,  physiologically,  retina,  optic  nerve,  and  visual 
nervous  centre  are  bound  together  in  an  indissoluble  chain.  W^e 
cannot  say  that  the  retina  sees,  we  cannot  say  that  the  optic  nerve 
sees — the  optic  nerve  in  itself  is  blind — we  cannot  say  that  the  \-isual 
centre  sees.  The  ethereal  waves  falling  on  the  retina  set  up  impulses 
in  it  which  ascend  the  optic  nerve;  certain  portions  of  the  brain  are 
stirred  to  action,  and  the  resulting  sensations  of  light  springing  up,  we 
know  not  where,  are  elaborated,  we  know  not  how  (by  processes  of 
which  we  have  not  the  faintest  guess),  into  the  perception  of  what  we 
call  external  objects — trees,  houses,  men,  parts  of  our  own  bodies,  and 
into  judgments  of  the  relations  of  these  things  among  themselves,  of 
their  distance  and  movements. 

A  child  leams  to  see,  as  it  learns  to  speak,  by  a  process,  often  un- 
conscious or  subconscious,  of  '  putting  two  and  two  together.'  The 
musical  sounds  united  and  terminated  by  noises  which  make  up  the 
spoken  word  '  apple  '  are  gradually  associated  in  its  mind  with  the 
visual  sensation  of  a  red  or  green  object,  the  tactile  sensation  of  a 
smooth  and  round  object,  and  the  gustatory  and  olfactor^^  sensations 
which  we  call  the  taste  or  flavour  of  an  apple.  And  as  it  is  by  ex- 
perience that  the  child  leams  to  label  this  bundle  of  sensations  with  a 
spoken,  and  afterwards  with  a  written,  name,  so  it  is  by  experience 
that  it  learns  to  group  the  single  sensations  together,  and  to  make  the 
induction  that  if  the  hand  be  stretched  out  to  a  certain  distance  and  in 
a  certain  direction — i.e,  if  various  muscular  movements,  also  associated 
with  sensations,  be  made — the  tactile  sensation  of  grasping  a  smooth 
round  body  will  be  felt,  and  that  if  the  further  muscular  movements 
involved  in  conveying  it  to  the  mouth  be  carried  out,  a  sensation  agree- 
able to  the  youthful  palate  will  follow.  At  length  the  child  comes  to 
believe,  and,  unless  he  happens  to  be  specially  instructed,  carries  his 
belief  with  him  to  his  grave,  that  when  he  looks  at  an  apple  he  sees  a 
round,  smooth,  tolerably  hard  body,  of  definite  size  and  colour;  while 
in  reality  all  that  the  sense  of  sight  can  inform  him  of  is  the  difference 
in  the  intensity  and  colour  of  the  light  falling  on  his  retina  when  he 
turns  his  head  in  a  particular  direction. 

An  interesting  illustration  of  the  role  of  experience  in  shaping 
our  visual  judgments  is  found  in  the  sensations  of  persons  born 
blind  and  relieved  in  after-life  by  operation.  A  boy  between 
thirteen  and  fourteen  years  of  age,   operated  on  by  Cheselden, 


VISION 


1041 


thouglit  all  the  objects  he  looked  at  touched  his  eyes.  He  forgot 
which  was  the  dog  and  wliieli  the  cat,  but  catching  the  cat  (which 
he  knew  by  feeling),  lie  looked  at  her  steadfastly  and  said,  "  So, 
puss,  I  shall  know  you  another  time."  Pictures  seemed  to  him  only 
parti-coloured  planes;  but  all  at  once,  two  months  after  the  opera- 
tion, he  discovered  they  represented  solids.'  Nunnely,  perhaps 
renuMubeiing  the  dictum  of  Diderot,  that  '  to  prepare  and  interro- 


Fig.  439. — Illusion  of  Parallel  Lines  (Hering). 

gate  a  person  born  blind  would  not  have  been  an  occupation  un- 
worthy of  the  united  talents  of  Newton,  Des  Cartes,  Locke,  and 
Leibnitz,'  made  an  elaborate  investigation  in  the  case  of  a  boy  nine 
years  old,  on  whom  he  operated  for  congenital  cataract  of  both  eyes, 
and,  what  is  of  special  importance,  instituted  a  set  of  careful 
experiments  and  interrogations  before  the  operation,  so  as  to  gain 
data  for  comparison.  Objects  (cubes  and  spheres)  which  before 
the  operation  he  could  easily  recognize  by  touch  were  shown  hiim 
afterwards,     but     al- 


xmxmxmxm 


though  '  he  could  at 
once  perceive  a  differ- 
ence in  their  shapes, 
he  could  not  in  the 
least  say  which  was 
the  cube  and  which 
the  sphere.'  It  took 
several  days,  and  the 
objects  had  to  be 
placed  many  times  in 
his  hands  before  he 
could    tell    them    by 

the  eye.  '  He  said  everything  touched  his  eyes,  and  walked  most 
carefully  about,  with  his  hands  held  out  before  him  to  prevent 
things  hurting  his  eyes  by  touching  them.' 

Many  other  illustrations  might  be  given  of  the  fact  that  '  seeing  ' 
is  largely  an  act  of  reasoning  from  data  which  may  sometimes 
mislead.  Thus  in  Figs.  439  and  440  the  long  horizontal  lines  are 
really  parallel,  but  do  not  appear  so  owing  to  the  confusion  of 
judgment  produced  bv  the  short  sloping  lines.  In  Fig.  441  the 
spaces  covered  by  A,  B,  and  C  are  equal  squares,  but  A  appears 

66 


Fig.  4(o. — Illusion  of  Parallel  Lines  (Zollner). 


I042 


THE  SENSES 


<"     > 


taller  than  H,  and  C  smaller  than  either  A  or  B.  In  the  same 
figure  the  lines  D  and  E  are  of  the  same  length,  but  E  seems  con- 
sitlerablv  longer  than  D. 

Illusions  of  movement  are  among  the  most  interesting  optical 
illusions.  If  two  similar  objects  are  momentarily  shown  to  the 
eye  in  rapid  succession  and  at  points  in  space  not  separated  by  too 
great  a  distance,  the  illusion  is  produced  that  the  first  object  has 
moved  to  the  position  of  the  second.  Such  illusions  are  the  basis 
of  the  so-called  '  moving  pictures  '  shown  by  the  cinematograph. 
A  series  of  instantaneous  photographs  of  a  movement  are  taken, 
recording  the  successive  positions  assumed  by  the  moving  body. 
When  these  are  thrown  on  the  retina  in  the  same  order  and  in  rapid 
succession,  an  illusion  of  the  original  movement  is  produced. 

The  apparent  size  and  form  of  an  object  is  intimately  related  to 
the  size,  form,  and  sharpness  of  its  image  on  the  retina.     We  are, 

therefore,  able  to  dis- 
A  t  C  criminate  with  great 

precision      the     un- 
stimulated from  the 
excited    portions   of 
that   membrane,   es- 
peciallv  in  the  fovea 
centralis,     and    also 
the  degree  of  excita- 
tion of  neighbouring 
excited    parts.     But 
instead  of  localizing  the  image  on  the  retina  as  we  localize  on  the 
skin  the  pressure  of  an  object  in  contact  with  it,  we  project  the 
retinal  image  into  space,  and  see  everything  outside  the  eye. 

In  vision,  in  fact,  we  have  no  conception  of  the  existence  of  either 
retina  or  retinal  image;  and  even  the  shadows  of  objects  within  the 
eye — for  instance,  an  opacity  or  a  foreign  body  in  any  of  the  refractive 
media — are  referred  to  points  outside  it.  Generally  opacities  in  the 
vitreous  humour  are  movable,  in  the  lens  not. 

Purkinje's  Figures. — As  was  first  pointed  out  by  Purkinje,  the 
shadows  of  the  bloodvessels  in  the  retina  itself,  and  even  of  the 
corpuscles  circulating  in  them,  although  neglected  in  ordinary 
vision,  may  be  recognized  under  suitable  conditions,  a  conclusive 
proof  that  the  sensitive  layer  must  lie  behind  the  vessels. 

If  a  beam  of  sunlight  is  concentrated  on  the  sclerotic  as  far  as  possible 
from  the  margin  of  the  cornea,  and  the  eye  directed  to  a  dark  ground, 
the  network  of  retinal  bloodvessels  will  stand  out  on  it.  Another 
method  is  to  look  at  a  dark  ground  while  a  lighted  candle,  held  at  one 
side  of  the  eve  at  a  distance  from  the  visual  line,  is  moved  .slightly  to 
and  fro.  In  the  first  method,  a  point  of  the  sclerotic  behind  the  lens 
is  illuminated,  and  rays  passing  from  it  across  the  interior  of  the  eyeball 
in  every  direction  cast  shadows  of  the  vessels  of  the  retina  on  its  sensi- 


-< 


Fig.  441. — Illusions  of  Space-Perception. 


VISION 


1043 


tive  layer.  In  the  second  metliod,  the  image  of  the  flame  formed  on 
the  retina  by  rays  falling  obliquely  through  the  pupil  becomes  in  the 
general  darkness  itself  a  source  of  light,  by  interrupting  the  rays  from 
which  the  retinal  vessels  form  sliadows.  The  distance  of  the  sensitive 
from  the  vascular  layer  may  be  approximately  calculated  by  measuring 
the  amount  by  which  the  shadows  change  their  position,  wlien  the 
position  of  the  illuminated  point  of  the  sclerotic  is  altered.  The  nearer 
a  vessel  lies  to  the  sensitive  layer,  the  smaller  must  be  the  angle  through 
wiiich  the  apparent  position  of  its  shadow  moves  for  a  given  move- 
ment of  the  spot  of  light.  In  this  way  it  has  been  calculated  that  the 
sensitive  layer  is  about  o-z  to  0-3  mm.  behind  the  .stratum  which  con- 
tains the  bloodvessels. 
This  corresponds  suffi- 
ciently well  with  the 
position  of  the  layer  of 
rods  and  cones,  which  all 
other  evidence  shows  to 
be  the  portion  of  the 
retina  actually  stimulated 
by  light.  The  shadows  of 
the  blood -corpuscles  in 
the  retinal  vessels  may  be 
rendered  visible  by  look- 
ing at  a  bright  and  uni- 
formly illuminated  ground, 
like  the  milk  glass  shade 
of  a  lamp  or  the  blue  skv, 
and  moving  the  slightly 
separated  fingers  or  a 
perforated  card  rapidly 
before  the  eye.  From  the 
rate  of  their  apparent 
movement,  Vierordt  cal- 
culated the  velocity  of  the 
blood  in  the  retinal  capil- 
laries at  o*5  to  0'9  mm. 
per  second.  One  reason 
why  the  shadows  of  these 
intra-retinal  structures  do 
not  appear  in  ordinary 
vision  seems  to  be  their  small  size.  The  retinal  vessels  are  in  reality 
only  vascular  threads;  the  thickest  branch  of  the  central  vein  is  not 
.js  mm.  in  diameter.  The  apex  of  the  cone  of  complete  shadow 
fumbra)  cast  by  a  disc  of  this  size,  at  a  distance  of  20  mm.  from  a  pupil 
4  mm.  wide,  would  lie  only  1  mm.  behind  the  disc — that  is  to  say,  the 
umbra  of  the  retinal  vessels  would  not  reach  the  layer  of  the  rods  and 
cones  at  all,  and  only  the  penumbra,  or  region  of  relative  darkness, 
would  fall  upon  it. 

When  the  eyes,  after  being  closed  for  some  time,  are  suddenly  opened, 
the  branches  of  the  retinal  vessels  may  be  seen  for  a  moment.  This  is 
especially  the  case  after  sleep;  and  a  good  view  of  the  phenomenon 
may  be  obtained  by  looking  at  a  white  pillow  or  the  ceiling  immediatelv 
on  awaking.  If  the  eyes  are  kept  open  for  a  few  seconds,  the  branch- 
ing pattern  fades  away;  if  they  are  only  allowed  to  remain  open  for 
an  instant,  it  may  be  seen  many  times  in  succession.  The  main  vessels 
appear  to  radiate  out  from  a  central  point.  But  their  actual  junction 
there  is  not  seen,  since  it  lies  in  the  optic  disc  or  blind  spot. 


Fig.  442. — Method  of  rendering  the  Retinal  Blood- 
vessels visible  by  concentrating  a  Beam  of  Light 
on  the  Sclerotic.  From  the  brightly-illuminated 
point  of  the  sclerotic,  a,  rays  issue,  and  a  shadow 
of  a  vessel,  v,  is  cast  at  a'.  It  is  referred  to  an 
external  point,  a",  in  the  direction  of  the  straight 
line  joining  a'  with  the  nodal  point.  When  the 
light  is  shifted  so  as  to  be  focussed  at  b,  the 
shadow  cast  at  b'  is  referred  to  b" — i.e.,  it  appears 
to  move  in  the  same  direction  as  the  illuminated 
point  of  the  sclerotic. 


I044 


THE  SENSES 


The  Blind  Spot. — The  fibres  of  tlie  optic  nerve  are  insensible  to 
light;  light  only  stimulates  them  through  their  end-organs.  This 
can  be  proved  by  directing  by  means  of  an  ophthalmoscope  a  beam 
of  light  upon  the  optic  disc,  where  the  true  retinal  layers  do  not 
exist.  The  person  experimented  on  has  no  sensation  of  light  when 
the  beam  falls  entirely  upon  the  disc;  when  its  direction  is  shifted 
so  that  it  impinges  upon  any  other  portion  of  the  retina,  a  sensation 
of  light  is  at  once  experienced.  The  blind  spot  is  not  recognized 
in  ordinary  vision,  for  (i)  the  two  optic  discs  do  not  correspond. 

The  left  disc  has  its  corre- 
sponding points  on  a  sensitive 
part  of  the  right  retina,  and 
the  right  disc  on  a  sensitive 
part  of  the  left  retina;  and  the 
consequence  is  that  in  binoc- 
ular vision  the  objects  whose 
images  are  formed  on  the  cor- 
responding points  fill  up  the 
blind  spots.  (2)  The  optic 
disc  does  not  lie  in  the  line  of 
direct,  and  therefore  distinct, 
vision.  The  eye  is  constantly 
moving  so  as  to  bring  the 
surrounding  objects  succes- 
sively on  the  fovea  centralis; 
and  the  gap  which  the  blind 
spot  makes  in  the  visual  field 
of  a  single  eye  is  thus  more 
easily  neglected.  In  any  case 
we  ought  not  to  see  it  as  a 
dark  spot,  for  darkness  is  only  associated  with  the  absence  of 
excitation  in  parts  of  the  retina  capable  of  being  excited  by  light. 
There  is  no  more  reason  why  the  optic  discs  should  appear  dark 
than  there  is  for  our  having  a  sensation  of  darkness  behind  us  when 
we  are  looking  straight  in  front.  And  since  the  experience  of  our 
other  senses — the  sense  of  touch,  for  example — tells  us  that  the 
objects  we  look  at  do  not  in  general  have  a  gap  in  the  position  corre- 
sponding to  the  part  of  the  image  that  falls  on  the  blind  spot,  we 
see,  so  to  speak,  across  the  spot. 

By  Mariotte's  experiment,  however,  the  existence  of  the  blind  spot 
can  not  only  be  demonstrated,  but  its  size  determined  and  its  bounaaries 
mapped  out.  Let  the  left  eye  be  closed,  and  fix  with  the  right  the  small 
cross;  then,  if  the  eye  be  moved  towards  or  away  from  the  paper,  keeping 
the  cross  fixed  all  the  time,  a  position  will  be  found  in  whicli  the  while 
disc  disappears  altogether.  In  this  position  its  image  falls  on  the 
blind  spot  (Fig.  444). 


Fig-  443- — Method  of  rendering  the  Blood- 
vessels of  the  Retina  visible  by  Oblique 
Illumination  through  the  Cornea.  Light 
from  a  candle  at  a  illuminates  a',  and 
rays  proceeding  from  «'  cast  a  shadow  of 
the  bloodvessel,  v,  at  a",  which  is  referred 
to  a'".  When  a  is  moved  to  b,  the 
shadow  on  the  retina  moves  to  6*,  and 
the  shadow  in  the  visual  field  of  the  illu- 
minated eye  to  b'". 


VISION 


1045 


Relation  of  the  Rods  and  Cones  to  Vision. — We  have  more  than 
once  referred  to  the  rods  and  cones  us  the  sensitive  layer  of  the 
retina.  It  is  now  necessary  to  develop  a  little  more  the  evidence 
in  favour  of  this  statement.  And  at  the  outset,  since  the  sensitive 
layer  has  been  shown  to  lie  behind  the  plane  of  the  retinal  blood- 
vessels, the  only  competitors  of  the  rods  and  cones  are  the  external 
nuclear  layer  and  the  pigmented  epithelium.  The  nuclear  layer 
may  be  at  once  excluded  as  a  separate  mechanism,  since,  as  we  have 
seen  (p.  1015),  the  portions  of  the  rod  and  cone  elements  in  it  are 
continuous  with  the  portions  in  the  layer  of  the  rods  and  cones 
proper.  In  the  fovea  centralis,  where  vision  is  most  distinct,  the 
nuclear  layer  becomes  very  thin  and  inconspicuous. 

The  layer  of  pigmented  hexagonal  cells,  or  at. least  their  pigment, 
cannot  be  essential  to  vision,  for  albino  rats,  rabbits,  and  men,  in 
whose  eyes  pigment  is  absent,  can  see.  In  man  and  most  mammals 
there  are  cones,  but  no  rods  in  the  yellow  spot  and  fovea  centralis; 
the  relative  proportion  of  rods  increases  as  we  pass  out  from  the 
fovea  towards  the  ora  serrata.     But  this  does  not  enable  us  to 


Fig.   444, — Mariotte's  Experiment. 

analyze  the  bacillary  layer  into  sensitive  cones  and  non-sensitive 
rods,  for  on  the  rim  of  the  retina,  which  is  still  sensitive  to  light, 
there  are  only  rods;  in  the  bat  and  mole  there  are  said  to  be  no 
cones  even  in  the  yellow  spot,  in  the  rabbit  very  few.  Reptiles 
possess  only  cones  over  the  whole  retinal  surface,  and  birds,  true 
to  their  reptilian  affinities,  have  every\vhere  more  cones  than  rods, 
as  have  also  fishes. 

One  of  the  difficulties  in  the  way  of  understanding  how  a  ray  of 
light  can  set  up  an  excitation  in  a  rod  or  cones  is  the  transparency 
of  these  structures.  An  absolutely  transparent  substance — that 
is,  a  substance  which  would  allow  light  to  traverse  it  without  the 
least  absorption — would,  after  the  passage  of  a  ray,  remain  in 
precisely  the  same  state  as  before;  its  condition  could  not  be 
altered  by  the  passage  of  the  light  unless  some  of  the  energy  of  the 
ethereal  vibrations  was  transferred  to  it.  But  an  absolutely  trans- 
parent body  does  not  exist  in  Nature;  and  it  is  not  necessary  to 
suppose  that  all  the  energy  required  to  stimulate  the  end-organs 
of  the  optic  nerve  comes  from  the  luminous  vibrations.  These 
may,  and  probably  do,  act  by  setting  free  energy  stored  up  in  the 


I046  THE  SENSES 

retina,  just  as  the  touch  of  a  child's  hand  could  be  made  to  fire  a 
mine,  or  launch  a  ship,  or  flood  a  province.  Some  have  looked  upon 
the  transverse  lamellae  into  which  the  outer  members  of  the  rods 
and  cones  can  be  made  to  split  as  an  arrangement  for  reflecting 
back  the  light  to  the  inner  members,  and  have  compared  them 
to  a  pile  of  plates  of  glass,  which,  transparent  as  it  is,  is  a  most 
efficient  reflector.  It  is  even  possible,  although  here  we  are  already 
treading  the  thin  air  of  pure  speculation,  that  the  light  may  be 
polarized  in  the  process  of  reflection,  and  that  the  rods  and  cones 
may  be  less  transparent  to  light  polarized  in  certain  planes  than  to 
unpolarized  light. 

As  to  the  nature  of  the  transformation  undergone  by  the  ethereal 
vibrations  in  the  rods  and  cones,  various  theories  have  been  formu- 
lated. Some  have  supposed  that  the  absorbed  light-waves  are 
transformed  into  long  heat-waves,  and  that  the  endings  of  the  optic 
nerve  are  thus  excited  by  thermal  stimuli.  This  hypothesis  has  so 
little  evidence  in  its  favour  that  it  is  perhaps  an  unjustifiable  waste 
of  time  even  to  mention  it.  It  is  ruled  out  of  court  b}'  the  mere  fact 
that  the  long  radiations  of  the  ultra  red,  filtered  from  luminous  ra3's 
by  being  passed  through  a  solution  of  iodine,  and  focussed  on  the 
eye  by  a  lens  of  rock-salt,  produce  not  the  slightest  sensation  of 
light,  although  they  are  by  no  means  all  absorbed  in  their  passage 
through  the  dioptric  media.  Again,  it  has  been  suggested  that  the 
energy  of  the  waves  of  light  is  first  transformed  into  electrical  energy, 
and  that  the  visual  stimulus  is  really  electrical.  In  support  of 
this  view  it  has  been  urged  that  the  passage  of  a  voltaic  current 
through  the  eye  causes  sensations  of  light,  and  that  light,  un- 
doubtedly, causes  (p.  839)  an  electrical  change  in  the  retina  and 
optic  nerve.  But,  as  has  more  than  once  been  pointed  out,  an 
electrical  change  is  the  token  and  accompaniment  of  the  activity 
of  the  excitable  tissues  in  general;  and  all  that  the  currents  of 
action  of  the  retina  show  is  that  light  excites  the  retina — a  proposi- 
tion which  nobody  who  can  see  requires  an  objective  proof  of,  and 
which  does  not  carry  us  very  far  towards  the  solution  of  the 
problem  how  that  excitation  is  brought  about.  Then  there  is 
the  photo-mechanical  theory,  according  to  which  the  pigmented 
epithelial  cells  of  the  retina,  altering  their  shape  and  volume  under 
the  stimulus  of  light,  press  upon  the  rods  and  cones,  and  thus 
mechanically  stimulate  them.  Lastly,  there  is  the  photo-chemical 
theory,  which  supposes  that  some  chemical  change  produced  in  the 
rods  and  cones  under  the  influence  of  light  sets  up  impulses  in  them 
which  ascend  the  optic  nerve.  This  is  the  most  probable  of  all  the 
theories,  notwithstanding  the  fact  that  the  discovery  by  Boll  of 
the  famous  visual  purple  or  rhodopsin,  wliich  at  first  seemed  likely 
to  place  it  upon  a  sure  foundation,  has  lost  its  significance  in  this 
regard.     But  although  the  visual  purple  is  not  a  photo-chemical 


VISION  io»7 

substance  throut^h  which  the  retinal  elements  are  excited  by 
luminous  stimuli,  it  seems  to  fulhl  an  important  function  in  adapt- 
ing the  retina — i.e.,  rendering  it  more  sensitive — for  vision  in  dim 
light.  In  any  case,  its  discovery  is  in  itself  so  interesting  and  so 
suggestive  as  a  basis  for  future  work,  that  a  short  account  of  the 
properties  of  the  substance  cannot  be  omitted  here. 

Visual  Purple. — If  the  eye  of  a  frog  or  rabbit,  which  has  been  kept 
in  the  dark,  be  cut  out  in  a  dimly-lighted  chamber  or  in  a  chamber 
illuminated  only  by  red  light,  and  the  retina  removed,  it  is  seen,  when 
viewed  in  ordinary  light,  to  be  of  a  beautiful  red  or  purple  colour. 
Exposed  to  bright  light,  the  colour  soon  fades,  passing  through  red  and 
orange  to  yellou-,  and  then  disappearing  altogether.  The  yellow  colour 
is  due  to  the  formation  of  another  pigment,  visual  yellow;  the  preceding 
stages  are  due  to  the  intermixture  of  this  v-isual  yellow  with  the  un- 
changed visual  purple  in  ciifterent  proportions.  With  the  microscope 
it  may  be  seen  that  the  pigment  is  entirely  confined  to  the  outer  segment 
of  the  rods,  where  it  exists  in  most  vertebrate  animals.  It  may  be  ex- 
tracted by  a  watery  solution  of  bile-salts,  and  the  properties  of  the 
pigment  in  solution  are  very  much  the  same 
as  its  properties  in  situ  ;  light  bleaches  the 
solution  as  it  does  the  retina.  Examined  w\\\\ 
the  spectroscope,  the  solution  shows  no  definite 
bands,  but  only  a  general  absorption,  which  is 
very  slight  in  the  red,  and  reaches  its  ma.xi- 
mum  in  the  yello%\T,sh-green.  In  accordance 
with  this,  it  is  found  that  of  all  kinds  of  mono- 
chromatic light  the  yellowish -green  rays  bleach 
the  purple  most  rapidly,  the  red  rays  most 
slowly. 

If  a  portion  of  the  retina  is  kept  dark  while 

the   rest   is  exposed  to  light,  onlv  the  latter     p-     ^^^      n,.f^^^,^  d-,-* 
•     -Li        u    J        4     J       i!        Jl\^     •  r     i^ig- 445- — Optogram.  Part 

portion  is  bleached.  And  when  the  image  of  ^f  retina  of  rabbit,  the 
an  object  possessing  weU-marked  contrasts  of  eye  of  which  had  been 
light  and  shadow  [e.g.,  a  glass  plate  with  strips  directed  to  an  illumin- 
of  black  paper  pasted  on  it  at  intervals,  or  a  ated  plate  of  glass  cov- 
window  with  dark  bars)  is  allowed  to  fall  on  an  ered  with  strips  of  black 
eye  otherwise  protected  from  light,  the  pattern  paper, 
of  the   object  is  picked  out  on  the  retina  in 

purple  and  white.  A  veritable  photograph  or  '  optogram  '  may  thus  be 
formed  even  on  the  retina  of  a  living  rabbit;  and  if  the  eye  be  rapidly 
excised,  the  picture  may  be  '  fixed  '  by  a  solution  of  alum,  and  thus 
rendered  permanent. 

These  facts  certainly  suggest  that  light  falling  on  the  retina  may 
cause  in  some  sensitive  substance  or  substances  chemical  changes, 
the  products  of  which  stimulate  the  endings  of  the  optic  nerve, 
and  set  up  the  impulses  that  result  in  visual  sensations. 

The  visual  purple  cannot  itself  be  such  a  substance,  for  it  is 
absent  from  the  cones  of  all  animals  and  the  rods  of  some.  Frogs 
and  rabbits  can  undoubtedly  see  at  a  time  when,  by  continued 
exposure  to  bright  sunlight,  the  purple  must  have  been  completely 
bleached.  And  although  the  alleged  absence  of  the  pigment  in 
the  eye  of  the  bat  might  seem  to  afford  a  ready  explanation  of  the 


1048  THE  SENSES 

proverbial  '  blindness  '  of  that  animal,  such  a  hasty  deduction 
would  be  at  once  corrected  by  the  fact  that  birds  with  as  sharp 
vision  as  the  pigeon  are  equally  devoid  of  visual  purple,  while  in 
other  nocturnal  animals,  like  the  owl,  it  is  plentifully  found.  The 
most  probable  hypothesis  of  the  function  of  the  visual  purple  is 
indeed  that  which  attributes  to  it  the  property,  in  virtue  of  its 
capacity  for  regeneration  in  the  dark,  of  adapting  the  eye  for  night 
or  twilight  vision — in  other  words,  of  increasing  the  sensitiveness 
of  the  retina  for  faint  light,  especially  of  the  shorter  wave-lengths. 
If  this  is  the  case,  it  is  precisely  in  nocturnal  animals  that  we  should 
expect  to  find  it  in  large  amount;  and  recently  visual  purple  has 
been  obtained  from  more  than  one  species  of  bat  (Trendelenburg). 
The  fact  that  central  vision  (p.  1058)  in  which  the  rodless  fovea  is 
concerned  is  but  little,  if  at  all,  susceptible  of  dark-adaptation, 
while  peripheral  vision  shows  a  marked  capacity  of  adaptation, 
agrees  well  with  this  hypothesis.  We  shall  see  later  that  there  is 
some  evidence  that  it  is  the  mere  perception  of  luminous  impressions 
as  such  and  of  their  intensity,  without  any  distinction  of  quality 
or  colour,  with  which  the  rods  have  to  do.  They  are,  then,  on  the 
hypothesis  under  discussion,  elements  concerned  in  achromatic 
sensations  under  conditions  of  feeble  illumination  (twilight  vision). 
The  cones  are  supposed  on  this  theory  to  be  more  highly  developed 
elements  than  the  rods,  their  function  being  connected,  especially 
with  the  perception  of  colour,  but  also  with  the  perception  of 
achromatic  sensations  under  daylight  conditions. 

The  pigmented  retinal  epithelium  is  undoubtedly  sensitive  to  light, 
and  has  important  relations  to  the  formation  of  the  visual  purple! 
When  the  eye  is  exposed  to  light,  black  pigment  migrates  along  the 
processes  of  the  epithelial  cells  between  the  rods,  even  as  far  as  the 
external  limiting  membrane.  In  the  dark  the  pigment  moves  back 
again,  and  gathers  around  the  outer  portions  of  the  rods,  where  the 
visual  purple  is  being  regenerated.  That  the  central  nervous  system 
is  not  concerned  in  the  pigment  migration,  or  at  least  that  it  is  not 
indispensable  for  it,  has  been  shown  in  the  larvsr  of  Amblystoma.  one 
of  the  tailed  amphibia.  Optic  cups  were  transplanted  to  various  parts 
of  the  body,  where  they  flcvclopcd  to  form  more  or  less  perfect  eyes. 
The  forward  movement  of  the  pigment  in  these  transplanted  eyes  when 
exposed  to  light  was  fully  as  great  as  in  the  normal  eyes.  Contraction 
of  the  cones  was  also  observed  in  them  just  as  in  the  normal  eyes.  In 
the  eye  exposed  to  the  light,  the  cones,  whose  expanded  length  is  23^ 
shortened  by  more  than  ^fi  (Laurens  and  Williams).  The  precise  mean- 
ing of  the  changes  in  the  pigmented  cells  is  obscure. 

The  pigmented  epithelium  is  known  to  be  concerned  in  the  regenera- 
tion of  the  visual  purple.  When  a  frog  is  curarizcd,  oedema  occurs 
between  the  retina  and  the  choroid,  so  that  the  former  membrane  is 
separated  from  the  hexagonal  epithelium.  If  the  frog  is  now  exposed 
to  sunlight  till  the  visual  purple  is  bleached,  and  the  retina  then  taken 
out  and  placed  in  the  dark,  no  regeneration  of  the  purple  takes  place. 
When  the  same  experiment  is  repeated  on  a  non-curarized  frog,  the 
visual  purple  is  restored  in  the  dark,  and  may  be  seen  under  the  micro- 
scope in  the  rods.  The  only  difference  in  the  two  experiments  is  that 
in  the  latter  the  pigmented  epithelium  adheres  to  the  retina,  and  it 


VISION  1049 

must  therefore  have  a  hand  in  the  regeneration  of  the  jngment.  Evcr 
thc  visual  pin-ple  of  a  retina  from  which  the  epitliehum  has  been  de- 
tached will,  after  being  bleached,  be  restored  if  the  retina  is  simply  laid 
again  on  the  ejiithelial  surface.  And  it  docs  not  seem  to  be  the  black 
pignient  of  the  hexagonal  cells  which  is  the  agent  in  this  restoration, 
for  it  takes  place  in  the  pigment-free  retina'  of  albiiKj  rabbits  or  rats. 
Even  a  retina  isolated  from  the  pigmented  epithelium,  and  then 
bleached,  may,  to  a  certain  extent,  develop  new  visual  purple  in  the 
dark.  This  is  even  true  when  it  has  been  kept  in  the  dark  in  a  saturated 
solution  of  sodium  chloride,  and  is  then,  after  washing  with  physio- 
logical salt  solution,  bleached  by  light.  Here  the  regeneration  of  the 
pigment  cannot  be  the  result  of  vital  processes,  but  must  be  due  to 
chemical  changes  in  products  formed  from  the  original  pigment  by  the 
action  of  light.  No  such  regeneration  takes  place  in  a  retina  which, 
after  having  been  bleached  m  situ,  is  removed  without  the  pigmented 
epithelium  and  placed  in  the  dark;  and  the  only  probable  explanation 
of  the  difference  is  that  in  this  case  the  photo-chemical  substances 
from  which  visual  purple  can  be  formed  have  been  absorbed  into  the 
circulation,  and  have  so  escaped. 

The  inner  segments  of  the  cones  of  certain  animals  (birds,  reptiles, 
amphibia,  and  some  fishes)  contain  globules  of  various  colours,  ranging 
over  almost  the  whole  spectrum,  and  including,  besides,  the  non-spectral 
colour,  purple.  The  globules  are  composed  chiefly  of  fat  with  the 
pigments  (chromophanes,  as  they  have  been  called)  dissolved  in  it. 
The  function  of  these  globules  is  unknown.  They  cannot  be  concerned 
in  colour  vision,  or,  at  least,  they  cannot  be  essential  to  it,  for  in  the 
human  retina  they  do  not  exist. 

The  yellow  pigment  of  the  macula  lutea  does  not  belong  to  the  layer 
of  rods  and  cones;  it  only  exists  in  the  external  molecular  layer  and  the 
layers  in  front  of  it;  in  the  fovea  centralis  it  is  absent. 

Time  necessary  for  Excitation  of  the  Retina  by  Light — Fusion  of 
Stimuli. — Whatever  the  exact  nature  of  retinal  excitation  may  be, 
it   is   called   forth   by  exceedingly  slight   stimuli.     A   lightning  flash, 

although  it  may  last  only th  of  a  second,  lasts  long  enough 

°  ■^  -^    1,000,000  °  ° 

to  be  seen.     A  beam  of  light  thrown  from  a  rotating  mirror  on  the 

eye  stimulates  when  it  only  acts  for  ^ th  of  a  second.     The 

•^  ^  8,000,000 

minimum  stimulus  in  the  form  of  green  light  corresponds,  as  we  have 

already  seen   (p.  784),  to  a  quantity  of  work  equivalent  to  no  more 

than  — 8  erg — that  is,  about  — jg  gramme-millimetre,  or  — ^  milli- 
gramme-millimetre,   which   is   the   work   done   by    th   of  a 

°  .  •'    10,000,000 

milligramme  in  falling  through  a  millimetre;  and  it  cannot  be  doubted 
that  a  portion  even  of  this  Lilliputian  bombardment  is  wasted  as  heat. 
So  quickly,  too,  is  the  stimulus  followed  by  the  response  that  no  latent 
period  has  as  yet  ever  been  measured.  It  is  certain,  however,  that 
there  is  a  latent  period,  as  surely  as  there  is  a  latent  period  in  the 
excitation  of  a  naked  nerve-trunk,  although  this  also  has  never  been 
experimentally  detected.  The  analogies,  in  fact,  between  a  muscular 
contraction  and  a  retinal  excitation  are  numerous  and  close.  Like  the 
muscle,  the  retina  seems  to  possess  a  store  of  explosive  material  wdiich 
the  stimulus  serves  only  to  fire  off.  The  retina,  like  the  muscle,  is 
exhausted  by  its  activity,  and  recovers  during  rest.  Like  the  muscle 
curve,  the  curve  of  retinal  excitation  rises  not  abruptly,  but  with  a 
measurable  slowness  to  its  height,  and  when  stimulation  is  stopped, 


I050  THE  SENSES 

takes  a  sensible  time  to  fall  again,  the  retinal  impression  outlasting  the 
luminous  stimulus  by  about  one-eighth  of  a  second.  With  compara- 
tively slow  intermittent  stimuli  the  retinal,  like  the  muscle  curve, 
flickers  up  and  down.  When  the  rate  of  stimulation  is  increased,  the 
steady  contraction  of  the  tetanized  muscle  is  analogous  to  the  fusion 
of  the  individual  stimuli  by  the  tetanized  retina  (or  retino-cerebral 
apparatus)  into  a  continuous  sensation  of  light,  such,  e.g-,  as  the  bright 
'  trail  '  of  a  falling  star,  or  the  fiery  circle  traced  in  the  air  when  a  fire- 
brand is  rapidly  whirled  round.  But  the  maximum  retinal  excitation 
which  a  stimulus  of  given  strength  can  call  forth  depends  much  more 
closely  upon  the  time  during  which  the  stimulus  acts  than  the  maximum 
contraction  does  upon  the  length  of  the  muscular  stimulus. 

As  the  strength  of  the  light  increases  in  geometrical  progression,  the 
time  during  which  it  must  act  in  order  to  produce  its  maximum  effect 
decreases  approximately  in  arithmetical  progression  (Exner).  For  light 
of  moderate  intensity  this  time  is  about  ^  second.  Since  for  complete 
fusion  the  stimuli  must  follow^  each  other  at  a  much  more  rapid  rate 
than  four  in  the  second,  the  intensity  of  the  resultant  sensation  is 
always  less  when  a  succession  of  similar  stimuli  are  fused  than  when  one 
of  the  stimuli  is  allowed  to  produce  its  maximum  effect. 

If  the  time  of  each  stimulus  is  equal  to  the  interval  during  which 
there  is  no  stimulation,  the  sensation,  when  complete  fusion  has  been 
reached,  is  the  same  as  would  be  produced  by  a  constant  light  of  half 
the  strength  employed.  And,  in  general,  if  m  be  the  proportion  of  the 
time  during  which  the  eye  is  stimulated  by  a  light  of  intensity  /,  and  n 
the  proportion  of  the  time  during  which  it  is  not  stimulated,  the  resultant 
impression  is  the  same  as  that  which  wonld  be  produced  by  an  un- 

I/.     This  is  Talbot's  law,  which 

may  be  expressed  without  the  aid  of  symbols  thus:  When  a  light  of 
given  intensity  is  allowed  to  act  on  the  eye  at  intervals  so  short  that  the 
impressions  are  completely  fused,  the  resultant 
sensation  is  independent  of  the  absolute  length  of 
each  flash,  and  is  proportional  only  to  the  fraction 
of  the  whole  time  which  is  occupied  by  flashes  and 
to  the  intensity  of  the  light.  Talbot's  law  may  be 
readily  demonstrated  by  means  of  a  rotating  disc 
with  alternate  white  and  black  sectors  (Fig. 
4271,  so  arranged  that  the  same  proportion  of  the 
circumference  of  each  of  the  three  concentric 
zones  is  black. 

When  the  rotation  is  sufficiently  rapid  to  give 

Fig.  446.— Disc  for  de-     complete  fusion  (say  20  to  30  times  a  second), 

monstrating    Talbot's     the  whole  disc  appears  equally  bright.    However 

law,  much  the  rate  of  rotation  is  now  increased,  no 

further  change  occurs.     It  has  been  sho^vn  that 

even  for  stimuli  as  short  as  the  nTjffJijTRi'th  of  a  second,  repeated   at 

intervals  of  yigth  second,  Talbot's  law  holds  good.      So  that  not  only 

does  a  flash  so  inconceivably  brief  affect  the   retina,  but  it   sets  up 

changes  which  last  for  a  measurable  time.      For  intense  stimuli  Talbot's 

law  ceases  to  be  true :    the  field  appears  brighter  than  it  should  be 

(Griinbaum). 

Two  chief  theories  have  been  proposed  to  account  for  the  fusion  of 
intermittent  retinal  stimuli:  (i)  The  persistence  theory,  according  to 
which  the  excitatory  process  in  the  retina  remains  for  a  short  time  at 
the  maximum  reached  when  the  light  ceases  to  act.  Steady  fusion  is 
supposed  to  be  obtained  when  the  interval  between  successive  stimuli 
does  not  exceed  this  time.      (2)  The  theory  of  Fick,  who  maintains  that 


VISION  1051 

as  sr>on  as  the  light  is  withdrawn  the  retinal  excitation  begins  to  sink, 
at  first  rapidly,  then  more  gradually.  As  the  rate  of  stimulation  is 
increased  the  time  allowed  for  the  decline  of  the  excitation  is,  of  course, 
correspondingly  shortened,  and  ultimately  the  oscillations  become  so 
small  that  a  continuous  smooth  sensation  results.  I'ick's  theory 
appears  to  explain  the  phenomena  best. 

The  experiments  of  Charpentier  have  shown  that  the  retina  when 
stimulated  has  a  natural  tendency  to  enter  into  oscillations  at  the  rate 
of  about  36  in  the  second,  so  that  the  effect  of  a  flash  of  light  when  it 
falls  on  a  retinal  area  is  not  a  single  excitation  which  rises  smoothly  to 
its  maximum  and  then  declines  smoothly  to  zero,  but  a  series  of  swings 
which  die  away  like  the  vibrations  of  an  elastic  body.  This  may  be 
demonstrated  by  slowly  rotating  a  well-illuminated  disc,  one  quadrant 
of  which  is  white  and  the  rest  black,  while  the  eye  is  kept  fixed  on  the 
centre.  A  black  band,  or  rather  sector,  running  out  from  centre  to 
circumference,  will  be  seen  in  the  white  quadrant  a  little  behind  the 
border  of  it  which  first  passes  the  eye.  This  band  may  be  succeeded  by 
one  or  more  fainter  black  bands  placed  at  regular  intervals  in  the  white 
portion  of  the  disc.  The  explanation  is  this.  At  the  moment  when  the 
image  of  the  advancing  edge  of  the  white  quadrant  falls  upon  the 
retinr.  it  is  excited,  and  we  get  the  sensation  of  white.  Then  comes  a 
swing  in  the  opposite  direction  which  gives  rise  to  the  first  black  band, 
and  succeeding  swings  cause  the  other  bands.  The  period  of  the  oscil- 
latory process  can  be  calculated  from  the  speed  of  the  disc,  and  the 
distance  of  the  first  band  from  the  edge  of  the  white  quadrant.  The 
well-known  fact  that  a  single  flash  of  lightning,  or  other  intense  stimulus, 
may  appear  .j.s  two  flashes,  finds  its  explanation  in  these  retinal  oscilla- 
tions. 

Colour  Vision. — Besides  differences  in  the  distance,  size,  shape, 
and  brightness  of  objects,  the  eye  recognizes  differences  in  their 
colour;  and  we  have  now  to  consider  the  physical  and  physiological 
differences  on  which  these  depend. 

Colours  may  differ  from  each  other — ^(i)  In  tone  or  hue,  e.g.,  red, 
yellow,  green.  (2)  In  degree  of  saturation  or  fulness  or  purity,  i.e.,  in 
the  degree  in  which  they  are  free  from  admixture  with  white  light,  e.g., 
a  '  pale  '  or  '  light  '  blue  is  a  blue  mixed  with  much  white  light,  a  '  deep  ' 
or  '  full  '  blue  with  kttle  or  none.  {3)  In  brightness  or  intensity,  i.e.,  in 
the  amount  of  the  light  coming  from  unit  area  of  the  coloured  object. 
Thus,  a  '  dark  '  red  cloth  sends  comparatively  little  light  to  the  eye,  a 
'  bright  '  red  cloth  sends  a  great  deal. 

When  a  beam  of  sunlight  falls  into  the  eye,  a  sensation  of  '  white 
light  '  results.  When  a  prism  is  placed  before  the  eye,  the  sensation 
is  entirely  different ;  we  see  a  spectrum  running  up  from  red  through 
green  to  violet,  with  a  multitude  of  intermediate  shades,  the  eye 
being  able  to  distinguish  in  the  solar  spectrum  at  least  one  thousand 
different  hues  (Aubert).  What,  then,  has  happened  ?  Physically, 
nothing  more  has  taken  place  than  a  rearrangement  of  the  rays 
in  the  beam  of  white  light.  A  few  of  them  may  have  been  lost  by 
reflection,  but  upon  the  whole  the  beam  is  made  up  of  exactly  the 
same  constituents  as  before;  only  the  rays  are  now  arranged  in  the 
precise  order  of  their  refrangibility,  the  more  refrangible,  which  are 
also  those  of  shortest  wave-length,  being  displaced  more  towards  the 
base  of  the  prism  than  the  longer  and  less  refrangible  rays.     In- 


I052  THE  SENSES 

stead  of  the  long  and  short  rays  falling  together  on  the  same  ele- 
ments of  the  retina,  as  they  did  in  the  absence  of  the  prism,  they 
now  fall,  if  proper  precautions  have  been  taken  to  secure  a  pure 
spectrum,  in  regular  order  from  one  side  to  the  other  of  the  portion 
of  retma  on  which  the  image  is  termed.  The  physical  condition, 
then,  of  our  sensations  of  the  prismatic  colours  is,  that  rays  of 
approximately  the  same  wave-length  should  fall  unmixed  with 
other  rays  upon  the  retinal  elements.  Rays  of  a  wave-length  of 
760  /iijj,*  to  650  /x/A  give  the  sensation  of  red;  from  650  jufi  to  590  ^/t, 
the  sensation  of  orange;  from  430  fjju  to  400  jbijn,  the  sensation  of 
violet,  and  so  on.  When  rays  of  all  these  wave-lengths  fall  together, 
in  the  proportion  in  which  they  are  present  in  sunlight,  upon  the 
same  part  of  the  retina,  the  resultant  physiological  effect  is  very 
different ;  we  are  no  longer  able  to  distinguish  red,  blue,  green,  etc. ; 
we  receive  the  single  sensation  of  white  light.  The  sensation  is  a 
simple  one;  in  consciousness  we  have  no  hint  that  it  has  a  multiple 
physical  cause. 

But  we  find  further  that  it  is  not  necessary  for  the  sensation  of 
white  light  that  waves  of  every  length  present  in  the  solar  spectrum 
should  be  mixed.  If  rays  of  wave-lengths  675  jliju  (which  acting 
alone  produce  the  sensation  of  red)  be  mixed  in  certain  proportions 
— i.e.,  be  allowed  to  fall  on  the  same  part  of  the  retina — with  rays 
of  wave-length  496  /xju  (which  give  the  sensation  of  bluish-green), 
the  resultant  sensation  is  also  that  of  white  light.  And  an  in- 
definite number  of  sets  can  be  combined,  two  and  two,  so  as  to  give 
the  same  sensation  of  white.  Such  colours  are  called  comple- 
mentary.    The  following  are  pairs  of  complementary  colours: 

Red  and  bluish-green.  Yellow  and  ultramarine-blue. 

Orange  and  cyan-blue. f  Greenish-yellow  and  violet. 

The  green  of  the  spectrum  has  no  simple  complementary  colour; 
purple,  a  colour  not  present  in  the  spectrum,  but  obtained  by 
mixing  light  from  the  two  spectral  extremes — i.e.,  by  mixing  red 
and  violet — may  be  considered  complementary  to  it.  Suppose  now 
that  one  of  a  pair  of  complementary  colours  is  added  to  the  other 
in  greater  intensity  than  is  required  to  give  white,  the  resultant 
sensation  is  a  colour  which  has  a  certain  amount  of  resemblance  both 
to  white  and  to  the  colour  present  in  excess.  Thus,  if  the  two 
colours  are  orange  and  blue,  and  the  blue  is  present  in  greater  in- 
tensity than  is  necessary  to  give  white,  the  resultant  colour  is  a 
whitish  or  pale  blue,  or,  to  use  the  technical  phrase,  an  unsaturated 
blue.  The  more  nearly  the  intensity  of  the  blue  rays  in  the  mixed 
light  approaches  the  proportion  necessary  to  give  white,  the  less 
saturated  is  the  resultant  colour;  the  greater  the  excess  of  blue, 
the  more  nearly  does  the  resultant  sensation  approach  that  of  the 
saturated  blue  of  the  spectrum.     But  any  non-saturated  spectral 

*  /*//.  is  a  symbol  representing  one-millionth  of  a  millimetre, 
t  Cyan-blue  is  a  greenish-blue. 


VISION  1053 

colour  produced  by  the  mixture  of  two  complementary  colours  may 
be  equally  well  produced  by  the  mixture  of  the  corresponding 
spectral  colour  with  a  certain  quantity  of  ordinary  white  light. 
And  it  is  found  that  when  two  spectral  colours  which  are  not  com- 
plementary are  mixed  together  the  resultant  is  not  white,  but  a 
colour  which  may  be  matched  by  some  spectral  colour  lying  between 
the  two  (or  by  purple),  either  without  addition  or  plus  a  larger  or 
smaller  quantity  of  ordinary  white  light.  From  all  this  it  follows 
that  the  retina  may  be  excited  by  an  infinite  nurriber  of  different 
physical  stimuH,  and  yet  the  resultant  sensation  may  be  the  same. 
This  leads  straight  to  the  conclusion  that  somewhere  or  other  in 
the  retino-cerebral  apparatus  simplification,  or  synthesis,  of  im- 
pressions must  take  place;  and  we  have  to  inquire  what  the  simplest 
assumptions  are  which  will  explain  all  the  phenomena.  Now,  it  is 
not  possible,  from  two  spectral  colours  alone,  to  produce  a  sensation 
corresponding  to  all  the  others.  By  mixing  three  standard  spectral 
colours,  however,  in  various  proportions,  we  can  produce  not  only 
the  sensation  of  white  light,  but  that  of  every  colour  of  the  spectrum 
(and  of  purple).  These  statements  are  based  on  demonstrated  facts 
obtained  by  very  numerous  experiments  on  colour  mixtures.  The 
hypotheses  framed  to  explain  the  facts  are  to  be  carefully  dis- 
criminated from  the  facts  themselves. 

Primary  Colours. — The  simplest  assumption  we  can  make,  then, 
is  that  there  are  three  standard  sensations,  and  that  either  the 
retina  itself  can  respond  by  no  more  than  three  distinct  modes  of 
excitation  to  the  multiplex  stimuli  of  the  luminous  vibrations,  or 
that  complex  impulses  set  up  in  the  retina  are  reduced  to  simplicity 
because  the  central  apparatus  is  capable  of  responding  by  only 
three  distinct  kinds  of  sensation.  Which  three  sensations  we  select 
as  fundamental  or  primary  is,  to  a  certain  extent,  arbitrary.  Fick 
chose  red,  green,  and  blue;  most  commonly  red,  green,  and  violet 
are  accepted  as  the  primary  colours.  Red,  yellow,  and  blue, 
although  so  long  considered  the  primary  colours,  from  data  yielded 
by  the  mixture  of  pigments,  will  not  do;  for  no  possible  combination 
of  them  will  produce  either  a  pure  green  or  white  light. 

The  Young-Helmholtz  Theory, — The  theory  which  has  been  most 
widely  accepted  is  that  of  Young,  generally  called,  on  account  of 
its  adoption  and  extension  by  Helmholtz,  the  Young-Helmholtz 
theory.  Red,  green,  and  violet  are  taken  as  the  fundamental  or 
elementary  colour  sensations.  In  its  more  modern  form  it  assumes 
that  in  the  retina,  or  in  the  retino-cerebral  apparatus,  there  are 
three  kinds  of  elements — (i)  a  substance  or  a  component  chiefly 
affected  by  light  of  comparatively  long  wave-length  (red),  to  a  less 
extent  by  light  of  medium  wave-length  (green),  and  to  a  still  less 
extent  by  the  shortest  visible  waves  (violet) ;  (2)  a  component  mainly 
affected  by  medium,  but  also  to  a  certain  extent  by  long  and  short 
waves;  (3)  a  component  chiefly  affected  by  the  short  vibrations, 


I054 


THE  SENSES 


less  by  tlic  iiicdiuiii,  and  still   less  ])y  the  hn\^  waves.      The  curves 
in  Fig.  44(7  illustrat<>  tlusc  relations. 

The  theory  explains  as  follows  the  phenomena  of  colour- rrwxture 
referred  to  above.  When  all  the  rays  of  the  spectrum  act  upon 
tlie  retina  together,  the  three  components  are  about  equally  affected, 
and  this  equal  effect  is  supposed  to  be  the  condition  of  the  sensation 
of  white  light.  When  the  green  of  the  spectrum  alone  falls  on  the 
retina,  tlu;  'green  '  component   is  strongly  excited,  the  other  two 


Fig.  447. — Curves  of  Excitability  of  Primary  Sensations  from  Observations  on 
Colour  Mixtures  (Konig).  The  numbers  give  wave-leugths  of  the  spectrum  in 
millionths  of  a  millimetre. 


only  slightly;  this  is  the  relation  between  the  amount  of  excitation 
in  the  three  components  which  is  associated  with  a  sensation  of 
spectral  green.  When  two  complementary  colours,  such  as  red  and 
bluish-green,  fall  together  on  the  same  portion  of  the  retina,  the 
three  components  are  excited  in  the  relative  proportions  associated 
with  the  sensation  of  white  light. 

The  colour  triangle  is  a  graphic  method  of  representing  various  facts 
in  colour-mixture  (Fig.  44^). 

The  chief  points  to  be  noted  are  tlie  following:   (i)   On  the  curve 

tlic  spectral  colours  are 


CtjanBlue 


Green 


Xeilour 


A)ran(/f 


arranged  at  such  dis- 
tances that  the  angle  con- 
tained between  straight 
lines  drawn  from  the 
point  marked  '  white,' 
and  intersecting  the 
curve  at  the  positions 
corresponding  to  any  two 
colours  is  proportional  to 
their  difference  in  tone. 
(2)  The  distance  of  any 
point  of  the  curve  from 
the  point  marked  'white' 
is  proportional  to  the  stimulation  intensity  of  the  colour  corresponding 
to  it.'  (if  the  stimulatii'Ti  intensities  of  all  tlie  colours  be  represented  by 


Purple 


Fig.  448. — Colour  Triangle. 


VISION  1035 

proportiDnal  \vcMp;hts  lyiiif;  at  the  corresponding^  points  on  tlu;  curve,  the 
point  'white  '  will  be  the  centre  of  gravity  of  the  system.)  (3)  The  position 
of  a  colour  proiUiced  by  the  mixture  of  any  pair  of  spectral  colours  is 
found  by  joiuiiig  the  corresjjonding  points  by  a  straight  line.  The  mixed 
colour  lies  on  tiiis  line  at  distances  from  tlie  two  points  inversely  proi)or- 
tional  to  tile  stimulation  intensity  of  the  two  colours — i.e.,  it  lies  in  the 
centre  of  gravity  of  the  weiglits  rejiresenting  tlie  twocolours.  (4)  It  is  a 
particular  case  of  (3)  that  the  complementary  colours  are  situated  at 
the  jHjints  where  straight  lines  lirawn  llirough  '  white  '  intersect  the 
curve,  since  the  point  marked  '  white  '  is  the  centre  of  gravity  corre- 
sponding to  a  pair  of  colours  only  when  it  lies  on  the  straight  line 
joining  them.  Thus  tlie  orange  and  yellow  lying  between  the  red  and 
green  are  mixtures  of  the  red  and  green  sensations  in  different  propor- 
tions; tile  cyan-blue  anil  indigo-blue  are  mixtures  of  the  green  and 
violet  sensations.  Tlie  purj>les,  representctl  by  a  broken  line,  are  not 
present  in  the  spectrum,  and  are  mixtures  of  red  and  violet. 

It  is  a  point  of  great  theoretical  interest  that  on  the  Young-Helm- 
holtz  theory  the  pure  spectral  colours,  although  physically  saturaued 
[i.e.,  due  to  ethereal  vibrations  of  a  definite  wave-length  for  each 
colour),  ought  not  to  be  physiologically  saturated,  since  they  all  affect 
the  three  components,  although  in  different  degrees.  In  other  words, 
the  red,  let  us  say,  of  the  spectrum  ought  not  to  be  the  purest  or  fullest 
red  which  it  is  possible  to  perceive.  Now,  it  is  found  that  this  is  really 
the  case.  If,  for  example,  we  look  first  at  the  bluish-green,  and  then 
at  the  red  of  the  spectrum,  the  sensation  of  red  is  fuller  or  more  saturated 
than  if  we  had  looked  at  the  red  directly.  Similarly,  if  we  look  first  at 
a  small  bluish-green  square  on  a  black  ground,  and  then  at  a  red  ground, 
we  see  a  more  fully  saturated  square  in  the  middle  of  the  latter.  The 
explanation,  on  the  Young-Helmholtz  theory,  is  that  the  '  green  ' 
component,  being  fatigued  before  the  eye  is  turned  upon  the  red,  the 
latter  colour  no  longer  affects  it,  or  afifects  it  less  than  it  would  other- 
wise do,  and  tlierefore  the  excitation  is  almost  entirely  confined  to  the 
red  component  in  the  area  fatigued  for  green.  This  brings  us  to  the 
subject  of  retinal  fatigue,  and  the  related  phenomena  of  after-images 
and  contrast. 

After-images. — We  have  seen  that  the  retinal  excitation  always  takes 
time  to  die  away  after  the  stimulus  is  removed.  If  a  white  object  is 
looked  at,  especially  when  the  eye  is  fresh,  for  a  time  not  long  enough 
to  cause  fatigue,  and  the  eye  is  then  closed,  an  image  of  the  object 
remains  for  a  short  time,  diminishing  in  brightness  at  first  rapidly',  then 
more  slowly.  This  is  a  positive  after-image,  and  by  careful  observa- 
tion it  may,  under  certain  conditions,  be  seen  that  the  positive  after- 
image of  a  white  object,  of  a  slit  illuminated  by  sunlight,  for  example, 
undergoes  changes  of  colour  as  it  fades,  passing  through  greenish-blue, 
indigo,  violet,  or  rose,  to  dirty  orange.  On  the  Young-Helmholtz 
theory  this  is  explained  by  the  supposition  that  the  excitation  does 
not  decline  with  the  same  rapidity  in  the  three  hypothetical  components. 
If  the  object  is  looked  at  for  a  longer  time,  or  if  the  eye  is  fatigued,  a 
dark  or  negative  image  may  be  seen  upon  the  faintly-illuminated  ground 
of  the  closed  eyes;  but  negative  after-images  may  be  more  easily 
obtained  when  the  eye,  after  being  made  to  fix  a  small  white  object  on 
a  black  ground,  is  suddenly  turned  upon  a  white  or  neutral  tint  surface. 

Here  Helmholtz  supposed  the  portion  of  the  retina  on  which  the 
image  of  the  object  is  formed  to  be  more  or  less  fatigued.  And  this 
fatigue  will  extend  to  all  three  kinds  of  fibres;  so  that  white  light  of  a 
given  intensity  will  now  cause  less  excitation  in  this  part  than  in  the 
rest  of  the  retina.  It  is  easy  to  understana  that  the  negative  after- 
image of  a  coloured  object  will  be  seen,  upon  a  white  ground,  in  the 


I056  THE  SENSES 

complementary  colour,  for  the  components  chiefly  excited  by  the  latter 
will  have  been  least  fatigued.  The  negative  atter-images  seen  when 
the  eye,  after  receiving  the  positive  impression,  is  turned  upon  a  coloured 
ground,  vary  with  the  colour  of  the  object  and  ground  in  a  manner  which 
has  been  cxjjlained  as  due  to  fatigue  of  one  or  other  component.  It 
is  difficult,  however,  to  reconcile  the  fatigue  hypothesis  of  the  after- 
image with  all  the  facts.  Hering  supposes  that  the  retina  is  not 
passively  fatigued,  but  that  a  metabolic  change  is  set  up  in  it  which  is 
of  the  opposite  kind  to  that  caused  by  the  original  excitation  (see 
P-,i057)- 

J  he  phenomena  of  negative  after-images  are  often  included  together 
as  examples  of  successive  contrast,  the  name  implying  mutual  in- 
fluences of  the  portions  of  the  retina  (or  retino-cerebral  apparatus) 
successively  stimulated.  We  have  now  to  consider  simultaneous 
contrast,  often  spoken  of  simply  as  contrast. 

Contrast. —  A  small  white  disc  in  a  black  field  appears  whiter,  and  a 
small  black  disc  in  a  white  field  darker,  than  a  large  surface  of  exactly 
the  same  objective  brightness.  A  disc  with  alternate  sectors  of  white 
and  black,  so  arranged  that  the  proportion  of  white  to  black  increases 
in  each  zone  from  centre  to  circumference,  when  set  in  rotation,  ought, 
by  Talbot's  law,  to  show  sharply  marked  and  uniform  rings,  of  which 
each  is  brighter  than  that  internal  to  it.  But  each  zone  appears 
brightest  at  its  inner  edge,  where  it  borders  on  a  zone  darker  than  itself, 
and  darkest  at  its  outer  edge,  where  it  borders  on  a  brighter  zone.  A 
plausible  explanation  of  this  is  based  on  the  assumption  that  in  the 
neighbourhood  of  an  excited  area  of  the  retina,  as  well  as  within  the 
area  itself,  the  excitability  is  diminished;  and  the  same  explanation  has 
been  extended  to  the  contrast  phenomena  of  coloured  objects.  A  small 
piece  of  grey  paper,  e.g.,  is  placed  on  a  green  sheet.  The  grey  patch 
appears  in  the  complementary  colour  of  the  ground — viz.,  pink  or 
rose-red  (Meyer).  The  red  colour  is  much  stronger  if  the  whole  is 
covered  with  translucent  tracing-paper.  Here  we  may  suppose  that 
the  fatigue  of  the  substance  or  component  chiefly  affected  by  the  ground 
colour  spreads  into  the  portion  of  the  retina  occupied  by  the  image  oi 
the  grey  paper;  the  white  light  coming  from  the  latter,  therefore, 
affects  mainly  the  component  connected  with  the  sensation  of  the  com- 
plementary colour. 

The  curious  phenomenon  of  coloured  shadows  is  also  an  illustration 
of  contrast.  'Ihey  may  be  produced  in  various  ways.  For  example, 
when  a  lamp  is  lit  in  a  room  in  the  twilight,  before  it  has  yet  grown 
too  dark,  the  shadows  cast  by  opaque  objects  on  a  white  wmdow-blind 
are  coloured  blue.  The  yellow  light  of  the  lamp  overpowers  the  feeble 
daylight  which  passes  through  the  blind,  and  the  general  ground  is 
yellowish ;  but  wherever  a  shadow  is  thrown  it  appears  of  a  bluish  tint 
in  contrast  to  the  yellow  ground.  Here  the  only  illumination  the  eye 
receives  from  the  region  occupied  by  the  shadow  is  the  feeble  daylight. 
Falling  upon  an  area  in  which  the  component  chiefly  affected  by  vellow 
rays  is  more  or  less  fatigued,  it  causes  a  sensation  of  the  complementary 
colour.  As  darkness  comes  on,  the  shadows  become  black,  for  now 
practically  no  light  at  all  comes  from  them. 

Helmholtz  looked  upon  simultaneous  contrast  as  a  result  of  false 
judgment,  and  not  of  a  change  of  excitability  in  parts  of  the  retina 
bordering  on  the  actually  excited  parts.  For  the  sake  of  perspective, 
it  \\ill  be  worth  while  to  apply  this  theory  by  way  of  illustrating  it,  to 
the  explanation  of  the  case  of  contrast  we  have  just  been  considering, 
from  the  other  point  of  view,  in  Meyer's  experiment.  Helmholtz's  ex- 
planation of  this  experiment  is  as  follows:  When  a  coloured  surface  is 


VISION  1057 

covered  with  translucent  paper,  Uie  latter  appears  as  a  coloured  covering 
spread  over  the  field.  1  he  mind  does  not  recognize  that  at  the  grey 
patch  there  is  any  breach  of  continuity  in  this  covering;  it  is  therefore 
assumed  that  the  greenish  veil  extends  over  this  spot  too.  Now,  the 
grey  seen  through  the  translucent  white  paper  is  objectively  white — i.e., 
sends  to  the  eye  the  vibrations  which  together  would  give  the  sensation 
of  white  light.  But  with  a  green  veil  in  front  of  it,  this  could  only 
happen  if  the  really  grey  patch  was  the  colour  complementary  to  green 
— that  is,  rose-red.  The  mind,  therefore,  judges  falsely  that  the  patch 
is  red.  Hering  has  severely  criticized  this  theory  of  Helmholtz  as  to 
false  judgments;  and  the  weight  of  evidence  certainly  seems  to  be  in 
favour  of  the  view  that  simultaneous,  like  successive,  contrast  is  due 
to  the  influence  of  one  portion  of  the  retina,  or  retino-cerebral  apparatus, 
on  another. 

Hering's  Theory  of  Colotir  Vision. — The  Young-Helmholtz  theory 
of  colour  vision  has  not  met  with  universal  acceptance.  The  best- 
known  rival  theory  is  that  of  Hering,  who  takes  his  stand  upon  the 
fact  that  certain  visual  sensations  (red,  yellow,  green,  blue,  white, 
black)  do  appear  to  us  to  be  fundamentally  distinct  from  each  other, 
while  all  the  rest  are  obviously  mixtures  of  these.  Accepting  these 
six  as  primary  sensations,  he  assumes  the  existence  in  the  visual 
nervous  apparatus  of  substances  of  three  different  kinds,  which  may 
be  called  the  black-white,  the  green-red,  and  the  blue-yellow.  Like 
all  other  constituents  of  the  body,  these  substances  are  broken  down 
and  built  up  again — in  other  words,  undergo  disassimilation  and 
assimilation,  destructive  and  constructive  metabolism.  The  sensa- 
tions of  black,  of  green,  and  of  blue  he  supposes  to  be  associated  with 
the  constructive,  and  the  sensations  of  white,  of  red,  and  of  \ellow 
with  the  destructive,  processes  in  the  three  substances.  The  black- 
white  substance  is  used  up  under  the  influence  of  all  the  rays  of  the 
spectrum,  but  in  different  degrees;  the  smaller  the  quantity  of  hght 
falling  on  the  retina,  the  more  rapidly  is  it  restored,  and  the  more 
intense  is  the  sensation  of  black.  The  green-red  substance  is  built 
up  by  green  rays,  broken  down  by  red.  The  blue-yellow  substance 
is  destroyed  by  yellow  rays,  restored  by  blue.  A  prominent  dif- 
ference between  this  and  the  Young-Helmholtz  theory,  and,  so  far 
as  it  goes,  an  advantage,  is  that  Hering's  theory  attempts  to  assign 
a  direct  objective  cause  for  the  visual  sensations  of  white,  black, 
and  yellow,  as  well  as  for  red,  green,  and  blue,  instead  of  making 
the  sensations  depend  upon  the  magnitude  of  the  stimulation  pro- 
cess. When  any  of  the  visual  substances  are  consumed  at  one  part 
of  the  retina,  they  are  supposed  to  be  more  rapidly  built  up  in  the 
surrounding  parts,  and  in  this  way  many  of  the  phenomena  of 
simultaneous  contrast  receive  an  easy  and  natural  explanation.  The 
same  is  true  of  the  simpler  phenomena  of  after-images  or  successive 
contrast.  But  in  applying  the  theory  to  the  more  complicated 
phenomena  difficulties  soon  emerge,  which,  to  say  the  least,  are  not 

less  formidable  thein  those  connected  with  the  Young-Helmholtz 

67 


1038 


THE  SENSES 


theory.  Neither  theory,  in  short,  can  be  considered  more  than  a 
partially  successful  attempt  to  grapple  with  a  very  complex  mass  of 
facts.  Each,  however,  has  been  fruitful  in  leading  to  the  discovery 
of  new  facts — a  great  merit  in  a  scientific  hypothesis. 

Sensibility  of  Different  Parts  of  the  Retina — Perimetry. — The 
perception  of  colours,  like  the  perception  of  white  light,  is  not 
equally  distinct  over  the  whole  retina.  We  have  repeatedly  had 
occasion  to  refer  to  the  fovea  centralis  as  the  region  of  most  distinct 
vision;  but  it  would  be  a  mistake  to  suppose  that  it  is  therefore 
necessarily  more  sensitive  than  the  rest  of  the  retina.  As  a  matter 
of  fact,  when  the  minimum  intensity  of  white  light  which  will  cause 
an  impression  at  all  is  determined  for  each  portion  of  the  retina,  it 

is  found  that  the  fovea 
centralis  requires  a  some- 
what stronger  stimulus 
than  the  zone  immedi- 
ately surrounding  it.  Ob- 
jects only  a  little  brighter 
than  the  general  ground 
on  which  they  lie — e.g., 
verj^  faint  stars — are  best 
seen  when  the  eye  is 
directed  a  little  to  one 
side.  This  has  been  attri- 
buted to  the  absence  of 
visual  purple  from  the 
fovea,  in  accordance  with 
the  theory  previously 
alluded  to  that  the  visual 
purple  acts  as  a  mechan- 
ism which  '  adapts  '  the 
retina  for  the  perception 
of  light  of  var\ing  inten- 
sity. But,  with  this  ex- 
ception, the  sensibility  of 
the  retina  diminishes  steadily  from  centre  to  periphery,  both  for 
white  and  for  coloured  light. 

When  the  eye  is  fixed,  and  the  visual  field — that  is,  the  whole 
space  from  which  light  can  reach  the  retina  in  the  given  position,  or, 
what  comes  to  the  same  thing,  the  projection  of  the  visual  field  on 
the  retina  by  straight  lines  passing  through  the  nodal  point — 
explored  by  means  of  a  perimeter  (Figs.  44^,  450),  it  is  found  that, 
under  ordinary  conditions,  a  white  object  is  seen  over  a  wider  field 
than  any  coloured  object,  a  blue  object  over  a  wider  field  than  a 
red,  and  a  red  over  a  wider  field  than  a  green  object.  The  exact 
shape,  as  well  as  size,  of  the  visual  field  also  differs  somewhat  for 


Fig.  449. — Priestley  Smith's  Perimeter.  A",  rest 
for  chin ;  0,  position  of  eye ;  Ob,  object,  white  or 
coloured,  which  slides  on  the  graduated  arc  B ; 
/,  point  fixed  by  the  eye. 


VISION 


1059 


different  colours.  In  disease  of  the  retina,  or  of  the  visual  path 
between  it  and  the  cortex,  or  of  the  visual  cortex  itself,  the  abridg- 
ment of  the  field  for  white  and  for  monochromatic  light  as  mapped 
out  bv  observations  with  the  perimeter  is  often  of  value  in  diagnosis. 
Although  it  has  been  shown  by  Aubert  and  others  that  monochro- 
matic light  of  considerable  intensity  can  bo  perceived  over  the  whole 
retina,  yet  it  may  be  said  that  the  retinal  rim  is  even  then  relatively 
and,  under  ordinary  conditions,  absolutely  colour-blind.     This  and 


xn 


Fig.  450. — Perimetric  Chart  of  Right  Eye  (after  Hirschberg).  The  numbers  repre- 
sent degrees  of  the  visual  field  measured  on  the  graduated  arc  of  the  perimeter. 
w,  boundary  of  field  for  white  object ;  b,  for  blue ;  r,  for  red ;  g,  for  green ;  m,  blind 
spot;  M,  medial,  and  L,  lateral  side  of  the  field  of  vision.  The  Roman  immbers 
represent  twelve  meridians  of  the  retina,  each  making  an  angle  of  30°  with 
the  next.  They  fix  the  'longitude  '  of  any  point  in  the  fieid.  The  concentric 
circles  indicated  by  Arabic  numbers  represent  angular  distances  from  the 
fixation  point  in  the  planes  of  these  meridians.  They  give  the  '  latitude  '  of  any 
point. 

other  facts  have  given  rise  to  the  theory  (p.  1047)  that  the  rods,  which 
are  alone  present  at  the  ora  serrata,  are  concerned  in  achromatic 
vision  (under  conditions  of  dark  adaptation),  the  cones  in  colour 
vision  as  well  as  in  achromatic  vision  (under  daylight  conditions). 

This  brings  us  to  the  subject  of  colour-blindness,  a  phenomenon 
of  great  interest  in  its  theoretical  as  well  as  in  its  practical  bearings. 

Colour-Blindness. — A  considerable  number  of  persons  (about 
4  per  cent,  of  all  males,  but  only  one-tenth  of  this  proportion  of 


io6o  THE  SENSES 

females)  are  deikient  in  the  power  of  distinguisliing  between  certain 
colours.  They  are  said  to  be  colour-blind;  but  the  term  must  not 
be  taken  to  signify  that  they  are  absolutely  devoid  of  colour-sensa- 
tions. A  very  small  minority  of  the  colour-blind  appear  to  have 
but  one  sensation  of  colour  tone,  everything  appearing  as  white, 
grey,  or  black  (total  colour-blindness,  sometimes  called  mono- 
chromatic vision).  All  colours  are  confused  by  them,  but  differences 
of  brightness  are  correctly  appreciated.  Probably  the  totally 
colour-blind  person  receives  somewhat  the  same  impressions  from 
a  coloured  picture  as  the  normal  person  does  from  a  reproduction 
of  the  same  picture  in  black-and-white.  There  are  close  resemblances 
between  the  vision  of  the  totally  colour-blind  eye  and  that  of  the 
normal  eye  adapted  by  resting  in  the  dark  for  twilight  vision.  The 
fovea  is  relatively,  and  in  some  cases  absolutely,_  insensitive  to 
light,  while  the  peripheral  portion  of  the  retina  is  normal,  or  nearly 
normal,  in  this  regard.  This  is  the  foundation  of  the  theory  that  in 
total  colour-blindness  the  cones  are  devoid  of  their  normal  func- 
tions, and  that  the  hypothetical  mechanism  for  twilight  vision  (the 
rods)  is  functioning  alone.  In  another  condition  (night-blindness, 
or  hcmeralopia)  it  is  sometimes  assumed  that  the  other  mechanism 
(that  of  the  cones)  which  is  adapted  for  daylight  vision,  and  has 
little  power  of  dark-adaptation,  is  alone  acting.  But  it  cannot  be 
said  that  this  has  been  proved. 

The  rest  of  the  colour-blind  are  dichromatic — i.e.,  their  colour 
reactions  seem  to  correspond  only  to  two  of  the  fundamental  colour 
sensations  of  the  normal  person  and  their  combinations,  in  addition 
to  white.  Of  the  dichromates  a  very  few  confuse  blue  with  yellow. 
The  great  majority  are  unable  to  distinguish  between  red  and  green. 
The  condition  will  be  most  easily  understood  by  considering  some 
of  the  extraordinary  mistakes  which  may  be  made  by  the  colour- 
blind, without  necessarily  leading  them  to  suspect  that  there  is  any- 
thing abnormal  in  their  vision.  Thus,  to  quote  the  words  of  a 
distinguished  writer  on  this  subject,  himself  a  sufferer  from  the 
deliciency:  '  A  naval  officer  purchases  red  breeches  to  match  his 
blue  uniform;  a  tailor  repairs  a  black  article  of  dress  with  crimson 
cloth;  a  painter  colours  trees  red,  the  sky  pink,  and  human  cheeks 
blue.'  The  shoemaker,  Harris,  the  discoverer  of  colour-blindness, 
picked  up  a  stocking,  and  was  surprised  to  hear  other  people 
describe  it  as  a  red  stocking;  it  seemed  to  him  only  a  stocking. 
The  celebrated  Dalton  was  twenty-six  years  of  age  before  he  knew 
that  he  was  colour-blind.  He  matched  samples  of  red,  pink, 
orange,  and  brown  silk  with  green  of  different  shades;  blue  both 
with  pink  and  with  violet ;  lilac  with  grey. 

When  the  condition  of  vision  in  dichromates  is  tested  by  means  of 
the  spectrum,  it  is  found  that  they  fall  into  two  classes:  (i)  A  class 
(of  green-blind)  by  whom  the  whole  of  the  spectrum  from  red  to  yellow  is 
described  as  yellow  of  different  degrees  of  brightness  (intensity) ;  the  green 


VISION  loOi 

appears  as  a  pale  yellow  with  a  grey  or  wiiite  band  in  its  midst;  while 
the  violet  end  is  seen  as  different  shades  of  blue.  (2)  A  class  of  (red- 
blind)  whose  whole  spectrum,  from  rod  to  green,  is  seen  as  green  of 
different  intensities,  the  extreme  red  being  entirely  invisible.  The 
violet  end  is  blue,  as  in  (i),  and  there  is  a  band  of  white  or  grey  near 
the  blue  end  of  the  green. 

Sir  John  Hcrschcll  explained  Dalton's  peculiarity  of  vision  on  the 
hypothesis  that  hv  only  possessed  two,  instead  of  three,  primary 
sensations. 

On  the  Young-flelmholtz  theory,  the  missing  sensation  is  supposed 
to  be  either  red  or  green.  At  the  intersection  of  the  curves  that  repre- 
sent the  violet  and  green  sensations  (Fig.  447),  the  red-blind  individual 
will  see  what  he  describes  as  white — viz.,  the  sensation  produced  by 
tlie  stimulation  of  the  only  two  components  he  possesses.  Similarly, 
at  the  intersection  of  the  red  and  violet  curves  the  green-blind  person 
will  see  what  is  wiiite  to  him. 

Those  who  have  attempted  to  explain  colour-blindness  on  Hering's 
theorj'  have  usually  assumed  that  the  colour-blind  possess  the  blue- 
yellow,  but  lack  the  green-red  visual  substance.  So  that  on  this  theory 
there  should  be  no  difference  between  red-blindness  and  green-blind- 
ness. But  V.  Kries,  in  a  study  of  twenty  cases  of  congenital  partial 
colour-blindness,  brings  forward  strong  evidence  that  the  red-green 
blind  can  be  divided,  as  regards  the  comparison  of  red  (lithium)  and 
orange  (sodium)  light,  into  two  sharply-separated  groups— a  result 
which  is,  so  far  as  it  goes,  in  favour  of  the  Young-Helmholtz  theory, 
and  against  the  theory  of  Hering. 

The  observations  of  Burch  on  temporary  colour-blindness  produced 
by  placing  the  eye  behind  a  transparent  coloured  screen  and  focussing 
a  beam  of  strong  sunlight  on  it,  lend  additional  support  to  the  former 
theory.  Thus,  if  a  spectrum  is  looked  at  after  green-blindness  has  been 
induced  by  exposure  of  the  eye  to  green  light,  the  red  portion  of  the 
specti"um  seems  to  pass  into  the  blue,  and  no  intermediate  green  band 
is  seen.  If  the  eye  is  exposed  to  yellow  light  it  becomes  temporarily 
blind  not  only  for  yellow,  but  also  for  red  and  green.  This  is  in  favour 
of  the  assumption  of  the  Young-Helmholtz  theory  that  the  sensation 
of  yellow  is  caused  when  the  retinal  eletnents  concerned  in  the  production 
of  the  sensations  of  red  and  green  are  simultaneously  stimulated.  It  is, 
however,  equally  difficult  to  reconcile  some  of  the  phenomena  of  colour- 
blindness with  the  Young-Helmholtz  theory.  Anomalies  and  defects 
of  colour-sensation  are  common  accompaniments  of  pathological  lesions 
of  the  visual  apparatus,  and  can  be  produced  by  various  drugs,  as  by 
abuse  of  tobacco.  But  colour-blindness,  in  its  true  sense,  is  con- 
genital, often  hereditary;  the  colour-blind  are  '  bom,  not  made.'  And 
although  the  condition  cannot  be  cured,  it  is  of  great  importance  that 
it  should  be  recognized  in  the  case  of  persons  occupying  positions  such 
as  those  of  engine-drivers,  railway-guards,  and  sailors,  in  which  coloured 
lights  have  to  be  distinguished.  For,  while  it  is  true  that  the  sensations 
which  red  and  green  lights  give  the  colour-blind  are  far  from  baing 
identical  (Pole)  under  favourable  conditions,  it  is  precisely  when  the 
conditions  are  unfavourable — as  in  a  fog  or  a  snow-storm — that  the 
capacity  of  distinguishing  them  becomes  invaluable  (Practical  Ex- 
ercises, p.  1 1 12). 

Irradiation.  —  The  phenomenon  known  as  irradiation  was  first 
described  by  Kepler,  who  gave  as  an  example  the  appearance  known 
as  the  'new  moon  in  the  old  moon's  arms,'  where  the  crescent  of  the 
new  moon  seems  to  overlap  and  embrace  the  unilluminated  portion  of  the 
lunar  disc.     A  white  circle  on  a  black  ground  (Fig.  451)  appears,  in 


,o62  THE  SENSES 

a  good  lig'it,  to  be  larger  tlian  an  exactly  equal  black  circle  on  a  white 
ground.  The  explanation  is  as  follows:  Owing  to  the  aberration  of  the 
refractive  media  of  the  eye  (p.  1027),  all  the  rays  proceeding  from  the 
luminous  object  are  not  brought  accurately  to  a  focus  on  the  retina, 
and  the  image  is  surrounded  by  dilfusion  circles  (p.  1028)  which  encroach 
upon  the  unilluminated  boundary.  Physically  these  represent  a 
weaker  illumination  than  that  of  the  image  proper,  and  therefore  the 
latter  ought  to  stand  out  in  its  real  size  as  a  brightei  area  surrounded  by 
weaker  haloes.  That  this  is  not  the  case,  and  that  the  image  is  pro- 
jected in  its  full  brightness  for  a  certain  distance  over  its  dark  boundary, 
is  due  to  the  fact  that  the  eye  does  not  recognize  verj'  small  differences 
of, brightness.  Wlien  the  accommodation  is  not  perfect,  the  diffusion 
circles  are,  of  course,  much  \\dder,  and  irradiation  is  better  marked  when 
the  object  is  a  little  out  of  focus. 

The  Movements  of  the  Eyes. — That  the  eyes  may  be  efhcient 
instruments  of«'vision,  it  is  necessary  that  they  should  have  the 
power,  of  moving  independently  of  the  head.  An  eye  which  could 
not  move,  though  certainly  better  than  an  eye  which  could  not  see, 

would  \^et  be  as  imperfect  after 
its  kind  as  a  ship  which  could 
/       ^^^       \       run  before  the  \vind,  but  could 
not   lack.     The  mere  fact  that 
the    angle   between  the   visual 
axes  must  be  adapted  to   the 
distance  of  the  object  looked  at 
renders   this   obvious;  and  the 
beauty  of  the  intrinsic  mechan- 
ism  of  the  eyeball   has  its  fitting  complement   in  the  precision, 
delicacy,  and  range  of  movement  conferred  upon  it  by  its  extrinsic 
muscles. 

Not  only  are  movements  of  convergence  and  divergence  of  the 
eyeballs  necessary  in  accommodating  for  objects  at  different  dis- 
tances, but  without  compensatory  movements  of  the  eyes  it  would 
be  impossible  to  avoid  diplopia  with  every  movement  of  the  head; 
for  the  images  of  an  object  fixed  in  one  position  of  the  head  would 
not  continue  to  fall  on  corresponding  points  of  the  retinse  in  another 
position. 

All  the  complicated  movements  of  the  eyeball  may  be  looked 
upon  as  rotatioris  round  axes  passing  through  a  single  point,  which 
to  a  near  approximation  always  remains  fixed,  and  is  situated  about 
177  mm.  behind  the  centre  of  the  eye. 

The  position  which  the  eyeballs  take  up  when  the  gaze  is  directed  to 
the  horizon,  or  to  any  distant  point  at  the  level  of  the  eyes,  is  called 
the  primary  position. '  Here  the  visual  axes  are  parallel,  and  the  plane 
passing  through  them  horizontal.  WTiile  the  head  remains  fixed  in  this 
position,  the  eyeballs  can  rotate  up  or  down  around  a  horizontal  axis, 
or  from  side  to  side  around  a  vertical  axis;  or  upwards  and  inwards, 
downwards  and  outwards,  downwards  and  inwards,  and  upwards  and 
outwards  around  oblique  axes,  which  always  lie  in  the  same  plane  as 
the  vertical  and  horizontal  axes  of  rotation— i.e.,  in  the  vertical  plane 


VISION 


ro03 


passing  through  the  fixed  centre  of  rotation.  These  facts,  spoken  of 
collectively  as  Listing's  law,  and  first  detliicpd  by  him  from  theoretical 
considerai^ions,  were  afterwanls  proved  experimentally  by  MelmJioltz 
and  Donders.  It  necessarily  follows  from  i.isting's  law  (and  this  is, 
indeed,  another  way  of  stating  it)  that  in  moving  from  the  primary  posi- 
tion into  any  other,  there  is  no  rotation  of  tiie  eyeball  round  the  visual 
axis — no  wheel-movement,  as  it  is  called. 

A  true  rotation  of  the  eye  round  the  visual  axis  does,  however,  occur 
when  the  eyes  are  converged  as  in  accommodation  for  a  near  object, 
each  eyeball  rotating  towards  the  temporal  side.  This  is  especially  the 
case  when  the  eyes  are  at  the  same  time  converged  and  directed  down- 
wards; and  the  rotation  may  amount  to  as  much  as  5°.  When  the 
head  is  rolled  from  side  to  side,  while  the  eyes  are  kept  fixed  on  an 
object,  a  slight  compensatory  rotation  of  the  eyeballs  takes  place 
against  the  direction  of  rotation  of  the  head.  The  amount  of  rotation 
of  the  eyes  is  relatively  greater  for  small  than  for  large  movements  of 
the  head  (eye  5°  for  head  20°;  eye  10°  for  head  80° — Kiister). 

The  Extrinsic  Muscles  of  the  Eyes. — The  eyeball  is  acted  upon  by 
six  nuiscles  arranged  in  three  pairs,  whicli  may  be  considered, 
rouglily  speaking,  as  antagonistic  sets.  These  are  the  internal  and 
external  recti,  the  superior  and 
inferior  recti,  and  the  superior 
and  inferior  obliqui. 

Although  the  movements  of  the 
eye  have  been  very  fully  studied, 
and  are,  upon  the  whole,  well 
understood,  our  knowledge  of  the 
manner  in  which  any  given  move- 
ment is  brought  about,  and  of  the 
exact  action  of  the  muscles  which 
take  part  in  it,  is  by  no  means 
as  copious  and  precise.  From 
the  nature  of  the  case,  the  greater 
part  of  what  we  do  know  has 
been  inferred  from  the  anatomical 
relations  of  the  muscles  as  re- 
vealed by  dissection  in  the  dead 
body  rather  than  gained  from  actual  observation  of  the  living  eye. 
A  plane,  called  the  plane  of  traction,  is  supposed  to  pass  through  the 
middle  points  of  the  origin  and  insertion  of  the  muscle  whose  action 
is  to  be  investigated,  and  through  the  centre  of  rotation  of  the 
eyeball.  A  straight  line  drawn  at  right  angles  to  this  plane  through 
the  centre  of  rotation  is  evidently  the  axis  round  which  the  muscle 
when  it  contracts  will  cause  the  eye  to  rotate,  provided  thai  the 
fibres  of  the  muscle  are  symmetrically  distributed  on  each  side  of 
the  plane  of  traction.  The  axes  of  rotation  of  the  antagonistic 
pairs  almost,  but  not  completely,  coincide  with  each  other.  The 
common  axis  of  the  external  and  internal  recti  practically  coincides 
with  the  vertical  axis  of  the  eyeball  (Fig.  452)  in  the  primary  posi- 


int 


B  sup 
H  in/ 

Fig.  452.— Horizontal  Section  of  Left 
Eye.  Arrows  show  direction  of 
pull  of  the  muscles.  The  axis  of 
rotation  of  the  external  and  internal 
recti  would  pass  through  the  inter- 
section of  a  and  /3  at  right  angles 
to  the  plane  of  the  paper. 


io64  THE  SENSES 

tion.  The  eye  is  turned  towards  the  temple  when  the  external 
rectus  alone  contracts,  towards  the  nose  when  the  internal  rectus 
alone  contracts.  The  common  axis  of  the  superior  and  inferior 
recti,  13,  lies  in  the  horizontal  visual  plane  in  the  primary  position, 
but  makes  an  angle  of  about  20"  with  the  transverse  axis,  its  inner 
end  being  tilted  forwards.  The  consequence  is  that  contraction 
of  the  superior  rectus  turns  the  eye  up,  and  contraction  of  the 
inferior  rectus  turns  it  down,  but  both  movements  are  also  com- 
bined with  a  slight  inward  rotation.  The  common  axis  of  the 
oblique  muscles,  a,  makes  an  angle  of  60''  with  the  transverse  axis, 
the  outer  end  of  it  being  the  most  anterior.  The  direction  of  traction 
of  the  superior  oblique  is,  of  course,  given  not  by  the  line  joining 
its  bony  origin  and  its  insertion,  but  by  the  direction  of  the  portion 
reflected  over  the  pulley.  When  the  superior  oblique  contracts 
alone,  the  eyeball  is  rotated  outwards  and  downwards;  the  inferior 
oblique  causes  an  outward  and  upward  rotation.  None  of  the 
common  axes  of  rotation  of  the  pairs  of  muscles,  except  that  of  the 
external  and  internal  recti,  lies  in  Listing's  plane.  Now,  as  we  have 
seen  that  every  movement  which  the  eye,  supposed  to  be  originally 
in  the  primary  position,  can  execute  may  be  considered  as  a  rota- 
tion round  an  axis  in  this  plane,  it  is  clear  that  every  movement, 
except  truly  transverse  rotation,  must  be  brought  about  by  more 
than  one  pair  of  muscles.  For  vertical  rotation,  the  inward  pull  of 
the  superior  rectus  is  antagonized  by  a  simultaneous  outward  pull 
of  the  inferior  oblique;  for  downward  rotation,  the  inferior  rectus 
and  superior  oblique  act  together.  In  oblique  movements,  a  muscle 
of  each  of  the  three  pairs  is  concerned.  The  effect  on  the  eyeball 
of  simultaneous  contraction  of  certain  pairs  of  muscles  may  be 
summarized  thus: 

External  rectus  (outward)  +  internal  rectus  (inward)  =  none. 

Superior  rectus  (upward  and  inward)  +  inferior  oblique  (upward  and 
outward)  =  upward. 

Inferior  rectus  (do%\Tiward  and  inward)  +  superior  oblique  (downward 
and  outward)  =  downward. 

Section  IL — He.\ring. 

The  transverse  vibrations  of  the  ether  fall  upon  all  parts  of  the  surface 
of  the  body,  but  only  find  nerve-endings  capable  of  giving  the  sensa- 
tion of  light  in  the  little  discs,  which  we  call  the  retinae.  So  the  much 
longer  and  slower  longitudinal  waves  of  condensation  and  rarefaction 
which  are  being  constantly  originated  in  the  air  or  imparted  to  it  by 
solid  or  liquid  bodies  that  have  been  themselves  set  vibrating  fall  upon 
all  parts  of  the  surface,  but  only  produce  the  sensation  of  sound  when 
they  strike  upon  the  tiny  mechanism  of  the  internal  ear. 

But  just  as  the  etliereal  vibrations,  and  especially  those  of  greater 
wave-length,  are  able  to  excite  certain  end-organs  in  the  skin  which 
have  to  do  with  the  sensation  of  temperature,  so  the  sound-waves, 
when  sufficiently  large,  are  aJso  capable  of  stimulating  certain  cutaneous 


HEARING 


1-165 


nerves  and  of  givuig  rise  to  a  sensation  of  intermittent  pressure  or  tliriU. 
This  is  readily  perceived  when  the  finger  is  immersed  in  a  vessel  ol 
water  into  which  dips  a  tube  connected  with  a  source  of  sound,  or  when 
a  vibrating  bell  or  tuning-fork  is  touched.  So  far  as  we  know,  what 
takes  place  in  the  ear  is  essentially  similar — that  is  to  say,  a  mechanical 
stimulation  of  the  ends  of  the  auditory  nerve,  but  a  stimulation  which 
acts  through,  and  is  gratluated  and  controlled  by,  a  special  intermediate 
mechanism. 

As  the  visual  apparatus  consists  of  a  sensitive  surface,  the  retina, 
vvhich  contains  the  end-organs  of  the  optic  nerve  and  of  dioptric 
arrangements  which  receive  and  focus  the  rays  of  light,  the  auditory 
apparatus  consists  of  the  sensitive  end-organs  of  the  cochlear  divi- 
sion of  the  eighth  nerve  and  of  a  mechanism  which  receives  the 
sound-waves  and  communicates  them  to  these. 

Physiological  Anatomy  of  the  Ear. — At  the  bottom  of  the  external 
auditory  meatus  lies  the  membrana  tympani,  a  nearly  circular  mem- 
brane set  like  a  drum-skin  in  a 
ring  of  bone,  and  separating  the 
meatus  from  the  tympanum  or 
middle  ear.  Its  external  surface 
looks  obliquely  do%vnwards,  and 
at  the  same  time  somewhat  for- 
wards, so  that  if  prolonged  the 
membranes  of  the  two  ears  would 
cut  each  other  in  front  of,  and  also 
below,  the  horizontal  line  passing 
through  the  centre  of  each  (Figs. 

453.454)- 

Ihe  tympanum  contains  a 
chain  of  little  bones  stretching 
right  across  it  from  outer  to  inner 
wall.  Of  these  the  malleus,  or 
hammer,  is  the  most  external. 
Its  manubrium,  or  handle,  is  in- 
serted into  the  membrana  tym- 
pani, which  is  not  stretched  taut 
within  its  bony  ring,  but  bulges 
inwards  at  the  centre,  where  the 
handle  of  the  malleus  is  attached. 
The  stapes,  or  stirrup,  is  the  most 
internal  of  the  chain  of  ossicles, 
and  is  inserted  bj'  its  foot-plate 
into  a  small  oval  opening — the 
foramen  ovale — on  the  inner  wall  of  the  tympanic  cavity.  A  mem- 
branous ring — the  orbicular  membrane — surrounds  the  foot  of  the 
stapes,  helping  to  fill  up  the  foramen  and  attaching  the  bone  to  its 
edges.  The  inner  surface  of  the  foot  of  the  stapes  is  in  contact  with 
the  perilymph  of  the  internal  ear.  The  incus,  or  anvil,  forms  a  link 
between  the  malleus  and  the  stapes.  The  auditor>^  ossicles,  as  well  as 
the  whole  cavity  of  the  tympanum,  are  covered  by  pavement  epithelium. 

The  tympanum  is  not  an  absolutely  closed  chamber;  it  has  one 
channel  of  communication  with  the  external  air — the  Eustachian  tube 
— which  opens  into  the  phary-nx.  By  the  action  of  the  cilia  lining  this 
tube  the  scanty  secretion  of  the  middle  ear  is  moved  towards  its 
phar>Tigeal  opeiiing,  which,  usually  closed,  is  opened  when  a  swallowing 


Fig.  453.— The  Ear.  in,  external  meatus; 
/,  head  of  malleus;  0,  short  process  of 
malleus;  g,  handle  of  malleus;  h,  incus; 
i,  foot  of  stapes  in  oval  foramen;  e,  tym- 
panic membrane. 


to66 


THE  SENSES 


movement  occurs.  Its  function  is  to  keep  the  pressure  in  the  middle 
ear  approximately  tliat  oi  the  atmosphere.  In  a  balloon  ascent  an 
excess  of  pressure  is  establislicd  on  the  internal  surface  of  the  tympanic 
membrane.  In  the  air-lock  of  a  caisson  wlien  the  air  is  being  com- 
pressed the  excess  of  pressure  is  on  the  external  surface  of  the  membrane. 
The  feeling  of  uncomfortable  tension  is  relieved  in  both  cases  by  swallow- 
ing movements  which  allow  the  pressure  in  the  tympanum  to  adjust 
itself  to  that  in  the  pharynx.  In  catarrh  of  the  naso-pharynx  the 
orifice  may  be  occluded,  and  this  is  accompanied  by  impairment  of 
hearing  and  a  disagreeable  sensation  of  tension  in  the  ear,  owing  to 
absorption  and  consequent  rarefaction  of  the  air  in  the  tympanum. 

The    patient    instinc- 
tively   makes    efforts 

.       which  increase  the  pha- 

:„  ryngeal    pressure    from 

--  time  to   time  so  as  to 

1    open  the  tube. 

The  loosely  -  jointed 
chain  of  ossicles  is 
steadied  and  its  move- 
ments directed  by  liga- 
ments and  by  the  ten- 
sion of  its  terminal  mem- 
branes. It  forms  a  kind 
of  bent  lever  by  which 
tlie  oscillations  of  the 
membrana  tympani  are 
transferred  to  the  mem- 
brane covering  the  oval 
foramen,  and  at  the 
same  time  reduced  in 
size.  Two  slender 
muscles,  the  tensor  tym- 
pani and  stapedius,  con- 
tained in  the  tympanic 

Fig.  454— Tympanum  of  Left  Ear.  showing  the  ^^^1^^'  ^^.f.  ^^^°  ^°"" 
Ossicles  (Mon-is).  i.  superior,  and  4.  external.  ^^Cted  with  and  may 
ligament  of  malleus;  2.  head;  7.  short  process,  and  ^^  upon  the  ossicles. 
10,  manubrium  or  handle,  of  malleus;  5,  long  process  -"^"^  former  lies  in  a 
of  incus,  terminating  in  9,  the  os  otbicufare ;  6.  base,  groove  above  the  Eusta- 
and  H.  head.of  stapee;  II.  EusfftcBlan  tube;  12.  ex-  chian  tube,  and  its 
ternal  auditory  meatus;  13.  membrana  tympani;  tendon,  passing  round  a 
3,  upper,  and  14,  lower,  part  of  t'/mpanum.  kind  of   osseous   pulley 

(processus  cochleari- 
formis),  is  inserted  into  the  handle  of  the  malleus;  the  stapedius  is 
lodged  in  a  hollow  of  the  inner  bony  wall  of  the  tympanum.  Its 
tendon  is  attached  to  the  neck  of  the  stapes  near  its  articulation  with 
the  incus.  This  inner  wall  is  pierced  not  only  by  the  oval  foramen, 
but  also  by  a  round  opening,  the  fenestra  rotunda,  which  is  dosed  by 
a  membrane  to  which  the  name  of  secondary  membrana  tympani  is 
sometimes  given. 

The  internal  ear  consists  of  the  bony  labyrinth,  a  series  of  curiously 
excavated  and  communicating  spaces  in  the  substance  of  the  petrous 
portion  of  the  temporal  bone,  filled  \vith  a  liquid  called  the  perilymph, 
in  which,  anchored  bv  strands  of  connective  tissue,  floats  a  correspond- 
ing series  of  membranous  canals  (the  membranous  labyrinth),  filled 
with  a  liquid  called  endolymph.     The  labyrinth  of  the  internal  ear  is 


HEARING 


1067 


divided  into  three  well-marked  parts:  the  cochlea,  the  vestibule,  and 
the  semicircular  canals  (I'ig.  455).  Ihe  cochlea,  the  most  anterior  of 
the  three,  consists  of  a  convoluted  lube  which  coils  round  a  central 
pillar,  tlie  columella  or  modiolus,  like  a  spiral  staircase.  The  lamina 
spiralis  projects  from  the  modiolus  and  divides  the  tube  into  an  upper 
compartment,  the  scala  vcstibuli,  antl  a  lower,  the  scala  tympani 
(Fig.  456).  The  part  of  the  lamina  next  the  modiolus  is  of  bone,  but  it 
is  completed  at  its  outer  edge  by  a  membiane,  the  lamina  spiralis  mem- 
branacea,  or  basUar  membrane.  The  scala  tympani  abuts  on  the 
fenestra  rotunda,  and  its  perilymph  is  only  separated  from  the  air  of 
the  tympanic  cavity  by  the  membrane  which  closes  tliat  opening. 
At  the  apex  of  the  cochlea  the  lamina  spiralis  is  incomplete,  ending  in 
a  crescentic  border,  so  that  the  scala  tympani  and  the  scala  vestibuli 
here  communicate  by  a  small  opening,  the  helicotrema.  The  scala 
vestibuli  communicates  with  the  vestibule,  and  Ihe  vestibule  with  the 
semicircular  canals,  so  that  the  perilvmph  of  the  entire  labyrinth  forms 
a  continuous  sheet  separated  from  the  cavity  of  the  middle  ear  by  tiie 


—  9 


Fig-  455- — Diagram  of  Right  (Membranous  Labyrinth  (after  lestut).  i,  utricle; 
2,  3,  4,  superior,  posterior,  and  horizontal  semicircular  canals;  5,  saccule; 
6,  ductus  endolymphaticus  arising  by  two  branches,  7,  7';  8,  saccus  endo- 
lymphaticus;  9,  canalis  cocdilearis  (canal  of  the  cochlea)  ending  at  9',  and  9'; 
10,  canalis  reuniens. 


structures  that  fill  up  the  round  and  oval  foramina.  In  the  mem- 
branous labyrinth,  and  in  it  alone,  are  contained  the  end-organs  of  the 
auditory  nerve.  The  membranous  portion  of  the  cochlea  is  a  small 
canal  of  triangidar  section,  cut  off  from  the  scala  vestibuli  by  the  mem- 
brane of  Reissner,  which  stretches  from  near  the  edge  of  the  bony 
spiral  lamina  to  the  outer  wall  (Fig.  457),  to  which  it  is  attached  by  the 
spiral  ligament.  The  canal  has  received  the  name  of  the  scala  media, 
or  canal  of  the  cochlea.  The  membrane  of  Reissner  forms  its  roof. 
Its  floor  is  composed  (i)  of  the  projecting  edge  of  the  spiral  lamina, 
called  the  limbus,  and  (2)  of  the  basilar  membrane.  The  most  con- 
spicuous constituent  of  the  basilar  membrane  is  a  layer  of  stiff,  parallel, 
transparent  fibres  arranged  radially — i.e.,  in  the  direction  from  limbus 
to  spiral  ligament.  They  are  embedded  in  a  homogeneous  material. 
Below  the  cochlear  canal  ends  blindly,  but  communicates  by  a  side- 
channel  with  the  portion  of  the  membranous  vestibule  called  the  sac- 
cule, which  in  its  turn  communicates  wdth  the  utricle  by  the  Y-shaped 
origin  of  the  ductus  endolymphaticus.     Into  the  utricle  open  the  three 


io68 


THE  SENSES 


semicircular  canals,  the  endolymph  of  which  has,  therefore,  free  com- 
inunicatioii  with  that  of  the  vestibule  and  cochlea.  But  although  the 
semicircular  canals  and  vestibule  belong  anatomically  to  the  internal 
ear,  and  arc  supplied  by  branches  of  the  auditory  nerve,  we  have  no 
positive  proof  that  in  the  higlicr  animals,  at  least,  they  are  in  any  way 
concerned  in  hearing;  and  since  experiment  has  assigned  them  a 
definite  function  of  another  kind  (p.  936),  vve  shall  not  consider  them 


/r.v. 


Fig.  45r>. — Longitudinal  Section  through  the  Cochlea  of  a  Cat  (Schafer,  after  Sobotta) 
X  25.  c/c,  canal  or  duct  of  cochlea  ;sci;,scalavestibuli;sc/,scalatympani;ii',  bony 
wall  of  cochlea;  C,  organ  of  Corti ;  mi?,  Reissner's  membrane ;  »,  fibres  of  cochlear 
nerve;  gsp,  ganglion  spirale;  str.v.,  stria  vascularis. 

further  in  this  connection.  The  scala  media  contains  the  organ  of  Corti, 
which  (Fig.  458)  consists  of  a  series  of  modified  epithelial  cells  planted 
upon  the  basilar  membrane.  The  epithelial  cells  are  of  three  kinds: 
(1)  supporting  epithelial  cells;  (2)  the  pillars  or  rods  of  Corti,  in  two 
series  (inner  and  outer),  sloped  against  each  other  like  tlie  rafters  of  a 
roof,  and  covering  in  a  vault  or  tunnel  which  runs  along  the  whole  of 
the  scala  media  from  tlie  base  to  the  apex  of  the  cochlea;  (3)  the  hair- 
cells,  around  which  the  fibres  of  the  auditory  nerve  arborize.  These 
last   are   columnar   epithelial   cells,   surmounted  by  hairs.     They  are 


HEARING 


io6q 


arranged  in  several  rows,  one  row  lying  just  internal  to  the  inner  line 
of  pillars,  and  several  rows  external  to  the  outer  line  of  pillars.  Be- 
tween the  outer  hair-cells  arc  supporting  cells  {cells  of  Deiters).  A  thin 
membrane,  the  reticular  lamina  or  membrana  reticularis,  composed  of 
tiddle-shaped  rings  or  phalanges,  covers  the  hair-cells,  and  through 
openings  in  it  the  hairs  project.  A  thicker  membrane,  the  membrana 
tectoria,  springing  from  the  edge  of  the  osseous  spiral  lamina  near  the 
attachment  of  Reissner's  membrane,  forms  a  kind  of  canopy  over  both 
pillars  and  hair-cells.  The  outer  wall  of  the  canal  of  the  cochlea  is 
clad  by  cubical  epithelium  covering  a  membrane  richly  supplied  with 
bloodvessels  [stria  vascularis).  The  fact  that  the  hair-cells  of  Corti's 
organ  are  connected  with  the  fibres  of  the  cochlear  division  of  the 


Fig.  457.  -Vertical  Section  of  the  First  Turn  of  the  Cochlea  (after  Retzius).  D.C 
canal  of  cochlea;  tC,  tunnel  of  Corti;  h.m.  basilar  membrane;  h.i,  h.e,  internal 
and  external  hair-cells;  Mt,  membrana  tectoria;  s.sp,  spiral  groove;  str.v,  stria 
vascularis;  sp.l,  spiral  lamina;  n,  fibres  of  the  cochlear  nerve;  /,  limbus  lamindB 
spiralis;  R,  Reissner's  membrane;  s.v,  scala  vestibuli;  s.t,  scala  tympani;  l.sp, 
spiral  ligament. 

auditory  nerve,  and  its  elaborate  structure,  suggest  that  it  must  play 
a  peculiar  part  in  auditory  sensation.  Comparative  anatomy  shows 
us  that  the  cochlea  is  the  most  highly  developed  portion  of  the  internal 
ear,  the  last  to  appear  in  its  evolution,  and  the  most  specialized.  It 
is  absent  in  fishes,  which  possess  only  a  vestibule  and  one  to  three  semi- 
circular canals.  It  first  acquires  importance  in  reptiles,  but  attains 
its  highest  development  in  mammals;  and  there  is  every  reason  to 
believe  that  it  is  the  terminal  apparatus  of  the  sense  of  hearing. 

Functions  of  the  Auditory  Ossicles. — The  anatomical  arrange 
ments  of  the  middle  ear  suggest  that  the  tympanic  membrane  and 
the  chain  of  ossicles  have  the  function  of  transmitting  the  sound- 
waves to  the  liquids  of  the  labyrinth ;  and  observation  and  experi- 


T070 


THE  SENSES 


ment  fully  confirm  this  idea.  Tracings  of  the  movements  of  thj 
ossicles  have  been  obtained  by  attaching  very  small  levers  to  them, 
and  their  movements  have  been  directly  observed  with  the  micro- 
scope. Even  in  man  it  may  be  shown,  by  viewing  the  membrane 
through  a  series  of  slits  in  a  rapidly-revolving  disc  (stroboscope), 
that  it  vibrates  when  sound-waves  fall  on  it. 

When  the  handle  of  the  malleus  moves  inwards,  rotating  around 
an  axis  which  may  be  supposed  to  pass  through  its  neck,  its  head 
moves  in  the  opposite  direction.  The  joint  between  that  bone  and 
the  incus  is  thus  locked,  on  account  of  the  shape  of  the  articular 
surfaces.     The  long  process  of  the  incus,  constituting  the  second 


458. — Organ  of  Corti  (Barker,  after  Retzius).  mb,  basilar  membrane;  tb.  its 
tympanal  covering;  vs.  bloodvessel  (vas  spirale):  re,  medullated  distal  processes 
of  bipolar  nerve-cells  in  the  ganglion  spirale,  passing  in  to  arborize  around  the 
hair-cells;  iS,  epithelial  cells  continuous  with  the  epithelium  of  the  sulcus 
spiralis  internus;  p,  inner  pillar  of  Corti,  with  its  basal  cell,  b  ;  p',  outer  pillar 
with  its  basal  cell,  b' ;  i,  2,  3,  supporting  cells  of  Deiters,  whose  processes  run  up 
to  be  attached  to  the  lamina  reticularis,  r  :  H,  Hensen's  supporting  cells;  C,  cells 
of  Claudius;  /,  internal  hair-cell  with  its  liairs.  i'  (the  upper  part  of  the  hair-cell 
is  concealed  by  the  head  of  the  inner  pillar  of  Corti):  c,  external  hair-cell:  c',  hairs 
of  three  external  hair-cells;  n,  n^.  to  n*.  cross-sections  of  the  spiral  strand  of 
cochlear  nerve-fibres. 

portion  of  the  bent  lever,  passes  inwards,  carrying  with  it  the  stapes, 
which  is  attached  to  it  by  an  almost  rigid  joint,  and  the  stapes  is 
pressed  into  the  oval  foramen.  Since  the  long  process  of  the  incus 
is  about  one-third  shorter  than  the  handle  of  the  malleus,  the  ex- 
cursion of  the  point  of  the  former  is  correspondingly  smaller  than 
that  of  the  latter,  but  at  the  same  time  more  powerful.  When  the 
tympanic  membrane  passes  outwards,  the  handle  of  the  malleus 
and  foot  of  the  stapes  do  the  same.  But  the  joint  now  unlocks,  and 
excessive  outward  movement  of  the  stapes,  which  might  result  in 
its  being  torn  from  its  orbicular  attachment,  is  prevented.  The 
ossicles  vibrate  en  masse.     It  is  only  to  a  trifling  extent  that  sound 


HEARING  1071 

can  he  cDnducti'd  tliiou{^'li  them  to  the  hibyrinth  as  a  molecular 
vibration;  for  when  they  are  anchylosed,  and  the  foot  of  the  stapes 
fixed  immovably  in  the  foramen  ovale,  as  sometimes  occurs  in 
disease,  hearing  is  greatly  impaired. 

Of  course,  every  vibration  of  the  tympanic  membrane  must  cause 
a  corresponding  condensation  and  rarefaction  of  the  air  in  the 
middle  ear;  and  this  may  act  on  the  membrane  closing  the  fenestra 
rotunda,  and  set  up  oscillations  in  the  perilymph  of  the  scala  tym- 
pani.  That  this  is  a  possible  method  of  conduction  of  sound  is 
shown  by  the  fact  that,  even  after  closure  of  the  oval  foramen,  a 
slight  power  of  hearing  may  remain.  But  under  ordinary  con- 
ditions by  far  the  most  important  part  of  the  conduction  takes 
place  via  the  ossicles.  And  when  it  is  remembered  that  the  tym- 
panic membrane  is  about  thirty  times  larger  than  that  which  fills 
the  oval  foramen,  it  will  be  seen  that  the  force  acting  on  unit  area 
of  the  foot  of  the  stapes  may  be  much  greater  than  that  acting  on 
unit  area  of  the  membrana  tympani,  and  that  the  mode  of  trans- 
mission by  the  ossicles  is  a  very  advantageous  method  of  trans- 
forming the  feeble  but  comparatively  large  excursions  of  the  tym- 
panic membrane  into  the  smaller  but  more  powerful  movements  of 
the  stapes.  The  average  excursion  of  the  membrane  of  the  oval 
foramen  does  not  at  most  amount  to  more  than  o  04  millimetre. 
Even  the  so-called  cranial  conduction  of  sound  when  a  tuning-fork 
is  held  between  the  teeth  or  put  in  contact  with  the  head,  which 
was  at  one  time  supposed  to  be  due  solely  to  direct  transmission 
of  the  vibrations  through  the  bones  of  the  skull  to  the  liquids  of 
the  labyrinth  or  the  end-organs  of  the  auditory  nerve,  has  been 
shown  to  take  place,  in  great  part,  through  the  membrana  tympani 
and  ossicles;  the  vibrations  travel  through  the  bones  to  the  tym- 
panic membrane,  and  set  it  oscillating.  So  that  this  test,  when 
appHed  to  distinguish  deafness  caused  by  disease  of  the  middle  ear 
from  deafness  due  to  disease  of  the  labyrinth  or  the  central  nervous 
system,  may  easily  mislead,  although  it  enables  us  to  say  whether 
the  auditory  meatus  is  blocked — by  wax,  e.g. — beyond  the  tym- 
panic membrane. 

A  membrane  like  a  drum-head  has  a  note  of  its  own,  which  it  gives 
out  when  struck,  and  it  vibrates  more  readily  to  this  note  than  to  any 
other.  It  would  evidently  be  a  serious  disadvantage  if  the  tympanic 
membrane,  whose  office  it  is  to  receive  all  kinds  of  vibrations,  and 
respond  to  all,  had  a  marked  fundamental  tone  which  would  be  con- 
tinually obtruding  itself  among  other  notes.  The  difficulty  is  obviated 
by  the  damping  action  of  the  ossicles  and  the  liquids  of  the  labyrinth 
on  the  movements  of  the  membrane,  which  in  addition  is  not  stretched, 
but  lies  slacldy  in  its  bony  frame,  so  that  when  the  handle  of  the  malleus 
is  detached  from  it,  it  retains  its  shape  and  position. 

The  tensor  tympani,  when  it  contracts,  pulls  inwards  the  handle  of 
the  malleus,  and  thus  increases  the  tension  of  the  tympanic  membrane. 
The  precise  object  of  this  is  obscure.     It  has  been  suggested  that  damp- 


I072  THE  SENSES 

ing  of  the  movements  of  the  auditory  ossicles  is  thus  secured.  Another 
theory  is  that  the  increased  tension  of  the  membrane  renders  it  more 
capable  of  responding  to  higher  tones,  and  that  the  muscle  thus  acts  as 
a  kind  of  accommodating  mechanism.  But  Hensen  has  observed  that 
the  tensor  only  contracts  at  the  beginning  of  a  sound,  and  relaxes  again 
when  the  sound  is  continued ;  and  this  is  difficult  to  reconcile  with  either 
of  these  hypotheses.  The  muscle  is  normally  excited  refiexly  through 
the  vibrations  of  the  membrana  tympani,  but  some  individuals  have 
the  power  of  throwing  it  into  voluntary  contraction,  which  is  accom- 
panied by  a  feeling  of  pressure  in  the  ear,  and  a  harsh  sound.  The 
function  of  the  stapedius  is  unknown.  Its  contraction  would  tend  to 
press  the  posterior  end  of  the  foot-plate  of  the  stapes  deeper  into  the 
foramen  ovale,  and  cause  the  anterior  end  to  move  in  the  opposite 
direction ;  but  it  is  not  easy  to  see  how  this  would  affect  the  action  of 
the  auditory  mechanism. 

The  tensor  tympani  is  supplied  by  the  fifth  nerve  through  a  branch 
from  the  otic  ganglion;  the  stapedius  is  supplied  by  the  seventh. 
Paralysis  of  the  fifth  nerve  may  be  accompanied  with  difficulty  of 
hearing,  especially  for  faint  sounds.  WTien  the  seventh  nerve  is 
paralyzed,  increased  sensitiveness  to  loud  sounds  has  been  observed. 

We  have  already  recognized  tlie  organ  of  Corti,  particularly  the 
hair-cells,  as  a  sensory  epithelium  which  constitutes  the  terminal 
apparatus  of  the  cochlear  nerve.  The  adequate  stimulus  of  the 
auditory  receptors  is  the  periodic  changes  of  pressure  in  the  endo- 
lymph.  But  there  are  various  opinions  as  to  how  these  vibrations 
are  transmitted  to  the  hair-cells,  and  as  to  how  the  vibrations  of 
the  hair-cells  are  translated  into  nerve  impulses  in  the  auditory 
fibres.  The  pillars  of  Corti,  the  basilar  membrane,  and  the  mem- 
brana tectoria,  have  in  turn  been  regarded  as  the  structures  im- 
mediately set  into  vibration  by  the  changes  in  the  endolymph. 
The  case  for  the  tectorial  membrane  is  perhaps  the  most  plausible, 
for  its  position  renders  it  most  capable  of  acting  on  thi;  hairs. 
Others  have  supposed  that  the  hairs  of  the  hair-cells  are  directl}' 
affected  by  the  endolymph.  Some,  despairing  of  further  analysis, 
content  themselves  with  the  conclusion  that  the  organ  of  Corti 
vibrates  as  a  whole.  Some  of  these  theories  will  be  again  referred 
to  in  considering  what  is  the  greatest  problem  of  the  physiology  of 
hearing,  viz. : 

The  Perception  of  Pitch — Analysis  of  Complex  Sounds.— As  the 
eye,  or,  ratlier,  the  retina  plus  the  brain,  can  perceive  colour,  so  the 
labyrinth  plus  the  brain  can  perceive  pitch.  The  colour-sensation 
produced  by  ethereal  waves  of  definite  frequency  depends  on  that 
frequency;  and  upon  the  frequency  of  the  aerial  vibrations  depends 
also  the  pitch  of  a  musical  note.  But  there  is  this  difference  be- 
tween the  eye  and  the  ear:  that  while  the  sensation  produced  by  a 
mixture  of  rays  of  light  of  diticrent  wave-len,utli  is  always  a  simple 
sensation — that  is,  a  sensation  which  we  do  not  perceive  to  be  built 
up  of  a  number  of  sensations,  which,  in  other  words,  we  do  not 
analyze — the  ear  can  perceive  at  the  same  time,  and  distinguish 


HEARING  1*^73 

from  eacli  other,  the  components  of  a  compU'X  sound.  When  a 
number  of  notes  of  different  pitch  are  souncU'd  together  at  the 
same  distance  from  tlie  ear  the  disturbance  which  reaches  the  mem- 
brana  tympani  is  the  physical  resultant  of  all  the  disturbances  pro- 
duced by  the  individual  notes,  and  it  strikes  upon  the  membrane  as 
a  single  wave.  '  A  single  curve  describes  all  that  the  ear  can  possibly 
hear  as  the  result  of  the  most  compHcated  musical  performance. 
...  In  the  complicated  sound  the  variations  of  the  pressure  of  the 
air  are  more  abrupt,  more  sudden,  less  smooth,  and  less  distinctly 
periodic  than  they  are  in  softer,  purer,  and  simpler  sound.  But  the 
superposition  of  the  dit^erent  effects  is  really  a  marvel  of  marvels  ' 
(Kelvin).  The  ear  or  brain  must,  therefore,  possess  the  power  of 
resolving  the  complex  vibrations  into  their  constituents,  else  we 
should  have  a  mixed  or  blended  sensation,  and  not  a  sensation  in 
which  it  is  possible  to  distinguish  the  constituents  of  which  it  is 
made  up.  Several  hypotheses  have  been  proposed  to  explain  this 
physiological  analysis  of  sound,  on  the  assumption  that  the  analysis 
takes  place  in  the  labyrinth.  The  most  important,  in  spite  of  certain 
defects,  is  still  that  of  Helmholtz. 

Helmholtz  attempted  to  explain  the  perception  of  pitch  on  the 
assumption  that  in  the  internal  ear  there  exists  a  series  of  resonators, 
each  of  which  is  fitted  to  respond  by  sympathetic  vibration  to  a 
particular  note,  while  the  others  are  una^ected;  just  as  when  a  note 
is  sung  before  an  open  piano  it  is  taken  up  by  the  string  which  is 
attuned  to  the  same  pitch  and  ignored  by  the  rest.  Let  us  sup- 
pose that  a  given  fibre  of  the  auditory  nerve  ends  in  an  organ  which 
is  only  set  vibrating  by  waves  impinging  on  it  at  the  rate  of  lOO  a 
second,  and  that  the  end-organ  of  another  fibre  is  only  influenced 
by  waves  wnth  a  frequency  of  200  a  second.  Then,  on  the  doctrine 
of  '  specific  energy  '  (according  to  which  the  sensation  caused  by 
stimulation  of  a  nerve  depends  not  on  the  particular  kind  of  stimu- 
lus but  on  the  anatomical  connection  of  the  nerve  with  certain 
nerve  centres),  in  whatever  wa^'  the  first  fibre  is  excited,  a  sensation 
corresponding  to  a  note  with  a  pitch  of  100  a  second  will  be  per- 
ceived. Whenever  the  second  fibre  is  excited,  the  sensation  will  be 
that  of  a  note  of  200  a  second,  or  the  octave  of  the  first.  If  both 
fibres  are  excited  at  the  same  time  the  two  notes  will  be  heard 
together.  Now,  Hensen  actually  observed  that  in  the  auditory 
organs  of  some  crustaceans,  the  hair-like  processes  of  certain 
epithelial  cells  can  be  set  swinging  by  waves  of  sound,  and,  further, 
that  they  do  not  all  vibrate  to  the  same  note  unless  the  sound  is 
very  loud.  In  the  lobster  there  are  between  four  and  five  hundred 
of  these  hairs,  varying  in  length  from  14  fx  to  740  [i;  and  in  some 
insects,  such  as  the  locust,  similar  hairs,  also  graduated  in  length, 
exist. 

To  gain  an  anatomical  basis  for  his  theory,  Helmholtz  supposed 
first  of  ail  that  the  pillars  of  Corti  were  the  vibrating  structures, 

68 


1074  THE  SENSES 

and  that,  diroctly  or  through  the  hair-cells,  their  mechanical  vibra- 
tions were  translated  into  impulses  in  the  auditory  nerve-fibres. 
But  apart  from  the  fact  that  their  number  is  too  small  (about  3,000) 
to  allow  us  to  assign  one  rod  to  each  perceptible  difference  of  pitch, 
and  their  dimensions  too  similar  to  permit  of  the  requisite  range 
of  vibration  frequency,  it  was  pointed  out  that  birds  do  not  possess 
pillars  of  Corti — a  fact  which  was  decisive  against  the  assumption 
of  Helmholtz,  since  nobody  denies  to  singing-birds  the  power  of 
appreciating  pitch.  Helmholtz  accordingly,  choosing  between  the 
remaining  possibilities,  gave  up  the  pillars  of  Corti,  and  adopting 
a  suggestion  of  Hensen,  substituted  the  radial  fibres  of  the  basilar 
membrane  as  his  hypothetical  resonators.  These  are  more  ade- 
quate to  the  task  imposed  on  them,  since  their  range  of  length  is 
far  greater  (41  ju  at  the  base  to  495  jli  at  the  apex  of  the  cochlea — 
Hensen);  and  the  elaborate  structure  of  Corti's  organ  certainly 
suggests  that  some  one  or  other  of  its  elements  may  be  endowed 
with  such  a  function.  Experimentally,  too,  it  has  been  shown 
that  destruction  of  the  apex  of  the  cochlea  causes  loss  of  appreciation 
of  low  notes,  and  destruction  of  the  base  loss  of  appreciation  of  high 
notes,  which  agrees  with  Helmholtz's  view.  But  while  the  theory 
of  peripheral  analysis  of  pitch  tends  upon  the  whole  to  be  strength- 
ened as  evidence  gathers,  it  is  possible  that  the  analysis  is  accom- 
plished in  some  other  way  than  by  sympathetic  resonance. 

Ewald  has  developed  a  theory  according  to  which  each  note  causes 
the  basilar  membrane  to  vibrate  throughout  its  whole  extent  in  such 
a  way  that  stationary  waves  are  Droduced  in  it,  like  the  Chladni's 
figures  seen  on  a  metal  plate  strewed  with  sand  when  it  is  set  into 
vibration.  The  pattern  of  the  movement,  the  '  sound-picture,'  will  be 
different  for  each  tone,  since  the  interval  between  the  waves  will  be 
different.  The  hair-cells  and  auditory  fibres  of  particular  parts  of  the 
organ  of  Corti  will  therefore  be  stimulated  by  the  pressure  of  the  mem- 
brane, or  escape  stimulation,  according  to  the  position  of  the  stationary 
waves  with  reference  to  them  for  each  note.  In  this  way  each  sound- 
picture  will  be  printed,  so  to  speak,  upon  the  sensitive  terminal  appa- 
ratus of  the  auditory  nerve,  as  a  letter  is  printed  upon  a  piece  of  paper 
by  a  type.  The  corrcsj^onding  excitation  pattern — i.e.,  the  particular 
distribution  of  cochlear  fibres  stimulated — is  supposed  to  be  associated 
in  consciousness  \\dth  the  appreciation  of  the  pitch  of  the  particular 
note.  Ewald  has  endeavoured  to  suj)port  his  theory  by  showing  that 
fine  membranes  of  the  dimensions  of  the  basilar  membrane  do  yield 
very  distinct  sound-pictures  for  different  simple  tones  as  well  as  for 
complex  tones.  These  can  be  observed  with  the  microscope  and  photo- 
graphed (Fig.  459). 

One  of  the  best-known  theories  of  central  analj'sis  may  be  con- 
veniently labelled  the  'telephone  theory,'  in  accordance  with  the  simile 
used  by  Rutherford.  He  supposed  that  the  organ  of  Corti  (or  at  any 
rate  the  hair-cells)  is  set  into  vibration  as  a  whole  by  all  audible  sounds, 
and  that  its  vibrations  are  translated  into  impulses  in  the  auditory 
nerve,  which  are  the  physiological  counter])art  of  \h^  aerial  waves 
and  the  waves  of  increased  and  diminished  pressure  in  the  liquids 
of  the  labyrinth  to  which  they  give  rise.  Thus,  a  sound  of  100 
vibrations  a  second  would  start  100  impulses  a  second  in  the  auditory 


SMELL  AND  TASTE  1075 

nerve;  a  loud  sound  would  set  up  impulses  more  intense  than  a 
feeble  sound;  and  a  camplox  wave,  which  is  the  resultant  of  several 
sounds  of  difterent  vibration-frequency,  would  also  in  some  way  or 
other  stamp  the  iin])ress  of  its  /o/m  on  the  auditory  excitation  wave; 
just  as  in  a  telephone  every  wave  in  the  air  causes  a  swing  of  the 
vibr  \ting  plate,  and  thus  sets  up  a  current  of 
corresponding  intensity  and  duration  in  the 
wires.  This  theory  evidently  abandons  the 
doctrine  of  specilic  energy  for  the  particular 
case  of  the  analysis  of  pitch,  for  it  assumes 
that  differences  of  auditory  sensation  are 
related  to  differences  in  the  nature  of  the  im- 
pulses travelling  up  the  auditory  nerve,  and 
not  merely  to  diiferences  in  the  anatomical 
connections  (peripheral  and  central)  of  the 
auditor v  nerve-fibres.  It  is  unsatisfactory 
because  it  takes  no  account  of  the  remarkable 
and  suggestive  structure  of  the  telephone  plate 
— i.e.,  of  the  organ  of  Corti — and  gives  no  hint 
of  how  the  analysis  is  accomplished  in  the 
central  organ. 

The  range  of  hearing  is   very   great.     The 
highest  audible  tone  corresponds  to  30,000  to 
40,000  vibrations  a  second,  the  lowest  to  about     pig.  459.— Photograph  of  a 
30.    Between   these   limits   as  many  as  6,000       Sound-Picture  (Ewald). 
variations  of  pitch  can  be  perceived. 

Wien  has  elaborately  investigated  the  question  how  the  sensitive- 
ness of  the  ear  varies  for  tones  of  different  pitch .  A  tone  of  50  vibrations 
a  second,  in  order  to  be  just  heard,  must  have  an  intensity  corre- 
sponding to  about  100  million  times  as  much  energy  as  is  needed  for  a 
tone  of  2,000  vibrations.  It  is  only  on  the  extraordinary  sensibility 
of  the  ear  for  the  range  of  tones  used  in  ordinary  speech  that  the 
possibility  of  understanding  speech  depends  when  the  circumstances 
are  unfavourable — e.g.,  at  a  great  distance,  or  in  the  presence  of  much 
stronger  accompanying  noises. 

Section  III. — Smell  and  Taste. 

Smell  was  defined  by  Kant  as  '  taste  at  a  distance  ';  and  it  is 
obvious  that  these  two  senses  not  only  form  a  natural  group  when 
the  quality  of  the  sensations  is  considered,  but  are  closely  associated 
in  their  physiological  action,  especially  in  connection  with  the 
perception  of  the  flavour  of  the  food.  Their  intimate  relation  is 
further  indicated  by  the  fact  that  the  cortical  areas  in  which  smdl 
and  taste  are  represented  lie  close  together  or  overlap  each  other 
on  the  gyrus  hippocampi  and  uncus  (p.  968).  The  olfactory  end- 
organs  in  the  mucous  membrane  of  the  upper  part  of  the  nostrils, 
the  so-called  regio  olfactoria,  have  been  already  described  (p.  921). 
In  cases  of  anosmia,  in  which  the  olfactory  nerve  is  absent  or 
paralyzed,  smell  is  abolished;  but  substances  such  as  ammonia  and 
acetic  acid,  which  stimulate  the  ordinary  sensory  nerves  (nasal 
branch  of  fifth)  of  the  olfactory  mucous  membrane,  are  still  per- 
ceived, though  not  distinguished  from  each  other.  In  fact,  the 
so-called  pungent  odour  of  these  substances  is  no  more  a  true  smell 


I076  THE  SENSES 

than  the  sense  of  smarting  they  produce  when  their  vapour  comes 
in  contact  with  a  sensory  surface  hke  the  conjunctiva,  or  a  piece 
of  skin  devoid  of  epidermis. 

It  was  at  one  time  behevcd  tliat  odoriferous  particles  could  not 
be  appreciated  unless  they  were  borne  by  the  air  into  the  nostrils; 
but  this  appears  not  to  be  the  case,  for  the  smell  of  substances 
dissolved  in  physiological  salt  solution  is  distinctly  perceived  when 
the  nostrils  are  filled  with  the  liquid;  and  fish,  as  every  line-fisher- 
man knows,  have  no  difficult}-  in  finding  a  bait  in  the  dark.  The 
odoriferous  substances,  even  when  air-borne,  are  dissolved  in  the 
nasal  secretion  before  they  can  affect  the  olfactory  end-organs,  and 
it  may  be  due  to  the  peculiarities  of  this  solvent  that  it  is  so  difftcult 
to  imitate  a  normal  stimulation  of  the  olfactory  organs  by  solutions 
experimentally  introduced  into  the  nose  (Parker). 

The  substances  which  can  affect  the  olfactory  mucous  membrane 
can  be  divided  into  four  groups : 

1.  Those  which  act  only  on  the  olfactory  nerves,  the  odours  proper. 

2.  Substances  which  act  at  the  same  time  on  olfactory  nerves,  and  on 

nerves  of  common  sensation  (tactile  nerves) — e.g.,  acetic  acid. 

3.  Substances  which  act  at  the  same  time  on  the  gustatory  nerves. 

4.  Substances   which   act   only   on   the   nerves   of  common   sen- 

sation (tactile  nerves) — e.g.,  carbon  dioxide. 
Zwaardemaker  has  classified  the  pure  odours  as  follows : 

(1)  Ethereal  odours,  as  those  of  fruits;  (2)  aromatic  odours,  as  of 
camphor  or  bitter  almonds;  (3)  fragrant  odours,  as  of  flowers;  (4)  am- 
brosial odours,  as  of  amber  or  musk;  (5)  garlic  odours,  as  of  onion, 
garlic,  asafoetida;  (6)  empyrcumatic,  or  burning  odours,  as  of  burnt 
coffee  or  tobacco  smoke;  (7)  caprylic  or  goat  odours,  as  of  sweat; 
(8)  repulsive  odours,  as  the  odour  of  the  disease  oza?na;  (9)  nauseating 
odours,  as  of  faeces  or  putrefying  material. 

The  most  interesting  form  of  inadequate  stimulation  is  electrical 
excitation  of  the  olfactory  mucous  membrane,  which  causes  a  sensation 
like  the  smell  of  phosphorus.  The  sensation  is  experienced  at  the 
kathode  on  closure  and  the  anode  on  opening.  As  to  the  manner  in 
which  the  multitiidinous  adequate  stimuli  excite  the  olfactory  nerves, 
we  can  only  suppose  that  they  act  as  chemical  stimuli.  Smell  and 
taste  are  pre-eminently  the  '  chemical  '  senses,  as  sight  and  hearing  are 
pre-eminently  '  physical  '  senses.  But  little  is  known  of  the  relation 
between  the  chemical  constitution  or  physical  properties  of  substances 
and  the  quality  of  the  odoriferous  sensation  which  they  excite,  although 
Haycraft  has  pointed  out  some  interesting  relations  between  the  atomic 
weights  of  certain  elements  and  their  power  of  exciting  odours.  The 
number  of  distinct  odours  which  can  be  perceived  is  so  great  that  it  is 
scarcely  conceivable  that  each  is  subserved  by  special  olfactory  fibres. 
Marked  changes  occur  in  disease,  and  all  odours  need  not  be  affected 
to  the  same  extent.  Some  may  be  almost  normally  perceived,  while 
relative  or  complete  loss  of  smell  exists  as  regards  others.  These  and 
other  facts  have  given  rise  to  the  idea  that  there  are  several  groups  of 
olfactory  fibres,  each  concerned  in  the  appreciation  of  a  particular 
odour  or  group  of  odours.  Yet  it  has  not  proved  possible  to  reduce  them 
to  a  limited  number  of  fundamental  odours  and  their  combinations. 

Acviteness  of  smell  may  be  measured  by  arrangements  called  olfac- 
tometers. Zwaardemaker's  olfactometer  consists  of  a  piece  of  india- 
rubber  tubing  fitted  inside  a  glass  tube,  through  which  air  is  drawn 


SMELL  AND  TASTE  1077 

into  the  nostrils.  Another  glass  tube  just  fitting  the  rubber  tube  is 
pushed  inside  it,  so  as  to  cover  a  portion  of  it.  The  minimum  amount 
of  surface  of  the  indiarubber  tube  which  must  be  left  exposed  so  that 
the  smell  of  the  rubber  may  be  perceived  is  a  measure  of  the  acutcness 
of  smell.  To  investigate  other  odours  tubes  of  the  corresponding 
odorous  substances  can  be  constructed. 

Taste. — The  sense  of  taste  is  not  so  strictly  localized  as  the  sense 
of  smell.  The  tip  and  sides  of  the  tongue,  its  root,  the  neighbour- 
ing portions  of  the  soft  palate,  and  a  strip  in  the  centre  of  the  dorsum, 
are  certainly  endowed  with  the  sense  of  taste;  but  the  exact  hmits  of 
the  sensitive  areas  have  not  been  defined,  and,  indeed,  vary  in 
different  individuals. 

The  nerves  of  taste  are  the  glosso-pharyngeal,  which  innervates  the 
posterior  part  of  the  tongue,  and  the  lingual,  which  supplies  its  tip 
(see  p.  925).  The  end-organs  of  the  gustatory  nerves  are  the  taste- 
buds  or  taste-bulbs,  which  stud  the  fungiform  and  circumvallate 
papillae,  and  are  most  characteristically  seen  in  the  moats  surrounding 
the  latter.  They  are  barrel-like  bodies,  the  staves  of  the  barrel  being 
representctl  by  supporting  cells;  each  bud  encloses  a  number  of  gusta- 
tory cells  with  fine  processes  at  their  free  ends  projecting  through  the 
superficial  end  of  the  barrel.  They  are  surrounded  by  the  end  arboriza- 
tions of  the  fibres  of  the  gustatory  nerves.  Taste-buds  are  also  found 
on  the  posterior  surface  of  the  epiglottis  and  in  the  larynx.  It  has 
been  suggested  that  these  form  the  afferent  end-organs  of  a  reflex 
apparatus  which  guards  the  glottis  against  the  entrance  of  food  in 
deglutition  (Wilson).  Epithelial  buds,  different  from  the  olfactory 
elements,  also  occur  in  the  olfactory  region  of  the  nasal  mucous  mem- 
brane. It  is  possible  that  the  so-called  nasal  taste — e.g.,  the  sweet 
taste  caused  by  chloroform  when  aspirated  in  not  too  small  an  amount 
through  the  nose — depends  upon  these  buds. 

As  to  the  properties  in  virtue  of  which  sapid  substances  are 
enabled  to  stimulate  the  gustatory  nerve-endings,  we  know  that 
they  must  be  soluble  in  the  hquids  of  the  mouth,  and  there  our 
knowledge  ends.  An  attempt  has  been  made  by  various  authors 
to  connect  the  taste  of  such  bodies  with  their  chemical  composition, 
but  researches  of  this  kind  have  not  hitherto  yielded  much  fruit. 
The  number  of  distinct  qualities  of  taste  sensation  is  considerable, 
but  by  no  means  so  great  as  the  number  of  qualities  of  olfactory 
sensations,  and  they  are  more  easily  reduced  to  a  few  primary  or 
fundamental  sensations.  Sapid  substances  have  generally  been 
divided  into  four  classes  as  regards  the  fundamental  sensations  pro- 
duced by  them — viz.:  (i)  Sweet,  (2)  acid,  (3)  bitter,  (4)  saHne. 
All  taste  sensations  seem  to  be  combinations  of  these,  or  combina- 
tions of  one  or  more  of  them  with  olfactory  sensations,  or  with  sensa- 
tions due  to  excitation  of  the  ordinary  sensory  nerves  of  the  tongue. 

Sweet  and  acid  tastes  are  best  appreciated  by  the  tip,  and  bitter 
tastes  by  the  base,  of  the  tongue.  Differences  have  been  detected 
between  individual  papilhe  in  their  power  of  reaction  to  sapid  sub- 
stances which  produce  one  or  other  of  the  fundamental  sensation*. 
Of  125  fungiform  papillae  tested  with  solutions  of  tartaric  acid,  sugar, 
and  quinine,  27  gave  no  sensation  of  taste.     Tartaric  acid  evoked 


I078  THE  SENSES 

its  acid  tasti-  in  91  of  the  remaining  98,  sugar  its  sweet  taste  in  79, 
and  (jxiinine  its  bitter  taste  in  71 ;  12  reacted  only  to  tartaric  acid, 
and  3  only  to  sugar  (Ohrwall).  Such  facts  indicate,  althcmgh  they 
do  not  definitely  prove,  the  existence  of  specific  receptors  for  each 
of  the  fundamental  taste  sensations — i.e.,  gustatory  end-organs, 
which  are  easily  excited  by  an  adequate  stimulus  (acid,  e.g.,  in  the 
case  of  an  '  acid'  taste-bud),  with  difficulty  or  not  at  all  by  an  in- 
adequate stimulus. 

The  form  of  inadequate  stimulation  most  investigated  is  that  pro- 
duced when  a  constant  current  is  passed  through  the  tongue.  An  acid 
taste  is  experienced  at  the  positive,  and  an  alkaUnc  or  bitter  taste  at  the 
negative  pole;  and  this  is  the  case  even  wlicn  the  current  is  conducted 
to  and  from  the  tongue  by  unpolarizable  combinations,  which  prevent  the 
deposition  of  electrolytic  products  on  the  mucous  membrane  (p.  731). 
The  sensations  are  due  to  stimulation  of  the  gustatory  end-organs  and 
not  of  the  nerve-trunks. 

Normal  lymph,  which  bathes  these  end-organs,  does  not  excite  any 
sensation  of  taste,  but  when  the  composition  of  the  blood  is  altered  in 
di-sease  or  by  the  introduction  of  foreign  substances,  tastes  of  various 
kinds  may  be  perceived.  Sometimes  this  may  be  due  to  the  stimula- 
tion of  substances  excreted  in  the  saliva;  but  in  other  cases  it  seems 
that,  without  passing  beyond  the  blood  and  lymph,  foreign  substances 
may  excite  the  gustatorv  nerves. 

Flavour  embraces  a  group  of  mixed  sensations  in  which  smell  and 
taste  are  both  concerned,  as  is  shown  by  the  common  observation  that 
a  person  suffering  from  a  cold  in  the  head,  which  blunts  his  sense  of 
smell,  loses  the  proper  flavour  of  his  food,  and  that  some  nauseous 
medicines  do  not  taste  so  badly  when  the  nostrils  are  held. 

In  common  speech,  the  two  sensations  are  frequently  confounded 
with  each  other  and  with  tactile  sensations.  Thus  the  '  bouquet  '  of 
wines,  which  most  people  imagine  to  be  a  sensation  of  taste,  is  in 
reality  a  sensation  of  smell;  the  astringent  '  taste  '  of  tannic  acid  is  not 
a  taste  at  all,  but  a  tactile  sensation ;  the  '  hot  '  taste  of  mustard  is  no 
more  a  true  sensation  of  taste  than  the  sensation  produced  by  the  same 
substance  when  applied  in  the  form  of  a  mustard  poultice  to  the  skin. 

As  already  remarked,  the  substances  which  affect  the  olfactory  end- 
organs  in  air-breathing  animals,  like  those  which  affect  the  gustatory 
end-organs,  must  eventually  go  into  solution  before  causing  stimulation. 
The  most  striking  distinction  between  the  two  senses  is  the  astonishingly 
small  concentration  in  which  substances  can  elicit  sensations  of  smell, 
as  compared  with  sensations  of  taste.  Thus  ethyl  alcohol  is  a  stimulus 
for  both  smell  and  taste,  but  it  can  be  recognized  by  smell  in  a  dilution 
24,000  times  greater  than  the  dilution  necessary  for  taste  (Parker). 

Section  IV. — Cutaneous  and  Intern.xl  Sensations. 
Under  the  sens?  of  touch  it  was  at  one  time  usual  to  include  a 
group  of  sensations  which  differ  in  quality — and  that  in  some  in- 
stances to  as  great  an  extent  as  any  of  the  sensations  which  are 
universally  considered  as  separate^  and  distinct — but  agree  in  this, 
that  the  end-organs  by  which  they  are  perceived  are  all  situated  in 
the  skin,  the  mucous  membranes,  or  the  subcutaneous  tissue. 
They  are  more  correctly  designated  '  cutaneous  sensations.'  Such 
are  the  common  tactile  sensations — including  pressure,  tickling, 
and  itching — and  the  sensations  of  temperature,  or,  more  correctly, 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


to79 


of  change  of  tcnipmature,  or  of  warmth  and  cold.  The  sensation 
of  pain,  although  it  cannot  be  absolutely  separated  from  these,  ought 
not  to  be  grouped  along  with  them.  It  is  called  forth  by  the  stimula- 
tion of  afferent  nerve-iibres  in  their  course;  and  it  may  originate, 
under  certain  conditions,  in  internal  organs  which  are  devoid  of 
tactile  sensibility,  and  the  functional  activity  of  which  in  their 
normal  state  gives  rise  to  no  special  sensation  at  all.  The  peculiar 
sensation  associated  with  voluntary  muscular  effort,  to  which  the 
name  of  the  muscular  sense  has  been  given,  also  deserves  a  separate 
place;  for  although  it  may  in  part  depend  on  tactile  sensations  set 
up  through  the  medium  of  end-organs  situated  in  muscle,  tendon, 
or  the  structures  which  enter  into  the  formation 
of  the  joints,  other  elements  are,  in  all  proba- 
bility, involved. 

The  simplest  form  of  tactile  sensation  is  that 
of  mere  contact,  as  when  the  skin  is  lightly 
touched  with  the  blunt  end  of  a  pencil.  This 
soon  deepens  into  the  sensation  of  pressure 
the  contact  is  made  closer;  and  eventually  the 
sense  of  pressure  merges  into  a  feeling  of  pain. 
Most  physiologists  agree  that  in  the  skin  itself 
four  fundamental  qualities  of  sensation  are  re- 
presented— 'touch  in  the  restricted  sense  (the 
sensation  elicited  by  hght  contact),  warmth, 
cold,  and  pain.  Pressure  is  mainly  a  sensation 
connected  with  the  stimulation  of  structures 
deeper  than  the  skin — e.g.,  the  sensation  of 
contact  is  abolished  in  cicatrices  where  the 
true  skin  has  been  destroyed,  while  sensibility 
to  pressure  persists — although  the  sensation  of 
light  pressure  may  be  to  some  extent  re- 
presented in  the  skin  itself  in  association 
with  touch.  In  a  somewhat  diagrammatic 
sense  it  may  be  said  that  the  surface  of  the  skin  is  divided  into  a 
great  number  of  very  small  areas,  each  of  which  is  related  especially 
to  one  or  other  of  the  four  fundamental  sensations.  Areas  con- 
cerned in  one  sensation  are  everywhere  mingled  with  areas  con- 
cerned in  the  others.  By  appropriate  methods  it  has  been  found 
possible  to  determine  the  existence  on  the  skin  of  the  trunk  and 
limbs  of  not  less  than  30,000  '  warm-spots,'  which  always  react  to 
stimulation  by  a  sensation  of  warmth;  250,000  '  cold-spots,'  which 
react  by  a  sensation  of  cold;  and  half  a  million  touch-spots,  whose 
specific  reaction  is  a  sensation  of  touch.  It  is  more  difficult  to 
locahze  definitely  bounded  '  pain-spots,'  partly  because  of  the  very 
rich  supply  of  pain-fibres  to  the  '^kin.  Yet  there  is  reason  to  beheve 
that  pain,  like  touch,  warmth,  and  cold,  is  subserved  by  separate 


Fig.  460. — Tactile  Cor- 
puscle from  Skin  of 
Finger  (Smirnow). 
(Golgi  preparation.) 
The  winding  and  in- 
tersecting black  lines 
are  the  non-medul- 
lated  endings  of  the 
one  or  more  nerve- 
fibres  that  enter  the 
corpuscle. 


loSo  THE  SENSES 

receptors.  The  simplest  assumption  wliicli  will  satislactorilv 
account  for  the  distribution  of  the  four  fundamental  cutaneous 
sensations  is  that  the  skin  is  supplied  with  four  kinds  of  nerve- 
fibres,  anatomically  as  well  as  functionally  distinct.  Some  fibres 
minister  to  the  sensation  of  cold,  (others  to  that  of  waniith.  others 
to  that  of  touch,  and  others  still  to  pain.  And  just  as  stimulation 
of  the  optic  ner\c  gives  rise  to  a  sensation  of  light,  so  stimulation 
of  any  one  of  the  cutaneous  n(  rves  gives  rise  to  the  specific  sensa- 
tion proper  to  the  group  to  which  it  belongs.  The  existence  of 
different  forms  of  sensory  end-organs  in  the  skin  and  other  tissues 
(tactile  or  touch-corpuscles,  corpuscles  of  Pacini,  end-bulbs  of 
Krause,  etc.)  points  in  the  same  direction.  The  end-organs  of  the 
touch  sensations  are  believed  to  be  the  ring-like  arrangements  of 
non-medullated  nerve-fibres  encircling  the  hair-follicles,  and  in 
parts  of  the  skin  devoid  of  hairs  the  corpuscles  of  Meissner  (v.  Frey) 

Touch-spots  can  easily  be  demonstrated  by  touching  the  skin  lightly 
with  some  small  object  such  as  a  hair.  The  most  exact  quantitative 
observations  have  been  made  by  means  of  v.  Frey's  hair  aesthesiometer. 
This  consists  of  a  handle  in  which  hairs  of  different  diameter  can  be 
fixed.  The  area  of  the  cross  section  of  each  hair  is  measured  under  the 
microscope,  and  the  pressure  necessary  to  bend  it  is  determined  by 
pressing  it  upon  the  scale-pan  of  a  balance.  The  pressure  in  milli- 
grammes, divided  by  the  cross  section  in  square  millimeters,  gives  the 
pressure  per  square  millimetre,  which,  according  to  v.  Frey,  permits 
hairs  to  be  chosen  so  as  to  give  a  uniform  intensity  of  stimulation  or 
a  variable  intensity,  according  to  the  object  of  the  investigation.  Many 
observers,  however,  believe  that  it  is  more  accurate  to  take  no  account 
of  the  pressure  per  unit  of  area,  but  to  graduate  the  hairs  according  to 
the  total  pressure  needed  to  bend  them.  When  touch-spots  ascer- 
tained in  this  way  are  excited,  by  an  inadequate  stimulus — e.g.,  an 
alternating  current  of  minimal  strength,  applied  by  the  unipolar 
method  through  the  head  of  a  pin  as  an  electrode — they  still  respond 
by  their  characteristic  or  specific  reaction — namely,  a  sensation  of 
touch — in  the  case  supposed,  a  vibrating  sensation  like  that  caused  by 
a  tuning-fork  in  contact  with  the  skin.  In  the  spaces  between  the 
touch-spots  the  sensation  produced  by  the  same  strength  of  current,  or 
even  by  a  weaker  current,  is  not  one  of  touch,  but  a  painful  pricking 
sensation  which  has  no  vibratory  character,  but  is  permanent  as  long 
as  the  current  lasts. 

The  spots  most  sensitive  to  touch  lie  close  to  the  hairs  on  their 
'  windward  '  side — i.e.,  on  the  side  awav  from  which  they  slope.  The 
minimum  pressure  necessary  to  evoke  a  sensation  of  contact  is  not  the 
same  for  every  portion  of  the  skin.  The  forehead  and  palm  of  the 
hand  are  most  sensitive.  According  to  Lombard  the  cutaneous  pres- 
sure and  tickle  sensations  called  out  by  delicate  mechanical  stimuli 
(hairs,  etc.),  do  not  arise  from  the  same  spots. 

If  two  points  of  the  skin  are  touched  at  the  same  time  there  is  a 
double  sensation  when  the  distance  between  the  points  exceeds  a  cer- 
tain minimum,  which  varies  for  different  parts  of  the  sensitive  surface. 

Practice  increases  the  acuity  of  touch  for  the  two  points  test.  Even 
in  a  few  hours  it  mav  be  temporarilv  quadrupled  on  some  parts  of  the 
skin.  Since  at  the  same  time  it  is  increased  m  the  corresponding  part 
of  the  opposite  side  of  the  body,  it  is  argued  that  the  modification  takes 
place  in  the  central  nervous  system,  not  in  the  end-organs  themselves. 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


•1081 


Few  of  the  internal  organs  are  supplied  with  tactile  nerves.  The 
mucous  membrane  of  the  alimentary-  canal  from  the  upper  end  of  the 
oesophagus  to  the  junction  of  the  rectum  with  the  anal  canal  is  in- 
sensitive to  tactile  stimulation  (Hertz).  The  movements  of  a  tape- 
worm in  the  intestines  are  not  recognized  as  tactile  sensations,  nor  the 
movements  of  the  alimentary  canal  during  digestion,  nor  the  rubbing 
of  one  muscle  on  another  during  its  contraction. 


Number  of  Touch- 
Spots  per  Sq.  Cm. 

Mean  Threshold  Value 
.     Grammes 

in  7; r; 

bq.  Mm. 

Wrist  (ventral  surface) 
Wrist  (dorsal  surface)   ... 
Forearm       .         -         .         -         - 
Elbow  ------ 

Upper  arm    -         -         -         -         - 

Foot  (dorsal  surface)     -         -         - 
Leg  (ventral  surface)    - 
Thigh  (ventral  surface) 
Breast-         .         -         -         .         - 
Back 

28 
28 
16 
12 
10 
23 
5 
14 
21 
26 

I«I 

I'2 
1*2 

1-3 
1*4 

I'2 
2'I 

1-3 

2-7 

4-3 

(Ktesow). 

Pressure  is  only  perceived  when  it  affects  two  neighbouring  areas  to 
a  different  degree.  Thus,  the  atmospheric  pressure,  bearing  uniformly 
on  the  whole  surface  of  the  body,  causes  no  scrsation;  we  are  so  entirely 
unconscious  of  it  that  it  needed  the  inspiration  of  genius  to  discover 
it,  and  the  persistence  of  genius  to  force  the  discovery  on  the  world. 
When  the  finger  is  dipped  in  a  trough  of  mercury  at  its  own  temperature, 
no  sensation  is  perceived  except  a  feeling  of  constriction  at  the  surface 
of  the  liquid.  The  perception  of  light  pressure  and  of  the  form  and  size 
of  objects  in  contact  with  the  skin  is  believed  to  be  due  to  the  touch- 
spots.  Deep  pressure,  however,  is  appreciated,  not  by  the  skin,  but 
through  sensory  end-organs  in  deeper  structures — probably,  e.g., 
Pacini's  corpuscles  and  the  muscle-spindles  (Fig.  471,  p.  1096). 


Distance  at  which  Two  Points 

can  be  distinctly  felt,  in  Mm. 

Point  of  tongue    - 

I  "I 

Palmar  surface  of  third 

phalanx  of  finger 

2-2 

Dorsal  surface  of  third 

phalanx  of  finger 

6-7 

Tip  of  nose  -         -         - 

6-7 

Back    -         -         -         - 

II-2 

Eyelids         -         -         _ 

II-2 

Skin  over  sacrum 

40-5 

Upper  arm  -         -         - 

67-6 

Sensations  of  Warmth  and  Cold. — When  a  body  colder  or  hotter 
than  the  skin  is  placed  on  it,  or  when  heat  is  in  any  other  way 


1082 


THE  SENSES 


withdrawn  from  or  imparted  to  the  cutaneous  tissues  with  sufficit-nl 
abrujitnoss,  a  sensation  of  cold  or  warmth  is  experienced.  And 
when  two  portions  of  the  skin  at  different  temperatures  are  put  in 
contact,  we  feel  that,  relatively  to  one  another,  one  is  warm  and 
the  other  cold.     But  it  is  worthy  of  remark  that  it  is  only  difference 

of  temperature  (or,  perhaps,  rather  the 
rate  at  which  heat  is  being  gained  or 
lost  by  the  skin),  and  not  absolute 
height,  which  we  are  able  to  estimate 
by  our  sensations.  Thus,  a  hand  which 
has  been  working  in  ice-cold  water  will 
feel  water  at  io°  C.  as  warm ;  whereas  it 
would  appear  cold  to  a  warm  hand. 

Blix,  Goldscheider,  and  others  have 
shown  that  the  whole  skin  is  not  en- 
dowed with  the  capacity  of  distin- 
guishing temperature,  but  that  the 
temperature  sensations  are  confined 
to  minute  areas  scattered  over  the 
cutaneous  surface.  The  great  majority 
of  these  are  '  cold  '  spots — i.e.,  respond 
to  stimulation  only  by  a  sensation  of 
cold  —  while  a  smaller  number  are 
*  warm  '  spots,  and  respond  only  by  a 
sensation  of  warmth  (Fig.  461).  These 
spots  can  be  mapped  out  by  bringing 
into  contact  with  the  skin  small  pieces 
of  wire  at  a  temperature  a  few  degrees 
above  or  below  that  of  the  skin.  With 
such  mild  stimuli  a  response  can 
generally  be  obtained  only  from  one 
kind  of  spot — that  is,  the  cold  wire 
stimulates  only  the  cold  and  not  the 
warm  spots,  and  vice  versa-— hut  with 
much  more  intense  thermal  stimuli — 
say,  temperatures  of  45°  to  50°  C. — 
not  only  do  the  warm  spots  respond 
with  the  appropriate  sensation,  but 
the  cold  spots  respond  with  a  sensation 
of  cold.  This  is  well  seen  when  a 
beam  of  sunlight  is  focussed  succes- 
sively on  a  warm  and  a  cold  spot.  Inadequate  stimuli  (mechanical 
and  electrical)  also  evoke  the  specific  response  of  warmth  from 
warm  spots,  and  of  cold  from  cold  spots. 

When  the  hand  is  put  into  water  at  the  temperature  of  the  skin, 
and  the  water  slowly  heated,  the  warm  spots  are  at  first  alone  stimu- 


Fig.  461. — 'Warm'  and  'Cold' 
Areas  on  Skin  (Goldscheider). 
The  areas  are  mapped  out  on 
the  palm  of  the  left  hand.  In 
the  upper  figure  the  relative 
sensitiveness  to  warmth  is 
represented  by  the  depth  of  the 
shading,  the  black  areas  being 
most  sensitive,  then  the  lined 
areas,  then  the  dotted,  and 
last  of  all  the  white  areas.  In 
the  lower  figure  the  relative 
sensitiveness  to  cold  stimuli  is 
shown  in  the  same  way. 


CUTANEOUS  A\D  INTERNAL  SENSATIONS  1083 

lated,  and  the  sensations  of  lukewarm  and  then  of  warm  are  experi- 
enced. When  the  temperature  of  the  water  reaches  45°  C.,  the 
quahty  of  t  he  sensation  changes  to  '  hot . '  At  a  still  higher  tempera- 
ture the  sensation  becomes  painful  or  burning.  The  most  probable 
explanation  of  these  facts  is  mentioned  below  (p.  1084). 

It  is  not  only  of  physiological  interest,  but  of  practical  importance, 
that  most  mucous  membranes  are  in  comparison  with  the  skin  but 
slightly  sensitive  to  changes  of  temperature.  Only  towards  the  ends 
of  the  alimentary  canal,  in  the  mouth,  pharynx,  oesophagus,  and  anal 
canal,  is  it  possible  to  elicit  warmth  or  cold  sensations.  There  is  some 
difference  of  opinion  whether  a  blunted  sensibility  appears  in  the 
stomach  also.  The  uterus,  too,  is  quite  insensible  to  moderate  heat; 
and  hot  liquids  may  be  injected  into  its  cavity  at  a  temperature  higher 
than  that  which  can  be  borne  by  the  hand,  without  causing  inconveni- 
ence— a  fact  which  finds  its  application  in  the  practice  of  g^-naecologv 
and  obstetrics.  It  is.  indeed,  obvious  that  in  the  greater  number  of 
the  internal  organs  the  conditions  necessary  for  stimulation  of  tem- 
perature nerves,  even  if  such  were  present,  could  hardly  ever  exist. 

It  has  already  been  mentioned  that  changes  of  external  temperature 
exert  a  remarkable  influence  on  the  intensity-  of  metabolism  (p.  693), 
and  it  has  been  supposed  that  this  is  brought  about  by  afferent  impulses 
travelling  up  the  cutaneous  nerves.  We  have  also  seen  that  for  certain 
kinds  of  stimuli  the  excitability  of  nerve-fibres  is  increased  by  cooling 
(p.  784).  It  is  possible  that  this  is  the  case  for  the  fibres  in  the  skin 
which  are  concerned  in  the  regulation  of  the  production  of  heat,  and  it 
has  been  suggested  that  this  fact  may  have  a  bearing  on  the  reflex 
regulation  of  temperature  (Lorrain  Smith) . 

Pain  Sensations. — \\'hile  the  cold  and  the  warmth  spots  are  irregu- 
larly distributed  over  the  skin  in  more  or  less  compact  groups,  and 
the  touch  sensations  are  intimately  associated  wath  the  hair  follicles, 
the  pain  spots  are  more  uniformly  spread,  and  at  the  same  time  set 
closer  together.  In  parts  of  the  body  where  but  one  of  these 
elementary  forms  of  general  sensibility  is  present,  as  in  the  central 
parts  of  the  cornea  and  in  the  dentine  and  pulp  of  the  teeth,  it  is 
always  pain. 

In  certain  situations  pain  and  temperature  sensibihty  are  found 
together,  but  not  touch — e.g.,  at  the  margin  of  the  cornea  and  on 
the  conjunctiva. 

In  general,  the  skin  is  far  more  sensitive  to  pain  than  the  deeper 
structures.  The  most  painful  part  of  an  operation  is  generally  the 
stitching  of  the  wound.  The  cutting  of  healthy  muscle  causes  no 
pain.  In  an  operation  in  which  an  artificial  connection  was  estab- 
lished between  the  stomach  and  the  small  intestine  (gastro-enter- 
ostomy),  and  in  which  no  anaesthetic  was  administered,  the  only 
pain  of  which  the  patient  complained  was  produced  by  the  incision 
in  the  skin  (Senn).  This,  however,  does  not  prove  that  the 
abdominal  viscera  are  devoid  of  pain  nerves,  for  it  has  been  showTi 
in  animals  that  exposure  of  the  intestines,  etc.,  as  in  laparotomv, 
leads  to  a  rapid  depression  (exhaustion  ?)  of  the  sensibility  for  pain 


io84  THE  SENSES 

(Kast  and  Mdtzei).  In  the  intact  animal  and  human  being  painful 
impressions  can  unquestioneibly  be  excited  in  tlie  viscera  by  adequate 
stinmli  (p.  9<Ji).  Thus,  the  spasmodic  contraction  of  tlie  intestines 
and  stomach  causes  the  intense  pain  of  cohc  and  gastralgia.  Labour 
is  an  example  of  a  strictly  physiological  function  which  is  the 
occasion  of  severe  pain.  It  would  appear  from  the  observations 
of  Hertz  that  the  only  immediate  cause  of  true  visceral  pain,  as 
distinguished  from  referred  pain  (p.  891)  is  distension  acting  on  the 
muscular  coat  of  hollow  organs  and  on  the  fibrous  capsule  of  solid 
organs.  The  sensation  of  pain  in  the  alimentary  canal  is  due  to  a 
more  rapid  or  a  greater  distension  than  that  which  constitutes  the 
adequate  stimulus  for  the  sensation  of  fulness.  Visceral  sensi- 
bility seems  to  be  exaggerated  in  such  conditions  as  hypochondri- 
asis, neurasthenia,  and  anaemia.  Tissues  normally  insensible,  or, 
rather,  but  slightly  sensible,  to  pain  may  become  acutely  painful 
when  inflamed. 

The  question  has  been  raised  whether  the  sensation  of  pain  can 
be  caused  by  excessive  stimulation  of  the  nerves  of  common  tactile 
sensibility,  or  of  the  nerves  that  subserve  the  sensations  of  coolness 
and  warmth.  It  is  true  that  when  the  skin  is  lightly  touched  in 
the  region  of  a  touch-spot  with  a  small  object  at  its  own  temperature 
the  sensation  is  one  of  pure  touch.  As  the  pressure  is  increased,  a 
sensation  of  pressure,  quite  distinct  from  that  of  contact,  may  be 
felt ;  and  if  the  pressure  is  stiU  further  increased,  a  sensation  of  pain 
may  be  elicited.  It  seems  to  be  quite  clearly  made  out  that  the 
pressure  sensation  in  this  case  is  due  not  to  excessive  stimulation 
of  the  touch-nerves,  but  to  stimulation  of  the  specific  pressure- 
nerves  when  the  threshold  is  reached.  The  most  natural  explana- 
tion of  the  pain  sensation  is  that  it,  too,  is  due  to  excitation  of  the 
nervous  apparatus  for  pain.  Similarly  (as  was  stated  on  p.  1082), 
if  the  skin  is  raised  to  higher  and  higher  temperatures,  the  response 
is  at  first  a  pure  sensation  of  warmth,  increasing  in  intensity  without 
changing  its  quality.  When  a  certain  temperature  (about  45°  C) 
is  exceeded,  the  sensation  changes  to  '  hot,'  either  because  a  pain 
element  is  now  added  to  the  pure  thermal  sensation,  or  because  the 
cold  spots  are  now  stimulated  as  well  as  the  warm  spots,  and  mingle 
their  specific  response  (cold  sensation)  with  that  of  the  warm  spots. 
Further  increase  of  the  temperature  will  cause  distinct  pain,  the 
sensation  assuming  a  burning  character.  When  a  cold  spot  is 
tested  with  decreasing  temperatures,  an  analogous  series  of  sensa- 
tions is  run  through,  the  pure  sensation  of  coolness  eventually  giving 
place  to  cold,  intense  cold,  and  finally  pain.  Here,  also,  it  is  simplest 
to  assume  that  the  pain  sensation  is  caused  not  by  excessive  stimu- 
lation of  warm  or  cold  spots,  but  by  excitation  of  the  specific  pain- 
spots.  In  any  case,  there  is  no  doubt  that  afferent  '  pain  '  fibres 
exist  which  are  anatomically  distinct  from  the  fibres  of  tactile  and 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1085 

of  temperature  sensations.  For  the  conducting  paths  in  the  spinal 
cord  are  not  the  same  for  tactile  and  for  painful  impression*;.  And 
in  certain  cases  of  disease  sensibility  to  pain  may  be  lost,  while 
tactile  sensations  are  still  perceived ;  or,  on  the  other  hand,  pain  may 
be  felt  in  cases  where  tactile  sensibility  is  abolished.  Loss  of  tem- 
perature sensation,  however,  is  usually  accompanied  by  loss  of 
sensibility  to  pain.  When  a  nerve  is  compressed,  the  sensibility 
of  the  tract  supplied  by  it  disappears  for  cold  sooner  than  for 
warmth. 

Pain  has  been  defined  as  '  the  prayer  of  a  nerve  for  pure  blood.'  The 
idea  is  not  only  true  as  poetry,  but,  with  certain  deductions  and  limita- 
tions, true  as  physiology;  that  is  to  say,  pain,  as  a  rule,  is  a  sign 
that  something  has  gone  wrong  with  the  bodily  machinery;  freedom 
from  pain  is  the  normal  state  of  the  healthy  body.  Physiologically, 
pain  acts  as  a  danger-signal.  It  points  out  the  seat  of  the  mischief, 
and  even,  in  certain  cases,  by  compelling  rest,  favours  the  process  of 
repair.  Thus,  the  surgeon  has  sometimes  looked  upon  pain  as  '  Nature's 
splint.'  But,  as  a  matter  of  fact,  a  certain  amount  of  pain  occurring 
at  intervals  is  not  incompatible  with  high  health;  and  probably  nobody, 
even  when  accidents  and  indiscretions  of  all  kinds  are  avoided,  is  en- 
tirely free  from  pain  for  any  considerable  time.  Sometimes,  indeed, 
the  mere  fixing  of  the  attention  on  a  particular  part  of  the  body  is 
suJB&cient  to  bring  out  or  to  detect  a  slight  sensation  of  pain  in  it;  and 
it  is  matter  of  common  experience  that  a  dull  continuous  pain,  like  that 
of  some  forms  of  toothache,  is  aggravated  by  thinking  of  it,  and  relieved 
when  the  attention  is  diverted. 

As  to  the  sensations  of  tickling  and  itching,  it  is  enough  to  say 
that  physiologists  are  not  agreed  whether  they  represent  specific 
sensibilities  subserved  by  special  nerves  distinct  from  those  of  touch 
and  pain,  or  merely  modifications  or  mixtures  of  these  sensations. 

Phenomena  observed  after  Section  of  Cutaneous  Nerves. — ^The 
innervation  of  the  skin  can  be  explored  not  only  by  appropriate 
stimulation  of  the  normal  skin,  but  by  study  of  the  defects  or  altera- 
tions of  sensibility  which  follow  section  of  a  cutaneous  nerve,  and 
which  may  be  observed  at  different  stages  in  its  regeneration.  In 
recent  years  this  has  proved  a  fruitful  method,  especially  in  experi- 
ments made  by  skilled  observers  in  whom  one  or  more  cutaneous 
nerves  were  intentionally  divided. 

An  extensive  investigation  was  made  by  Trotter  and  Davies. 
They  divided  at  different  times,  extending  over  more  than  a 
year,  no  fewer  than  seven  of  their  own  <;utaneous  nerves,  in- 
cluding the  internal  saphenous  at  the  knee,  the  great  auricular, 
three  divisions  or  branches  of  the  internal  cutaneous  of  the  arm 
just  below  the  elbow,  and  a  branch  of  the  middle  cutaneous  of 
the  thigh.  The  operations  were  purposely  done  at  such  intervals 
as  would  allow  the  experience  gained  in  investigating  one  area 
to  be  applied  to  others.  About  a  quarter  of  an  inch  was  cut  out 
of  each  nerve,  and   the   ends   then  sutured  together.     '  In  each 


io86 


THE  SENSES 


case  the  area  of  skin  supplied  by  the  nerve  showed  defcc^ts  in  seven 
distinct  functions:  four  sensory — namely,  sensibihty  to  touch,  cold, 
heat,  pain — and  three  motor — namely,  vaso-motor,  pilo-motor, 
sudo-motor  (sweat -secretory).  The  sensory  changes  showed  a 
central  area  of  profound  loss,  an  area  of  moderate  extent  surrounding 


Stpokinc  oi/nim 


Fig.  46i:. — .\reas  of  Altered  Sensibility  produced  by  Section  of  all  Three  Branches 
of  the  Internal  Cutaneous  Nerve  of  the  Left  Forearm  (Trotter  and  Davies). 
(Reduced  by  Two-thirds.)  The  thick  lines  show  the  areas  of  anaesthesia  to  the 
brush.  The  thick  continuous  lines  enclose  the  areas  of  the  anterior  and  posterior 
branches.  The  thick  broken  line  and  heavy  shading  mark  the  area  of  the  in- 
crease in  anffisthesia  which  followed  section  of  the  middle  branch.  The  thin 
lines  show  the  areas  of  minimal  hypoa;sthesia — i.e.,  the  '  stroking  outline.'  The 
complete  oval  outline  is  the  '  stroking  outline  '  which  followed  section  of  the  pos- 
terior branch.  The  large  addition  to  the  oval  on  the  right  of  the  diagram  shows  the 
increase  in  the  '  stroking  outline  '  which  followed  section  of  the  anterior  branch. 
The  thin  broken  line  and  fine  shading  show  the  additions  to  the  '  stroking  out- 
line '  produced  by  division  of  the  middle  branch. 

this  of  partial  loss,  and  a  large  area  in  which  a  qualitative  change 
could  be  alone  detected.'  The  maximal  extent  of  change,  and 
therefore  the  outer  boundary  of  this  third  area,  can  be  mapped  out 
by  getting  the  subject  to  determine  by  light,  stroking  touches  the 
area  which  feels  in  any  way  unnatural  when  he  touches  it  himself. 
The  most  common  feeling  is  that  the  skin  has  become  smoother  at 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


IO&7 


llu!  bijundary  as  the  stroking  linger  crosses  it,  coming  from  the 
normal  skin.  This  area  is  always  much  larger  than  the  area  in- 
cluded in  it,  in  which  by  quantitative  methods — e.g.,  the  use  of  a 
very  fine  camel's-hair  brush,  or  more  exactly  by  the  v.  Frey  hairs — 
the  sensibility  to  touch  can  be  shf)wn  to  be  diminished  (region  of 
hypotcsthesia  to  touch)  (Fig.  4^-)- 

For  a  variable  distance  within  the  '  stroking  outline  '  the  hypo- 


Fig.  463. — Middle  Cutaneous:  Left  Thigh  (Trotter  and  Uavies)  (reduced  by  One- 
third  Linear).  Twenty-six  days  after  section.  Results  of  examination  with 
V.  Frey  hairs.  Touch  spots  marked  •  responded  to  hair  of  280  milligrammes' 
pressure;  those  marked  o  to  hair  of  800  milligrammes;  and  those  marked  +  to 
liair  of  2,280  milligrammes.  The  continuous  line  marks  the  limit  within  which 
there  was  anaesthesia  to  the  camel's-hair  brusli. 

aesthesia  for  tactile  stimuli  is  so  slight  that  it  cannot  be  detected 
with  the  brush  or  udth  cotton-wool,  or  even  with  the  v.  Frey  hairs. 
Like  those  of  normal  skin,  90  per  cent,  of  its  hair-bulbs  respond  to 
a  hair  exerting  a  pressure  of  70  milligrammes,  and  the  remaining 
10  per  cent,  to  hairs  exerting  a  pressure  of  140  or  280  milligrammes. 
Inside  this  zone  of  minimal  hypoaesthesia  the  defect  of  sensibility 


io88 


THE  SENSES 


rapidly  increases  as  we  pass  inwards,  each  line  of  hair  bulbs  re- 
quiring a  heavier  pressure  than  the  lin«'  external  to  it,  till  at 
last  3I  or  4  grammes'  pressure  is  needed  to  cause  a  sensation  of 
touch,  and  inside  of  this  line  of  hairs  the  skin  does  not  respond 
at  all  (Fig.  463). 

For  thermal  sensibility  there  is  also  a  region  of  complete  anaes- 
thesia and  a  region  of  partial  anaesthesia.     The  best  way  of  out- 


*.  •  •  *  •  J  •  •*•  •  • 

•• »     .       •  •  •  ••  •«• 

•     •••••••• 


Fig.  464.— Middle  Cutaneous:  Left  Thigh  (Trotter  and  Davies).  Twenty-one  da>'S 
after  section.  Results  of  examination  with  temperature  of  o"  C.  On  spots 
marked  •  stimulus  was  felt  as  cold;  on  spots  marked  o  it  was  felt  as  cool.  The 
blank  area  is  that  of  thermal  anaesthesia.  The  continuous  outline  marks  the 
limit  within  which  there  was  anaesthesia  to  the  camel's-hair  brush. 

lining  these  is  the  use  of  a  temperature  of  0°  C.  as  the  stimulus 
(Fig.  464). 

Outside  the  zone  of  complete  thermal  anaesthesia  there  is  a  region 
in  which  temperature  sensations  are  distinctly  elicited,  but  do  not 
possess  the  normal  intensity,  the  temperature  of  0°  C,  for  example, 
being  felt  only  as  cool,  and  not  as  cold.  The  outer  limit  of  this 
region  is  the  line  at  which  the  temperature  of  0°  C.  is  first  felt  as 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1089 


we  work  inwards  from  the  normal  skin  to  yield  the  sensation  of 
cool  instead  of  cold.  Similarly,  the  outer  limit  of  thcrmo-hypo- 
aesthesia  can  be  determined  by  using  a  high  temperature  (50°  C  ). 
It  is  the  line  at  which  the  sensation  of  hot  yielded  by  the  normal 
skin  gives  place  to  the  sensation  of  warm.  The  two  boundaries 
correspond  closely  when  allowance  is  made  for  the  separate  grouping 
of  cold  and  warmth  spots  on  the  normal  skin. 


•V 


Fig.  465. — Middle  Cutaneous  (External  Branch):  Left  Thigh  (Trotter  and  Davies). 
Twenty-three  da\-s  after  section.  Results  of  examination  with  algometer  (an 
arrangement  by  which  a  needle  is  pressed  against  the  skin  by  a  hair  whose 
pressure  value  has  been  determined).  Spots  marked  •  reacted  by  sensation  of 
pain  to  pressure  of  i,86o  milligrammes  (normal  threshold);  spots  marked  o  re- 
quired 2,280  milligrammes.  The  continuous  line  marks  the  area  within  which 
there  was  anaesthesia  to  the  camel's-hair  brush. 


The  investigation  of  the  sensibility  of  the  skin  areas  for  painful 
stimuli  is  complicated  by  the  fact  that  during  a  certain  period; 
from  about  the  second  to  the  sixth  week  after  division  of  the  nerve, 
hyperalgesia  (increased  sensitiveness  to  painfuJ  impressions)  may 
appear.  This,  however,  does  not  seem  to  be  a  consequence  of  any 
sensory  loss,  but  rather  a  complication  due  to  an  irritative  change. 
When  this  is  taken  account  of,  it  is  found  that  the  defect  of  sensi- 
bility to  pain  after  nerve  section  resembles  the  defects  of   sensi- 

69 


lo^d  THE  SENSES 

bility  to  touch  and  temperature,  showing  a  central  area  of  absolute 
anaesthesia  surrounded  by  a  zone  of  ])artial  loss,  which  is  slight 
towards  the  outer  boundary,  but  increases  as  we  pass  inwards 
(Fig.  4^)5)- 

After  section  of  a  nerve  function  is  recovered  only  as  a  result  of 
regeneration.  This  is  true  of  all  the  sensory  functions  of  the  skin 
and  of  the  pilo-motor  and  sudo-motor  functions.  Vaso-motor  tone 
in  the  affected  area  is  restored  much  sooner  than  the  other  functions. 
This  rapid  recovery  probably  depends  upon  a  local  compensatory 
mechanism,  and  not  upon  regeneration  of  the  vaso-motor  fibres. 
Recovery  of  all  the  functions  dependent  upon  regeneration  begins 
about  the  same  time,  and  this  recovery  progresses  over  the  area  at 
about  the  same  rate  for  all,  although  the  rate  at  which  they  progress 
towards  normal  acuitj^  is  different. 

Sensibility  to  touch  probably  appears  a  little  earlier  than  sensi- 
bility to  cold  and  pain.  Yet  the  recovery  of  touch  does  not  progress 
so  fast,  and  for  awhile  a  given  zone  of  the  recovering  area  remains 
hypoaesthetic  (less  sensitive  than  normal)  to  touch,  while  to  cold 
and  pain  it  soon  becomes  even  hypersensitive.  The  most  remark- 
able peculiarities  of  a  recovering  area  are  :  (i)  This  qualitative 
change,  in  virtue  of  which  cold,  pain,  and  the  pain  element  of  heat 
are  intensified,  while  touch  is  little  altered,  although  more  difficult 
to  elicit ;  (2)  the  reference  of  sensations,  not  to  the  point  stimulated, 
but  to  distant  parts  of  the  area. 

'When  a  spot  which  has  developed  this  peripheral  reference  is 
touched,  one  of  two  possibilities  may  occur:  either  the  touch  is 
felt  locally,  and  is  referred  as  well,  or  nothing  is  felt  locally,  and 
the  touch  is  felt  in  the  area  of  peripheral  reference.  The  region 
in  which  the  referred  touch  is  felt  is  always  at  the  edge  of  the  most 
peripheral  part  of  the  anaesthesia,'  perhaps  more  than  a  foot  awaj' 
from  the  spot  actually  touched.  The  peripheral  reference  of  cold 
is  even  more  striking,  particularly  in  the  remarkable  intensity  of 
the  referred  sensation. 

Peripheral  reference  occurs  also  with  pain.  '  The  referred  pain 
shows  three  well-marked  qualities:  it  is,  proportionately  to  the 
stimulus,  very  intense  ;  it  does  not  reproduce  a  normal  sensation 
with  the  exactitude  found  in  the  case  of  touch  or  cold,  but  has  a 
special  quality  of  strangeness  and  unpleasantness,  such  as  no  pin- 
prick on  normal  skin  can  give;  finally,  it  produces  an  almost  irre- 
sistible desire  on  the  part  of  the  subject  to  rub  or  scratch  the  region 
in  which  it  is  felt.'  As  recovery  proceeds  the  local  sensory  response 
becomes  more  distinct,  and  the  abnormal  quality  of  both  local  and 
referred  sensations  fades.  But  '  while  peripheral  reference  is  the 
earliest  phenomenon  of  recovery,  it  persists  until  recovery  is  so  far 
advanced  that  hypoaesthesia  is  scarcely  detectable  by  any  quanti- 
tative methods.' 


CUTANEOUS  A\D  INTERNAL  SENSATIONS  1091 

The  work  of  Heatl,  who  was  the  pioneer  in  this  method  of  investiga- 
tion, must  also  be  mentioned.  He  found  that  when  tlie  median  nerve 
was  divided  in  his  own  arm,  recovery  of  sensation  began  with  the 
restoration  of  scnsibihty  to  pain  and  to  extreme  degrees  of  heat  and 
cold;  but  the  hand  stiUremained  for  a  time  as  insensitive  as  before  to 
such  stimuH  as  sUght  toucli.  In  the  parts  which  had  regained  their 
sensibiUty  to  severe  stimuh,  hke  pricking  and  extremes  of  heat  and  cold, 
the  sensation  radiated  widely,  was  referred  to  remote  parts,  and  could  not 
be  accurately  localized.  This  form  of  sensibility  I  lead  calls  protohathic. 
As  the  nerve  recovered  further,  a  second  form  of  sensibility  appeared, 
associated  with  accurate  localization  of  cutaneous  stimuli  and  dis- 
crimination of  two  compass  pcjints.  Light  touch  and  moderate  degrees 
of  heat  and  cold  could  now  be  again  ap])rcciatcd.  This  form  of  sensi- 
bilit\-  he  terms  epicrHic.  \  third  form  of  sensibility  {deep  sensibility) 
was  investigated  after  complete  division  of  the  radial  and  external 
cutaneous  nerves  at  the  elbow.  The  radial  half  of  the  arm  and  back 
of  the  hand  became  totally  insensitive  to  cutaneous  stimuli,  but  re- 
tained their  sensibility  to  pressure  or  to  any  stimulus  which  deformed 
the  subcutaneous  structures,  as  well  as  their  power  of  localization  of 
such  stimuli.  The  afferent  fibres  upon  which  this  deep  sensibility 
depends  must  run  with  the  motor  nerves.  According  to  Head,  the 
other  two  forms  of  sensibility  (protopathic  and  epicritic)  also  depend 
on  two  separate  systems  of  nerves,  of  which  the  protopathic  is  the  older 
in  the  phvlogenetic  sense,  and  has  a  wider  distribution.  It  is  assumed 
that  the  protopathic  fibres  regenerate  more  easily  and  speedily  than  the 
epicritic  or  than  the  motor  nerves  of  voluntary  muscle.  The  proto- 
pathic fibres  are  supposed  by  Head  to  exert  a  trophic  influence.  A 
part  deprived  of  its  nerve-supply  is  liable  to  injuries,  and  the  sores  so 
produced  heal  slowly.  But  as  soon  as  '  protopathic  '  sensibility  returns 
to  the  part,  they  heal  rapidly,  even  in  the  absence  of  all  epicritic  sensa- 
tion. The  intestine  is  described  as  possessing  'protopathic,'  but  not 
'  epicritic,'  sensibility — i.e.,  it  reacts  to  extremes  of  heat  and  cold,  but 
not  to  moderate  heat  and  cold  or  light  touch. 

Quite  recently  an  elaborate  study  of  the  loss  and  return  of  the 
skin  sensations  alter  section  of  a  cutaneous  nerve  has  been  made  by 
Boring.  His  work  is  distinguished  from  that  of  all  previous  ob- 
servers by  the  fact  that  he  brought  to  his  task  the  training  of  a 
professional  psychologist,  and  that  he  studied  in  detail  for  fifteen 
months  the  area  of  skin  with  whose  innervation  he  intended  to 
interfere.  Section  of  the  nerve  chosen  (the  anterior  branch  of  the 
internal  cutaneous  nerve  in  the  forearm)  caused  amesthesia  and 
hypoKsthesia  of  a  relatively  small  area  of  skin  (on  the  volar  aspect 
of  the  forearm  near  the  wrist),  so  that  it  was  possible  to  make  an 
intensive  study  of  it,  and  the  observations  were  continued  for  more 
than  1,000  days  after  the  operation.  Points  on  the  affected  area 
were  identified  by  reference  to  a  series  of  points  tattooed  on  the 
skin  represented  by  crosses  in  Fig.  466. 

The  sensations  studied,  in  addition  to  those  of  warmth  and  cold, 
were  the  four  qualities  which  appear  upon  mechanical  stimulation 
of  the  skin:  Contact,  cutaneous  pressure,  subcutaneous  or  deep 
pressure  and  pain.  Boring  uses  the  terms  '  tickle-contact,'  '  pene- 
trating pressure,'  '  dull  pressure,'  and  '  sharpness  '  for  these  quali- 


togl 


THE  SENSES 


ties.     Th(^  localization  of  the  sensations  and  the  power  of  discrimi- 
nating iwo  points  were  also  investigated. 

Tiie  general  tendency  during  recovery  was  from  anaesthesia  or 
h\  pcoicsthesia  through  decreasing  degrees  of  hypoiesthesia  to  normal. 
\\'armth  and  cold,  however,  passed  from  hypoiesthesia  through  a 
stage  of  h\T)ercesthcsia  on  their  way  to  normal.  Pain,  pressure,  and 
cold  approached  nonnality  at  about  the  same  rate,  but  in  compari- 
son with  these  the  return  of  warmth  sensation  was  much  delayed 


Fig.  466.— Volar  Aspect  of  Left  Forearm,  showing  Affected  Region  in  Outline. 
The  larger  area  was  that  marked  off  by  the  subject  with  the  camel's  hair 
brush  as  insensiti%-e.  The  inclosed  smaller  area  is  that  which  was  marked  ofi 
when  the  e.xpcrimenter  manipulated  the  brush,  and  the  subject  with  closed 
eyes  reported  when  he  felt  anything  at  all.  This  smaller  area  was  taken  as 
the  region  of  greatest  change  in  sensitivity,  and  the  experiments  on  localization 
and  the  discrimination  of  two  points  were  mainly  made  within  this  area.  The 
dotted  Une  shows  the  approximate  course  of  the  nerve,  divided  at  S.  The 
horizontal  and  vertical  lines  dividing  the  area  into  small  squares  were  impressed 
by  a  rubber  stamp  on  the  skin,  to  facilitate  identification  of  points.  The 
position  of  each  point  stimulated  was  fixed  with  reference  to  these  rectilinear 
co-ordinates,  the  tattooed  point  represented  by  the  Maltese  cross  behig  taken 
as  the  origin,  and  the  distances  in  mm.  measured  in  the  central  (C),  peri- 
pheral (P),  radial  (R),  and  ulnar  (U)  directions  (Boring). 

For  all  four  the  distribution  of  sensitivity  over  the  skin  was  irregular 
and  patchy,  and  no  definite  boundaries  could  be  drawn.  In  general, 
however,  immediately  after  division  of  the  nerve  the  central  zone 
of  the  affected  area  was  practi  ally  anaesthetic  as  regards  cutaneous 
sensation.  This  was  surrounded  by  a  zone  of  decreased  sensiti\ity. 
In  the  return  of  sensibihty  the  outer  zone  preceded  the  inner. 
No  new  modes  or  quahties  of  sensation  were  observed  at  any  time, 
although  '  a  number  of  unusual  sensory  complexes,  which  might  be 
described  by  an  untrained  observer  as  new  sensations,  were  noted. 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1003 

.  ,  .  The  most  striking  single  experience  was  the  intense  algesic  cold, 
whicli  occurred  when  the  skin  was  hyperasthetic  to  cold.'  Deep 
sensibility  to  pressure  and  pain  was  not  altered.  Localization 
of  pressures  (of  20  gm.)  and  discrimination  of  two  pressures  (two- 
point  chscrimination)  remained  unaffected. 

This  stuJy  on  the  vshole  confirms  that  of  Trotter  and  Davies.  How- 
ever, the  larger  outer  or  third  area  defined  by  the  so-called  '  stroking 
outline  '  of  Trotter  and  Davies  is  probably  not  an  area  of  sensory 
abnormality  at  all,  but  merely  an  area  in  which  a  physical  change  in 
the  skin,  due,  e.g.,  to  some  interference  with  the  action  of  the  sweat 
glands,  IS  appreciated  by  the  stroking  finger.  This  follows  from  the 
fact  that  it  can  be  mapped  out  approximately  by  an  observer  who 
strokes  it  with  his  own  finger  without  asking  the  subject  to  report  his 
sensations.  The  results  of  Boring's  investigation  are  quite  opposed  to 
the  most  essential  of  Head's  conclusions.  No  evidence  was  found  in 
favour  of  Head's  distinction  between  epicritic  and  protopathic  sensi- 
bility, and  weighty  evidence  against  it.  There  does  not  seem  to  be 
any  real  necessity  in  the  observed  facts  for  introducing  so  revolutionary 
a  conception  of  the  nervous  system.  Nor  is  it  possible  to  uphold  the 
distinction  in  any  thoroughgoing  fashion  for  all  structures.  For  in- 
stance, in  abdominal  operations  performed  under  local  anaesthesia  it 
has  been  seen  that  the  parietal  peritoneum  is  quite  insensitive  to  touch, 
pressure,  and  temperature  stimuli,  including  extreme  temperatures 
(Ramstrom),  while  pain  is  caused  ,by  traction  on  it.  Its  sensibility 
is  therefore  neither  purely  epicritic  nor  purely  protopathic  in  Head's 
sense.  In  like  manner  the  mucous  membrane  of  the  mouth,  in  which 
sensibility  only  to  touch  and  temperature  is  present,  conforms  entirely 
to  neither  type.  Its  sensibility  is  not  alone  epicritic,  since  it  responds 
to  extreme  temperatures,  nor  is  it  purely  protopathic,  since  a  pin-prick 
prodiices  no  painful  sensation.  These  terms  and  the  theory  associated 
with  them  should  be  dropped. 

Localization  of  Cutaneous  Sensations. —  We  not  only  perceive  the 
quality  and  estimate  the  intensity  of  sensations  of  touch,  warmth,  cold 
pain,  etc.,  but  are  able,  more  or  less  accurately,  to  localize  the  part  of 
the  body  from  which  the  sensory  impressions  come.  In  other  words, 
two  impressions  from  different  parts  of  the  tx)dy,  although  identical 
in  quality  and  intensity,  are  nevertheless  stamped  with  a  distinctive 
something,  which  may  be  called  the  local  sign.  This  power  of  localiza- 
tion is  not  equal  for  all  portions  of  the  body  nor  for  all  kinds  of  sensa- 
tions. It  is  best  developed  for  touch  (in  the  restricted  sense),  and  all 
the  varieties  of  common  sensation  are  better  localized  on  the  skin  than 
in  any  of  the  deeper  structures.  The  precise  mechanism  of  the  localiza- 
tion IS  unknown.  But  we  must  suppose  that  each  peripheral  area  is 
'  represented  '  in  the  brain,  so  that  the  arrival  of  afferent  impulses  from 
it  affects  particularly  the  related  cerebral  area.  The  brain,  therefore, 
so  to  speak,  associates  excitation  of  a  given  cerebral  area  with  stimula- 
tion of  the  corresponding  peripheral  area,  and  thus  not  only  recognizes 
the  quality  and  quantity  of  the  resultant  sensation,  but  also  localizes 
it;  just  as  a  waiter  who  watches  the  bell-indicator  not  only  learns  how 
a  bell  has  been  rung,  whether  once  or  twice,  peremptorilv  or  languidly, 
but  also  in  which  room  it  has  been  rung.  If,  to  pursue  the  illustration 
a  little  farther,  he  is  aware  that  two  rooms  are  connected  with  one 
bell,  but  that  one  of  the  rooms  is  scarcely  ever  occupied,  he  associates 
the  ringing  of  the  bell  with  a  summons  from  the  other  room  even  when 
it  happens  to  be  rung  from  the  usually  vacant  room.     In  like  manner 


1094 


THE  SENSES 


the  brain  seems  to  connect  the  arrival  of  sensory  impulses  from  the 
internal  organs,  which  have  few  sensory  fibres,  and  tliese  perhaps  not 
often  stimulated,  with  excitation  in  a  related  cutaneous  region,  from 
which  it  is  constantly  receiving  sensory  impressions.  The  fact  already 
mentioned  (p.  802),  that  in  disease  of  internal  organs  the  pain  is  re- 
terrcd  to  some  portion  ot  the  skin,  mav  be  thus  explained. 

An  attempt  has  been  made  to  explain  certain  illusions  of  touch 
on  the  theory  that  just  as  an  object  is  recognized  as  single  by  the  eye 
when  its  images  fall  on  corresponding  points  of  the  two  retina?  (p.  1037). 
so  an  object  is  recognized  as  single  by  tl,e  fingers  when  it  comes  into 
contact  witii  corresponding  points  or  rather  areas  of  the  skin.  These 
are  the  areas  which  experience  has  taught  us  are  in  contact  with  an 
object  when  it  is  held  in  the  natural  way.  When  now  a  single  object  is 
made,  by  placing  the  fingers  in  an  unnatural  position,  to  touch  areas 
which  could  ordinarily  be  touched  at  the  same  time  only  by  two  or 
by  three  objects,  we  experience  the  sensation  of  contact  with  two  or  with 
three  objects. 


Fig.  467. — Illusion  of  Touch  of 
Aristotle.  A  small  oljject  placed 
between  the  index  and  middle 
fingers,  crossed  as  shown,  is  felt 
as  two  objects  (Wassenaar). 


y 

..->.            /■ 

A 

Fig.  468. — An  Object  placed  in  contact  with 
the  Index,  Middle  and  Ring  Fingers, 
crossed  as  shown,  is  fdt  as  three  objects 
(Wassenaar). 


It  is  through  the  localization  of  touch  sensations  that  the  size  and 
form  of  objects  in  contact  with  the  skin  are  percoi\ed  in  the  absence 
of  other  tlian  the  cutaneous  sensations,  and  especially  in  the  absence 
of  visual  and  muscular  sensations  (stcreognosis). 

Muscular  Sensations  (Muscular  Sense),  etc. — Sometimes,  although 
rather  loosely,  grouped  together  as  muscular  sensations,  arc  a  number 
of  forms  of  .sensation  of  which  our  knowledge  is  much  less  accurate 
than  it  is  in  the  case  of  the  fundamental  skin  sensations.  Among 
these  may  be  mentioned  especially  (i)  the  sensations  by  which  the 
position  in  space  of  the  body  as  a  whole  or  of  particular  parts  is  recog- 
nized in  the  absence  of  visual  sensations;  (j)  the  sensations  associated 
with  movements,  passive  as  well  as  active:  (3)  the  sensations  associated 


CUTAXEOUS  AXD  IXTERXAL  SEXSATIOS'S 


1093 


with  resistance  to  movement.  In  none  of  these  groups  are  we  dcahng 
with  purely  muscular  sensations;  cutaneous  tactile  sensations  and 
pressure  sensations  elicited  from  other  structures  than  muscles  are 
also  involved. 

Voluntary  muscular  movements  arc  accompanied  with  a  peculiar 
sensatioii  of  ettort,  graduated  according  to  the  strength  of  the  con- 
traction, and  affording  data  from  which  a  judgment  as  to  its  amount 
and  direction  may  be  formed. 

It  has  been  shown,  however,  that  when  pressure  sensations  are  elimi- 
nated or  reduced  to  a  minimum  by  enclosing  the  arm,  held  horizontally, 
in  a  rigid  apparatus  suc'a  as  that  shown  in  Fig.  ^dq,  the  moments  of 
rotation  of  a  weight*  fastened  at  ditferent  distances  from  the  shoulder 
can  be  discriminated  with  great  exactness.  The  sensation  of  effort  is 
therefore  an  independent  sensation  (v.  Frey). 


^^f'^ 


'J'"L\^.^x    W  " 


Fig.  469.— Apparatus  for  Arm  for  Testing  Muscle  Sense.    At  the  right  is  shown  a  lead 
weight  which  can  be  placed  on  either  of  the  hoops  of  the  apparatus  (v.  Frey). 

Some  writers  have  supposed  that  this  so-called  muscular  sense  does 
not  depend  upon  afferent  impulses  at  all,  but  that  the  nervous  centres 
from  which  the  voluntary  impulses  depart  take  cognizance,  retain  a 
record,  so  to  speak,  of  the  quantity  of  outgoing  nervous  force  that  the 
effort  which  we  feel  in  lifting  a  heavy  weight  is  an  effort  of  the  cells 
of  the  motor  centres  from  which  the  groups  of  muscles  are  innervated, 
and  not  of  the  muscles  themselves. 

But  although  this  feeling  of  central  effort  or  outflow  (we  can  hardly  say 
of  central  fatigue)  may  be  a  factor,  it  cannot  be  doubted  that  the  braiii 
is  kept  in  touch  with  the  contracting  muscle  by  impulses  of  various 
kinds  which  reach  it  by  different  afferent  channels. 

The  corpuscles  of  Pacini,  which  exist  in  considerable  numbers  in  the 
neighbourhood  of  joints  and  ligaments,  and  in  the  periosteum  of  bones, 


^C*'^J<^1f''^'^^^^*~^^T:'>f-^^>£7'::^ 


F'g.  iyo. — Nerve-Ending  in  Tendon  near  the  Insertion  of  the  Muscular 
Fibres  (Golgi). 

would  seem  well  fitted  to  play  the  part  of  end-organs  for  the  tactile 
sensations  causetl  by  the  movements  of  flexion,  extension,  or  rotation 
of  one  bone  on  another,  which  form  so  large  a  portion  of  all  voluntary 

*  With  the  arm  horizontal  the  moment  is  the  product  of  the  weight  by  its 
distance  from  the  shoulder  joint  (see  p.  749). 


1 096 


THE  SENSES 


muscular  movements.  And  it  has  been  stated  that  paralysis  of  these 
bodies  in  the  limbs  of  a  cat  by  section  of  the  ner\cs  going  to  them 
causes  a  characteristic  uncertainty  of  movement  which  suggests  that 
something  necessary  to  normal  co-ordinati<jn  has  been  taken  away. 
Tendons  also  possess  afferent  ner\'e-fibres,  which  terminate  by  breaking 
up  into  reticulated  end-plates  (Fig.  470).  We  have  already  seen  that 
the  skeletal  muscles  possess  numerous  afferent  fibres  (p.  941).  Some 
of  these  must  be  nerves  of  ordinary  sensation.  For.  although  when  a 
muscle  is  laid  ba-  »  in  man  and  stimulated  electrically,  the  sensation 
docs  not  in  general  amount  to  actual  pain,  it  is  capable,  under  the 
influence  of  strong  .stimuli,  of  taking  on  a  painful  character.  And 
nobody  who  has  felt  the  severe  and  sometimes  almost  intolerable  pain 
of  muscular  cramp  would  be  likely  to  deny  the  existence  of  sensory 
muscular  nerves.     But  after  deducting  these,  we  must  assume  that  a 


m.'n.h 


Fig.  448. — Muscle  Spindle  (after  Ruffini).  c,  sheath  of  the  spindle  ;  n.tr.,  trunk 
of  nerve,  which  sends  fibres  through  the  sheath  into  the  spindle,  where  they 
form  endings  (pr.e.,  s.e.,  pl.e.)  of  various  kinds;  m.n.b.,  bundle  of  motor  fibres. 

large  proportion  of  the  afferent  nerves  of  muscle  have  other  functions, 
and  among  them  may  be  the  conveyance  of  impulses  connected  with 
the  muscular  sense.  The  muscle-spmdles  or  neuro-muscular  spindles 
(Fig.  471),  peculiar  structures  which  occur  in  large  number  in  most 
of  the  skeletal  muscles,  and  have  been  carefully  studied  by  Huber, 
Sihler,  Ruffini,  and  other  observers,  are  the  terminations  of  many  of 
the  sensory  fibres.  They  are  long  narrow  bodies,  with  a  thick  sheath 
of  connective  tissue  enclosing  fine  striped  muscular  fibres.  Medul- 
lated  nerve-fibres  enter  the  spindle,  and  there,  dividing  into  branches 
and  losing  their  medullary  sheath,  form  endings  of  various  kinds  around  . 
and  between  the  muscular  fibres.  It  is  possible  tliat  in  contraction 
of  the  muscles  the  nerve-fibres  in  the  spindles  are  compressed,  and  thus 
mechanically  stimulated. 

In  the  spinal  cord  these  impulses  are  conducted  up  through  the 
posterior  colimin;  and,  although  less  is  known  as  to  the  paths  they 
follow  in  the  higher  parts  of  the  central  nervous  system,  it  is  certain 
that  there  is  some  afferent  bond  of  connection  between  the  cortical 
motor  areas  and  the  muscles  which  they  control  (p.  963). 

Tactile  sensations  set  up  in  the  skin  or  mucous  membrane  lying 
over  contracting  muscles  may  also  help  the  nervous  motor  mechanism 
in  appreciating  and  regulating  the  amount  of  contraction;  but  the  fact 
that,  in  anaesthesia  of  the  mucous  membrane  covering  the  vocal  cords 
produced  by  cocaine,  the  voice  is  not  at  all  impaired,  shows  that  mus- 
cular contractions  of  extreme  nicety  can  be  carried  on  without  any 
such  aid. 

Sensations  of  Hunger  and  Thirst. — These  are  representatives  of 
the  group  of  interior  sensations.     As  Tiedemann  pointed  out  long 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1097 

ago.  at  least  two  elements  are  iincjlved  in  the  somewliat  va;,Mi<' 
sensation  oi  hunger:  the  local  sensation  of  emptiness  in  the  stomach, 
and  the  general  sensations  of  malaise,  depression,  and  weakness. 
There  is  some  evidence  that  the  general  sensations  are — in  part  at, 
least — dependent  upon  the  state  of  the  stomach.  But  it  would 
appear  that — at  any  rate,  during  prolonged  deprivation  of  food — a 
general  condition  of  the  tissues  may  exist  which  can  arouse  in  con- 
sciousness the  sensation  of  hunger,  even  after  the  stomach  has  been 
amply  filled.  Thus  a  patient  with  a  fistula  in  the  upper  part  of 
the  small  intestine  constantly  suffered  from  hunger  in  spite  of  the 
enormous  quantities  of  food  consumed.  The  stomach  always  felt 
full,  but  as  most  of  the  food  escaped  from  the  fistula,  the  tissues 
continued  to  be  starved,  and  the  general  sensation  of  hunger  re- 
mained (Hertz).  In  diabetes  the  same  thing  may  be  observed. 
On  the  other  hand,  it  was  noted  by  Carlson  and  one  of  his  pupils 
that  after  a  fast  of  five  days  practically  all  of  the  mental  depression 
and  some  of  the  feeling  of  weakness  disappeared  during  the  first 
meal.  He  therefore  concluded  that  the  depression  of  the  central 
ner\''ous  system  was  essentially  a  reflex  condition,  depending  prob- 
ably on  afferent  impulses  from  the  digestive  tract,  rather  than  a 
result  of  deficiency  of  nutrient  material  in  the  blood.  Complete 
recovery  from  the  bodily  weakness,  however,  did  not  take  place 
till  the  second  or  third  day  after  breaking  the  fast. 


Fig.  472. — Commencement  of  Gastric  Hunger  Contractions  (the  Large  Elevations 
in  a  Man.  At  X  she  belt  was  tightened  and  the  hunger  contractions  inhibited. 
To  be  read  from  left  to  right  (Carlson  and  Lewis). 

An  important  factor  in  the  local  sensations  associated  with 
hunger  is  the  strong  periodical  contractions  of  the  empty  stomach, 
which  have  been  shown  to  coincide  with  the  hunger  pains  (Cannon 
and  Washburn). 

Carlson  was  able  in  observations  on  a  man  with  a  permanent 
gastric  fistula  to  confirm  this  coincidence  Even  when  the  empty 
stomach  was  artificially  caused  to  contract  by  distending  it  with  a 


1098 


THE  SENSES 


balloon,  the  man  experienced  a  typical  hun^'cr  jKiin.  During  his 
own  h\e  (lays'  fast  Carlson  recorded  these  contractions  by  means 
of  a  small  balloon  attached  to  a  rubber  tube,  which  was  swallowrd 
and  allowed  to  remain  in  the  stomach.  The  tube  was  connected 
to  a  recording  apparatus.  It  was  found  possible  to  go  to  sleep 
witli  the  balloon  in  the  stomach,  and  to  obtain  a  record  all  thnni-di 


Fig.  473. — Gastric  Hunger  Contractions  in  a  Man  at  a  More  Advanced  and  Intense 
Stage  than  in  Fig.  472.  Tightening  of  the  belt  at  x  did  not  stop  the  con- 
tractions which  ran  the  usual  course  to  their  termination.  To  be  read  from 
left  to  right  (Carlson  and  Lewis). 


the  night.  After  the  first  day  of  starvation  the  hunger  sensation 
referred  to  the  epigastrium  was  almost  continuous,  and  did  not 
wholly  disappear  during  the  intervals  between  the  periods  of 
vigorous  gastric  contractions.  This  feeble  continuous  hunger  sen- 
sation was  obviously  associated  with  the  increased  tonus  and  the 
more  or  less  continuous,  although  weak,  rhythmical  contractions 
that  correspond  to  the  periods  of  relative  quiescence  of  the  empty 
stomach  during  prolonged  starvation.  The  precise  manner  in  which 
the  hunger  contractions  of  the  stomach  arouse  the  pangs  or  pains 
of  hunger  remains  in  doubt.  Since  the  sensation  has  a  specific 
character,  it  is  to  be  supposed  that  it  is  subserved  by  a  special 
sensory  apparatus  with  receptors  in  the  stomach.  The  vagi  do  not 
seem  to  be  concerned.  But  thegastriccontracticjns  duringdigestion  of 
a  meal  notoriously  do  not  cause  such  sensations,  and  tln'refore  it  has 
been  suggested  that  the  nervous  mechanism  associated  with  the 
local  sensation  of  hunger  becomes  more  and  more  excitable  in  the 
absence  of  food,  until  at  last  the  threshold  is  reached  at  which  the 
stimulus  connected  with  the  hunger  contractions  becomes  effective. 
It  comes  to  the  same  thing  to  say  that  the  presence  of  food  in  some 
way  inhibits  the  discharge  which  leads  to  the  sensation.      This, 


CUTAXEOrS  AXD  IXTERXAL  SEXSATIOXS  1099 

however,  is  only  another  way  of  saying  that  the  true  explanation  is 
still  to  seek. 

Carlson  was  unable  to  confirm  the  common  statement  that 
hunger  disappears  after  the  third  day  of  staivation,  although  there 
was  certainly  some  decrease  in  the  sensation  of  hunger,  and  especi- 
ally in  appetite,  on  the  fourth  and  fifth  days.  As  has  been  often 
sliown.the  deprivation  of  food  for  long  periods,  or  even  till  death, 
when  water  is  allowed,  is  not  associated  with  acute  suffering. 

Appetite  is  distinguished  from  hunger  by  those  observers  who 
have  studied  the  question  most  precisely,  but  of  the  physiological 
basis  of  the  sensations  that  constitute  appetite  we  know  even  less 
than  we  do  of  the  physiological  basis  of  hunger.  The  taking  of 
food  blunts  the  appetite,  as  it  stills  hunger.  Fasting  evokes  both. 
Yet  during  a  prolonged  fast,  appetite,  the  desire  for  food  and  the 
pleasure  in  the  thought  or  at  the  sight  of  it,  may  disappear,  or  be 
much  lessened,  while  the  hunger  pangs  are  still  sharp.  The  smell 
and  taste  of  agreeable  food  and  the  mental  representations  of  these 
sensations  are  elements  in  appetite,  and  even  the  associations  con- 
nected with  the  time  and  place  of  a  customary  meal  and  with  those 
who  share  it.  But  there  is  a  gastric  element  as  well:  the  mere 
filling  of  the  stomach  apart  from  the  passage  of  nutrient  material 
into  the  blood  helps  to  satisfy  the  appetite;  the  emptying  of  the 
stomach  in  the  course  of  digestion  seems  of  itself  to  take  a  part  in 
restoring  the  appetite  for  the  next  meal.  To  what  extent,  if  at  all, 
the  gastric  element  in  the  sensation  of  appetite  is  dependent  upon 
the  same  mechanism  as  the  gastric  element  in  hunger  is  unknown. 
Some  have  supposed  that  the  same  stimulation  which,  when  its  inten- 
sity' is  sufficiently  increased,  cau.ses  gastric  hunger  pains,  causes  in  smaller 
intensity  a  milder  hunger  sensation,  which  is  the  gastric  factor  in 
appetite.  According  to  Carlson,  a  factor  in  appetite  is  the  memor^^ 
process  of  removal  of  hunger  pangs  by  feeding,  and  he  assumes  that 
the  revival  of  such  memories  in  consciousness  depends  upon  the  con- 
dition of  the  alimentary  canal,  and  is  inhibited  when  the  stream  of 
afferent  impulses  from  the  viscera  is  altered  by  changes  in  the  motility 
or  secretory  activity  of  the  gastro-intestinal  tract.  He  believes  that 
the  secretion  of  the  so-called  appetite  gastric  juice,  in  man  at  least, 
although  clearlv  demonstrated  on  a  case  of  gastric  fistula  during 
mastication  of  palatable  food,  does  not  possess  the  great  importance 
attributed  to  it  bv  Pawlow  (p.  404),  since  normally  there  is  a  continuous 
secretion  of  gastric  juice  in  the  absence  of  food  in  the  stomach  and  of 
psychical  stimulation,  and  this  is  sufficient  to  initiate  gastric  digestion, 
and  therefore  to  insure  a  sufficient  gastric  secretion.  The  vagi  do  not 
seem  to  contain  fibres  concerned  in  the  sensations  of  hunger  or  appetite. 
After  section  of  these  nerves,  dogs,  when  they  survive  some  time,  eat 
ravenously,  although  the  food  is  often  regurgitated. 

Thirst. — This  is  a  sensation,  referred  chiefly  to  the  pharynx,  and 
certain  of  the  sensory  nerve  fibres  of  this  region,  supphed  by  the 


iioo  TTfE  SENSES 

glosso-pharvnfjeal  norv^,  may  be  assumed  to  be  specificallv  related 
to  it.  I'luler  ordinary  conditions  the  sensation  is  elicited  through 
the  afferent  nerves  of  the  pharynx  when  the  mucous  membrane 
becomes  dry,  as  when  dry  or  salt  food  is  eaten,  or  dry  and  dusty 
air  inhaled,  and  local  moistening  of  the  area  in  question  gives 
temporary  relief,  e\'en  when  no  water  is  swallowed.  When  water 
is  long  withheld,  the  water-content  of  all  the  tissues  sinks,  and  a 
more  intense  and  distressing  thirst,  which  cannot  be  allayed  in  any 
way  except  by  the  ingestion  of  water,  ensues.  Probably  in  this 
case  afferent  impulses  originating  in  many  organs,  and  conditioned 
in  some  way  by  the  abnormally  low  water-content  of  the  blood  and 
tissues,  as  well  as  a  more  direct  action  of  the  loss  of  water  upon  the 
(imknown)  centre  in  which  the  sensation  is  represented,  are  re- 
sponsible. 

Relation  of  Stimulus  to  Sensation. — It  i.s  impossible  to  measure 
sensation  in  terms  of  stimuhis.  All  that  we  can  do  is  to  compare 
differences  in  the  intensity  of  stimuli  and  differences  in  the  resultant 
sensations,  or,  in  other  words,  to  compare  stimuli  together  and  to  com- 
pare sensations  together.  And  when  we  determine  the  amount  by 
which  a  given  stimuhis  must  be  increased  or  diminished  in  order  that 
there  may  be  a  just  perceptible  increase  or  diminution  in  the  sensation, 
it  is  found  that  (with  certain  limitations)  the  two  are  connected  by  a 
simple  law:  Whatever  the  absolute  strength  of  a  stimuhis  of  given  kind 
may  be,  it  must  be  increased  by  the  same  fraction  of  its  amount  in  order 
that  a  difference  in  the  sensation  may  he  perceived  (sometimes  called 
Weber's  laiv).  Thus,  a  light  of  the  strength  of  one  standard  candle 
must  be  increased  by  ,^,jth  candle,  a  light  of  lo  candles  bv  ,'^'o,  and  in 
light  of  ICO  candles  by  a  candle,  in  order  that  the  eye  may  perceive 
that  an  increase  has  taken  place,  just  as  the  weight  neces.sary  to  turn 
a  balance  increases  with  the  amount  alreadv  in  the  pans.  The  fractiou 
varies  for  the  different  senses.  It  is  about  ^}-,^^  for  light,  ^  for  sound. 
But  it  would  appear  that  Weber's  law  does  not  hold  for  the  pressure 
sense,  nor  for  the  other  senses  above  and  below  certain  limits.  Fechner, 
making  various  assumptions,  has  thrown  Weber's  law  into  the  form 

y=k    _S — ^  where  y  is  the  intensity  of  .sensation,  x  the  intensity  of 

stimulation,  x„  the  smallest  intensity  of  stimulus  which  can  be  perceived 
(liminal  intensity),  and  k,  a  constant.  This  so-called  psycho-physical 
law  of  Fechner  states  that  the  sensation  varies  as  the  logarithm  of  the 
stimulus.  But  Fechner's  law  has  been  subjected  to  serious  criticism, 
and  the  subject  cannot  be  further  pursued  here. 


pTdCTTc AT.  r.xr.nrT'^F<;  noi 


PRACTICAL  KXERCISES  ON  CHAPTER  XVIII. 
VISION. 

I.  Dissection  of  the  Eye. —  I  he  stiuleiit  may  profitably  refresh  his 
niemorv  on  the  .uiatomy  of  the  eye  by  dissecting  a  fresh  eye — that  of 
a  large  animal  like  an  ox  is  preferable,  but  the  eye  of  a  sheep  or  dog 
may  also  be  used.  The  eye  is  removed  from  the  orbit  by  cutting 
tlirough  the  conjunctiva  where  it  is  reflected  on  to  the  eyelids,  care- 
fully severing  the  extrinsic  muscles  and  scooping  the  eyeball  out  of  the 
mass  of  loose  connective  tissue  and  fat  in  which  it  is  embedded,  and 
which  serves  as  a  cushion  to  protect  it  from  injmy  during  its  move- 
ments. Observe  the  transparent  cornea  in  front,  blending  at  its  pos- 
terior border  with  the  opaque  sclerotic,  which  is  covered  by  a  layer  of 
conjunctiva  reflected  from  the  lids.  On  clearing  the  fat  cautiously 
away,  the  tentlinous  insertions  of  the  external  or  extrinsic  muscles  of 
the  eyeball  into  the  anterior  part  of  the  sclerotic  will  be  seen.  Identify 
the  \arious  muscles  (p.  1063). 

Immerse  the  eye  in  water  in  a  small  glass  dish,  with  the  cornea 
uppermost.  The  interior  can  now  be  seen,  because  the  refractive 
index  of  the  cornea  being  nearly  the  same  as  that  of  water,  the  light  is 
only  very  slightly  refracted  there.  The  same  effect  is  produced  when 
a  cover-slip  is  placed  over  the  cornea  in  the  air;  a  plane  surface  being 
substituted  for  the  curved  anterior  surface  of  the  cornea,  its  refraction 
is  abolished.  Observe  in  the  fundus  of  the  eye  the  optic  disc,  eccentric- 
ally placed  in  the  retina,  and  the  retinal  vessels  radiating  out  from  it. 
A  portion  of  the  fundus  shows  brilliant  iridescent  colours  in  many 
animals  (the  tapetum  lucidum).  This  portion  is  abruptly  bounded  by 
a  line  a  little  above  the  optic  disc.  The  appearance  is  due  to  a  peculiar 
arrangement  of  the  connective-tissue  (including  elastic)  fibres  in  this 
part  of  the  choroid. 

Pinch  up  with  forceps  a  small  portion  of  the  sclerotic  a  little  posterior 
to  its  junction  with  the  cornea,  and  clip  it  away  with  fine,  blunt- 
pointed  scissors,  being  careful  not  to  penetrate  the  choroid  layer,  which 
lies  immediately  beneath  the  sclerotic.  Extend  the  incision  through 
the  sclerotic  backwards,  and  then  transversely,  and  peel  off  strips  of 
the  sclerotic  from  behind  forwards.  The  lower  surface  of  the  sclerotic 
(the  so-called  lamina  fusca)  is  dark,  owing  to  the  presence  in  it  of  the 
same  pigment  which  is  so  abundant  in  the  choroid  coat.  Go  on  re- 
moving the  sclerotic  piecemeal  until  a  considerable  area  of  the  dark 
choroid  layer  is  exposed  with  the  ciliary  nerves  passing  forward  on  its 
surface  towards  the  iris.  One  or  other  of  the  long  ciliary  arteries  may 
also  be  seen  coursing  between  the  sclerotic  and  choroid  if  the  sclerotic 
happens  to  have  been  removed  at  its  position.  On  the  anterior  part  of 
the  choroid  may  be  observed  some  pale  fibres  passing  backwards  from 
the  comeo-sclerotic  junction.  They  are  the  meridional  fibres  of  the 
ciliary  muscle  (p.  1022). 

The  eye  being  immersed  in  water,  remove  cautiously  with  the  forceps 
and  scissors  the  portion  of  the  choroid  exposed.  The  retina  is  now  seen 
as  a  pale  membrane,  transparent  when  quite  fresh,  but  becoming  whitish 
soon  after  death.  Cut  through  sclerotic,  choroid,  and  retina  about  half- 
way round  the  eyeball,  a  little  posterior  to  the  comeo-sclerotic  junction. 
The  vitreous  humour  will  bulge  out.  Since  its  refractive  index  is 
nearly  the  same  as  that  of  water,  it  is  scarcely  observed  when  im- 
mersed, and  the  interior  of  the  eye  can  be  easily  seen  through  it. 

The  optic  disc  can  now  be  again  studied,  with  the  stump  of  the  optic 


tio2  THE  SENSES 

nerve  entering  it  and   llie   retinal   vessels  piercing  the  disc.     In  the 
centre  of  the  retina  is  the  yellow  spot. 

In  the  anterior  portion  of  the  eyeball  note  the  crystalline  lens,  and 
at  its  circumference  the  radiating  folds  of  the  choroid  called  the  ciliary 
processes.  Closely  covering  the  ciliary-  processes,  the  anterior  border 
of  the  retina  forms  the  ora  serrata,  a  plaited  arrangement  like  an  old- 
time  ruff. 

Now  complete  the  separation  of  the  anterior  and  posterior  portions 
of  the  eyeball.  Remove  the  vitreous  humour,  noting  that  it  is  attached 
to  the  ciliary  processes  and  the  posterior  surface  of  the  capsule  of  the 
lens  by  its  enveloping  membrane,  the  hyaloid  membrane.  With 
scissors  snip  through  the  corneo-sclerotic  junction  at  one  point  down 
to  the  border  of  the  lens,  and  observe  the  suspensory  ligament  passing 
from  the  ciliary  body  chiefly  towards  the  anterior  surface  of  the  lens, 
where  it  blends  with  the  lens  capsule.  Open  the  anterior  chamber  of 
the  eye  by  an  incision  through  the  cornea  in  front  of  its  junction 
with  the  sclerotic.  It  is  filled  with  the  clear,  watery,  aqueous  humour. 
Xote  the  pigmented  iris  projecting  in  front  of  the  lens. 

Remove  the  sclerotic  and  cornea  for  some  distance  along  their  line 
Df  junction,  using  gentle  pressure  with  the  edge  of  a  fine  knife  to  separate 
the  junction  from  the  attached  border  of  the  iris.  The  ciliary  muscle, 
forming  a  pale,  narrow  ring  around  the  eye  at  the  corneo-sclerotic 
junction  will  be  thus  exposed.  Its  external  surface  is  closely  adherent 
to  the  sclerotic,  and  its  internal  blends  with  the  ciliary  body.  The 
circumference  of  the  iris  is  attached  at  its  anterior  border.  Posteriorly 
it  passes  into  the  choroid. 

Take  out  the  lens  and  observe  the  curvature  of  its  anterior  and 
posterior  surfaces.  Determine  which  has  the  greater  curvature.  In 
the  excised  eye  the  lens  will,  of  course,  be  in  the  condition  of  relaxed 
accommodation . 

2.  Formation  of  Inverted  Image  on  the  Retina. — Fix  the  eye  of  an  ox 
or  of  a  dog  or  rabbit,  after  careful  removal  of  part  of  the  posterior 
surface  of  the  sclerotic,  in  one  end  of  a  blackened  tube,  with  the  cornea 
in  front.  A  tube  made  by  rolling  up  a  piece  of  thick  brown  paper  will 
do.  Place  a  candle  in  front  of  the  eye.  Look  through  the  other  end 
of  the  tube,  and  observe  the  inverted  image  of  the  candle  formed  on 
the  retina.  Move  the  candle  until  the  image  is  as  sharp  as  possible. 
Now  bring  between  the  candle  and  the  eye  a  concave  lens.  The  image 
becomes  blurred,  the  candle  must  be  put  farther  away  to  render  it 
distinct,  and  perhaps  no  position  of  the  candle  can  be  found  which  will 
give  a  sharp  image.  If  the  lens  is  convex,  the  candle  must  be  brought 
nearer,  and  a  sharp  image  can  always  be  formed  by  bringing  it  near 
enough.  If  both  a  convex  and  a  concave  glass  be  placed  in  front  of 
the  eye,  they  will  partially  or  whollv  neutralize  each  other.  Instead 
of  the  candle  a  window  may  be  looked  at.  If  the  eye  of  an  albino 
rabbit  can  be  obtained,  it  is  not  necessary  to  remove  a  part  of  the 
sclerotic. 

3.  Helmholtz's  Phakoscope  (Fig.  474). — This  instrument  is  em- 
ployed in  studying  the  changes  that  take  place  in  the  curvature  of  the 
lens  during  accommodation.  It  is  to  be  used  in  a  dark  room.  A  candle 
is  placed  in  front  of  the  two  prisms  P,  P'.  The  observer  looks  through 
the  hole  B;  the  observed  eye  is  placed  at  a  hole  opposite  the  hole  A. 
The  candle  or  the  observed  eye  is  moved  till  the  observer  sees  three 
pairs  of  images,  one  pair,  the  brightest  of  all,  reflected  from  the  anterior 
surface  of  the  cornea;  another,  the  largest  of  the  three,  but  dim,  re- 
flected from  the  anterior  surface  of  the  lens;  and  a  third  pair,  the 
smallest  of  all,  reflected  from  the  posterior  surface  of  the  lens  (Fig.  421, 


PRACTICAL  EXERCISES 


tioi 


Fig.  474. — Phakoscope. 


p.  102  1).  I'hc  last  two  pairs  can,  of  course,  only  be  seen  within  the  pupil 
The  observed  eye  is  now  focussed  first  for  a  distant  object  (it  is  enough 
that  the  person  should  simply  leave  his  eye  at  rest,  or  imagine  he  is 
looking  far  away),  and  then  for  a  near  object  (an  ivory  pin  at  A). 
During  accommodation  for  a  near  object  no  change  takes  place  in  the 
size,  brightness,  or  position  of  the  first  or  third  pair  of  images;  there- 
fore the  cornea  and  the  posterior  surface  of  the  lens  are  not  altered. 
The  middle  images  become  smaller,  somewhat  brighter,  approach  each 
other,  and  also  come  nearer  to  the  corneal  images.  This  proves  (a)  that 
the  anterior  surface  of  the  lens  undergoes  a  change  ;  (b)  that  the 
change  is  increase  of  curvature  (diminution  of  the  radius  of  curvature), 
for  the  virtual  image  reflected  from  a  convex  mirror  is  smaller  the 
smaller  is  its  radius  of  curvature.      (The  third  pair  of  images  really 

undergo  a  slight  change,  such 
as  would  be  caused  by  a  small 
increase  in  the  curvature  of 
the  posterior  surface  of  the 
lens  ;  but  the  student  need 
not  attempt  to  make  this 
out.) 

4.  Scheiner's  Experiment, — 
Two  small  holes  are  pricked 
with  a  needle  in  a  card,  the 
distance  between  them  being 
less  than  the  diameter  of  the 
pupil.  The  card  is  nailed  on 
a  wooden  holder,  and  a  needle 
stuck  into  a  piece  of  wood  is  looked  at  with  one  eye  through  the  holes. 
When  the  eye  is  accommodated  for  the  needle,  it  appears  single;  when 
it  is  accommodated  for  a  more  distant  object,  or  not  accommodated  at 
all,  the  needle  appears  double.  The  two  images  approach  each  other 
when  the  needle  is  moved  away  from  the  eye,  and  separate  out  from 
each  other  when  it  is  moved  towards  the  eye.  When  the  eye  is  ac- 
commodated for  a  point  nearer  than  the  needle,  the  image  is  also 
double ;  the  images  approach  each  other  when  the  needle  is  brought 
closer  to  the  eye,  and  move  away  from  each  other  when  it  is  moved 
away  from  the  eye.  If  while  the  needle  is  in  focus  one  of  the  holes  be 
stopped  by  the  finger,  the  image  is  not  affected.  When  the  eye  is 
focussed  for  a  greater  distance  than  that  of  the  needle,  stopping  one 
of  the  holes  causes  the  image  on  the  other  side  of  the  field  of  vision 
to  disappear;  if  the  eye  is  focussed  for  a  smaller  distance,  the  image 
on  the  same  side  as  the  blocked  hole  disappears  (Fig.  475).  To  de- 
termine the  near-point  of  distinct  vision  (p.  1029)  the  card  may  be 
mounted  vertically  on  a  cork,  and  this  fastened  by  a  rubber  band  to 
the  end  of  a  foot-rule.  Mo\-e  a  needle,  also  inserted  vertically  into  a 
cork,  along  the  rule,  beginning  at  the  end  farthest  from  the  eye,  until 
with  the  strongest  effort  of  accommodation  it  is  seen  double.  Then 
push  it  back  slightly  to  the  point  at  which,  again  with  maximum 
accommodation,  it  is  just  seen  single.  Repeat  the  measurement  with 
a  needle  mounted  horizontally.  If  regular  astigmatism  is  present, 
the  distances  will  not  be  the  same.  Most  eyes  have  slight  regular 
astigmatism. 

In  myopic  persons  the  far-point  of  distinct  vision  can  also  be  de- 
termined by  Scheiner's  experiment.  The  needle  being  left  on  a  shelf 
at  the  level  of  the  eye,  the  person  walks  away  from  it  backwards,  re- 
garding it  all  the  time  through  the  perforated  card,  till  it  is  no  longer 
seen  single. 


1104 


THE  SENSES 


5.  Kuhne's  Artificial  Eye. — This  is  an  elongated  box  provided  with 
a  glass  k'vs  to  rei)nsrnt  the  tiystalline,  and  a  ground-glass  plate  to 
represent  the  retina.  The  box  is  filled  with  water  to  which  a  little 
eosin  has  been  added.  The  water  must  be  perfectly  clear.  If  the 
tap-water  is  turbid  it  should  be  filtered  or  allowed  to  settle,  or  dis- 
tilled water  should  be  used.     A  beam  of  sunlight  or  electric  light,  or, 

in  case  these  are  not  available,  a  beam  from  an  oil  stereopticon,  is  made 

to  pass  through  the  box.     Many  of  the  facts  of  vision  can  be  illustrated 

by  means  of  this  piece  of  apparatus.     The  modification  of  it  introduced 

by  Lyon  is  ver^^  convenient. 

(a)  Let  the  rays  of  light  pass  through  an  arrow-shaped  slit  in  a  piece 

of  cardboard.     An  inverted  image  of  the  arrow  is  formed  on  the  retina. 

Move  the  retina  nearer  to  or  farther  from  the  lens  to  make  the  image 

sharp.     In  the  eye  of  man  and  of  most  animals,  accommodation  is 

not  brought  about  by  a  change  in  the  distance  of  retina  and  lens,  but 

by  a  change  of  curvature  in  the  lens. 

{b)  Remove  the  lens.     The  focus  is  now  far  behind  the  retina.     This 

illustrates  the  state  of  matters  after  the  lens  has  been  removed  for 

cataract.     The  arrow 

can  again  be  sharply 

focussed  on  the  retina 

by  putting  a  convex 

lens   in    front  of   the 

artificial    eye.       But 

this    must    be    much 

weaker  than  the  lens 

which    has    been    re- 
moved,    for     if     the 

latter    be   placed     in 

front  of  the  eye,  the 

image    is    formed     a 

little  behind  the 

cornea. 

(c)  Replace  the  lens. 

Move    the    retina    so 

far     back     that     the 

image  is   focussed  in 

front  of  it.      This  is 

the  condition  in  the 

myopic  eye.      Put    a 

weak  concave  lens  in 

front  of  the  eye;  the  image  now  falls  more  nearly  on  the  retina.     ]Move 

the  retina  forward  so  that  the  focus  is  behind  it.     This  corresponds 

to  the  hypermetropic  eye.     Put  a  weak  convex  lens  in  front  of  the 

eye  to  correct  the  defect. 

{d)  Observe  that  a  plate  with  a  hole  in  it,  placed  in  front  of  the  eye, 
renders  an  indistinctly  focussed  image  somewhat  sharper  by  cutting 
off  the  more  divergent  peripheral  rays. 

{e)  Fill  with  water  the  chamber  in  front  of  the  curved  glass  that  repre- 
sents the  cornea.  The  focus  is  now  behind  the  back  of  the  eye  alto- 
gether. Refraction  by  the  cornea  is  here  abolished,  as  is  the  case  in 
vision  under  water.  An  additional  lens  inside  the  eye,  or  a  weaker 
one  in  front  of  it,  corrects  the  defect.  Fishes  have  a  much  more  nearly 
spherical  lens  than  land  animals,  and  a  flat  cornea. 

(/)  Fill  the  hollow  cylindrical  lens  with  water,  and  place  it  in  front  of 
the  artificial  eye.  The  eye  is  now  astigmatic.  A  point  of  light  is 
focussed  on  the'  retina,  not  as  a  point,  but  as  a  line.     The  vertical  and 


Fig.  475. — Scheiiier's  E.xperiinent.  In  the  lower  figvire 
the  eye  is  focussed  for  a  point  farther  away  than  the 
needle,  in  the  upper  for  a  nearer  point.  The  con- 
tinuous  lines  represent  ra>-s  from  the  needle,  the  inter* 
rupted  lines  rays  from  the  point  in  focus. 


PRACTICAL  EXERCISES 


1 105 


horizontal  limbs  of  a  cross  cut  out  of  a  piece  (jf  cardboard  aud  placed 
in  the  path  of  the  beam  f)f  lij^'ht  cannot  be  both  focussed  at  the  same 
time. 

6.  Astigmatism  (Regular). —  (i)  Look  at  a  figure  showing  a  number 
of  lines  radiating  horizontally,  vertically,  and  in  intermediate  directions 
from  a  common  centre.  Fir.st  fix  the  figure  at  such  a  distance  tliat  one 
can  comfortably  accommodate.  If  astigmatism  is  present,  all  the  lines 
cannot  be  seen  with  etjual  di.slinctness  at  the  same  time,  iDut  they  can 

all  be  successively  accommodated  for. 
Next,  bring  the  figure  to  the  near- 
point  of  distinct  vision  for  the  hori- 
zontal and  neighbouring  lines.  Prob- 
ably the  vertit  al  lines  will  be  blurred 
antl  cannot  be  made  as  distinct  as  the 
horizontal  by  any  effort  of  accom- 
modation. If  the  eye  is  distinctly 
astigmatic,  the  diffe<ence  will  be 
marked. 

(2)  Use  the  Ophthalmometer.  —  A 
convenient  form  is  shown  in  Figs.  476 
and  477. 

Raise  or  lower  the  chin-rest  till  the 
upper  bar  of  the  head-rest  is  just 
above  the  patient's  eyebrows,  his  head 
being  exactly  vertical.  The  eye  not 
to  be  examined  is  covered  with  the 
blind.  The  patient  looks  steadily  into 
the  opening  of  the  tube  with  his  eye 
wide  open.  The  height  of  the  instru- 
ment having  been  adjusted,  a  clear 
image  of  the  mires  is  obtained  by 
focussing.  The  tube  is  then  turned 
horizontally  slightly  to  right  or  left 
until  the  two  images  of  the  mires  are 
close  together  and  equally  distinct. 
Rotate  the  outer  tube  (Fig.  477,  d) 
until  the  long  meridian  lines  of  the 
images  are  exactly  in  line  with  each 
other.  If  there  is  no  astigmatism, 
this  will  be  seen  at  all  axial  posi- 
tions ;  if  there  is  astigmatism,  at  only 
two  positions.  An  axis  having  thus 
been  obtained,  the  graduated  disc 
(Fig.  476,  A)  on  either  side  of  the 
tube  is  rotated  until  the  shorter  lines 
or  spurs  of  the  images  also  unite, 
forming  a  perfect  cross  with  the  longer  ones  (Fig.  478),  and  the  adjust- 
able pointer  on  the  left-hand  disc  is  made  to  coincide  with  the  stationary 
one  and  a  reading  taken.  Now  rotate  d  through  90  degrees;  the  long 
axial  lines  of  the  images  will  be  in  alignment  without  further  adjustment. 
But  if  the  eye  is  astigmatic,  the  short  lines  will  not  (Fig.  479).  By. 
rotating  A,  the  short  lines  are  made  to  coincide,  so  that  a  perfect  cross 
is  again  formed,  and  the  graduation  is  read.  The  difference  between 
this  and  the  previous  reading — i.e.,  the  difference  betw-een  the  two 
pointers — gives  the  difference  in  the  curvature  of  the  cornea  in  the  two 
meridians.  The  images  of  circles  which  form  the  outer  portion  of  the 
mires  are  oval  in  ordinary  astigmatism. 

70 


Fig.  476. — Ophthalmometer,  as  seen 
from  behind  the  Patient.  B,  blind 
for  covering  the  eye  not  being  ex- 
amined; H,  chin-rest;  A,  A,  gradu- 
ated discs  on  which  radii  of  cur\'a- 
ture  of  the  cornea  in  various  meri- 
dians are  read  off  or  their  equivalent 
in  diopters;  E,  eye-piece  of  telescope; 
C,  milled  head  for  raising  and  lower- 
ing chin-rest ;  F,  milled  head  for 
adjusting  height  of  the  ophthalmo- 
meter, and  G  for  moving  it  horizon- 
tally back  and  forth;  «.  graduated 
disc  fur  giving  the  rotation  of  the 
outer  tube  of  the  telescope  and  the 
black  disc  «.  In  u  are  seen  the  two 
illuminated  mires. 


iio6 


THE  SENSES 


J.  Spherical  Aberration.^C'losc  one  eye,  and  bring  a  small  object 
(a  pin  or  tlie  point  of  a  pencil)  towards  the  other  eye  till  it  becomes 
blurred.  Interpose  between  the  object  and  the  eye  a  card  perforated 
by  a  small  hole.  The  object  becomes  more  distinct  owing  to  the 
cutting  oil  of  the  peripheral  rays  (p.  1027). 

8.  Chromatic  Aberration. — Look  at  Fig.  424  (p.  1028)  from  a  distance 
too  small  for  perfect  accommodation,  and  verify  the  facts  given  in 
tl^  description  of  the  figure. 


Fh 


4yy. — Vertical  Section  of  Ophthalmometer.  d,  outer  tube  of  the  telescope 
rotating  in  sleeve  or  collar  s  (supported  by  stanflard  /,  which  is  swivelled  in 
tubular  support,  g);  k,  diaphragm;  10,  eye-piece  with  lenses  a  and  6;  »i,  a  station- 
ary disc,  borne  on  collar  s,  graduated  to  indicate  angle  of  rotation  of  «,  a  black 
concave  disc  rcjtating  with  tube  d,  and  having  fixed  in  it  two  illuminated  figures 
(or  mires),  w.  w,  whose  images  reflected  from  the  cornea  are  observed ;  ('  is  a  pointer 
carried  on  the  tube  d  which  shows  on  the  graduated  arc  the  amount  of  rotation; 
12,  12,  hemispherical  shells  containing  small  incandescent  lamps  for  illuminating 
the  translucent  mires.  The  lamps  are  connected  with  wires  running  in  the 
hollow  stem  t:fis  the  inner  tube  of  the  telescope  carrying  tlie  double  prism,  //,  It. 
By  means  of  the  rack  0,  projecting  through  the  slot  »t,  and  engaged  by  the  pinion 
p,/  is  moved  back  and  forth  in  the  outer  tube,  thus  approximating  or  separating 
the  corneal  images  of  the  mires.  On  the  axis  of  p  is  a  milled  head  for  turning  it, 
and  two  duplicate  discs  graduated  with  a  scale  showing  the  radii  of  curvature 
of  the  cornea  in  millimetres,  and  another  scale  showing  their  equivalent  in 
diopters. 


g.  Measurement  of  the  Extent  of  the  Field  of  Vision. — Use  the  peri- 
meter shown  in  Fig.  449  (p.  1058). 

(i)  For  White  Light. — Fix  In  the  holder,  Ob,  on  the  gradual ed  arc, 
a  small  piece  of  white  paper,  and  put  one  of  the  charts  supplied  with 
the  instrument  at  the  back  of  the  wheel  which  revolves  w'ith  the  arc. 
The  observations  can  be  recorded  on  this  chart.  The  patient  rests  his 
chin  on  K  and  adjusts  one  eye  against  O.  This  eye  is  kept  fixed  on 
the  mark  at  /during  the  whole  period  of  observation,  and  the  other  eye 


PRACTICAL  EXr.IiCISES 


H07 


is  covered.  The  arc  is  placed  in  a  definite  position,  and  the  white 
object  gradually  moved  from  the  end  of  the  arc  until  the  person  an- 
nounces that  he  can  just  see  it.  The  angle  at  whicli  this  occurs  is  read 
off  and  recorded  on  the  chart.  The  arc  is  then  rotated  into  a  new 
positit)n  and  the  observation  repeated.  A  line  is  drawn  througli  all 
the  points  thus  obtained,  and  this  constitutes  the  boundary  of  the 
field  of  vision  (Fig. 450). 

If  the  position  of  each  point  is  inserted  on  the  chart,  a  point  above 
the   horizontal   plane   passing   through   the    visual   axis   being  placed 


Fig.  478. 


Fig.  479 . 


below  it,  and  a  point  to  the  right  of  the  vertical  plane  being  moved  to 
the  left,  we  obtain  a  map  of  the  sensitive  portion  of  the  retina.  Usually 
perimeters  are  arranged  to  do  this  automatically. 

(2)  Repeat  the  mapping  of  the  field,  using  coloured  papers  (red, 
green,  and  blue)  instead  of  white. 

10.  Mapping  the  Blind  Spot. — Make  a  black  cross  on  a  piece  of  white 
paper  attached  to  the  wall,  the  centre  of  the  cross  being  at  the  height 
of  the  eye  in  the  erect  position.     Stand  about  12  inches  from  the  wall, 

the  chin  supported  on 
a  projecting  piece  of 
wood.  Fix  the  centre 
ot  the  cross  with  one 
eye,  the  other  being 
closed,  and  move  over 
the  paper  a  pencil 
covered,  except  at  the 
point,  with  white 
paper,  until  the  point 
j  ust  disappears .  Alake 
a  mark  on  the  paper 
at  this  point ,  and  repeat 
the  observation  for  all 
diameters  of  the  field. 
The  blind  spot  is  thus 
marked  out  (Fig.  480*. 
Its  shape  is  not  the  same  in  all  eyes  (Fig.  481).  Its  size  and  distance 
from  the  fovea  centralis  can  be  calculated  from  the  construction  given 
in  Fig.  420    (p.   loiq). 

11.  The  Macula  Lutea,  or  Yellow  Spot. — (i)  After  closing  the  eyes 
for  a  minute  or  two,  look  with  one  eye  through  a  strong  solution  of 
chrome  alum  in  a  clear  glass  bottle  with  parallel  sides.  Hold  the  bottle 
between  the  eye  and  a  white  screen  or  a  white  cloud.  An  oval  rose- 
coloured  spot  will  be  seen  in  a  greenish  field.  The  pigment  of  the 
yellow  spot  absorbs  the  bh.e  and  green  rays. 


Fig.  •♦80, — Map  of  Blind  Spot  (reduced  by  One-half). 
Right  eye.     Distance  of  eye  from  paper  12  inches. 


iio8  THE  SENSES 

(2)  Keep  the  eye  closed  for  a  short  time.  J  hen  direct  it  to  a  surface 
ilhiminated  by  a  weak  bhie  light.  A  dark  blue  or  almost  black  spot 
(Alaxwcll's  spot),  corrcsixjiuling  to  the  macula,  is  i-ecn  in  the  visual 
field,  owing  to  the  absorption  of  the  blue  rays. 


Fig.  461. — Composite  picture  of  Blind  S]M,t  (n.jt  rrjuci-d).  The-  Mind  spot  of  tlie 
right  eye  was  mapj)ed  by  31  men,  the  eye  being  always  at  a  distance  of  12  inches 
from  the  paper.  The  maps  were  then  superposed.  The  amount  of  white  at 
any  point  of  the  figure  is  intended  to  correspond  to  the  number  of  maps  which 
overlapped  at  that  point.  Although  the  mechanical  process  of  reproduction 
gives  rather  an  imperfect  view  of  the  composite  rna]),  the  area  in  the  centre  of 
the  figure  where  the  white  is  most  continuous,  and  which  represents  the  shape 
of  the  majority  of  the  blind  spots,  evidently  bears  a  general  resemblance  to  the 
outline  in  Fig.  480. 

12.  Ophthalmoscope — (i)  Human  Eye  (p.  T031). — Let  A  be  the  ob- 
server, and  B  the  iK-rson  whose  eye  is  to  be  examined.  A  and  B 
are  seated  facing  each  other.  Suppose  that  the  right  eye  of  B  is  to 
be  examined.  Close  to  the  left  ear  of  B  is  a  lamp  on  a  level  with  his 
eyes:  the  room  is  otherwise  dark.  For  a  clinical  examination,  the  pupil 
should  be  dilated   by  putting  into  the  eye  a  drop  of  a  0-5  per  cent. 


PRACTICAL  EXERCISES  nog 

solution  of  atropine  sulphate,  but  lliib  is  not  indispensable  for  the 
experiment. 

(a)  Direct  Method. — A  takes  the  mirror  in  his  right  hand,  and, 
holding  it  close  to  his  own  eye,  looks  through  the  central  hole,  and 
throws  a  beam  of  light  into  B's  eye.  A  red  glare,  the  so-called  '  reflex  ' 
from  the  choroidal  vessels,  is  now  seen.  A  then  brings  the  mirror 
to  within  2  or  3  inches  of  B's  eye,  keeping  his  own  eye  always  at  the 
aperture.  A  and  B  both  relax  their  accommodation,  as  if  they  were 
looking  away  to  a  distance.  If  both  eyes  are  emmetropic,  the  retinal 
vessels  will  be  seen.  B  should  now  look  away  past  the  little  finger  of 
A's  right  hand.  This  causes  slight  inward  rotation  of  B's  eye,  and 
brings  into  \iew  the  white  optic  disc  with  the  central  artery  and  vein 
of  the  retina  crossing  it. 

(6)  Indirect  Method. — A  takes  the  mirror  in  his  right  hand  to  ex- 
amine B's  right  eye,  places  his  own  eye  behind  the  aperture  as  before 
at  a  distance  of  about  18  inches  from  B,  and  throws  a  beam  of  light 
into  B's  eye.  Then  A  takes  a  small  biconvex  lens  in  his  left  hand,  and 
places  it  2  or  3  inches  in  front  of  B's  eye,  keeping  it  steady  by  resting 
his  little  finger  on  B's  temple.  A  now  moves  the  mirror  until  he  sees 
the  optic  disc. 

(2)  Examine  a  rabbit's  eye  by  the  direct  and  indirect  method. 
Dilate  the  pupil  by  a  drop  or  two  of  atropine  solution. 

For  practice,  before  doing  (i)  and  (2)  the  student  should  examine 
an  artificial  '  eye  '  by  both  methods,  so  as  to  get  a  clear  view  of  what 
represents  the  retina.  A  substitute  for  the  artificial  eye  may  be  made 
by  unscrewing  the  lower  lens  of  the  eyepiece  of  a  microscope,  and 
fastening  in  its  place  a  piece  of  paper  with  some  printed  matter  on  it. 
The  letters  must  be  made  out  with  the  ophthalmoscope. 

The  opportunitj'  should  also  be  taken  to  observe  the  eye  of  an 
anaesthetized  animal  by  the  simple  cover-glass  method  mentioned 
in  I  (p.  iioi).  Around  cover-glass  is  slipped  under  both  eyelids  and  so 
held  in  position  on  the  cornea.  The  fundus  of  the  eye  can  now  be 
clearly  seen,  including  the  optic  disc  and  retinal,  vessels.  The  instilla- 
tion of  a  little  cocaine  into  the  eye  of  a  rabbit  will  produce  local  an- 
aesthesia sufficient  to  permit  the  experiment. 

13.  Skiascopy  or  Retinoscopy. — The  simplest  method  is  as  follows: 
The  observer  places  himsclt  at  a  distance  of  a  metre  from  the  observed 
eye,  which  he  illuminates  by  a  beam  reflected  from  a  concave  ophthal- 
moscopic mirror  held  in  front  of  his  eye.  The  accommodation  of  the 
observed  eye  is  relaxed.  If,  now,  when  the  mirror  is  rotated  no  direc- 
tion of  movement  of  the  shadow  or  the  light  area  (p.  1035)  can  be  made 
out,  the  pupil  becoming  all  at  once  dark  throughout  its  whole  extent 
when  the  mirror  is  rotated  in  one  direction,  and  all  at  once  light 
throughout  its  whole  extent  when  the  mirror  is  rotated  in  the  opposite 
direction,  the  observer  is  in  the  far-point  of  the  observed  eye.  Since 
the  far-point  is  at  the  distance  of  a  metre,  there  is  in  this  case  myopia 
amounting  to  one  diopter.  If,  however,  the  light  area  moves  in  the 
same  direction  as  the  rotation  of  the  concave  mirror,  the  far-point  of 
the  observed  eve  lies  between  the  observer  and  the  observed  eye,  so 
that  the  myopia  amounts  to  more  than  one  diopter.  The  precise 
degree  of  myopia  can  be  estimated  by  interposing  biconcave  lenses  of 
different  strength  until  the  far-point  is  made  just  i  metre. 

If  the  light  area  mo\es  in  the  opposite  direction  to  the  rotation 
of  th?  mirror,  the  far-point  is  more  than  a  metre  distant,  and  therefore 
the  oDserved  eye  is  emmetiopic  or  hypermetiopic,  or  myopic  to  a  degree 
less  than  a  diopter.  The  lens,  convex  or  concave,  can  now  be  sought 
out  which  will  just  bring  the  far-point  to  a  metre,  and  from  the  strength 


IIIO 


THE  SENSES 


of  it,  minus  one  diopter,  the  refraction  can  be  estimated.  Suppose, 
for  instance,  that  a  convex  lens  of  two  diopters  is  required,  then  hyper- 
metropia  of  one  diopter  exists. 

In  order  to  facilitate  the  introduction  of  the  various   lenses,  instru- 


Fig 


^ii2. Geneva   Retinoscope   and   Ophthalmoscope.     A,   frame   of  instrument; 

B,  retinoscope  attachment;  C,  ophthalmoscope  attachment;  D,  base;  i,  mirror 
handle;  2,  clip  to  hold  the  proper  lens  to  correct  the  abnormality  of  refraction 
of  observer  or  patient  when  viewing  the  retina  with  the  ophthalmoscope;  3.  scale 
indicating  the  meridian  of  handle  and  pointer;  4,  ring  in  which  mirror  cup  rotates; 
6,  mirror;  7,  mirror  spring  for  reflecting  the  light  to  a  given  point;  8,  screws  for 
adjusting  mirror;  9,  screw  for  holding  light  and  ring  4  in  position;  10,  handle 
for  swinging  A  from  side  to  side;  13,  opening  iu  iris  diaphragm,  controlled  by 
handle  14;  15.  lamp  hood;  17,  knurled  handle  for  rotating  disc  containing  the 
full  diopter  lenses;  18,  handle  for  rotating  the  disc  containing  the  fractional 
lenses  (white  numbers  indicate  plus  lenses,  and  red  minus  lenses) ;  20,  opening 
through  which  observer  looks  when  adjusting  the  retinf)Scope  to  the  patient's 
eye;  21,  pinion  for  advancing  or  retracting  instrument;  24.  bracket  ring  of 
retinoscope  attachment  B,  which  is  slipped  over  ring  25  when  putting  retinoscope 
attachment  into  place;  28,  clips  for  '  fogging'  lenses  through  which  the  patient 
looks  to  relax  accommodation;  29,  opening  through  which  the  pupil  is  viewed  in 
retinoscopy;  30,  opening  containing  clip  in  which  extra  lenses  may  be  inserted 
when  required,  or  the  defect  is  over  8  diopters;  32,  patient's  eye-cup;  33.  ring  of 
ophthalmoscope  attachment  C,  which  telescopes  over  25;  34.  ophthalmoscope 
tube;  35,  binding-screw  which  holds  the  instrument  in  a  fixed  position  when 
retinoscope  is  being  used ;  37,  rack  to  raise  and  lower  the  instrument ;  40,  handle 
controlling  height  of  chin-rest  44;  46,  forehead-rest. 

ments  called  skiascopes  or  retinoscopes  may  be  used,  one  of  wliich  is 
shown  in  Fip.  482. 

14.  Pupillo-dilator  and  Constrictor  Fibres. — [a)  Set  up  an  induction 
machine  arranged  for  tetanus,  and  connect  a  pair  of  electrodes  through 


PRACTICAL  nXERCTSES  tin 

a  short-ciicuiting  key  with  the  secondary.  Etherize  a  cat  by  putting 
U  into  a  larf;c  vessel  with  a  lid,  sli]:)ping  into  the  vessel  a  piece  of  cotton- 
wool soaked  with  ether,  and  waiting  till  the  movements  of  the  animal 
inside  the  vessel  have  ceased.  Then  quickly  put  the  cat  on  a  holder 
and  maintain  an;csthesia  with  ether.  Expose  the  vago-sympathetic 
in  the  neck  (pp.  203,  212);  the  carotid  is  taken  as  the  guide  to  it. 
Ligature  the  nerve  and  cut  below  the  ligature.  On  stimulating  the 
upper  (cephalic)  end,  the  pupil  of  Die  corresponding  eye  dilates. 

Carefully  separate  the  sympathetic  from  the  vagus,  and  repeat  the 
observation  on  the  former.     'Jhe  result  on  the  pupil  is  the  same. 

[b)  Observe  in  the  eye  of  a  fellow-student,  or,  by  means  of  a  looking- 
glass,  in  your  own  eye,  that  when  light  falls  on  one  eye  both  pupils 
contract. 

{c)  Observe  that  when  the  eye  is  accommodated  for  a  near  object  the 
pupil  contracts,  and  that  it  dilates  when  a  distant  object  is  looked  at. 

15.  Colour-Mixing. —  [a)  Arrange  a  red  and  a  bluish-green  disc  on 
one  of  the  steel  discs  of  the  colour-mixing  apparatus  shown  in  Fig.  483, 
so  that  a  part  of  each  is  seen.  On  another  arrange  a  violet  and  a  yellow 
disc,  and  on  the  third  an  orange  and  a  blue  disc.  By  adjustment  of 
the  proportions  of  the  two  colours  a  uniform  grey  can  be  obtained 
from  each  of  these  combinations  (complementary-  colours)  when  the 
discs  are  rapidly  rotated. 

{h)  Mix  two  colours  that  are  not  complementary^ — e.g.,  blue  and  red — 
grey  or  white  cannot  be  obtained  by  any  adjustment  of  proportions; 
the  result  is  always  a  mixed  colour,  the  precise  hue  depending  on  the 
amount  of  each  ingredient. 

(c)  Take  papers  of  any  three  colours  from  widely-separated  parts  of 
the  spectrum — e.g.,  blue,  green,  and  red — and  arrange  them  on  one 
of  the  rotating  discs.  By  varying  the  proportions,  white  (grey)  can  be 
produced,  and  any  other  coloured  paper  fastened  on  another  of  the 
rotating  discs  can  be  matched  by  adding  white  to  the  three  colours. 

16.  After-images — (i)  Positive. — (a)  Rest  the  eyes  for  two  or  three 
minutes  by  closing  them,  or  by  going  into  a  dark  room.  Then  look  for 
an  instant  at  a  bright  object,  a  window  or  an  incandescent  lamp,  and 
at  once  close  the  eyes  again.  A  bright  positive  after-image  of  the 
object  looked  at  will  be  seen. 

[b)  Look  at  an  incandescent  lamp  through  a  coloured  glass  as  in  (a). 
The  positive  after-image  will  appear  in  the  same  colour  as  the  glass. 

(2)  Negative  After-image. — {a)  Look  at  an  incandescent  lamp  for 
thirty  seconds,  and  then  direct  the  eyes  to  a  white  surface.  The 
after-image  of  the  filament  will  appear  dark. 

(6)  Look  at  the  lamp  through  a  coloured  glass  for  thirty  or  forty 
seconds,  and  then  close  the  eye  of  look  at  a  white  ground.  The  after- 
image of  the  filament  will  appear  in  the  complementary  colour  of  the  glass . 
If  the  glass  was  red,  for  instance,  the  after-image  will  be  greenish. 

[c)  Look  at  a  white  square  on  a  dark  ground  for  thirty  seconds, 
then  quickly  cover  the  field  with  white  paper.  A  dark  square  will  be 
seen  on  the  white  ground. 

[d)  Repeat  (c)  with  coloured  squares.  The  after-image  of  the 
square  will  be  in  the  complementar\'  colour. 

Contrast. — Perform  Meyer's  experiment  (p.  1056). 

17.  Retinal  Fatigue. — Fix  the  eye  steadily  on  a  portion  of  a  printed 
page  a  considerable  distance  away.  Note  that  the  print  soon  be- 
comes blurred.  Wink  the  eye;  the  short  rest  causes  a  notable  recovery 
of  the  retina. 

18.  Visual  Acuity. — Draw  on  a  white  card  a  series  of  vertical  black 
lines  I  millimetre  thick,  and  separated  from  each  other  by  a  distance 


ma 


THE  SENSES 


of  a  millimetre.  Set  ihc  card  up  in  a  good  liplil,  and  walk  backwards 
from  it  till  the  individual  lines  just  fail  to  be  dis<  riniinated.  Measure 
the  distance  from  the  card  at  which  this  occurs,  and  calculate  the  size 
of  the  retinal  image  (p.  1019). 

10.  Colour-Blindness. — Spread  out  Holmgren's  coloured  wools  on 
a  sheet  of  white  lilter-paper  in  a  good  liglit.  Do  not  mention  the 
colours  of  any  of  the  wools,  but  (i)  ask  the  ])erson  who  is  being  tested 
to  pick  out  ail  the  wools  which  seem  to  him  to  m;itch  a  pale  pure  green 
wool  (neither  yellow  green  nor  blue  green),  whiili  is  handed  to  him. 
He  is  not  to  make  an  exact  match,  but  to  pii  k  out  the  skeins  which 


Fig.  483. — Apparatus  for  Colour-.Mixing. 

seem  to  have  the  same  colour.  If  he  makes  any  mistakes,  by  selecting, 
e.g.,  in  addition  to  the  green  skeins,  any  v)f  the  '  confusion  colours,' 
such  as  grey,  greyish-yellow,  or  blue  wools,  there  is  some  defect  of 
colour  discrimination.  Jo  determine  whether  the  person  is  red  or  green 
blind,  tests  (2)  and  (^)  are  then  made.  (2)  (live  him  a  medium  purple 
(magenta)  wool,  and  ask  him  to  pick  out  mat(  li*-s  for  it.  If  he  is  red- 
blind,  he  will  select  as  mat(  lies  to  it  only  blues  and  violets,  as  well  as 
other  purples.  If  he  is  green-blind,  he  will  select  only  greens  and 
greys.  (3)  The  third  test  is  a  red  wool.  In  selecting  matches  for  this, 
the  red-blind  will  choose  (with  reds)  greens,  greys,  or  browns  less  bright 


PRACTICAL  EXERCISES  IH3 

than  llic  lest.  The  Rrccn-blind  will  choose  (with  reds)  greens,  greys, 
or  browns  which  arc  brighter  than  the  test. 

It  must  bo  remembered  that  the  results  of  tests  with  the  coloured 
wools  need  not  be  precisely  the  same  as  those  with  coloured  lights, 
and  that  when  there  is  a  discrepancy  between  the  two  the  test  with 
the  coloured  liglits  should  be  accepted;  for  it  is  usually  the  normal 
perception  and  discrimination  of  coloured  lights  which  has  practical 
importance. 

zo.  Talbot's  Law. — Rotate  a  disc  one  sector  of  which  is  black  and  the 
rest  wdiite,  or  a  disc  like  that  in  Fig.  446  (p.  1050).  A  uniform  shade  is 
produced  as  soon  as  a  speed  of  about  25  revolutions  a  second  has  been 
attained,  and  this  is  not  altered  by  further  increase  in  the  speed. 

21.  Purkinje's  Figures. — (a)  Concentrate  a  beam  of  sunlight  by  a 
lens  on  the  sclerotic  at  a  point  as  far  as  possible  from  the  corneal  ma.rgin, 
passing  the  beam  through  a  parallel-sided  glass  trough  filled  with  a 
solution  of  alum  to  sift  out  the  long  heat-rays.  The  eye  is  turned 
towards  a  dark  ground.  The  field  of  vision  takes  on  a  bronzed  appear- 
ance, and  the  retinal  bloodvessels  stand  out  on  it  as  a  dark  network, 
which  appears  to  move  in  the  same  direction  as  the  spot  of  light  on  the 
sclerotic.  A  portion  of  the  field  corresponding  to  the  yellow  spot  ii 
devoid  of  shadows  (p.  1043). 

(6)  Direct  the  eyes  to  a  dark  ground  while  a  flame  held  at  the  side  of 
the  eye,  and  at  a  distance  from  the  visual  line,  is  moved  slightly  to  and 
fro.  A  picture  of  branching  bloodvessels  appears.  This  experiment 
is  performed  in  a  dark  room. 

(c)  Immediately  on  awaking  look  at  a  white  ceiling  for  an  instant; 
a  pattern  of  branched  bloodvessels  is  seen.  If  the  eye  be  at  once  closed, 
and  then  opened  with  a  blinking  movement,  this  may  be  observed  again 
and  again.     Ultimately  the  appearance  fades  away. 

HEARING,  TASTE,  SMELL,  TOUCH,  ETC. 

22.  Monochord. — Study  by  means  of  the  monochord,  a  stretched 
string  witli  a  movable  stop,  the  relation  between  the  pitch  of  the  note 
given  out  by  a  vibrating  string,  and  its  length  and  tension. 

23.  Beats. — Cause  two  tuning-forks  of  nearly  equal  pitch  to  vibrate  at 
the  same  time.     Make  out  the  beats,  and  count  their  number  per  second. 

24.  Sympathetic  Vibration. — Take  three  tuning-forks  mounted  on 
resonators.  Let  two  of  them  be  of  the  same  pitch.  Strike  one  of 
these;  the  other  is  thrown  into  sympathetic  vibration,  and  continues 
to  give  out  a  note  after  the  first  is  quickly  stopped  by  touching  it. 
The  third  fork  is  unaffected. 

25.  Determine  by  means  of  Galton's  whistle  the  pitch  of  the  highest 
audible  tone. 

26.  Cranial  Conduction  of  Sound. — When  a  tuning-fork  is  held 
between  the  teeth,  a  part  of  the  sound  passes  out  of  the  ear  from  the 
vibrating  membrana  tympani;  if  one  ear  is  closed,  the  sound  is  heard 
better  in  this  than  in  the  open  ear.  If  the  tuning-fork  is  held  between 
the  teeth,  till,  with  both  ears  open,  it  becomes  inaudible,  it  will  be 
heard  for  a  short  time  if  one  or  both  ears  be  stopped ;  and  when  in  this 
position  the  sound  again  becomes  inappreciable, it  can  still  be  caught 
if  the  handle  be  introduced  into  the  auditory  meatus. 

27.  Taste. — (i)  Apply  to  the  tongue  by  means  of  a  camel's-hair 
brush  a  solution  of  quinine  (i  to  i.ooo),  sodium  chloride  (i  to  200), 
cane-sugar  (i  to  50).  and  sulphuric  acid  (i  to  i.ooo).  Determine  at 
what  part  of  the  tongue  the  strongest  sensations  are  elicited  by  each. 


Ill  J  THE  SENSES 

(2)   Prepare  a  series  of  solutions  of  sulphuric  acid  of  gradually  in- 

M 
creasing  strength,  beginning  with  a  solution  (a   two-thousandth 

gramme-molecular  solution)  (p.  426;.  Put  into  the  mouth,  after 
previous  rinsing  with  distilled  water,  4  or  5  c.c.  of  one  of  the  solutions 
of  the  acid,  beginning  with  the  weakest,  and  determine  at  what  con- 
centration of  the  H  ions  the  acid  taste  first  appears,  rinsing  out  the 
mouth  after  each  observation.  Repeat  the  experiment  with  solutions 
of  hydrochloric  acid,  and  determine  whether  the  threshold  value  is  the 
same. 

A  similar  comparison  of  the  necessary  concentration  of  the  OH 
ions  can  be  made  with  solutions  of  sodium  hydroxide  and  potassium 
hydroxide. 

(3)  Connect  two  short  pieces  of  platinum  wire  with  the  copper  wire 
from  the  poles  of  a  Daniell  or  dry  cell.  Apply  one  platinum  wire  to 
the  inner  surface  of  the  lip  and  the  other  to  the' tip  of  the  tongue. 
Reverse  the  poles.  Note  the  difference  in  the  sensation  according  to 
whether  the  anode  or  the  kathode  is  on  the  tongue. 

28.  Smell. — (i)  Pass  a  current  tlirough  the  olfactory  mucous  mem- 
brane by  connecting  one  electrode  with  the  forehead  and  the  other 
by  means  of  a  small  piece  of  sponge  or  cotton-wool  soaked  in  physio- 
logical salt  solution  with  one  nostril.  An  odour  like  that  of  phosphorus 
will  be  perceived. 

(2)  To  distinguish  between  Taste  and  Smell. — Use  a  solution  of  clove- 
oil  in  water  which  can  just  be  distinguished  from  w^ater  when  it  is  placed 
on  the  tongue  by  means  of  a  camel's-hair  brush.  Close  the  nostrils, 
and  determine  whether  the  clove-oil  can  now  be  detected. 

29.  Touch  and  Pressure. — (i)  Prepare  a  number  of  hair  aesthesio- 
meters  by  fastening  hairs  of  different  thicknesses  to  small  wooden 
handles  about  3  inches  long  by  means  of  sealing-wax.  Hairs  as  straight 
as  possible  should  be  chosen,  or  straight  portions  of  hairs.  The  hair  is 
to  be  fastened  on  one  end  of  the  piece  of  wood  at  right  angles  to  the 
long  axis  of  the  handle,  so  that  about  an  inch  of  the  hair  projects  to 
one  side.  Determine  the  pressure  value  of  each  hair  by  pressing  it 
down  upon  the  scale  of  a  balance  till  it  is  slightly  bent,  and  observing 
the  greatest  weight  in  the  other  scale  which  it  will  lift.  Mark  the 
number  in  milligrammes  on  the  handle.  In  this  way,  when  a  hair  is 
placed  at  right  angles  to  a  point  of  the  skin,  and  pressure  exerted  on 
it  till  it  begins  to  bend,  the  intensity  of  the  touch  stimulus — i.e.,  the 
pressure  exerted  on  the  skin — is  definitely  measured,  and  by  using 
hairs  of  different  pressure  values  the  threshold  value  of  the  stimulus 
for  any  touch  area — i.e..  the  pressure  which  just  gives  the  sensation 
of  light  touch — can  be  determined  (p.  1081). 

(a)  Using  the  back  of  the  hand,  note  how  light  a  touch  of  the  aesthesi- 
ometer  applied  to  the  end  of  a  hair  suffices  to  elicit  a  sensation  of  touch, 
eis  compared  with  a  part  free  from  hairs.  The  hairs  diminish  the 
threshold  of  the  stimulation  by  acting  as  le\ers.  whose  short  arm 
presses  against  the  nerve-endings  surrounding  the  hair-follicles,  while 
the  stimulating  weight  acts  on  the  long  arm.  When  the  skin  is  shaved 
the  threshold  is  always  raised. 

(b)  Shave  an  area  on  the  back  of  the  hand,  and  make  out  the  relation 
of  the  touch-spots  to  the  hair  follicles.  Each  hair  has  an  especially 
sensitive  touch-spot  just  on  the  '  windward  '  side  of  the  follicle  (p.  1080). 
Using  aesthesiometers  of  different  pressure  \alues,  determine  the 
threshold  value  for  the  shaved  area.  Outline  an  area  of  a  square 
centimetre  on  the  skin,  and  determine  the  number  of  touch-spots, 
using  first  a  hair  of  the  threshold  value,  and  then  going  over  the  area 


PRACTICAL  EXERCISES  1115 

again  with  a  hair  of  a  decidedly  higher  pressure  value.  The  threshold 
value  for  many  parts  of  the  hairy  skin  is  obtained  with  a  hair  which 
bends  at  70  milligrammes.  Repeat  the  determinations  for  other  skin 
areas,  such  as  the  back  of  the  upper  arm,  the  palm  of  the  hand,  the 
anterior  surface  of  the  leg,  the  chest,  the  back,  and  the  cheek,  forehead, 
and  lips. 

It  is  well  that  the  subject  should  be  blindfolded  during  the  ex- 
amination of  the  skin  areas.  He  should  understand  by  preliminary 
practice  what  the  sensation  of  light  touch  is,  the  perception  of  which 
he  is  to  indicate.  With  strong  aesthesiometer  hairs  the  pricking  sen- 
sation due  to  stimulation  of  pain-spots  must  be  discriminated  from 
touch  sensation.  When  the  two  sensations  are  elicited  together,  the 
touch  sensation  is  momentary,  and  the  subject  must  be  alert  to  detect 
it  immediately  on  stimulation.  The  pain  sensation  develops  more 
slowly,  but  lasts  longer  and  becomes  much  more  conspicuous  than  the 
touch  sensation,  which  accordingly  is  apt  to  be  submerged  by  it  in 
consciousness. 

(2)  Touch  the  skin  with  a  blunt  point  (at  or  about  skin  temperature). 
With  light  contact  the  sensation  is  that  of  simple  touch.  On  in- 
creasing the  pressure,  the  quite  distinct  sensation  of  deep  pressure  is 
perceived. 

(3)  Touch  a  portion  of  skin  with  a  camel's-hair  brush  of  ordinary 
size,  pressing  on  it  till  the  hairs  of  the  brush  begin  to  bend.  The  first 
sensation  of  simple  contact  gives  place  to  a  sensation  of  pressure.  Re- 
peat with  a  camel's-hair  brush  of  the  finest  hairs  half  a  centimetre  in 
length,  cut  away  till  its  cross  section  is  only  half  a  millimetre  in  diameter 
at  the  base.  Probably  a  pure  sensation  of  touch,  without  any  pressure 
element,  will  be  obtained  when  the  brush  is  applied  so  as  just  to  bend 
the  hairs. 

(4)  Find  the  least  distance  apart  at  which  the  points  of  the  aesthesi- 
ometer compasses  can  be  recognized  as  two  when  applied  to  the  back  of 
the  hand,  the  forearm,  upper  arm,  forehead,  finger-tips,  or  tip  of  the 
tongue.  Both  points  of  the  compasses  must  be  placed  on  the  skin 
at  the  same  time,  and  the  same  pressure  applied  to  both.  The  subject 
must  not  see  the  points. 

(5)  Time  Discrimination  of  Touch. — Touch  the  prong  of  a  vibrating 
tuning-fork  lightly  with  the  tip  of  the  finger.  The  taps  of  the  prong 
on  the  skin  do  not  blend  into  a  continuous  sensation  even  when  the 
fork  vibrates  several  hundred  times  per  second. 

30.  Temperature  Sensations. — For  the  investigation  of  these,  pieces 
of  thick  copper  wire,  filed  at  one  end  to  a  blunt  point,  and  fixed  by 
the  other  in  a  small  wooden  handle,  may  be  used.  They  can  be  heated 
in  a  sand-bath  or  in  a  beaker  of  water  to  the  desired  temperature,  or 
cooled  in  cold  water  or  in  ice.  Or  a  metal  tube  drawn  out  at  one  end, 
through  which  water  at  the  required  temperature  can  be  passed  before 
use,  may  be  employed.  Another  device  is  a  metal  cylinder  ending  in 
a  point,  and  filled  with  water  at  the  given  temperature. 

(i)  On  the  dorsal  side  of  the  hand  outline  an  area  of  skin  with  a 
pen  or  a  coloured  pencil.  Divide  this  into  areas  of  4  square  milli- 
metres. Go  over  the  area  with  a  wire  or  cylinder  at  a  temperature  of 
about  40°  C,  and  determine  the  extent  and  position  of  the  spots  which 
on  contact  yield  a  sensation  of  warmth,  marking  them  on  the  skin  by 
ink-dots,  or  mapping  them  on  ruled  paper.  Then  repeat  the  ex- 
ploration with  points  at  a  temperature  of  about  15°  C,  and  map  the 
spots  which  yield  a  sensation  of  coolness.  Now  note  whether  a  warm 
spot  touched  with  a  pomt  at  15"  C.  or  a  cold  spot  touched  with  a  point 
at  40°  C,  yields  any  temperature  sensation. 


trifi  THE  SENSES 

(2)  Touch  the  skin  with  a  test-tube  containing  water  at  50°  C,  and 
again  with  a  test-tube  containing  ice.  Do  the  sensations  differ  in  any 
way  from  those  of  pure  warmtli  and  coohiess  ?  Repeat  (i)  with 
teni])eratuics  of  50°  and  0°,  and  note  wlictlicr  there  is  any  difierence 
in  the  quaUty  of  the  sensations  yickled  by  tlie  warm  and  cold  spots. 
When  a  cokl  spot  is  touched  with  a  point  at  a  temperature  of  50°,  or 
a  warm  spot  with  a  point  at  a  temperature  of  0°,  is  any  sensation 
obtained  ?     If  so,  what  ? 

(3)  Apply  successively  to  one  and  the  same  j)ortion  of  the  skin  test- 
tubes  containing  water  at  50°,  45°,  40°,  35°,  30°,  25°,  20°,  15°,  10°, 
5°,  and  0°  (ice),  and  determine  the  sensations  excited  in  each  case. 
The  contact  should  only  be  momentary,  so  as  not  to  cause  extensive 
and  lasting  change  of  temperature  of  the  skin.  Note  that  there  is  a 
certain  range  of  temperature  above  and  below  that  of  the  skin  within 
which  no  sensation  of  heat  or  cold  is  given. 

(4)  Take  three  beakers  of  water  at  20°,  30°,  and  40°  C.  respectively. 
Place  a  finger  of  one  hand  in  the  coldest  beaker,  a  finger  of  the  other 
hand  in  the  warmest,  until  no  definite  temperature  sensations  are  felt 
by  either  finger.  Plunge  both  fingers  into  the  beaker  at  30°  C,  and 
temperature  sensations  will  be  perceived. 

(5)  Teyyiperature  Discriminalion. — Find  the  least  perceptible  differ- 
ence in  temperature  between  two  beakers  of  water  at  about  0°  C. 
Repeat  the  experiment  with  two  beakers  of  water  at  about  30°  C,  and 
again  with  two  beakers  of  water  at  about  55°  C.  Use  the  same  hand. 
Expose  the  same  amount  of  surface  to  the  water. 

(6)  Compare  the  acuteness  of  the  temperature  sensations  of  the 
skin  and  the  mucous  membrane  of  the  mouth,  touching  a  given  portion 
of  skin  and  then  a  portion  of  mucous  membrane  with  tubes  containing 
water  at  various  temperatures. 

31.  Pain. — (i)  Using  a  pin,  explore  a  cutaneous  area  to  determine 
whether  every  point  of  the  skin  yields  the  painful  sensation  of  pricking. 
Especially  compare  the  result  of  stimulating  the  region  in  the  imme- 
diate neighbourhood  of  the  hairs  with  the  spaces  between  hairs.  Dis- 
criminate the  touch  sensation  given  by  the  light  contact  of  the  pin-point 
from  the  painful  impression  caused  when  the  pressure  is  increased. 
Note  that  the  touch  element  is  moie  evanescent  than  the  pain  element. 

(2)  With  strong  v.  Frey  hairs  determine  the  pressure  at  which  the 
sensation  of  touch  passes  into  that  of  pain. 

(3)  Compare  the  .sensibility  to  pin-pricks  of  the  mu(  ous  membrane 
within  the  mouth  with  that  of  the  skin. 

32.  Having  determined  the  systolic  blood-pressure  in  one  arm  of 
a  fellow-student  (p.  113),  release  the  pressure  in  tlie  cutl.  then  raise 
the  hand  in  the  air  so  as  to  empty  the  arm  of  blood,  and  while  it 
is  still  raised,  get  up  a  pressure  in  the  cuff  equal  to  the  systolic  })rcssurc. 
Lower  the  hand  and  maintain  this  pressure  by  squeezing  the  bulb  occa- 
sionally. Be  careful  not  to  increase  the  pressure  above  the  systolic 
pressure.  There  is  no  disadvantage  in  letting  it  drop  5  to  10  milli- 
metres below  systolic  pressure  from  time  to  time.  Now  compare  the 
acuity  of  the  sensations  of  contact,  pre.ssuie,  warmth,  cold,  and  pain 
in  the  anicmic  and  the  normal  hand,  always  on  symmetrically  placed 
areas  of  the  two  hands.  Repeat  the  comparison  at  intervals  till  a 
definite  difference  is  found,  and  note  the  sensation  for  which  the  acuity 
first  diminishes.  Do  not  prolong  the  experiment  unduly.  If  the  sub- 
ject experiences  discomfort,  the  pressure  in  the  armlet  is  to  be  at  once 
released. 


CHAPTER  XIX 
REPRODUCTION 

Regeneration  of  Tissues,-  In  lower  forms  of  animals  and  in  all 
or  most  })lants,  the  power  of  regeneration  is  much  greater  than  in 
the  higher  animals  and  in  man.  A  ninvt  can  reproduce  an  am- 
putated toe,  and  every  tissue — skin,  muscle,  nerves,  bone — will  be  in 
its  place.  After  extraction  of  the  crystaUine  lens  in  triton  larvae, 
a  new  lens  is  formed  from  the  iris  epithelium.  Artificial  mouths 
surrounded  by  tentacles  can  be  formed  in  Cerianthus,  an  animal 
belonging  to  the  same  group  as  the  sea-anemones,  merely  by 
making  a  cut  in  the  body-wall  and  preveuting  it  from  closing.  In 
an  Ascidian,  too  {Cynone  intestinalis) ,  artificial  openings  in  the 
bianchial  sac,  surrounded  by  numerous  pigmented  points  similar 
to  the  eye-spots  around  the  natural  mouth  and  anus,  have  been 
produced  (Loeb).  A  classical  example  of  regeneration  in  inverte- 
brates is  that  of  the  rays  of  starfishes  after  amputation.  According 
to  some  observers,  this  massive  regeneration,  as  well  as  other  in- 
stances of  the  regeneration  of  complicated  organs  in  invertebrates, 
depends,  in  some  degree  at  any  rate,  upon  the  nervous  system. 

Even  in  the  higher  animals  regeneration  of  tissues  is  a  common 
phenomenon.  Since  cells  are  constantly  dying  within  the  body, 
they  must  be  constantly  reproduced.  In  some  tissues  the  process 
by  which  this  is  accomplished  is  more  evident,  and  therefore  better 
known,  than  in  others.  The  most  highly-organized  tissues  are 
with  difficulty  repaired,  or  not  at  all.  The  epidermis  is  always 
wearing  away  at  its  surface,  and  is  being  constantly  replaced  by  the 
multiplication  of  the  cells  of  the  stratum  Malpighii.  In  the  corneous 
layer  we  have  only  dead  cells;  in  the  Malpighian  layer  we  have  every 
histological  gradation  from  squames  to  columns,  and  every  physio- 
logical gradation  from  cells  which  are  about  to  die  to  cells  that  have 
just  been  born.  The  corpuscles  of  the  blood  undoubtedly  arise  at 
first,  and  are  recruited  throughout  hfe,  by  the  proliferation  of 
mother-cells.  The  gravid  utenis  grows  by  the  formation  of  new 
fibres  from  the  old,  and  by  the  enlargement  of  both  old  and  new. 
A  severed  muscle  is  generally  united  only  by  connective  or  scar 
tissue,    but    under    favourable    conditions    a    complete    muscular 

H17 


1 1 1 8  RE  PROD  UCTION 

'  splice  '  may  be  formed.  A  broken  bone  is  regenerated  by  the 
proliferation  of  cells  of  the  periosteum,  which  become  bone- 
corpuscles.  Gland  cells — e.g.,  liver  cells — are  also,  under  certain 
circumstances,  capable  of  regeneration.  Some  of  the  most  striking 
instances  of  new  formation  of  glandular  tissues  ha\'e  already  been 
mentioned  in  connection  with  tlie  growth  of  grafts  of  certain  of  the 
endocrine  organs  {e.g.,  thyroid,  adrenal  cortex),  when  a  physio- 
logical insuthciency  has  been  created  by  removal  of  the  greater 
portion  of  the  organ  (p.  648).  There  is  no  evidence  that  the  influence 
of  the  nervous  system  is  a  factor.  It  is  doubtful  whether  there  is  any 
new  fonuation  of  nerve-cells  in  the  adult  organism,  but  peripheral 
nerve-filires  which  have  been  destrcjyed  by  accident  or  operation 
are  readily  regenerated,  and  the  end-organs  of  efferent  nerves  may 
share  in  this  regeneration. 

Thus,  in  a  sense,  reproduction  is  constantly  going  on  within  the 
bodies  even  of  the  higher  animals.  But  since  the  whole  organism 
eventually  dies,  as  well  as  its  constituent  cells,  a  reproduction  of  the 
whole,  a  regeneration  en  masse,  is  required. 

A  cell  of  the  stratum  Malpighii  can  only,  so  far  as  we  know, 
reproduce  a  similar  cell,  and  this  is  characteristic  of  cells  that  have 
undergone  a  certain  amount  of  differentiation,  especially  in  the 
higher  animals.  The  fertilized  ovum,  on  the  other  hand,  has  the 
power  of  reproducing  not  only  ova  like  itself,  but  the  counterparts 
of  every  cell  in  the  body.  And  this  is  only  the  highest  development 
of  a  power  which  is  in  a  smaller  degree  inherent  in  other  cells  in 
lower  forms.  Plants  and  the  lowest  animals  are  far  lees  dependent 
upon  reproduction  by  means  of  special  cells.  A  piece  of  a  Hydra 
separated  off  artificially  or  by  simple  fission  becomes  a  complete 
Hydra,  as  was  shown  by  Trembley  a  century  and  a  half  ago.  A 
cutting  from  a  branch,  a  root,  a  tuber,  or  even  a  leaf  of  a  plant,  may 
reproduce  the  whole  plant.  It  is  as  if  each  cell  in  these  lowly  forms 
carried  within  it  the  plan  of  the  complete  organism,  from  which  it 
built  up  the  perfect  plant  or  animal. 

Reproduction  in  the  Higher  Animals. — ^In  regard  to  the  secretions 
of  the  reproductive  glands,  all  that  is  necessary  to  be  said  here  is 
that,  unhke  other  secretions,  their  essential  constituents  are  living 
cells.  The  spermatozoa  in  the  male  have,  indeed,  diverged  far  from 
the  primitive  type.  Certain  cells  (spermocytes)  in  the  tubules  of  the 
testicle  divide,  each  forming  two  daughter  spermocytes.  Each  of 
the  daughter  spermocytes  in  turn  divides,  so  that  four  cells  (sperma- 
tids) are  formed  from  each  spermocyte.  In  the  final  division  which 
produces  the  spermatids  a  reduction  of  the  chromosomes  (p.  1122) 
occurs,  so  that  the  spermatid  possesses  only  one-half  the  number 
characteristic  of  the  somatic  cells  of  the  species.  The  spermatids 
elongate  and  become  spermatozoa,  the  head  of  the  latter  repre- 
senting the  nucleus  of  the  former;  and  it  is  this  nucleus  (with  the 


REPRODUCTION  IN   THE  HIGH  I. U  ANIMALS  1119 

middle  pirce  originally  containing  the  male  centrosome  and  attrac- 
tion sphere,  p.  5)  wliich  is  tlie  t-ssuntial  contribution  of  the  male  to  the 
reproductive  process.  The  tail  of  the  spermatozoon  is  simply,  from 
the  physiological  point  of  view,  a  motile  arrangement,  whose  function 
it  is  to  carry  the  nucleus  of  the  male  element,  freighted  with  all  that 
the  father  can  transmit  to  the  offspring,  into  the  neighbourhood  of 
the  female  reproductive  element  or  ovum.  After  the  spermatozoon 
has  penetrated  the  ovum  its  tail  disappears,  being  probably 
absorbed.  The  function  of  the  accessory  reproductive  glands,  the 
prostate,  the  seminal  vesicles,  and  Cowper's  gland,  are  not  well 
understood.  But  the  spermatozoa  in  the  act  of  ejaculation  are 
mi.xed  with  the  secretions  of  these  glands,  and  therefore  it  is  to  be 
supposed  that  they  are  of  importance.  When  the  prostate  and  the 
seminal  vesicles  are  removed  in  white  rats,  the  female  is  no  longer 
fertilized,  although  the  sexual  power  of  the  male  is  unaltered.  The 
testes  apparently  dexelop  spermatozoa  in  the  nomial  manner,  but 
for  some  reason  they  either  do  reach  the  ovum  or  do  not  react 
with  it  normally  if  they  do  reach  it.  When  the  testes  are  re- 
moved from  a  young  animal,  the  development  of  the  prostate  is 
interfered  with;  in  an  adult  animal  the  gland  atrophies. 

The  ovum  also  begins  as  a  typical  cell  with  nucleus  (germinal 
vesicle),  nucleolus  (germinal  spot),  centrosome  and  attraction  sphere, 
and  it  forms,  by  its  repeated  subdivision,  all  the  cells  of  the  foetal 
body.  But,  except  in  some  {parthenogenetic)  forms,  it  never 
awakens  to  this  reproductive  activity  till  fecundation  has  occurred; 
and  fecundation  essentially  consists  in  the  union  of  the  male  with  the 
female  element,  or  rather  in  the  union  of  the  male  and  female  nuclei. 

From  time  to  time  a  ripe  Graafian  foUicle,  overdistended  by  its 
hquor  folliculi,  bursts  on  the  surface  of  the  ovary  and  discharges  an 
ovum.  It  is  probable  that  in  the  majority  of  mammals  {e.g.,  the 
cow,  mare,  sow,  sheep,  and  bitch)  ovulation,  or  the  discharge  of 
the  ovum,  occurs  spontaneously  during  oestrus  (period  of  heat). 
In  others  {e.g.,  the  rabbit,  ferret,  and  cat),  it  seems  only  to  take  place 
as  a  result  of  copulation.  Whether  sexual  intercourse  has  any  in- 
fluence upon  ovulation  in  women  can  hardly  be  considered  as  settled. 
The  common  opinion  is  that  most  ova  are  discharged  spontaneously 
at  the  time  of  the  menstrual  period,  but  some  \vriters  take  the  view 
that  the  discharge  bears  no  relation  to  menstruation.  Only  one 
ovum  seems  to  be  shed  each  month.  It  was  foimerly  believed  that 
the  fra\'ed  or  fimbriated  end  of  the  Fallopian  tube,  rising  up  finger- 
like from  the  dilatation  of  its  bloodvessels,  grasps  the  ovum.  But 
it  is  more  than  doubtful  whether  this  occurs.  It  is  more  probable 
that  the  ovum  is  first  discharged  into  the  pelvic  cavity,  and 
is  guided  to  the  orifice  of  the  Fallopian  tube,  not  necessarily 
that  of  its  own  side,  by  the  movements  of  the  cilia  around  the 
orifice,  and  then  passed  slowly  along  the  tube  by  the  downward 


1120  REPRODUCTION 

lashing  cilia  which  line  it.  Probably  the  ovum  takes  as  a  rule  eight 
or  ten  days  to  reach  the  uterus,  and  it  is  during  this  time  that 
fertilization  takes  place.  If  not  impregnated,  it  soon  perishes  amid 
the  secretions  of  the  utenjs — how  soon  has  been  matter  of  discussion, 
and  can  hardly  be  considered  as  settled.  If,  however,  impregnation 
(Kcurs,  the  o\  um  penetrating  the  superiicial  e])ithelium  into  the 
subepithelial  connective  tissue  becomes  hxed  in  one  of  the  crypts  or 
pouches  of  the  uterine  mucous  membrane  {decidna  serolina),  which 
grows  round  it  as  the  decidna  reflexa.  The  Graafian  follicle,  after 
the  discharge  of  the  ovum,  fills  up  with  blood,  and  a  cellular  struc- 
ture, the  corpus  luteum,  is  developed  in  its  interior  from  cells  in 
the  wall  of  the  follicle.  In  the  absence  of  iniprt  gnation  the  corpus 
luteum  begins  to  disappear  before  the  next  menstrual  period,  and  is 
spoken  of  as  a  false  corpus  luteum.  But  when  pregnancy  occurs,  it 
continues  to  grow  till  the  fourth  or  fifth  month  of  pregnancy,  and  is 
called  a  true  corpus  luteum. 

Menstruation, — In  the  mature  female,  from  puberty,  the  age  at 
which  the  reproductive  power  begins  (thirteenth  to  fifteenth  year), 
on  till  the  time  of  the  menopause  (fortieth  to  fiftieth  year),  at  which 
it  ceases,  an  ovum — or  it  may  be  in  some  cases  more  than  one — is 
discharged  at  regular  intervals  of  about  four  weeks.  This  discharge 
is  accompanied  by  certain  constitutional  symptoms  and  local  signs 
that  last  for  a  \'ariable  number  of  days.  The  temperature  of  the 
body  diminishes  somewhat,  rarely  more  thi.n  i°  F.,  and  there  is 
also  a  slight  fall  in  the  pulse-rate.  The  genit;i  I  organs  are  congested, 
and  a  quantity  of  blood,  which  varies  in  diilerent  individuals,  but 
is  usually  not  over  50  c.c,  is  shed.  If  more  than  60  c.c.  is  lost,  the 
fiow  is  copious.  Over  100  c.c.  it  is  abnormally  great  (G.  Hoppa- 
Seyler).  At  the  same  time,  the  whole  or  a  portion  of  the  mucous 
membrane  of  the  uterus  is  cast  off. 

As  to  the  physiological  meaning  of  this  menstruation,  as  it  is 
called,  opinion  is  divided.  Two  chief  theories  have  been  proposed 
to  account  for  it,  both  of  which  agree  in  considering  the  phenomenon 
to  be  connected  with  a  preparation  of  the  uterus  for  the  reception 
of  the  ovum.  But  according  to  the  theory  of  Pfliiger,  the  mucous 
membrane  is  stripped  off  (by  a  process  analogous  to  the  '  f  eshening  ' 
or  paring  of  the  indurated  edges  of  a  wound  by  the  surgeon,  in 
order  that  nnion  may  occur  when  they  are  brought  together)  on 
the  chance,  so  to  speak,  that  an  impregnated  ovum  may  arrive.  On  the 
alternative  theory,  this  change  takes  place  because  the  ovum  has  not 
been  impregnated,  and  the  bed  prepared  for  it  not  being  required, 
the  swollen  and  congested  uterine  mucous  membrane  undergoes 
degeneration,  and  is  in  part  cast  off  (Keichert,  Williams,  etc.). 
However  this  may  be,  it  is  now  pretty  generally  agreed  that  the 
degenerative  process  involves  only  the  superficial  portion  of  the 
mucosa,  and  not  its  whole  thickness. 


MENSTRUATION  tt2t 

The  process  of  menstruation,  and  the  nutrition  of  the  genital 
organs,  espcciallv  the  uterus,  are  intimately  dependent  upon  the 
ovaries.  There  is  good  evidence  that  the  influence  is  exerted  through 
an  internal  secretion  formed  by  some  portion  of  the  ovarian  sub 
stance.  When,  for  instance,  the  ovaries  of  young  animals  (guinea- 
pigs)  are  removed  from  tlieir  normal  situation  and  transplanted  to 
a  distant  part  of  the  body,  the  external  genitals,  vagina,  and  uterus 
undergo  the  normal  development  instead  of  being  arrested  in  their 
growth,  as  is  the  case  when  the  ovaries  are  removed  altogether.  The 
removal  of  the  ovaries  in  adult  animals  leads  to  tibrous  degeneration 
of  uterus  and  Fallopian  tubes.  On  the  other  hand,  removal  of  the 
items  has  no  effect  on  the  development  of  the  ovaries  in  a  young 
animal,  and  does  not  cause  degeneration  of  the  ovaries  of  an  adult 
animal.  In  monkeys,  in  which  a  menstrual  flow  comparable  to  that 
in  the  human  female  occurs,  it  was  found  that  menstruation  took 
place  after  the  ovaries  had  been  transplanted  from  their  original  seat, 
and  the  flow  stopped  when  the  transplanted  ovaries  were  removed. 
The  view  has  been  put  forward  that  the  important  part  of  the  ovary 
for  these  functions  is  the  corpus  luteum,  which  is  considered  to  be 
a  gland  with  an  internal  secretion  (Born).  This  secretion  seems 
to  be  connected  with  the  implantation  of  the  ovum  and  the  sub- 
sequent growth  of  both  ovum  and  uterus.  According  to  Fraenkel, 
the  absence  of  the  corpus  luteum  prevents  implantation.  The 
experiments  of  Marshall  and  Jolly  also  indicate  that  the  corpus 
luteum  forms  some  substance,  which  exerts  an  action  on  the  uterine 
mucosa,  during  the  earher  stages  of  pregnancy.  When  the  ovum 
has  not  been  fertilized  the  corpus  luteum  brings  about  menstruation. 
Where  fertiHzation  has  occurred  it  prepares  the  uterus  for  the  im- 
plantation of  the  ovum.  It  is  generally  considered  that  as  regards 
their  origin  there  is  no  difference  between  the  true  and  the  false 
corpora  lutea. 

The  mode  of  origin  of  the  corpus  luteum  has  given  rise  to  much 
discussion.  Two  chief  views  have  been  put  forward:  (i)  That  it  is 
a  structure  derived  from  certain  large  epithelium-like  cells  (theca 
cells)  in  the  connective-tissue  wall  (theca)  of  the  discharged  folUcle 
(v.  Baer,  et  al.) ;  (2)  that  it  is  developed  from  the  folHcuIar  epitheHum 
(membrana  granulosa)  (Sobotta,  et  al.).  The  first  view  seems  to  be 
best  established.  The  theca  cells  multiply  and  grow  into  the  cavity 
of  the  discharged  folhcle.  Their  yellowish  colour  is  due  to  the 
presence  in  them  of  lipoid  droplets. 

The  influence  of  the  ovary  on  the  formation  of  the  decidua  has 
been  illustrated  in  a  very  interesting  way  by  the  investigations  of 
L.  Loeb  on  the  artificial  production  of  deciduomata.  He  has  shown 
that  if  a  number  of  incisions  are  made  into  the  uterus  of  a  rabbit  or 
guinea-pig  within  a  certain  interval  after  the  oestral  period  (period  of 
heat),  a  structure  with  the  histological  characters  of  the  decidua 

71 


1122  REPRODUCTION 

develops  at  each  wound.  Impregnation  does  not  appear  to  be  a 
necessary  factor,  nor  even  contact  of  tlic  o\uni  with  the  uterine 
mucous  membrane.  On  the  other  hand,  ovulation,  the  discharge  of 
an  ovum  or  ova,  or  at  any  rate  the  condition  of  the  ovary  associated 
with  this  discharge,  seems  to  be  indispensable.  For  extirpation  of 
the  ovaries  in  a  large  number  of  guinea-pigs  prevented  the  formation 
of  deciduomata  from  wounds  of  the  uterus  made  at  the  most  favour- 
able period  after  copulation.  Tlie  uterus  then  appears  to  have  an 
inherent  power  of  responding  to  such  a  stimulus  as  a  mechanical 
injury  by  the  production  of  a  decidual  structure,  but  only  under  the 
influence  of  the  ovary.  The  ovarian  factor  is  probably  not  nervous 
but  chemical,  some  specific  substance  which  acts  on  the  uterus 
being  liberated  periodically  in  connection  with  the  sexual  rhythm. 
Development  of  the  Ovum. — Before  fecundation,  and  apparently 
as  a  preparation  for  it,  the  ovum  is  the  seat  of  remarkable  changes, 
similar  upon  the  whole  to  those  seen  in  the  mitotic  or  indirect 
division  of  ordinary  cells.*  They  have  been  most  fully  studied  in 
the  eggs  of  certain  invertebrate  animals. 

The  di\ision  of  the  cell  is  initiated  by  changes  in  the  centrosome  and 
attraction  sphere.  The  centrosome  divides  into  two  daughter  centro- 
somes.  These  take  up  a  position  one  at  each  pole  of  the  nucleus. 
Each  daughter  centrosome  is  surrounded  by  a  system  of  radiating  lines 
or  filaments,  which  are  less  conspicuous  than  the  chromatin  filaments 
of  the  nucleus,  since  they  do  not  stain  as  these  do.  Meanwhile  the 
nuclear  membrane  and  the  nucleoli  disappear,  or  at  any  rate  become 
indistinguishable  from  the  rest  of  the  chromatin  skein.  The  skein 
breaks  up  into  chromosomes,  the  number  of  which  is  constant  for  a  given 
species,  but  is  not  the  same  in  all  species  of  animals. 

The  daughter  centrosomes  or  astrospheres  are  united  by.  meridional 
achromatic  fibres,  which  form  a  spindle  running  through  the  nucleus 
from  one  pole  to  the  other.  The  chromosomes  arrange  themselves  at 
right  angles  (equatorially)  to  the  spindle,  and  then  each  chromosome 
divides  longitudinally  into  two.  The  halves  of  the  chromosomes  now 
pass  toward  their  respective  centrosomes,  being  perhaps  guided  by  the 
fibres  of  the  spindle.  It  results  from  this  that  two  daughter  nuclei  are 
formed,  each  with  the  same  number  of  chromosomes  as  the  original 
nucleus,  although  with  only  half  the  amount  of  chromatin.  The  cyto- 
plasm divides  also,  so  that  the  parent  cell  is  now  represented  by  two 
daughter  cells.  In  ordinary  cell  division  the  two  daughter  cells  are  of 
equal  size,  but  in  the  division  of  the  ovum  which  occurs  before  fertiliza- 
tion the  two  resulting  cells  are  verv  unequal.  The  large  cell  continues 
to  be  kno\\Ti  as  the  ovum;  the  small  one  is  the  first  polar  body.  After 
extrusion  of  the  first  polar  body  the  ovum  again  divides  unequally.  A 
new  spindle  forms,  and  a  second  polar  body,  again  much  the  smaller  of 
the  two  daughter  cells,  is  cast  off.  There  is  a  difference,  howeve*, 
between  the  process  of  division  which  gives  rise  to  the  first  and  that 
which  gives  rise  to  the  second  polar  body.  In  the  case  of  the  latter  a 
so-called  reduction-division  occurs;  the  chromosomes  do  not  split  longi- 
tudinally, but  half  of  the  original  number  pass  into  each  daughter 
nucleus.  As  to  the  significance  of  these  changes  there  has  been  much 
discussion.  It  is  agreed  that  the  result  of  the  process  is  the  expulsion 
*   For  figures  illustrating  the  changes,  bee  any  good  textbook  of  Histology. 


DEVELOPMENT  Of  THE  OVUM  1123 

of  a  portion  of  the  chnjnialiii,  the  ovum  lunv  possessing  only  half  the 
original  nnmber  of  chromosomes,  although  nearly  all  the  origmal 
cytoplasm.  In  fertilization  the  original  number  is  restored  by  the  male 
element  when  it  arrives  and  penetrates  the  ovum.  For  in  the  final  cell 
division  by  which  the  mature  spermatozoon  is  formed  the  chromosomes 
of  its  nucleus  arc  also,  after  two  divisions  essentially  similar  to  those 
occurring  in  maturation  of  the  ovum,  reduced  to  half  the  normal  number. 
The  two  reduced  nuclei  in  the  fertilized  ovum  are  spoken  of  as  the 
male  and  female  pronuclei.  By  their  union  a  single  nucleus  is  formed 
with  the  number  of  chromosomes  normal  to  the  species. 

An  enormous  amount  of  interesting  work  has  been  done  with  the 
view  of  iUustrating  the  connection  of  the  compHcated  phenomena 
described  with  the  structure  of  the  ovum.  Only  a  bare  reference 
to  one  or  two  of  the  experiments  is  possible  here.  Driesch  and 
Hertvvig  find  that  the  nucleus  can  be  made  artificially  to  change  its 
place  with  reference  to  the  yolk,  without  hindering  the  development 
of  a  normal  animal.  Lilhe  has  shown  that  centrifugalization  of  the 
eggs  of  annelids,  although  it  markedly  alters  the  distribution  of  the 
yolk  and  other  substances,  does  not  affect  the  form  of  cleavage. 
The  polar  bodies  appear  in  the  position  which  they  would  normally 
occupy.  In  other  words,  no  redistribution  of  the  granules  or  nucleus 
affects  the  polarity  of  the  egg,  which  therefore  is  a  function  or 
property  of  the  ground  substance  of  the  protoplasm.  The  whole 
of  the  protoplasm,  however,  is  not  necessary  for  complete  develop- 
ment. Even  in  Amphioxus,  the  lowest  of  the  vertebrates,  the 
eggs  have  been  broken  up  by  shaking,  and  a  complete  animal 
evolved  from  as  little  as  one-eighth  of  an  ovum.  If  the  separation 
was  incomplete  a  kind  of  Siamese  twins,  or  even  triplets,  could  be 
obtained  (Wilson  and  Mathews).  Nor  is  it  always  indispensable 
that  both  pronuclei  should  be  present. 

Parthenogenesis. — Attempts  have  been  made  to  separate  the 
constituents  of  spermatozoa  which  are  essential  to  fertilization. 
From  the  sperm  of  a  sea-urchin  a  substance  can  be  extracted  by 
strongly  hypotonic  salt  solutions,  containing  ether,  which  acts  as  a 
powerful  fertilizing,  agglutinating,  and  cytolyzing  agent  upon  the 
eggs.  It  is  soluble  in  dilute  acid,  and  is  probably  identical  with  a 
fertihzing  agent  called  oocytase  present  in  blood-serum  (Robertson). 
Whatever  it  is  that  the  spermatozoon  suppHes,  the  process  of 
fertilization  can  in  certain  forms  be  started  artificially  in  the  absence 
of  spermatozoa  or  any  of  their  constituents.  The  studies  of  Loeb 
and  his  pupils  on  artificially  induced  parthenogenesis  are  of  special 
importance.  When  the  unfertiHzed  eggs  of  the  sea-urchin  are 
exposed  for  one  or  two  minutes  to  50  c.c.  of  sea-water,  to  which 
3  or  4  c.c.  of  decinormal  acetic  acid  has  been  added,  the  majority  of 
the  eggs  form  the  membrane  characteristic  of  the  entrance  of  the 
spermatozoon.  When  these  eggs  are  afterwards  exposed  for  thirty 
to  forty  minutes  to  100  c.c.  of  sea-water,  to  which  14  or  15  c.c.  of  a 
strong  solution  of  sodium  chloride  (two  and  a  half  times  the  strength 


11.-4  REPRODUCTION 

of  a  normal  solution,  or  about  14-6  per  cent.)  has  been  added,  those 
of  the  eggs  which  have  formed  membranes  develop  into  swimming 
larvas  that  rise  to  the  surface.  These  larvas  develop  into  perfect 
sea-urcliin  larvas  or  '  plutei  '  as  fast  as  the  larvas  of  eggs  fertilized 
with  sperm.  It  has  lately  been  shown  that  pricking  oi  tiie  unfer- 
tilized egg  of  a  frog  with  a  needle  suffices  to  induce  normal  develop- 
ment of  the  egg  (Bataillon).  These  parthenogenetic  frogs  have  been 
successfully  reared,  and  apparently  are  all  males  (Loeb).  These 
observations  have  an  important  bearing  on  the  question  of  the  deter- 
mination of  sex.  In  the  frog  it  would  seem  that  the  eggs  are  all 
alike,  since  in  the  absence  of  a  spermatozoon  only  one  sex  (the  male) 
is  developed.  The  male  frog  is  hetero-gametic  for  sex — i.e.,  there 
are  two  kinds  of  spermatozoa,  one  with  and  the  other  without  a  sex 
chromosome.  If  a  spermatozoon  of  the  former  type  enters  an  egg, 
a  female  is  produced.  If  a  spermatozoon  of  the  latter  type,  or  no 
spermatozoon  at  all,  enters  an  egg,  a  male  is  produced. 

It  is  impossible  to  enter  here  into  a  discussion  of  the  factors  which 
determine  sex.  While  due  weight  must  be  given  to  such  morphological 
distinctions  as  sex  chromosomes  in  the  gametes  (or  sexual  reproductive 
elements),  evidence  has  been  adduced  that  the  fundamental  factor  may 
be  chemical  and  metabolic  pecularities  in  the  gametes.  In  pigeonse  .g., 
— in  which  the  female  is  the  hetero-gametic  sex,  producing  two  kinds 
of  eggs — it  has  been  shown  that  the  egg  which  is  to  develop  a  female 
is  characterized  by  a  lower  metabolism,  a  lower  percentage  of  water 
and  a  higher  total  content  of  fat  and  phosphorus  or  of  phosphatides, 
than  the  egg  which  is  to  develop  a  male.  There  are  indications  that  by 
changing  these  chemical  conditions  sex  can  be  to  some  extent  controlled 
(Whitman,  Riddle). 

The  facts  of  parthenogenesis  show  that  it  is  not  absolutely  neces- 
sary for  development  that  the  ovum  should  have  the  normal  number 
of  chromosomes  restored.  It  can  develop  with  half  the  number,  the 
chromosomes  of  the  female  pronucleus  being  sufficient  for  growth, 
although,  of  course,  in  this  case  for  a  growth  uninfluenced  by  the 
properties  of  the  male  element.  In  like  maimer  it  is  stated  that 
portions  of  the  maturated  ovum  devoid  of  a  nucleus  can  undergo 
development  if  penetrated  by  a  spermatozoon,  the  chromosomes  of 
the  male  pronucleus  being  sufficient  for  growth. 

Formation  of  the  Embryo.- — Not  till  all  these  c\ tnts  have  taken  place 
— extrusion  of  the  two  polar  bodies,  or  maturation  ;  penetration  of  the 
spermatozoon,  and  blending  of  its  head  (the  male  pronucleus)  with  the 
remnant  of  the  nucleus  of  the  ovum  (female  pronucleus),  or  fecundation 
— not  till  then  does  the  ovum  begin  the  process  of  repeated  division  by 
which  the  whole  body  is  reproduced.  The  fused  or  segmentation  nucleus 
divides  into  two,  each  containing  the  normal  number  of  chromosomes 
derived  from  the  splitting  of  those  contributed  by  both  the  male  and 
female  elements.  It  is  believed  that  the  division  takes  place  in  such  a 
way  that  both  male  and  female  chromosomes  are  represented  in  each 
nucleus.     The  cytoplasm  being  also  cleft  by  a  corresponding  furrow. 


FORMATIOX  OF  THE  EMBRYO  1125 

two  complete  nucleated  cells  make  their  appearance.  These  divide  in 
turn,  till  at  length  (in  the  mammal)  the  embryo  is  represented  by  a 
hollow  sphere  or  vesicle,  with  a  cellular  crust.  During  division  the 
upper  or  outer  cells  have  always  been  larger  than  the  inner  and  lower, 
and  have  multiplied  more  rapidly;  and  thus  it  comes  about  that  the 
hollow  sphere  of  large  cells  encloses  a  mass  of  smaller  cells,  along  with 
remnants  of  broken-do\\-n  yolk  and  of  fluid  derived  by  absorption  from 
the  contents  of  the  uterus.  The  smaller  cells  continue  to  multiply  and 
arrange  themselves  as  a  lining  to  the  sphere  already  formed,  so  that  in  a 
short  time  it  becomes  double,  and  we  have  already  differentiated  two  of 
the  primary'  embryonic  layers — the  ectoderm,  also  called  the  epiblast,  or 
superficial,  and  the  endoderm,  also  called  the  hypoblast,  or  deep  layer. 
The  whole  sphere  is  called  the  blastoderm,  or  the  blastodermic  vesicle. 

WTiile  this  inner  shell  of  endodermic  cells  is  gradually  creeping  on  to 
completion,  there  appears  at  a  part  where  it  is  already  fully  formed  a 
small  opaque  whitish  disc,  the  germinal  area  or  embryonal  shield.  This 
represents  the  stocks  on  which  the  framework  of  the  embr^'O  is  to  be  laid 
down.  The  area  elongates;  at  its  posterior  end  appears  a  thickened 
line,  the  primitive  streak,  soon  furrowed  by  a  longitudinal  groove,  the 
primitive  groove,  that  marks  the  direction  in  which  the  long  axis  of  the 
future  embr\'0  ^-ill  lie,  but  is  not  itself  a  permanent  line  in  the  building, 
and  ultimately  vanishes.  The  appearance  of  the  primitive  streak  is  the 
signal  that  a  rapid  proliferation  of  the  cells  of  the  germinal  area,  and 
especially  of  the  ectoderm,  has  begun  ;  and  this  goes  on  until  a  third  layer 
is  formed,  intermediate  in  position  to  the  original  two,  and  therefore 
named  the  mesoderm.  WTiile  this  is  pushing  its  way  over  the  germinal 
area  and  into  the  rest  of  the  blastodermic  vesicle,  the  ectoderm  in  front 
of  the  primitive  streak  rises  up  in  two  lateral  ridges,  enclosing  between 
them  the  medullary  groove.  The  medullary  groove  is  the  beginning  of 
the  cerebro-spinal  axis;  its  walls  first  come  to  overhang  the  furrow,  and 
then  to  coalesce;  and  the  medullary  groove  has  now  become  the  neural 
canal.  Immediately  under  it  the  mesoderm  forms  a  rod  of  cells,  the 
notochord,  which  is  the  forerunner  of  the  vertebral  column ;  around  this 
the  bodies  of  the  vertebrae  are  afterwards  de\'eloped  from  cubical  masses 
of  mesodermic  cells,  arranged  in  pairs  alon.-;  the  notochord,  and  called 
the  protovertehrcB.  The  rest  of  the  mesoderm,  running  out  on  each  side 
from  the  proto vertebrae,  splits  into  two  layers,  an  upper  or  somatic  layer, 
which  unites  with  the  ectoderm,  forming  with  it  the  somatopleure,  and 
a  lower  or  splanchnic  layer,  which  unites  with  the  endoderm  to  form 
the  splanchnopleure.  Between  the  somatopleure  and  the  splanchno- 
pleure  is  a  space  called  the  coelom,  or  pleuro-peritoneal  cavity  (Fig.  485). 
The  layer  of  ectoderm  which  envelops  the  whole  (termed  the  tropho- 
blast,  from  its  nutritive  function),  in  conjunction  with  the  underlying 
mesoderm,  represents  the  prechorion,  the  early  stage  of  the  chorion. 

Up  to  the  present,  apart  from  the  enclosure  of  the  neural  canal,  all  this 
formative  activitv  is  buried  beneath  the  surface  of  the  blastoderm,  and 
has  not  showed  itself  bv  any  external  token  ;  the  embryo  still  appears  as 
a  portion  of  the  germinal  area,  and  lies  in  its  plane.  But  now  a  pocket, 
or  crease,  or  moat,  beginning  at  the  head  as  the  head-fold,  then  pushing 
under  the  tail,  gradually  creeps  round  and  undermines  the  whole 
embryo,  which  is  raised  above  the  general  level,  and,  as  it  were,  scooped 
out  from  the  rest  of  the  blastoderm;  till  at  length  it  lies  on  the  latter, 
something  like  an  upturned  canoe,  enclosing  a  tube,  complete  in  front 
and  behind,  but  still  open  in  the  middle,  where  it  communicates  with 
the  interior  of  the  yolk- vesicle.  Since  this  tube  has  been  formed  by  the 
tucking  in  of  the  three  ancestral  layers  of  the  blastoderm,  it  follows  that 
it  is  lined  by  endoderm,  supported  externally  by  the  splanchnic  sheet 


1 1 26  REPRODUCTION 

of  mesoderm.  So  that  now  tlit-  body  consists  of  a  dorsal  tube  ithe 
neural  canal),  essentially  of  ectodermic  origin,  a  ventral  tube  (the 
alimentar\'  canal),  essentially  of  endodermic  origin,  and  between  the 
two  a  massive  double  layer  of  mesodcrmic  tissue,  which  contributes 
supporting  elements  to  both.  At  this  point  it  mav  be  well  to  emphasize 
the  fact  that  this  embr\ological  distinction  of  the  three  primitive  layers 
has  a  deep  and  fundamental  meaning,  and  corresponds  to  a  physiological 
distinction  that  endures  throughout  life.  The  endoderm,  the  lowest 
layer  in  position,  may  also  be  described  as  the  lowest  in  the  physiological 
hierarchy.  It  furnishes  the  epithelial  lining  of  the  alimentary  canal 
from  the  beginning  of  the  oesophagus  to  near  the  end  of  the  rectum,  as 
well  as  the  epitlielium  of  the  organs  which  arise  from  diverticula  of  the 
primitive  intestine — viz.,  the  digestive  glands  (with  the  exception  of  the 
salivary  glands),  the  lungs,  and  the  passages  leading  to  them,  the 
thyroid,  and  the  greater  part  of  the  thymus  gland  in  its  primitive  con- 
dition before  th?  lymphoid  tissue  derived  from  the  mesoderm  has  as 
yet  grown  into  it.  According  to  some  authorities,  the  notochord  is  also 
derived  from  the  endoderm. 

Upon  the  whole,  it  may  be  said  that  the  tissues  of  endodermic 
origin  are  essentially  concerned  in  chemical  labours,  in  the  absorption 
of  food  material  ?nd  excretion  of  waste  products.  The  mesodermic 
tissues  are  essentially  concerned  in  mechanical  labour;  they  are  the 
tissues  of  movement  and  of  passive  support.  The  ectodermic  tissues 
are  at  the  top  of  the  pyramid ;  they  govern  the  rest. 

From  the  mesoderm  arise  the  muscles,  the  entire  vascular  system, 
with  its  blood-  and  lymph -corpuscles,  the  bones  and  connective  tissues; 
and  the  Wolffian  body  and  its  appendages,  which  are  the  predecessors 
of  the  genital  glands  and  ducts,  and  of  the  chief  portion  of  the  renal 
apparatus. 

The  ectoderm  forms  the  epidermis  and  its  appendages,  the  epithelial 
end-organs  of  the  nerves  of  special  sense,  and  the  nervous  system, 
cerebro-spinal  and  sympathetic.  The  salivan,-  glands  and  the  raucous 
lining  of  the  mouth  and  anus  are  developed  from  the  ectoderm,  which 
is  indented  to  meet  the  intestinal  canal  and  give  it  access  to  the  exterior 
at  either  end. 

It  is  not  possible  here  to  trace  in  detail  the  development  of  all  the 
organs  of  the  embr\-o.  Its  nutrition  and  metabolism  not  only  dis- 
tinctly belong  to  the  physiological  domain,  but,  carried  on  as  they  are 
under  conditions  that  seem  so  strange,  and  even  so  bizarre,  to  one 
acquainted  onlv  with  adult  physiology,  are  calculated  to  throw  light 
on  the  metabolic  processes  of  the  fully-developed  body.  And  they 
cannot  be  understood  without  reference  to  the  peculiarities  of  the 
vascular  svstem  in  foetal  life.  These  we  shall  accordingly  describe,  but 
for  further  details  as  to  the  anatomy  of  the  embr\'o  the  student  is 
referred  to  some  standard  anatomical  textbook,  such  as  Quain's 
'  Anatomv.' 

Development  of  the  Connections  between  the  Embryo  and  the 
Uterus. — In  the  first  period  of  its  development  the  ovum,  nc-stling  in 
the  pouch  formed  by  the  decidua  serotina  and  reflexa,  Is  fed  from  the 
maternal  blood  and  tissues  directly,  without  the  mediation  of  foetal 
bloodvessels,  through  the  finger-like  processes  or  villi  with  which  its 
external  layer,  the  zona  pellucida,  becomes  studded.  At  the  earliest 
stage  at  which  a  human  oxnim  has  been  studied  after  implantation  it  is 
already  enveloped  by  a  thick  ectodermic  covering  (the  trophoblastic 
envelop>e),  consisting  of  two  layers  of  cells,  one  unquestionably  of  foetal 
origin,  the  so-called  cells  of  Langhans,  and  the  other  the  SNTicytium,  the 
origin  of  which  is  assigned  by  some  authorities  to  the  ovum,  by  other» 


FORMATION  OF  THE  EMBRYO 


1127 


to  the  maternal  tissues  The  trophoblastic  covering  is  everywhere  in 
contact  with  the  maternal  blood,  w-liich,  pushing  its  way  into  tlie  tropho- 
blast  at  intervals,  divides  it  into  columns.  Later  on  the  foetal  mesoderm 
grows  into  these,  and  so  the  primary  chorionic  villi  are  formed.  It  is 
not  till  after  the  first  three  weeks  that  bloodvessels  make  their  way  into 
these  villi,  although  the  mesoderm  of  the  foetus  begins  to  enter  the  villi 
about  the  end  of  the  first,  or  the  beginning  of  the  second,  week.  The; 
scanty  yolk  of  the  human 


line  of  union 

-prechorion 
embryo 
-^ — amnion 

-somatopleure 
•coetom 

splanchnopieure 


Fig.  4S'. — Showing  the  Folds  of  the  Somatopleure 
in  a  Bird's  Ovum  uniting  over  the  Embryo 
and  becoming  demarcated  into  Amnion  and 
Prechorion  (Keith). 


ovum  IS  totally  inade- 
quate to  supply  it  with 
nutriment  for  the  time 
that  elapses  before  the 
bloodvessels  are  devel- 
oped, and  food  sub- 
stances must  be  obtained 
from  the  maternal  liquids 
by  imbibition,  osmosis, 
diffusion,  or  filtration, 
aided,  perhaps,  by  more 
special  absorptive  pro- 
cesses on  the  part  of  the 
foetal  tissues.  Soon  the 
heart  appears  as  a  tube 
(at  first  double),  formed 
by  cells  belonging  to  the 
splanchnic  layer  of  the 
mesoderm.  It  begins  to 
pulsate  in  the  chick  as 
early  as  the  middle  of  the 
second  day,  although  it  as 

yet  contains  neither  nerve-cells  nor  fuUy-formed  muscular  fibres.  In 
the  mammal  pulsation  is  late  in  making  its  appearance,  in  man  about 
the  beginning  of  the  third  week.  A  bloodvessel  grows  out  from  the 
anterior  end  of  the  heart  and  divides  into  two  primitive  aortic  arches, 
from  each  of  which  a  vessel  (omphalo-mesenteric  cr  vitelline  artery)  runs 
out  in  the  mesoderm  covering  the  umbilical  vesicle,  or  yolk-sac.  The 
blood  is  returned  to  the  heart  by  the  vitelline  veins  coursing  in  on  the 
walls  of  the  vitelline  duct.  In  this  way  the  store  of  nutriment  in  the 
umbilical  vesicle  of  the  chick,  which  is  the  only  solid  or  liquid  food  it 
receives  or  needs  during  the  whole  period  of  development,  is  tapped, 
and  a  regular  channel  of  supply  established.  Oxygen  is  at  the  same 
time  absorbed  through  the  porous  shell;  but  later  on  this  respiratory 
function  is  taken  over  by  the  second  or  allantoic  circulation.  In  the 
mammal  the  circulation  on  the  umbilical  vesicle  is  of  much  less  conse- 
quence, for  the  quantity  of  material  left  over  after  the  formation  of  the 
blastoderm  is  exceedingly  small;  it  is  only  with  a  few  days'  provision 
in  its  haversack  that  the  embryo  starts  out  on  its  developmental  march. 
And  the  vitelline  vessels  deriving  their  further  supply  of  food  and 
oxygen  from  the  tissues  of  the  mother  in  contact  with  the  ON-um  cease 
to  be  of  use  as  soon  as  the  second  and  more  perfect  placental  circulation 
is  established,  and  soon  shrivel  up  and  disappear,  as  the  umbilical 
vesicle  shrinks. 

The  second  circulation  of  the  embryo  is  developed  in  connection  with 
a  remarkable  offshoot  from  the  hind-gut  called  the  allantois,  which, 
before  the  fifth  day  in  the  chick  and  during  the  second  week  in  man, 
pushes  its  way  out  between  the  somatic  and  splanchnic  layers  of  the 
mesoderm — i.e.,  in  the  pleuro-peritoneal  cavity — and  grows  through  the 


II28 


liEPRODUCTIOS 


umbilicus,  carr\ing  bl<;odvessels  along  with  it  in  its  mesodcrmic  layer. 
Still  earlier,  and,  indeed,  while  the  embryo  is  beinf,'  separated  off  from 

and  raised  above 
the  level  of  the  rest 
of  the  blastoderm 
by  the  deepening 
nf  the  ditch  around 
it,  the  further 
banks  of  this  fur- 
row, formed  of 
ectoderm  and 
somatic  mesoderm, 
have  risen  up  on 
every  side,  and, 
growing  over  the 
back  of  the  em- 
bryo, have  finally 
coalesced  and  en- 
closed it  in  a 
double- walled 
pouch  (Fig.  4851. 
The  superficial 
layer  of  the  pouch 
is  called  the  false 
amnion  ;  it  soon 
blends  with  the 
tufted  chorion  or 
common  outer 
envelope  of  the 
o\-um.  The  inner 
layer  jjersists  as 
the  true  amnion  ;  a 
liquid,  the  ammotic 
fluid,  16  secreted  in  the  cavity  which  it  encloses;  and  the  embryo,  loosely 
anchored  for  the  rest  of  its  intra-uterine  life  by  the  umbilical  cord  alone, 
floats  freely  within  it.  The  amniotic  fluid  acts  as  a  water-jacket  or 
cushion,  to  break  the  force  of  the  inevitable  shocks  and  jars  transmitted 
from  the  mother  to  the  foetus  and  from  the  foetus  to  the  mother.  To 
some  extent,  in  addition,  it  may  serve  as  a  nutritive  fluid,  for  substances 
can  pass  from  the  blood  of  the  mother  into  the  amniotic  fluid,  and  the 
amniotic  fluid  can  be  swallowed  by  the  fcjetus.  This  is  shown  by  the 
fact  that  sodium  sulphindigotate,  when  injected  into  the  maternal 
circulation,  is  found  in  the  amniotic  fluid  and  in  the  alimentary  canal 
of  the  foetus,  although  not  in  any  of  the  foetal  tissues.  Fine  lanugo 
hairs  from  the  foetal  skin  have  also  been  found  in  the  meconium. 

The  precise  origin  and  manner  of  formation  of  the  amniotic  fluid 
have  not  been  puttied.  It  is  probably  in  the  main  a  maternal  secretion 
or  transudation.  But  something  is  contributed  by  the  foetus  in  tlie 
form  of  renal,  and  perhaps  of  skin,  secretions.  The  fluid  is  poor  in 
solids.  Its  maximum  content  of  protein,  reached  during  the  first  half 
of  pregnancy,  is  only  0-7  per  cent.  Later  on  it  diminishes,  and  at  full 
term  is  only  one-tenth  of  this  amount.  The  specific  gravity  is  1006  to 
1009.  Its  osmotic  concentration,  as  measured  by  the  depression  of  the 
freezing-point,  is  less  than  that  of  the  mother's  blood-serum. 

The  allantois,  growing  out  at  the  umbilicus,  in  the  manner  described, 
insinuates  itself  between  the  true  and  false  amnion,  and  soon  blends 
with  the  latter.  For  a  time  the  secretion  of  the  primitive  kidneys 
continues  to  be  poured  into  the  cavity  of  the  allantois,  so  that  it  serves 


Fig.  435  — Diagram  to  illustrate  Formation  of  Amnion  and 
Allantois.  A,  cavity  of  true  amnion;  F,  F',  folds  about 
to  coalesce  and  complete  the  amniotic  cavity;  m,  meso- 
dcrmic layer  of  amnion;  B,  allantois;  I,  intestinal  cavity 
of  embryo;  Y,  yolk-sac;  h.  endodermic  layer;  e,  ecto- 
dermic  layer  of  embryo.  The  embryo  is  the  shaded  por- 
tion in  the  middle  of  the  figure.  E  is  placed  over  the 
head  region.  Xo  attempt  is  made  to  delineate  its  actual 
form.  The  mesoderm  is  represented  by  the  interrupted 
line. 


NUTRITION  OF  THE  EMBRYO  1129 

in  pa'-t  as  an  excretory  organ,  while  in  the  bird  it  also  performs  the 
function  of  respiration  ;  anil  in  the  mammal  brjth  food  anu  oxygon  arc 
carried  by  its  vessels  to  the  f<i;tus  during  the  greater  part  of  intra- 
uterine life.  But  later  on  the  outgrowth  atrophies  and  disappears,  all 
except  its  origin  from  the  alimentary  canal,  wriich  dilates  and  persists 
as  the  urinary  bladder,  and  its  bloodvessels,  which  grow  in  the  form,  of 
tufts  or  loops  into  the  chorionic  villi.  The  vessels  are  fed  by  two 
umbilical  arteries  which  arise  from  the  hypogastric  arteries  and  run  out 
at  the  umbilicus  on  the  allantois.  The  blood  is  returned  by  an  umbilical 
vein,  whose  further  course  we  shall  have  soon  to  trace.  The  shrivelled 
stalk  of  the  allantois,  projecting  through  the  umbilicus,  takes  part,  with 
its  bloodvessels,  in  the  formation  of  the  umbilical  cord,  which  contains 
also  the  remains  of  the  yolk-sac  and  is  clothed  externally  by  a  layer  of 
the  amnion.  Continuous  with  the  umbilical  cord,  and  stretching  from 
the  umbilicus  to  the  urinary-  bladder,  is  a  portion  of  the  allantois  which 
is  represented  in  extra-uterine  life  by  a  thin  cord-like  structure,  the 
urachus.  The  vascular  tufts  of  the  chorion,  which  at  first  cover  the 
whole  surface  of  the  ovum  and  suck  up  food  and  oxygen  from  decidua 
serotina  and  reflexa  alike,  disappear  in  the  region  of  the  reflexa,  hyper- 
trophv  all  over  the  serotina — that  is,  where  the  o\'um  is  in  actual  contact 
with  the  uterine  wall— and  this  part  of  the  chorion  is  now  distinguished 
as  the  chorion  frondosum.  The  giant  villi  of  the  chorion  frondosum 
push  their  way  into  the  thickened  decidua  serotina,  and  ultimately 
penetrate  into  the  great  capillaries  or  sinuses  of  the  uterine  mucous 
membrane.  At  the  same  time  the  tissue  of  the  villi  external  to  the 
vessels  becomes  reduced  to  a  mere  film,  so  that,  except  for  a  thin  cover- 
ing of  decidual  cells,  the  foetal  vessels  are  bathed  in  maternal  blood. 
By  this  interweaving  of  decidua  and  chorion  frondosum  is  formed  the 
placenta,  which  for  the  rest  of  intra-uterine  life  acts  as  the  great 
respiratory,  alimentary,  and  excretory  organ  of  the  foetus. 

Exchange  of  Materials  in  the  Placenta. — ^The  maternal  blood,  as 
it  streams  through  the  colossal  capillaries  of  the  decidua,  gives  up 
to  the  foetal  blood  oxygen  and  food  substances  and  receives  from  it 
carbon  dioxide  and  in  all  probability  lurea.  It  is  true  that  the  blood 
in  the  uterine  sinuses  is  not  itself  fully  oxygenated;  it  is  not  bright 
red  arterial  blood.  But  it  yet  contains  more  oxygen,  and  oxygen  at 
a  higher  partial  pressure  (p.  247 ),  than  the  purest  blood  of  the  fcetus, 
and  is,  therefore,  able  to  part  with  some  of  the  surplus  to  the  dark 
stream  of  oxygen-impoverished  blood  brought  by  the  umbilical 
arteries  to  the  placenta.  Thus,  it  has  been  found  that  while  the 
blood  of  the  umbilical  artery  of  the  foetus  of  a  sheep  had  47  volumes 
per  cent,  of  carbon  dioxide,  and  only  23  of  oxygen,  that  of  the 
umbilical  veins  had  6*3  volumes  of  oxygen,  and  only  40  5  of  carbon 
dioxide  (Zuntz  and  Cohnstein).  In  the  exchange  of  gases  between 
the  placental  and  the  foetal  blood  the  same  general  features  present 
themselves  as  in  the  external  and  internal  respiration  of  the  mother, 
with  this  difference,  that  the  exchange  of  oxygen  is  neither  between 
air  and  haemoglobin,  as  in  the  lungs,  nor  between  hemoglobin  and 
tissue  elements,  as  in  the  organs;  but  between  maternal  and  foetal 
haemoglobin,  of  course,  through  the  mediation  of  the  maternal  and 
fcetal  plasma.     There  is  no  reason  to  suppose  that  the  mechanism 


1I30  REPRODUCTION 

of  the  exchange  is  essentially  different  from  that  of  the  more  famiUat 
forms  of  respiration.  Diffusion  of  the  gases  from  places  of  higher 
to  places  of  lower  tension  unquestionably  plays  an  important 
part.  But  this  does  not  exclude  the  possibility  of  a  more  active 
process  of  some  other  kind,  although  there  is  at  present  no  direct 
evidence  of  such  a  gaseous  secretion  as  has  been  previously  discussed 
in  connection  with  pulmonary  respiration  (p.  262).  The  presence  of 
oxydases  in  the  placenta  does  not  throw  any  light  on  the  question. 
For  there  is  no  proof  that  they  act  in  transferring  oxygen  from  the 
one  circulation  to  the  other,  and  oxydases  are  found  in  the  most 
diverse  tissues.  Their  significance  for  the  combustion  processes  of 
the  body  has  already  been  alluded  to  (p.  271 ). 

Salts  soluble  in  water,  including  not  only  those  necessary  for 
nutrition,  like  sodium  chloride,  but  many  foreign  salts,  pass  readily 
from  the  placenta  to  the  foetus,  and  in  general  more  easily  the  lower 
their  molecular  weight.  Such  salts  as  potassium  iodide,  e.g.,  when 
injected  into  the  maternal  circulation,  appear  in  the  foetus  in  a  very 
short  time.  On  the  other  hand,  colloidal  solutions — e.g.,  of  silver 
or  silicic  acid — do  not  pass  over  at  all.  It  is  of  practical  importance 
that  substances  like  chloroform,  ether,  and  other  narcotics,  and  alka- 
loids likemorphine  and  scopolamine,  when  administered  in  obstetrical 
practice,  may  find  their  way  from  the  mother  to  the  child,  although 
more  slowly  and  more  capriciously  than  the  salts.  While  diffusion 
and  osmosis  assuredly  take  part  in  the  passage  of  materials  from  the 
placenta  to  the  foetus,  there  is  no  more  reason  to  conclude  that  the 
whole  exchange,  even  for  the  salts,  depends  upon  such  simple  physical 
processes  than  there  is  in  the  case  of  the  exchange  between  any  one 
of  the  maternal  tissues  and  the  maternal  blood.  The  essential 
similarity  of  placental  and  intestinal  absorption,  to  take  one  instance, 
is  seen  in  the  mechanism  by  which  the  foetus  gains  the  iron  required 
for  the  development  of  its  haemoglobin.  The  haemoglobin  of  the 
mother  appears  to  be  the  most  important  source  of  this  iron. 
Erythrocytes  in  all  stages  of  decomposition  can  be  found  in  con- 
tact with  the  chorionic  villi,  and  even  in  the  epithelium  covering 
the  villi.  These  corpuscles  come  partly  from  extravasations  in 
the  maternal  portion  of  the  placenta,  but  it  is  possible  that  the 
villi  also  possess  the  power  of  haemolyzing  intact  corpu3cles  in  the 
circulatm'^  placental  blood.  Iron  can  be  demonstrated  by  micro- 
chemical  reactions  in  the  epithelial  cells  of  the  chorionic  villi  as  fine 
granules,  which  increase  in  size  towards  the  base  of  the  cells.  As  we 
pass  deeper  into  the  villus  towards  its  central  bloodvessel,  the 
granules  again  diminish  in  size.  The  picture  is  very  like  that  seen 
in  the  absorption  of  iron  from  the  intestine.  And  if  the  micro- 
chemical  picture  is  practically  the  same,  the  process  by  which  the 
iron  is  absorbed  is  not  likely  to  be  fundamentally  different  in  the 
two  cases  (p.  447). 


NUTRITION  OF  THE  EMBRYO  1131 

The  same  is  true  of  the  passage  of  fat  acfoss  the  placenta.  Fat 
can  always  be  demonstrated  microchcniieally  in  the  chorionic  villi. 
The  most  superficial  layer  of  tin;  villi  is  free  from  visible  fat  droplets. 
They  increase  in  numl)er  towards  the  base  of  the  epithelial  cells. 
As  in  the  case  of  the  intestine,  these  appearances  agree  well  with 
the  view  that  the  fat  is  split  before  being  absorbed  by  the  villi,  and 
undergoes  resynthesis  in  the  epithelium.  That,  as  a  matter  of  fact, 
fat  passes  from  the  mother  to  the  foetus  is  shown  by  the  observation 
that  when  pregnant  guinea-pigs  were  fed  with  a  foreign  fat  (from 
cocoanuts),  the  characteristic  fatty  acid  (lauric  acid)  was  found  in 
the  foetus.  This,  however,  does  not  exclude  the  possibility  that  the 
foetus  may  form  fat  in  its  own  tissues  from  carbo-hydrates,  and 
perhaps  from  proteins,  as  it  is  destined  to  do  in  extra-uterine  life. 

Among  the  carbo-hydrates  the  passage  of  dextrose  from  the 
maternal  to  the  foetal  blood  has  been  experimentally  demonstrated 
A  specially  interesting  proof  is  afforded  in  cases  where  the  mother 
suffers  from  diabetes  mellitus.  In  one  case  in  which  the  mother, 
during  diabetic  coma,  was  delivered  of  a  stillborn  child,  the  blood 
of  the  child  contained  2-2  per  cent,  of  sugar,  its  urine  5-24  per  cent., 
and  the  amniotic  fluid  047  per  cent.  The  blood  of  the  mother  had 
a  sugar  content  of  o-8  per  cent.,  and  her  urine  a  content  of  6-94  per 
cent.  The  sugar  of  the  maternal  blood  is  not  the  only  source  of  the 
carbo-hydrates  of  the  foetus.  The  glycogen  store  of  the  placenta  is 
to  be  regarded  as  a  second  source,  which  is  rendered  available  on 
conversion  into  dextrose  by  the  placental  diastatic  ferment.  This 
store  of  easily  available  food  material  is  especially  important  in  the 
early  stages  of  development  of  the  ovum  before  a  circulation  has 
been  established  in  the  villi.  In  the  youngest  ova  investigated  the 
decidual  covering  has  been  found  rich  in  glycogen. 

While  it  is  to  be  supposed  that  the  products  of  the  hydrolytic 
decomposition  of  proteins  can  be  absorbed  by  the  foetal  blood  in  its 
passage  through  the  placenta,  to  be  synthesized  to  the  appropriate 
tissue  proteins  in  the  foetal  organs,  there  is  evidence  that  certain 
proteins  can  be  taken  up  without  change.  In  this  connection  it 
must  be  remembered  that  the  mother  is  much  more  closely  related 
to  the  foetus  as  regards  her  protein  composition  than  any  ordinary 
protein  food  can  be  to  an  animal  in  extra-uterine  life.  In  some 
respects,  indeed,  the  foetus  may  be  considered,  especially,  perhaps, 
in  the  first  stages  of  its  development,  as  a  part  of  the  mother,  an 
additional,  although  very  complex,  organ  rather  than  an  independent 
organism. 

The  blood  of  the  umbilical  artery,  although  far  from  the  level  of 
the  ordinary  arterial  blood  of  the  mother  as  regards  its  gaseous 
content,  is  yet  the  best  the  foetus  ever  gets;  and  by  a  series  of  con- 
trivances it  is  assured  that  this  best  should  go  first  to  the  most 
important  parts — the  liver,  the  heart,  and  the  head — ^while  the  legs 


II  ?2  REPRODUCTION 

and  most  of  tlic  abdominal  organs  have  to  put  up  with  an  inferior 
supply.  This  is  brought  about  mainly  by  the  existence  ot  three 
short-cuts  for  the  blood,  which  disappear  in  the  adult  circulation,  the 
ductus  venosus,  the  ductus  arteriosus,  and  the  foramen  ovale. 

The  blood  of  the  umbilical  vein,  rich  in  oxygen  for  foetal  blood, 
passes  partly  through  the  circulation  of  the  liver,  but  a  part  takes 
the  route  of  the  ductus  venosus,  and  empties  itself  into  the  inferior 
vena  cava.  The  latter  gathers  up  the  more  or  less  vitiated  blood 
from  the  inferior  extremities  and  the  renal  and  hepatic  veins,  and 
pours  its  mixed,  but  still  fairly  oxygenated,  contents  into  the  right 
auricle.  By  means  of  the  Eustachian  valve,  the  jet  coming  from 
the  mouth  of  the  inferior  vena  cava  is  directed  into  the  left  auricle 
through  the  foramen  ovale  in  the  inter-auricular  septum.  There 
it  is  joined  by  the  trickle  of  blood  which  is  creeping  through  the 
unexpanded  lungs.  The  left  ventricle  propels  its  contents  through 
the  aorta,  and  thus  a  large  part  of  this  comparatively  pure  or 
second-best  blood  is  sent  to  the  head  and  upper  extremities.  It 
returns  in  a  vitiated  state  by  the  superior  vena  cava  into  the  right 
auricle,  and  owing  to  the  position  of  the  Eustachian  valve  and  the 
direction  of  the  current,  it  flows  now,  not  through  the  foramen  ovale, 
but  into  the  right  ventricle.  Thence  it  is  driven  through  the  pul- 
monary artery,  but  only  a  small  quantity  of  it  finds  its  way  through 
the  lungs;  the  main  stream  is  short-circuited  through  the  ductus 
arteriosus,  and  mingles  with  the  contents  of  the  thoracic  aorta 
below  the  origin  of  the  cephalic  and  brachial  vessels. 

We  may  now  give  something  more  of  precision  to  the  statements 
that  different  parts  of  the  body  receive  blood  of  different  quality; 
and  it  -is  possible  roughly  to  divide  the  organs  in  this  respect  into 
four  categories:  (i)  The  liver,  which  partakes  both  of  the  best  and 
the  worst,  the  purified  blood  of  the  umbihcal  veins  and  the  vitiated 
blood  of  the  intestines  and  spleen;  (2)  the  heart,  head,  and  upper 
limbs,  which  receive  the  blood  from  the  inferior  extremities  and 
kidneys,  mixed  with  the  pure  blood  of  the  venous  duct;  (3)  the 
legs,  trunk,  intestines,  and  kidneys,  which  are  fed  chiefly  by  the 
off-scourings  of  the  cephalic  end,  mitigated,  however,  by  a  pro- 
portion of  mixed  blood  from  the  inferior  cava;  (4)  the  lungs,  which 
receive  only  a  feeble  stream  of  unmixed  venous  blood. 

These  peculiarities  of  the  embryonic  circulation  are  in  obvious 
correspondence  with  the  physiological  events  taking  place  in  the 
foetal  body.  The  liver  is  not  only  the  greatest  gland  in  the  embryo, 
as  it  continues  to  be  in  the  adult,  but  its  activity  seems  to  dwarl 
that  of  all  the  other  glands  put  together,  and  is  in  striking  contrast 
with  the  functional  toipor  of  the  lungs.  From  the  third  month  of 
intra-uterine  life  the  secretion  of  bile  begins  and  the  intestines 
gradually  fill  with  meconium,  of  which  the  principal  constituent  is 
bile.     Accordingly  the  liver  is  most  lavishly  suppHed  with  blood, 


NUTRITION  OF  THE  EMBRYO  1133 

while  the  lunfjs  are  stinted.  And  since  the  hver  has,  as  we  have 
already  learnt,  other  and,  in  the  adult  at  least,  even  more  important 
labours  than  excretion,  a  large  portion  of  the  blood  it  receives 
is  of  the  best  quality:  it  enters  the  gland  comparatively  rich  in 
oxygen,  and  passes  out  comparatively  poor;  while  the  lungs,  which 
have  to  be  nourished  only  for  their  own  sake,  and  are  of  no  use 
whatever  till  the  child  is  born  and  respiration  has  begun,  must  be 
content  with  the  poorest  fare — with  the  crumbs  that  fall  from  the 
table  of  foetal  nutrition.  The  full-fed  cephalic  end  of  the  embryo 
grows  far  more  rapidly  than  the  half-starved  inferior  extremities, 
and  the  head  of  the  new-born  child  is  large  in  proportion  to  the  rest 
of  the  body. 

Metabolism  of  the  Embryo. — ^There  are  some  other  points  in  the 
physiology  of  intra-uterine  life  which  call  for  remark;  and,  to  sum 
up  in  a  few  w^ords  the  grand  distinction  between  foetal  and  adull 
life,  we  may  say  that  growth  is  the  keynote  of  the  former,  worK 
(functional  activity)  of  the  latter.  Thus,  the  muscles  at  an  early 
period  in  their  development,  long  before  anj'  glycogen  can  be 
found  in  the  liver,  become  the  seat  of  an  accumulation  of  glycogen, 
which,  since  it  cannot  be  used  up  in  contraction  as  in  the  adult 
muscles,  seems  to  be  intimately  connected  with  their  own  growth, 
and  perhaps  also  with  the  growth  of  other  tissues.  It  is  true 
that  the  foetal  tissues  as  a  whole,  including  the  muscles,  are  not 
richer,  as  used  to  be  taught,  but  poorer  in  glycogen  than  adult 
tissues,  and  therefore  the  old  doctrine  that  the  foetal  glycogen  fulfils 
a  special  '  formative  '  function  in  the  development  of  the  tissues, 
has  lost  its  experimental  basis.  Nevertheless,  there  is  a  paral- 
lelism between  the  growth  of  the  foetus  and  its  glycogen  content. 
In  cases  where  the  growth  of  the  foetus  has  been  spontaneously 
arrested,  the  percentage  amount  of  glycogen  in  its  organs  has  been 
found  to  be  diminished  out  of  proportion  to  the  diminution  in  weight. 
A  similar  retardation  of  development  can  be  produced  by  repeatedly 
injecting  phloridzin  into  the  mother,  and  thus  reducing  the  glycogen 
store  of  the  foetus  (Lochead  and  Cramer).  Probably,  then,  the  foetal 
glycogen  assists  the  growth  of  the  embryo,  which  is  known  to  be 
accompanied  by  an  intense  carbo-hydrate  metabolism,  by  furnishing 
a  store  of  easily  oxidized  material  for  the  nutrition  of  the  developing 
tissues.  When  the  muscles  have  been  formed,  their  glycogen  is 
still  consumed  in  growth,  and  their  functional  powers  lie  dormant, 
but  for  the  infrequent  and  feeble  movements,  generally  regarded  as 
reflex,  but  possibly  to  some  extent  originated  in  the  cerebral  cortex, 
which  give  the  mother  the  sensation  of  '  quickening.'  It  is  only 
late  in  development  that  the  embryonic  liver  takes  on  its  glycogenic 
function.  In  the  earlier  stages  it  is  entirely  free  from  gljxogen. '  It 
is  an  interesting  illustration  of  that  exact  adaptation  of  means  to 
ends  which  so  constantly  impresses  the  investigator  of  the  animal 


H34  REPRODUCTinS 

mechanism  tliat  the  kimcnt  which  converts  glycogen  into  dextrose 
(glycogenasc)  is  a'so  either  entirely  absent  from  the  Hver  early  in 
gestation,  or  present  only  in  traces;  anrl  that  astheglycogen-forming 
and  glycogen-storing  functions  of  the  organ  increase  in  importance,  it 
becomes  richer  in  glycogenoh'tic  ferment.  It  cannot  be  doubted  that 
the  glj'cogen  found  in  the  placenta  is  also  deposited  there  in  the 
interest  of  the  rapidly  growing  foetal  tissues,  perhaps  as  a  kind  of 
current  account  on  which  they  can  operate  at  any  moment  of 
emergency,  when  the  more  distant  maternal  reserves  cannot  be 
drawn  upon  in  time.  The  glycogen  is  formed  in  the  placenta,  prob- 
ably from  the  dextrose  of  the  maternal  blood.  By  means  of  a 
glycogen-splitting  ferment,  which  can  be  extracted  by  glycerin  from 
the  placenta,  the  glycogen  appears  to  be  reconverted  into  dextrose 
for  absorption  by  the  foetus.  In  the  earlier  period  of  gestation  the 
placenta  seems  to  perform  vicariously  the  glycogenic  function  of  the 
liver,  and  as  the  glycogen  content  of  the  liver  increases  in  the  later 
stages  of  intra-uterine  life,  that  of  the  placenta  diminishes  pro- 
portionally. 

The  excretory  glands  of  the  embryo,  except  the  liver,  scarcely 
awaken  to  activity  during  foetal  life.  Urine  may  indeed  be  some- 
times found  in  the  bladder  at  birth,  but  it  is  often  absent.  It  is  a 
dilute  urine,  with  a  molecular  concentration  only  about  half  as  great 
as  that  of  the  blood,  and  although  a  portion  of  the  amniotic  fluid, 
which  contains  traces  of  urea  and  salts,  in  addition  to  small  quantities 
of  albumin,  may  be  secreted  by  the  renal  tubules,  and  find  its  way 
through  the  still  open  urachus  into  the  amniotic  sac,  this  contribution 
cannot  imply  more  than  a  slight  degree  of  glandular  action.  Under 
certain  experimental  conditions,  however,  it  can  be  largely  increased. 
Thus,  extirpation  of  the  kidneys  in  a  pregnant  animal  causes  an 
increase  in  the  amount  of  amniotic  fluid  (hydramnios)  through  the 
stimulation  of  the  foetal  kidneys  to  increased  activity  by  the  passage 
of  the  unexcreted  urinary  constituents  of  the  mother's  blood  into 
that  of  the  foetus.  After  the  injection  of  phloridzin  into  the  foetus 
sugar  has  been  found  in  abundance  in  the  amniotic  fluid,  although 
the  injection  of  that  drug  into  the  mother  caused  no  such  effect.  On 
the  other  hand,  after  injection  of  sodium  sulphindigotate  into  the 
circulation  of  the  foetus  in  the  sheep,  the  foetal  kidneys  contained 
particles  of  the  pigment,  while  the  amniotic  fluid  remained  un- 
coloured.  Long  before  full  term  the  sebaceous  glands  have 
begun  their  work  by  the  secretion  of  the  vernix  caseosa,  an 
oily  material  which  covers  the  skin  and  serves  to  protect  it 
from  the  continual  irritation  of  the  fluid  in  which  the  embryo 
floats. 

The  nervous  system  is  even  less  active  than  the  glandular  tissues, 
and  nut  more  active  than  the  muscles.  There  is  evidently  no  scope 
for  the  exercise  of  the  special  senses.     Psychical  activity  of  every 


NUTRITIOX  01'   THE  EMDRVO  I135 

kind  must  he  at  its  lowrsi  i-bb.  Consciousness,  if  it  exists  at  all, 
must  be  dull  and  mulHcd.  And  if  motor  impulses  are  discharged 
from  the  cortex,  the  psychical  accompaniments  of  such  discharge  are 
doubtless  widely  different  from  those  which  we  associate  with 
voluntary  effort. 

It  is  a  remarkable  fact  that  this  functional  calm,  broken  only  by 
the  beat  of  the  heart,  is  accompanied  by  a  relatively  intense 
metabolism  of  the  same  order  of  magnitude  as  that  of  the  adult. 
In  the  hen's  egg  at  all  stages  of  development  the  consumption  of 
oxygen  and  production  of  heat  (per  kilogramme  and  hour)  are  the 
same  as  in  the  adult  hen.  The  oxygen  consumption  and  carbon 
dioxide  production  of  pregnant  guinea-pigs  were  determined  before 
and  during  compression  of  the  umbilical  cord  of  a  foetus,  and  a  dis- 
tinct diminution  was  observed  when  the  respiratory  exchange  of  the 
foetus  was  eliminated.  From  the  results  of  a  number  of  observations 
it  was  calculated  that  the  carbon  dioxide  produced  by  the  mother 
was  462  c.c,  and  by  the  foetus  509  c.c.  per  kilogramme  of  body- 
weight  per  hour  (Bohr  and  Hasselbach).  A  similar  comparison 
betweeai  women  before  and  during  pregnancy  never  showed  any 
diminution  in  the  respiratory  exchange  reckoned  on  the  unit  of  body- 
weight  in  the  pregnant  condition.  In  one  case,  indeed,  and  that 
the  most  exactly  observed,  there  was  an  increase  in  pregnancy. 
Now,  in  the  pregnant  woman  a  considerable  part  of  the  increase  of 
body-weight  is  due  to  the  amniotic  fluid,  in  which,  of  course,  meta- 
bolism does  not  go  on.  It  is  evident,  then,  that  in  the  human  foetus 
also  the  intensity  of  metabolism  is  at  any  rate  not  of  a  lesser  order  of 
magnitude  than  in  the  mother,  in  spite  of  the  much  smaller  amount 
of  muscular  contraction  taking  place.  The  heat  production  of  mother 
and  child  together  has  been  directly  estimated  in  several  cases  in  a 
respiration  calorimeter  provided  with  a  bed  just  before  parturition 
and  just  after  it.  After  parturition  the  heat  production  of  the 
mother  was  also  separately  determined.  From  the  difference  it  was 
concluded  that  the  heat  production  of  the  child  per  kilogramme 
of  body-weight  per  hour  is  approximately  two  and  a  half  times 
that  of  the  mother  under  the  same  conditions.  (Carpenter  and 
Murlin.) 

The  foetal  heart  beats  at  the  rate  of  about  140  tiilies  a  minute  at 
full  term.*  The  blood-pressure  in  the  umbilical  artery  of  the 
mature  embryo  (sheep)  varies  from  60  to  So  mm.  of  mercury; 
but  at  the  beginning  of  the  aorta  it  will  be  more.     The  pressure  in 

*  It  has  not  been  finally  determined  whether  the  rate  of  the  heart  varies 
with  the  size  or,  what  probably  comes  to  the  same  thing,  with  the  sex  of  the 
fcBtus.  As  we  have  seen,  the  variation  of  the  rate  in  the  adult  with  the  size 
of  the  body  is  associated  with  a  corresponding  variation  in  the  metabohsm 
and  heat-loss,  which  are  proportionally  greater  in  a  small  than  in  a  large 
animal.  If  this  is  a  causal  connection  we  should  not  expect  that  in  the 
cmhrvo  in  utevo.  where  the  conditions  as  regards  heat-loss  arc  entirely  different, 
?uch  a  relation  should  cxi.st,  at  any  rate  within  the  same  species. 


1136  REPRODUCTION 

the  pulmonary  trunk  must  be  about  equal  to  that  in  the  aorta,  since 
the  comparatively  short  and  easy  circuit  through  the  lungs  does 
not  as  yet  exist ;  and  in  accordance  with  this  equality  of  pressure 
(of  work  to  be  done)  is  the  equality  of  thickness  (of  working  power) 
in  the  walls  of  the  two  sides  of  the  heart. 

Suppose,  now,  that  the  embryo  contains  60  grammes  of  blood  for 
every  kilo  of  body- weight,  and  that  the  whole  of  the  blood  passes 
through  the  circulation  in  twenty  seconds.  Then  in  twenty-four 
hours  2592  kilos  of  blood  will  be  forced  through  the  heart  for  every 
kilo  of  body-weight  against  a  pressure  of,  say,  80  mm.  of  mercury, 
or  I  metre  of  blood.  This  is  equivalent,  in  round  numbers,  to  260 
kilogramme-metres  of  work,  or  06  calories.  Now,  taking  the  total 
heat-production  of  the  heart  at  three  times  the  equivalent  of  its 
mechanical  work,  we  get  i-8  calories  per  kilo  of  body- weight  in 
twenty-four  hours  (see  p.  676),  or  about  ^^  of  the  heat-production 
of  a  resting  adult. 

Such  movements  of  the  skeletal  muscles  as  occur  cannot  account 
for  any  large  proportion  of  the  total  metabolism,  since  they  are 
executed  in  a  medium  (the  amniotic  fluid)  of  nearly  the  same  specific 
gravity  as  that  of  the  body,  and  therefore  require  the  expenditure  of 
a  very  limited  amount  of  energy.  The  ordinary  functional  activity 
of  the  embryo,  then,  is  quite  incapable  of  accounting  for  the  intensity 
of  the  foetal  metabolic  processes.  Still  less  can  it  be  due  to  an  active 
combustion  in  the  tissues  to  compensate  for  a  rapid  loss  of  heat, 
for  the  foetus  lies  sheltered  in  the  uterus  as  in  a  thermostat  at  its 
own  temperature,  and  can  lose  practically  no  heat  unless  its  tempera- 
ture be  kept  a  little  above  that  of  the  maternal  blood.  The  only 
remaining  explanation  of  the  magnitude  of  the  foetal  metabolism 
is  that  the  growth  processes  are  associated  with  a  large  amount  of 
oxidation  (and  cleavage). 

Notwithstanding  the  intensity  of  metabolism  in  the  embryo,  not 
only  is  even  the  purest  blood,  as  has  already  been  stated,  far  from 
saturated  with  oxygen,  but  the  relative  proportion  of  haemoglobin, 
the  oxygen-carrier,  is  less  than  in  the  adult ;  and  although  constantly 
increasing  in  amount  from  the  moment  of  its  first  appearance,  it  is 
still  somewhat  deficient,  even  at  full  term,  but  leaps  sharply  up  at 
birth.  At  an  early  period  of  development  the  embr\'o  also  contains 
much  more  water  than  the  adult ;  the  specific  gravity  of  its  tissues 
increases  as  development  goes  on. 

The  remarkable  vitality  of  the  foetus,  and  its  resistance  to 
asphyxia,  are  related  not  to  the  feebleness  of  its  metabolism,  but  to 
the  comparatively  slight  excitability  and  high  endurance  of  ner\'ous 
centres  like  the  respiratory,  vaso-motor,  and  cardio-inhibitorj-. 
Even  when  totally  deprived  of  oxygen,  as  by  pressure  on  the  um- 
.  bilical  cord  during  delivery,  the  child  does  not  perish  in  the  two  or 


PARTURITION  1137 

three  minutes  which  deride  the  fate  of  the  asphyxiated  adult ;  nor  are 
the  convulsions,  rise  of  blood-pressure,  and  slowing  of  the  heart-beat 
associated  with  asphyxia  in  the  latter,  so  n^adily  induced,  nor 
})remature  and  fatal  efforts  at  respiration  easily  excited  in  utero. 
But  although  in  such  a  case  the  enil)ryo  behaves  as  a  separate 
organism,  governed  by  its  own  laws,  there  are  circumstances  in 
which  it  becomes  merely  a  part  of  the  mother  and  participates  in  her 
fate.  Thus,  the  stream  of  oxygen  which  normally  passes  from  the 
maternal  to  the  foetal  blood  is  turned  back  if  asphyxia  threatens 
the  mother;  the  blood  of  the  umbilical  arteries,  instead  of  being 
purified  in  the  placenta,  loses  the  little  oxygen  it  holds  to  the 
blood  of  the  uterine  sinuses,  and  the  tissues  of  the  embryo  are 
impoverished  to  support  the  metabolism  of  the  maternal  organs. 
In  the  same  way,  the  phenomena  of  starvation  have  taught  us 
that  the  nutrition  of  the  organism  is  not  subject  to  the  rules  of 
red  tape.  In  normal  circumstances  the  flow  of  nutriment  follows 
definite  lines:  the  blood  feeds  the  tissues  through  its  intermediary, 
the  lymph,  and  recoups  itself  from  the  contents  of  the  alimentary 
canal.  But  when  the  normal  sources  of  nutrient  material  fail,  the 
body  falls  back  upon  its  stores.  The  organs  immediately  necessary 
to  life  are  kept,  as  far  as  possible,  on  full  diet;  organs  of  secondary 
importance  have  to  be  content  with  half-rations;  organs  less  im- 
portant still  are  drawn  upon  for  supplies. 

Parturition. — The  period  of  gestation  is  abruptly  closed  about 
280  days  after  the  last  menstruation,  usually  in  what  would  have 
been  the  tenth  intermenstrual  period  had  menstruation  been  occur- 
ring. There  is  necessarily  a  considerable  variation  in  the  time  when 
reckoned  in  this  way,  since  the  cessation  of  the  menses  merely  an- 
nounces that  conception  has  occurred  some  time  after  the  last 
period.  It  may  even  be  disputed  whether  the  fertilized  ovum 
corresponds  to  the  last  menstruation  or  to  the  first  absent 
period.  Parturition,  or  the  expulsion  of  the  foetus,  is  accom- 
plished by  periodical  contractions,  the  '  pains  '  of  labour,  at  first 
confined  to  the  uterus.  Soon  the  os  uteri  begins  to  soften  and 
dilate,  the  walls  of  the  vagina  become  congested,  and  its  secretions 
are  augmented.  The  uterine  contractions  increase  in  frequency 
and  force,  and  are  now  accompanied  by  reflex  contractions  of  the 
abdominal  muscles,  and,  if  the  woman  is  not  anaesthetized,  also  by 
voluntary  contractions  of  these  and  of  other  muscles,  which  can 
increase  the  intra-abdominal  pressure.  The  uterine  contractions 
can  be  initiated  and  modified  by  impulses  coming  from  the  central 
nervous  system  by  way  of  the  extrinsic  nerves  of  the  organ.  It  is 
known,  e.g.,  that  the  gravid  uterus  can  be  excited  to  contraction  by 
the  stimulation  of  various  sensory  nerves.  Powerful  mental  impres- 
sions, such  as  fright,  may  bring  on  premature  labour.  Conversely, 
sudden  cessation  of  labouj-  pains  during  parturition  is  not  uncom- 

72 


1 138  REPRODUCTION 

inoiily  obs  rvcd  t<»  be  produced  by  emotional  disturbances — for 
instance,  llie  entrance  of  a  stranger  into  the  room.  Yet  the  con- 
tract ic)n>  of  the  uterus  are  not  essentially  dependent  upon  extrinsic 
impulses.  For  not  only  do  rhythmical  contractions  occur,  but  the 
whole  process  of  parturition  has  been  seen  to  take  place  in  a  uterus 
whose  nerves  have  all  been  cut.  Even  the  excised  uterus  may  be 
kept  alive  for  as  long  as  forty-eight  hours,  and  may  go  on  executing 
periodical  contractions  when  its  bloodvessels  are  perfused  with  such 
an  artificial  fluid  as  Locke's  solution,  or,  indeed,  when  it  is  simply 
immersed  in  the  oxygenated  solution  (Kurdinowski)  (Practical 
Exercises,  p.  1147)- 

It  is  a  question  of  great  interest  how  the  uterine  contractions  are 
started  so  abruptly  at  full  term  after  so  long  a  period  of  quiescence. 
It  can  hardly  be  that  the  increasing  mechanical  distension  of  the 
uterus,  tolerated  for  so  many  months,  should  suddenly,  in  an  hour, 
become  intolerable.  For  if  the  foetus  dies  before  full  term  it  is 
expelled  without  reference  to  the  bulk  which  the  uterus  has  reached. 
It  is  more  likely  that  some  chemical  change  associated  \vith  the 
completion  of  intra-uterine  development,  a  change  which  leads, 
perhaps,  to  the  production  of  some  specific  substance  in  the  placenta 
or  the  foetus,  is  the  determining  event.  The  placenta  is  a  structure 
whose  function  is  strictlv  limited  to  the  term  of  intra-uterine  develop- 
ment. The  foetus  is  to  Hve  on,  and  so  is  the  mother.  Ma\'  it  not 
be  that  the  placenta  or  essential  elements  in  it  are  timed  to  die,  or 
to  begin  to  die,  at  full  term,  and  that  in  their  death  or  degeneration 
the  substance  or  substances  are  produced  which  start,  and  later 
sustain,  the  uterine  contractions  ?  And  ma}'  not  the  contractions  of 
the  uterus,  by  exciting  its  afferent  nerves,  or  through  the  pressure 
of  the  foetus  the  afferent  nerves  of  the  vagina,  in  turn  evoke  the 
associated  reflex  contractions  of  the  abdominal  walls  ?  These  are 
questions  which  have  been  asked,  but  not  as  yet  satisfactorily 
answered.  It  has  also  been  suggested  that  a  hormone  formed  in  the 
mammary  gland  at  full  term  stimulates  the  uterus  and  thus  brings 
on  labour. 

At  birth,  great  changes  take  place  in  the  fcetal  circulation,  and  these 
are  intimately  connected  with  the  commencement  of  the  respiratory 
activity  of  the  lungs.  The  causes  of  the  first  respiration  are:  (i)  The 
increasing  venosity  of  the  blood  circulating  in  the  bulb,  which  stimu- 
lates the  respiratory  centre  when  the  umbilical  cord  has  been  cut  o: 
tied  and  the  placental  circulation  thus  interfered  with;  (2)  the  stimula- 
tion of  the  skin  by  the  air,  which,  as  we  ha\e  seen,  acts  reflexlj-  upon  the 
respiratory  centre.  That  both  of  these  factors  may  be  involved  is 
shown  by  the  fact  that  either  compression  of  the  umbilical  cord  alone, 
or  exposure  of  the  foetus  by  opening  the  uterus  of  an  animal  wthout 
interference  with  the  circulation,  has  been  observed  to  be  followed 
by  attempts  at  breathing.  Once  distended,  the  lungs  never  again 
completely  collapse — ^not  even  after  death,  nor  when  the  chest  is 
opened.     The  aspiration  caused  by  the  elevation  of  the  chest-walls  in 


MILK  1 1 39 

inspiration  (for  the  respiration  of  the  newborn  child  is  mainly  costal) 
SUCKS  blood  into  the  thorax,  and  expands  the  vessels  of  the  lungs  for 
its  reception  ;  and  in  the  measure  in  which  the  blood  passing  through  the 
pulmonary  trunk  finds  an  easy  way  through  the  lungs,  tlie  quantity 
which  takes  the  route  of  the  ductus  arteriosus  diminishes.  Ihe  pul- 
monary veins,  and  consequently  the  left  auricle,  are  better  filled ;  and 
the  increasing  pressure  on  this  side  of  the  septum  tends  to  oppose  the 
passage  of  the  blood  through  the  foramen  ovale,  to  approximate  its 
valve,  and  to  close  its  orifice. 

By  the  second  or  third  day  the  ductus  arteriosus  has  usually  become 
obliterated.  The  umbilical  arteries  and  veins  and  the  ductus  venosus 
become  impervious  so(>n  after  the  intcrruptioia  of  the  placental  circula- 
tion. The  vein  and  venous  duct  remain  in  the  adult  as  the  round 
ligament  of  the  liver,  the  arteries  as  the  lateral  ligaments  of  the  bladder. 

Although  from  birth  onwards  the  young  mammal  obtains  its 
oxygen  and  gets  rid  of  its  carbon  dioxide  through  its  own  pulmonary 
surface  instead  of  through  the  placenta,  it  still  lives,  as  regards  its 
food  proper,  on  the  tissues  of  the  mother,  and  that  in  as  literal  a 
sense  as  when  it  drew  its  supplies  directly  from  the  maternal  blood. 

Milk. — ^The  milk  secreted  during  the  first  few  days  of  each  lacta- 
tion, the  colostrum,  as  it  is  called,  indeed  may  represent  in  part  the 
fragments  of  cells  lining  the  alveoli  of  the  mammary  glands,  which 
have  undergone  a  fatty  change  and  been  bodily  broken  down.  The 
colostrum  corpuscles  are  leucocytes  filled  with  fat  globules  taken  up 
from  the  contents  of  the  alveoli.  The  chief  chemical  difference 
between  colostrum  and  ordinary  milk  is  the  greater  richness  of  the 
former  in  protein.  It  has  been  supposed  that  it  is  of  special  impor- 
tance for  the  nutrition  of  the  suckling,  perhaps  in  virtue  of  the 
enzymes  contained  in  it,  and  it  is  said  that  young  animals  bear 
artificial  feeding  much  better  if  they  have  been  allowed  to  suckle  the 
mother  for  the  colostrum. 

In  addition  to  the  fat,  which  w^hen  milk  is  allowed  to  stand  rises  to 
the  top  as  cream,  milk  contains  a  considerable  quantity  of  caseinogen, 
to  whose  coagulation,  under  the  influence  of  the  lactic  acid  produced 
from  the  lactose,  or  milk-sugar,  by  certain  bacteria,  spontaneous 
curdling  is  due.  Another  protein,  lact-albumin  (Halliburton),  a  large 
amount  of  water,  and  some  inorganic  salts,  are  the  most  important  of  its 
remaining  constituents.  Recently  the  presence  of  small  amounts  of 
phosphatides  intimatelv  associated  with  the  protein  constituents,  and 
possibly  combined  with  them  as  '  lecith-albumins  '  has  been  shown 
(Osborne  and  Wakeman ) .  The  molecular  concentration  (p.  426)  of  milk, 
as  measured  by  its  freezing-point,  is  almost  exactly  the  same  as  that  of 
blood-serum.  Its  electrical  conductivity  varies  extremely,  since  it 
depends  on  the  quantity  of  fat  present,  the  fat  globules,  like  the  blood- 
corpuscles,  being  practically  non-conductors.  The  hydrogen-ion  con- 
centration of  fresh  cow's  milk  has  been  found  to  vary  from  o-i8  .  lo-^N 
(Ph=6'75*)  too'25  .  io-«N(Ph=6'6o)  in  the  great  majority  of  specimens. 

*  Instead  of  expressing  the  hydrogen-ion  concentration  as  a  fraction  of  a 
normal  solution,  it  is  more  convenient  for  many  purposes  to  take  as  a  measure 
of  the  concentration  the  logarithm  of  this  number,  omitting  the  negative  sign, 
represented  by  the  symbol  Pg . 


II40 


REPRODUCTION 


This  is  distinctly  greater  than  the  hydrogen-ion  concentration  of  blood. 
— 6mo -8(1'h  =7*-2)  to  2-iu -*(P,,  =7-7).  During  the  course  of  rennin 
action  there  is  no  change  in  the  hydrogen-ion  contentration  of  milk 
(Milroy). 

The  inorganic  composition  of  milk  is  particularly  interesting  when 
compared  with  that  of  the  blood  on  the  one  hand  and  that  of  the 
suckling  on  the  other.  Thus,  100  grammes  of  ash  from  each  source 
gave  the  following  values  for  the  rabbit  (Abderhalden) : 


Rabbits  (14  Days 
Old;. 


K2O 

Nap 
CaO 

Ci 


10-84 
5-9<J 

35-0^ 
2-\g 
0-23 

41-94 
4-94 


Rabbit's  Milk. 

Rabbit's  Blood. 

io-o6 

-^3-75 

7-92 

31-38 

35-(^5 

0-81 

2 -20 

O-O4 

0-08 

(j-93 

39-86 

11-11 

.5-4- 

32-()6 

Rabbit's  Blood- 
Scruni. 


319 

54-7^ 
1-42 
0-56 

O-OO 

2-98 

47-83 


The  richness  of  the  milk  (and  of  the  suckling)  in  calcium,  phos- 
phorus, and  magnesium,  as  compared  with  the  serum,  is  to  be  especially 
remarked.  This  is,  of  course,  essential  for  the  development  of  the 
bones.  Whereas  sodium  predominates  greatly  over  potassium  in  the 
serum,  the  opposite  is  the  case  in  the  milk  (and  the  suckling).  This  is 
connected  with  the  development  of  the  tissue  cells,  which  are  richer  in 
potassium  than  in  sodium.  The  high  chlorine  content  of  the  serum  is 
in  sharp  contrast  with  the  relative  poverty  of  the  milk  in  that  element, 
which  preponderates  in  the  tissue  liquids  and  is  relatively  scanty  in  the 
cells. 

In  addition  to  substances  susceptible  of  chemical  analysis,  milk 
contains  enzymes  like  those  present  in  blood-serum,  including 
oxydases  and  various  hydrolytic  ferments  (proteolytic,  diastatic, 
and  perhaps  lipolytic).  It  is  now  universally  acknowledged  that 
mother's  milk  is  superior  for  the  feeding  of  the  infant  to  any 
artifif'ial  substitut'^,  and  one  factor  in  this  superiority  may  be  the 
presence  of  ferments  specifically  adapted  for  the  digestion  of  the 
human  suckling.  More  important  is  the  practical  sterility  of  the 
human  milk  and  the  necessarily  finer  adaptation  of  its  quantitative 
and  qualitative  composition,  particularly  the  closer  relationship  of 
its  proteins  with  those  of  the  child.  In  addition,  there  is  some 
evidence  that  the  maternal  milk  contains  immune  bodies  (anti- 
bodies) which  may  increase  the  resistance  of  the  suckling  to 
infections. 

However  this  may  be,  there  is  no  question  that  much  of  the  high 
infant  mortality  associated  with  the  industrial  conditions  of  our 
great  cities  could  be  prevented  if  breast-feeding  were  carried  out  by 
every  mother  physically  capable  of  it. 

As  to  the  manner  in  which  milk  is  secreted,  there  is  no  doubt 
that  its  chief  constituents  are  formed  in  the  gland-cells.     Caseinogen 


CULTIVATION  01-   TISSUES  1141 

and  lactose  do  not  exist  in  the  blood  or  lynipli.  The  former  is 
probably  produced  by  an  alteration  in  one  or  other  of  the  serum 
proteins,  the  latter  by  a  change  in  the  dextrose  of  the  blood.  The 
fat  of  the  milk  may  come  partly  from  the  fat  of  the  blood,  but  it 
may  also  be  formed  in  the  gland-celh  from  proteins,  and  carbo- 
hydrates. The  precise  manner  in  which  the  fat  globules  are  extruded 
from  the  cells  into  the  lumen  of  the  alveoli  is  not  clear,  but  there  is 
no  good  ground  for  believing  that  the  cells  or  their  free  ends  break 
up  bodily  in  the  process. 

Little  is  known  as  to  the  influence  of  the  nervous  system  on  the 
secretion  of  milk,  and  no  definite  secretory  fibres  have  as  yet  been 
clearly  demonstrated,  although  the  fact  that  marked  changes  may 
be  produced  in  the  milk  of  nursing  women  as  the  result  of  emotional 
disturbances  indicates  that  such  nerves  do  exist.  There  is  reason 
to  suppose  that  the  stimulus  for  growth  and  development  of  the 
mammary  glands  may  be  distinct  from  the  stimulus  which  causes 
increased  secretion.  Some  observers  lean  to  the  opinion  that  milk 
secretion  is  governed  in  an  important  degree  by  hormones  carried 
to  the  glands  in  the  blood.  The  effect  of  pituitrin  has  already  been 
alluded  to  (p.  669. ). 

Pregnancy  is  accompanied  with  vascular  dilatation  and  hyper- 
trophy of  the  mammary  glands,  but  the  mechanism  by  which  these 
changes  are  produced  is  unknown.  It  is  probable  that  they  depend 
upon  some  internal  secretion  of  the  ovary  or  some  other  of  the 
organs  of  reproduction.  Pregnancy  is  not  an  absolutely  indispens- 
able condition,  and  therefore  it  would  seem  that  the  exciting 
substance,  if  any  specific  substance  exists,  is  not  a  product  of  the 
foetus  or  of  the  placenta.  Intravenous  injection  of  extract  of 
placenta  is  said  to  cause  an  increase  in  the  flow  of  milk  in  goats,  and 
the  deduction  has  been  drawn  that  some  '  internal  secretion  '  of 
the  placenta  may  be  responsible  for  initiating  the  activity  of  the 
mammary  gland  at  the  time  of  parturition.  But  precisely  similar 
phenomena  are  occasionally  seen  in  animals  which  have  not  been 
impregnated  and  even  in  men.  Himiboldt  relates  the  case  of  an 
Indian  father,  who  so  well  understood  the  responsibihties  of  pater- 
nity, and  was  so  capable  of  lulfiUing  them,  that  he  suckled  his  child 
for  five  months  on  the  death  of  the  mother.  Virgin  bitches  are 
frequently  known  to  produce  milk,  occasionally  even  in  quantity 
sufficient  to  rear  pups,  the  flow  occurring  about  the  time  when  they 
would  have  whelped  had  they  conceived  during  the  pre\'ious  oestrus. 
Bitches  which  after  copulation  have  '  missed  '  having  pups  have 
been  known  to  produce  so  much  milk,  beginning  at  the  time  they 
were  due  to  whelp,  that  they  were  able  to  rear  litters  of  puppies 
belonging  to  other  bitches.  Mules,  which  are  themselves  sterile, 
may  have  enough  milk  to  suckle  a  foal.  The  nipples  of  certain 
monkeys   become   swollen   and   congested   at   each   menstruation 


1142  REPRODUCTION 

(Heapc),  and  in  women  some  development  of  the  mammary  glands 
is  often  associated  witli  the  menstrnal  ]XTiod.  The  stimnlus  to  the 
development  of  the  gland  in  these  cases  appears  to  be  some  change 
correlated  with  a-strus,  and  cannot  be  a  change  correlated  with 
pregnancy. 

Cultivation  of  Tissues  outside  of  the  Body.—  Closely  related  to  the 
marvellous  power  of  growth  of  the  fertilized  ovum  in  the  favourable 
nidus  of  the  pregnant  uterus,  although,  of  course,  incomparably 
inferior,  is  the  power  of  growth  and  reproduction  of  isolated  tissue 
cells  in  a  suitable  medium  outside  of  the  body.  An  instance  of  this 
has  already  been  described  in  the  case  of  nerve-cells  (pp.  803,  857). 
Many  other  tissues  have  been  successfully  cultivated  in  sterile 
coagulated  lymph  or  blood-plasma.  Connective-tissue  cells  grow 
very  easily,  and  can  apparently  be  preserved  indefinitely  in  the 
living  state.  A  strain  of  these  cells,  originally  obtained  from  a 
fragment  of  the  heart  of  an  embryo  chick  which  had  been  pulsating 
in  vitro  for  104  days,  has  been  seen  to  proliferate  rapidly  outside  of 
the  organism  for  more  than  sixteen  months,  and  after  more  than 
190  passages  into  fresh  media.  At  the  end  of  this  time  the  rate  of 
proliferation  of  the  connective-tissue  cells  was  even  greater  than 
that  of  fresh  connective  tissue  taken  from  an  embryo  eight  days  old. 
Extracts  of  tissues  and  tissue  juices  under  certain  conditions  acceler- 
ate the  growth  of  connective  tissue  from  three  to  forty  times,  the 
growth  being  measured  by  the  increase  in  area  of  the  minute  pieces 
of  tissue.  This  activating  power  is  especially  marked  in  extracts 
of  embryos,  of  adult  spleen,  and  of  certain  sarcomas.  This  is 
noteworthy  as  the  great  characteristic  of  malignant  tumours  is 
their  indefinite  power  of  growth.  The  activating  substance  is 
unable  to  pass  through  a  Chamberland  filter  (Carrel).  Cultures  of 
adult  tissue  have  a  smaller  power  of  persistent  growth.  In  the 
majority  of  cases  growth  in  plasma  without  the  addition  of  a 
;  timulating  tissue  extract  ceases  after  three  or  four  generations 
(Walton). 

The  time  of  survival  of  tissues  at  low  temperatures  under  con- 
chtions  which  do  not  encourage  growth  is  also  a  matter  of  consider- 
able interest,  both  from  the  physiological  and  the  practical  point  of 
view,  since  living  sterile  tissue  is  required  for  a  number  of  surgical 
operations — for  example,  skin  for  grafting.  Skin  has  been  suc- 
cessfully grafted  after  being  kept  two  to  seven  weeks  in  cold  storage, 
but  after  a  longer  period  there  were  many  failures.  Embryonic 
chick  and  rat  tissues  Uve  longest  at  about  ()°  C,  but  not  more  than 
twenty  days  under  the  most  favourable  conditions,  according  to 
Lambert. 

Transplantation  of  Tissues.  —Besides  the  growth  and  regeneration 
of  tissues  or  organs,  the  simple  displacement  of  them  from  their 
normal  situation  and  their  implantation  in  a  new  en\ironment  have 


TRANSPLANTATION  OF  TISSUES  1143 

been  studii'd.  Normally,  a  migration  of  tissue  elements  is  only 
witnessed  in  the  adult  in  the  case  of  cells  moving  with  the  circulating 
liquids,  or  endowed  with  the  power  of  amoeboid  movement.  Under 
pathological  conditions  fragments  of  tissue,  such  as  tumour  cells, 
may  be  carried  by  the  blood  or  lymph  to  distant  parts,  and,  settling 
there,  may  undergo  development  (forniing  metastases).  In  the 
embryo  the  slow  migration  of  ti>sue  elements  is  a  process  which 
is  responsible  for  some  of  the  anatomical  pecularities  of  the  adult. 
The  migration  of  the  ovum  from  the  ovary  is  the  starting-point  of 
the  process  of  reproduction.  The  artificial  displacement  of  tissues 
within  the  body  of  one  and  the  same  animal  (auto-transplantation 
or  autografting)  can  be  successfully  accomplished  in  the  case  of 
most  normal  organs  and  tissues,  and  also  i  n  the  case  of  most  tumours. 
Instances  have  already  been  given  in  speaking  of  the  endocrine 
functions  of  the  ovary,  thyroid,  spleen,  thymus,  etc.  (Chap.  XL). 
A  small  piece  of  tissue  or  sometimes  a  small  organ  is  simply  inserted 
in  its  new  situation  without  provision  for  the  immediate  establish- 
ment of  a  circulation.  Necrosis  of  the  central  portion  occurs,  but 
the  peripheral  zone  soon  becomes  vascular,  the  graft  '  takes  '  and 
under  suitable  physiological  conditions  grows.  Hctero-transplan- 
tation,  or  grafting  between  animals  of  different  species,  does  not 
succeed.  Homoeo-transplantation,  or  grafting  from  one  animal  to 
another  of  the  same  species,  is  in  the  case  of  normal  tissues  success- 
ful only  in  rather  rare  instances.  In  most  cases,  although  some 
of  the  homoeo-grafted  tissue  may  remain  alive  for  some  time,  or 
even  begin  to  grow,  its  growth  is  soon  checked,  and  it  is  eventually 
absorbed.  Certain  tumours,  however,  can  be  readily  grafted  from 
one  animal  to  another  of  the  same  species,  and  can  live  and  grow  in 
the  new  environment. 

The  difference  in  the  fate  of  auto-  and  homa30grafts  illustrates  in  a 
striking  way  the  important  chemical  and  metabolic  differences  which 
exist,  not  only  between  different  species,  but  between  individuals  of  the 
same  species.  In  general,  a  piece  of  tissue  from  a  rabbit  is  treated  as 
an  '  unclean  '  thing,  which  must  eventually  be  cast  out,  not  onlv  when 
it  is  introduced  into  the  body  of  a  dog,  but  when  it  is  introduced  into  the 
body  of  another  rabbit.  It  is  unable  to  adapt  itself  to  its  new  en- 
vironment, and  soon  perishes.  But  a  bit  of  thyroid,  of  adrenal  cortex, 
or  of  uterus,  may  easily  settle  down  as  a  successful  colonist  in  very  out- 
landish places  witliin  the  body  of  the  animal  to  which  it  belongs.  An 
invasion  of  lymphocytes,  and  an  ingrowth  of  fibroblasts,  causing  develop- 
ment of  bands  of  connective  tissue,  have  beenregarded  by  some  observers 
as  the  immediate  causes  of  the  failure  of  homoeografts  to  grow.  It  is 
fully  as  probable,  however,  that  the  lymphocytes  gather  around  and 
invade  the  graft,  and  that  the  connective  tissue  trabecular  appear  in  it, 
because  it  has  already  been  injured  by  the  antibodies  of  the  host,  or,  if 
not  by  specific  antibodies,  then  simply  by  exposure  to  the  more  or  less 
altered  metabolic  conditions,  which  it  is  unable  to  face  successfully. 
The  difference  between  the  autograft  and  the  homoeograft  has  not  yet 
been  sufi&ciently  taken  account  of  by  surgeons,  e.g.,  in  connection  with 


"44 


REPRODUCTION 


transfusion  of  blood.  They  have  slowly  learnt  that  in  this  case  hetero- 
grafting  (for  wc  can  truly  call  transfusion  the  grafting  of  the  fluid 
tissue  blood)  is  not  permissible,  and  nobody  now  allows  sheep's  blood 
to  pass  into  the  veins  of  a  man.  But  the  danger  to  the  host  of  repeated 
and  massive  homcEO-transfusions  is  only  beginning  to  be  recognized 
by  the  men  who  have  the  power  to  '  bind  and  to  loose  '  veins  and  arteries. 

Some  normal  organs,  e.g.,  the  ovary,  arc  mf)re  readily  homoeograftcd 
than  others.  Guthrie  has  shown  that  hens  whose  ovaries  have  been 
interchanged  are  capable  of  laying  eggs.  When  the  hens  were  im- 
pregnated and  the  eggs  hatched  out  the  colour  characters  of  the  resulting 
offspring  seemed  to  have  been  infiuonced,  not  c)nly  by  the  hen  to  which 
the  o\ary  originally  belonged,  but  also  by  the  hen  to  which  it  had  been 
transferred. 

Young  have  also  been  obtained  from  guinea-pigs,  whose  (jv-aries  had 
been  replaced  by  ovaries  from  other  guinea-pigs.  Eighteen  months 
after  interchange  of  the  ovaries  in  two  sister  puppies,  it  was  shown  by 
histological  examination  that  the  engrafted  ovaries  contained  numerous 
normal  Graafian  follicles,  as  well  as  corpora  lutea.  Statements  arc  on 
record  of  successful  ovarian  homoeografts  even  in  women. 

Another  point  of  great  interest  in  connection  with  homtjeograf ti ng 
is  that  a  small  number  of  indi\iduals  of  a  species  may  constitute  more 
favourable  hosts  than  the  great  majority  for  a  tissue  from  anotlicr 


Fig.  486.— Method  of  Transplantation  (of  both  Kidneys)  in  Mass  (after  Guthrie) 
Segments  of  the  mferior  vena  cava  and  abdominal  aorta  are  removed  with  the 
kidneys  and  renal  vessels,  and  interposed  in  the  course  of  the  vena  cava  and  aorta 
of  another  animal,  according  to  the  method  of  Carrel  and  Guthrie. 

Individual  of  the  same  species.  For  instance,  a  rabbit's  thyroid 
cannot  as  a  rule  be  successfully  grafted  into  another  rabbit,  even 
when  thyroid  deficiency  has  been  caused  bv  removal  of  the  greater 
part  of  the  thyroid  from  the  host.  But  if  a  large  nuutbcr  of  rabbits 
are  tried  one  will  occasionally  be  found  in  which  thyroid  hom-ieo- 


TRANSPLANTATION  01-   TISSUES 


«I43 


grafts  succeed  (Marine  and  Manlcy).  It  is  not  as  yet  known  what 
the  circumstances  are  whicli  so  niud.f\'  the  u^ual  ad\  ir>e  condi- 
tions that  a  homoeograft  can  take,  grow  and  permanently  burvive. 


Fig.  487. —Suturing  Bloodvessels:  Prcliuiiuary  l-'ixation  of  Ends  of  Divided  Vessels 
(after  Gutiuie).  Three  fixing  ligatures  are  placed  at  equidistant  points  on  the 
circumference  of  the  cut  ends,  each  ligature  being  passed  through  corresponding 
points  of  the  two  vessels.  The  ends  of  the  vessels  are  approximated  by  drawing 
on  the  ligatures,  which  are  then  tied,  and  the  margins  of  the  vessels  sewed  together 
by  continuous  stitches  in  the  intervals  between  the  fixing  ligatures,  as  in  Fig.  .t88. 
(Carrel's  method). 

But  there  is  reason  to  beheve  that  the  solution  of  this  problem  would 
be  a  long  step  towards  answering  the  immensely  important  practical 
question  what  the  conditions  are  wliich  permit  the  development 
of  malignant  tumours. 


Fig.  488. — Suturing  Bloodvessels:  Method  of  approximating  Edges  aid  putting  in 
Continuous  Suture  (after  Guthrie).  The  needles  are  very  imt  ca  nbric  sewing- 
needles,  and  the  threads  single  strands  of  Chinese  twist  silk  ur  human  hair. 
Needles  and  threads  are  sterilized  in  paraflin-oil.    (Method  of  Carrel  and  Guthrie.) 


Transplantation  of  organs  may  also  be  done  with  anastomosis  of 
bloodxessels.  The  main  vessels  of  the  engrafted  organ  are  sutured 
to  suitable  arteries  and  veins  in  the  '  host,'  so  that  the  circulation 
is  at  once  effective.  Consequently  there  is  practically  no  hmit  to 
the  size  of  the  grafts.     The  kidney,  spleen,  and  even  a  limb,  have 


1146  REPRODUCTION 

been  transpUiiiU'd  in  this  way  from  one  clog  to  another.  Although 
from  the  operative  point  of  view  successful,  the  homoeo-transplants 
do  not  permanently  survive.  Reimplantation  of  organs,  however, 
in  one  and  the  same  animal  with  suturing  of  the  bloodvessels  has 
often  been  successfully  performed.  Such  organs  as  the  kidney  live 
and  function  after  reimplantation,  and  the  operation  is  now  a 
recognized  physiological  method  of  insuring  that  an  organ  has  been 
completely  disconnected  from  the  central  nervous  system,  since  even 
the  nerves  running  in  with  the  bloodvessels  must  have  been  cut. 
It  has  been  shown  that  a  reimplanted  kidney  suffices  to  maintain  a 
dog  in  complete  health  for  an  indefinite  period  after  tlie  removal 
of  the  other  kidney. 

In  the  case  of  structures  like  the  large  bloodvc-sels,  which 
perform  mainly  a  passive  mechanical  function,  homoeo-transplanta- 
tion  succeeds.  Segments  of  arteries  preserved  in  cold  storage 
for  a  few  days  or  even  weeks,  and  even  portions  of  arteries  fixed  by 
formaldehyde,  have  been  transplanted  so  as  to  take  the  place  of 
segments  removed  from  arteries  of  living  animals,  and  have  con- 
tinued to  function  perfectly  for  long  periods.  Portions  of  veins 
have  also  been  used  to  fill  up  gaps  in  arteries.  Even  heteroplastic 
vascular  grafts  have  been  found  to  succeed,  portions  of  dog's 
arteries,  e.g.,  grafted  into  a  cat,  and  portions  of  rabbit's,  cat's,  or 
human  arteries  grafted  into  a  dog.  Doubtless  the  favourable  result 
is  largely  due  to  the  fact  tliat  the  mechanical  function  of  the  large 
arteries  can  be  discharged  e\en  by  a  dead  tube  of  the  requisite 
strength,  and  with  the  smooth  interior  presented  by  a  dead  endo- 
thelial lining  (Carrel,  Guthrie). 

Parabiosis. — Not  only  may  an  organ  or  a  portion  of  tissue  from 
one  individual  be  engrafted  on  another,  but  two  individuals  may  be 
so  united  that  a  greater  or  smaller  degree  of  piiysiological  in- 
timacy is  produced  between  them.  Occasionally,  as  in  the  famous 
Siamese  twans,  an  anomaly  of  development  results  in  such  close 
anatomical  union  of  the  circulatory  and  other  systems  that  in 
certain  respects  the  two  individuals  constitute  almost  a  single 
organism,  and  cannot  be  separated  by  surgical  interference.  A 
less  intimate  union  can  be  established  c.xperimcntallv  by  opening 
the  peritoneal  cavities  of  the  two  animals,  and  suturing  the  skin 
and  connective  tissue  together  so  as  to  permit  of  permanent 
communication.  Pairs  of  animals  living  in  this  condition  (so- 
called  parabiosis)  have  been  utilized  for  the  study  of  certain 
questions  in  immunity.  White  rats  have  been  kept  alive  in  para- 
biosis for  as  long  as  thirty-four  days  in  order  to  test  the  question 
whether  destructive  antibodies  for  cancer  are  present  in  the  circula- 
tion (Rous),  since  it  has  been  shown  that  circulating  antibodies  easily 
pass  from  one  to  the  other  of  such  a  pair  of    animals  (Ehrlich). 


PRACTICAL  /:A'/.7i'(  /.S7:S  1 147 

Cm-  of  each  pair  of  rats  liad  a  j^iowiiif,'  tumour  prtxluccd  by 
traii^]ilantation,  while  the  other  liacl  been  proved  resi>taut  to  the 
same  type  of  tumour.  No  evidence  of  the  passage  of  an  antibody 
was  found  in  this  case. 


PRACTICAL   EXERCISES. 

I .  Contractions  of  Isolated  Uterine  Rings. — Kill  a  female  adult 
rabbit  by  strikinj^  it  at  the  back  of  the  neck,  A  rabbit  which  is  not 
pregnant,  or  only  at  the  beginning  of  pregnancy,  shoukl  be  selected. 
Open  the  abdomen,  and  carefully  remove  the  uterus.  While  separating 
the  organ  from  the  broad  ligament  and  vagina,  support  the  horns  o{ 
the  uterus  on  soft  threads       Ligature  the  vagina  before  cutting  through 


Fig.  489. — Contractions  of  Rabbit's   Uterus   Ring.      At  41   Ringer's  solution  was 
replaced  by  adrenalin  solutinn,  1:1,000,000.     Time-trace,  half-minutes. 

it,  and  cut  below  the  hgature,  which  can  then  be  used  to  manipulate 
the  uterus.  Do  not  pinch  the  uterus  with  forceps,  and  handle  it  as 
little  as  possible.  At  once  place  it  in  Ringer's  or  Tyrode's  solution* 
(p.  200),  kept  at  body  temperature  (38°  C.)  in  a  small  beaker  immersed 
in  a  water-bath,  as  in  the  experiment  on  the  contraction  of  isolated 
intestine  (p.  452).  Cut  a  ring  of  tissue  about  i-J-  centimetres  in  width 
from  one  of  the  horns.  Tie  a  loop  with  a  iine  silk  thread  at  each  end 
of  a  diameter  of  the  ring,  pinching  up  a  little  of  the  external  coat  to  do 
so  with  fine  forceps.  Make  the  arrangements  necessary  for  recording 
contractions  of  the  circular  fibres  of  the  ring  while  it  is  immersed  in  a  glass 
cylinder  in  the  bath,  as  in  Experiment  i ,  p.  452 .  Connect  another  segment 

*  Tyrode's  solution  contains  o'S  gm.  NaCl,  0-02  gm    KCl   o-o"  gm   CaCl 
o-oi  gm.  MgClg,  o  005  gm.  NaHaPO^  o-i  gm.  NaHCOj  and  o-i  gnf.  dextros^e 
in  too  CO.  of  water. 


1148 


REPRODUCTION 


longitudinally  to  a  lever  as  in  that  experiment,  and  make  all  the  arrange- 
ments mentioned  there.  After  a  longer  or  shorter  interval  spontaneous 
rhythmical  contractions  of  the  uterus  ring  commence.  As  soon  as  they 
are  well  established,  and  while  the  contractions  are  being  recorded  on  a 
very  slow  drum,  replace  the  Ringer's  solution  by  serum,  defibrinated 
blood,  blood  prevented  from  coagulating  by  citrate  solution  (p.  66),  or 
hirudin,  or  bv  plasma,  and  note  the  effect.  The  serum  or  plasma  may 
be  diluted  to 'a  known  amount  with  Ringer's  or  Tyro*!''-  -"Int-on  hrfnro 


i'ig 


^QQ  _At  II  Ringer's  solution  was  replaced  by  citrate  plasma.     M  39  RiiiRer  s 
station  was  replaced  by  hirudin  plasma  ;  at  41  by  the  corresponding  hirudin 


application  to  the  segment.  Wash  away  the  serum  or  plasma  thor- 
oughly with  Ringer's  solution.  Replace  the  Ringer's  solution  by 
adrenalin  solution  (i :  10,000,000).  Note  whether  the  tone  of  the  ring 
(as  shown  by  its  permanent  shortening)  or  the  rate  and  strength  of  the 
contractions  arc  increased.  While  a  tracing  is  being  taken  repeat  the 
observation,  adding  a  larger  propcjrtion  of  adrenalin.  Determine  in 
what  concentration  a  distinct  effect  is  produced.  A  sufficient  number  ot 
uterus  rings  can  be  obtained  from  one  animal  for  a  considerable  number 
of  experiments. 


PRACTICAL  EXERCISES 


IM9 


2.  Comparison  of  Changes  of  Tone  Produced  in  Uterus  Segments  by 
Different  Concentrations  of  Adrenalin.  l\)r  this  \\\v  uterus  of  a  virghi 
rabbit  (full-grown  or  nearly  so),  is  best,  as  it  is  advantageous  that  the 
spontaneous  contractions  should  be  absent  or  feeble.  Starting  always 
with  the  segment*  in  Ringer's  or  Tyrode's  solution  replace  the  solution 
by  adrenalin  in  different  dilutions  (i :  10,000,000,  i :  50,000,000. 
I :  r, 000, 000.  etc.),  washing  off  the  adrenalin  thoroughly  with  the 
Ringer's  solution.  Compare  the  effect  of  serum  or  defibrinated  blood 
obtained  from  the  rabbit  itself  or  from  some  other  laboratory  animal 
with  that  of  a  known  solution  of  adrenalin. 

If  blood  collected  from  the  adrenal  veins  of  an  animal  is  available  it 
should  be  compared  with  blood  from  the  same  animal  taken  from  the 


Fig.  491. — Action  on  Rabbit's  Uterus  Segment  of  Blood  Specimens  from  the  Adrenal 
Veins  (of  a  Dog)  with  Different  Concentrations  of  Epinephrin,  and  Comparison 
with  Adrenalin  added  t(j  Blood.  At  28  Ringer's  solution  was  replaced  by  the 
second  adrenal  specimen ;  at  29  by  the  third  adrenal  specimen;  at  30  by  the  fourth 
adrenal  specimen;  at  31  by  the  fifth  adrenal  specimen ;  at  37  by  the  sixth  adrmal 
specimen;  at  41  by  jugular  vein  blood.  All  bloods  diluted  with  15  volumes 
Ringer's  solution.  .\t  34  adrenalin  in  jugular  blood  (i :  2,000,000);  at  35  adrena- 
lin in  jugular  blood  (i :  3,000,000);  at  36  adrenalin  in  jugular  blood  (i :  4,000,000) 
replaced  Ringer's  solution.  The  adrenalin  bloods  after  being  made  up  to  the 
concentrations  mentioned,  were  diluted  with  15  volumes  of  Ringer's  sohuion 
bef'ire  application  to  the  segment.     (Reduced  to  one-half.) 


general  circulation  (jugular  vein  or  carotid  artery).  The  tone-increasing 
power  of  tlie  adrenal  vein  blood  will  be  greater  than  that  of  the  in- 
different blood,  because  both  the  serum  and  the  epinephrin  will  act  in 
the  same  sense  (Fig.  491). 

3.  Partition  of  Adrenalin  between  Serum  and  Corpiiscles. — Add  to 
100  c.c.  of  dog's  blood  0-5  c.c.  of  the  i  :  1,000  solution  of  adrenalin. 
Centrifuge  a  portion  of  the  mixture  to  obtain  clear  serum.  Centrifuge 
another  portion  of  the  dog's  blood  to  which  adrenalin  has  not  been 
added.      Test  on  rabbit's  uterus  segments  and  also  on  intestine  seg- 

*  It  is  best  to  arrange  the  segment  to  record  the  longitudinal  shortening. 


II50 


REPRODUCTION 


ments  (p.  453)  the  defibrinated  blood,  the  serum  and  the-  sediment  of 
corpuscles  from  the  original  blood  and  from  the  blood  tf.  which  arlrcnalin 
was  added.  The  adrenalin  action  of  the  serliment  will  be  much  less 
than  that  ol  the  serum  or  of  the  blood  (Fig.  492). 


Fig  492- — Action  of  Adrenadin  Defibrinated  Blood,  Sernjn  and  Sediment  on  Rabbit's 
Uterus  Segments.  At  42  Ringer's  solution  was  replaced  by  adrenalin  blood 
serum  (i  part  in  6  parts  of  Ringer's  solution) ;  at  43  by  the  same  serum  (i  in  ii); 
at  44  by  the  same  serum  (i  in  16);  at  52  by  the  same  serum  (i  in  24);  at  51 
Ringer's  solution  was  replaced  by  adrenalin  blood  (i  in  24);  at  53  by  adrenalin 
blood  sediment  (i  in  6);  at  54  by  the  adrenalin  blood  sediment  (i  in  24);  at  55  by 
the  ordinary  defibrinated  blood  (i  in  (">);  at  56  by  the  ordinary  defibrinated  blood 
(i  ui  24).      (Reduced  to  one-half.) 


APPENDIX    A 


C  "MPARISON  OF  METRICAL  WITH   KNGLISK  MEASURES. 


Measures  of  Length. 

I  millimetre    =  0'03937    inch. 
I  centimetre   =0-39371       ,. 
I   decimetre     =  3-93708  inches. 
I  metre  =  39*37079     ,, 

I  inch  =  25-3995  millimetres. 

Measures  of  Weight. 

I  gramme  =  15-432349  grains. 

I   kilogramme     =  2-2046213  pounds. 

I  ounce  =  28-3495  grammes. 

I  pound  =453-5926 

Measures  of  Volume. 

I  cubic  centimetre=  0-061027  cubic  inch. 

I  litre  (1,000  cubic  centimetres)   =61-027052  cubic  inches. 

=  1-760773     English     or     2-11 
American  pints. 

=  0-22009668  gallon. 

I  cubic  inch  =  16-3861759  cubic  centimetres. 

I  cubic  foot  =  28-31531 19  cubic  decimetres  (or  litres). 

I  pint  =0-567932  litre. 

I  gallon  =  4-5434579  litres. 

Measures  of  Work. 

I   kilogrammetre  =  about  7-24  foot-pounds. 

I  foot-pound  =0-1381  kilogrammetre. 

I   (kilo)calorie  of  heat  =  425-3  kilogrammetres  of  work. 

Temperature  Scales. — To  convert  degrees  Fahrenheit  into  degrees 
Cen^^'grade,  subtract  32,  and  multiply  the  remainder  by  ?,.  To  convert 
degrees  C.  into  degrees  F.,  multiply  by  i.  and  add  32  to  the  result. 


APPENDIX     B 
BIBLIOGRAPHY. 

CHAPTER  I. 

INTRODUCTION. 

Colloids. — Bechold.  Die  Kolloide  in  Biologic  unci  Mpdizin,  Dresden,  191  a. 
Van  Bemmelen,  Die  Absorption  {colloids).  Dresden,  1910.  Botazzi, 
Archivio  di  Fis.,  IQ09,  7,  579-  Bixton  and  Rahe,  Hofmeister's  Beit., 
1908,  11,  479.  Field  and  Teac.tte,  J.  Exp.  Med.,  1907,  9,  222  {electric 
charge  of  native  proteins  and  agglutinins).  Hardy,  J.  Phys.,  1905-6,  33, 
251  (colloidal  solution).  Heard,  J.  Phys.,  1912,  45,  27.  Hober. 
Hofmeister's  Beit.,  1908, 11,  64  {neutral  salt  actions).  Paili,  Hofmeister's 
Beit.,  1906,  7,  531 ;  3,  225.  Robertson  (T.  B.),  Die  physikalische  Chemie 
der  Proteine,  Dresden,  1912.  Schryver,  Proc.  Roy.  Soc,  1910,  B  83, 
96.     Wai.pole,  J.  Phys.,  191 3-  47,  P-  xiv. 

Coagulation  of  Proteins. — Buglia,  Arch.  Internat.  de  Phy.^iol.,  1910.  10, 
224.  Chick  and  Martin,  J.  Phys.,  1910,  40,  404;  1911,  43,  i ;  1912.  45, 
61,  261.  Mirray  IC).  Bioch.  j.,  1906,  1,  167.  Ramsden,  Proc.  Roy. 
Soc,  1903,  B  72,  I5'»  (surface  lay.'rs  of  solutions  and  suspensions — 
mechanical  coagulation).     Sutherland,  J.  Phys.,  1911,  42,  p.  vii. 

Structure  and  Aggregate  State  of  Protoplasm.— Chambers,  Am.  J.  Ph^-s.. 
1917,  43,  I.     Jensen,  PHUger's  Arch.,  1901,  87,  .^'jI-     Hardy,  J.  Phys., 

1899,  24,  158,  2o-».  Kite,  Am.  J.  Phys.,  1913,  32,  14'').  Mathews.  Biol. 
Bull.,  1906, 11, 141.  Rhi'mbler,  Z.  f.  allg.  Phys.,  1902. 1,  279.  SchXfer, 
Qu.  J.  Exp.  Phys.,  1910,  3,  285.  Schenck,  i^fluger's  Arch.,  1900, 
81,  584.  Macallum  (A.  B.),  J.  Phys.,  1905,  32,  95  [distribution  of  K  in 
cells). 

Reaction  of  Protoplasm. — Barratt,  Brit.  Med.  J.,  June  18,  1904,  p.  1413. 
Henderson  iL.  J.)  and  Black  (O.  P.),  Am.  J.  Phys.,  1907,  18,  250. 

Protoplasmic  Movement. — Jensen,  Ergeb.  d.  Phvsiol.  (Bioph.),  1902,  i. 
Kuhne,  Z.  f.  Biol..  1897,  35,  43;  ^t-.  1898,  36,  4^5-  Schenck,  Pfluger's 
Arch.,   1S07,  66,  241   (oxvgen  and  protoplasmic  movement) . 

Differentiation  and   Specificity   of   Starches. —  Reichert   (E.  T.),  Carnegie 

Instit.  Pub.,  1013  (Washington). 

Nucleus  Plasma  Relation.— Howard  (W.  T.),  J.  Exp.  Med..  1908.  10,  207. 

Combinations  of  Proteins  and  Inorganic  Substances.— Loeb  (J.),  Am.  J.  Phvs., 

1900,  3,  ^27  {wn-protem  compounds).  Rohertson  (T.  B.).  Ergeb.  d. 
Physiol.,  1910,  216.  Mann  (G.),  Chemistry  of  the  Proteids,  London, 
1906.     Pauli  and  Handowsky,  Hofmeister's  Beit.,  190S,  11,  415. 

Plant  Proteins. — Osborne  (T.  B.),  Ergeb.  d.  Phys.,  1910,  47;  Science,  1908, 
28.  4 1  - 

1 1 52 


THE  CIRLVLATISG  LHjllDS  Oi    JUL  liOUY  1153 

CHAPTER  II. 

Till-:  CIRCULATING  LIQUIDS  OF  THE  BODY. 

BuCKMASTER  (G.  A.),  The  Morphology  of  Normal  and  Pathological  Blood, 
London,  1906. 

Erythrocytes. — DiiiixjEN,  Virchow's  Arch.,  i9oi,165,  282  (envelope).  Meyer. 
Arch.  Int.  Med.,  1914,  14,  94  [colour  index).  Albrecht,  Zentr.  f.  Phys., 
1905,  19,  19  [envelope).  Meves,  Anat.  Anzrig.,  23,  212  (structure). 
Peskind,  Am.  J.  Phys.,  1903,  8,  414  [action  of  acids  and  acid  salts). 
L6HNEK,  .Arch.  Mikros.  Anat.,  1907,  71,  129  ('  membrane  '  of).  Rous 
and  Turner,  J.  E.\p.  Med.,  1916,  23,  219,  239  [livnig  erythrocytes  in  vitro). 
Schaeer.  Anat.  An/eig.,  1905,  26  (structure).  Weber  and  Suchard, 
Arch,  do  Plij-s.,  iSSo,  12,  521  (rouleaux).  Stewart  (G.  N.),  Am.  J. 
Phys.,  i9o_',  8,  iiH  (envelope  of  Xecturus  corpuscles). 

Blood  Formation  and  Regeneration. — Foot,  J.  Exp.  Med.,  1913,  17,  43 
(boue-)iiayrow  in  vitto).  IIall  and  Eubank,  ib.,  1896,  1,  656.  Noll, 
Ergeb.  d.  Phys.  (Bioch.),  1903,  433.  Malassez,  Arch,  de  Phys.,  1882, 
I.  Pearce  (R.  M.)  et  al.,  J.  Exp.  Med.,  1912,  16,  758,  7G9,  780  (spleen). 
Seemann,  Ergeb.  d.  Phys.  (Bioch.),  1904,  12.  Woolley,  J.  Lab.  Clin. 
Med.,  1916,  1,  347  (in  foetus).  Opie,  J.  Exp.  Med.,  1905,  7,  759-  See- 
mann, Ergt'h.  d.  Phys.  (Bioch.),  1904,  30. 

Blood  at  High  Altitudes. — Abderhalden,  Z.  f.  Biol.,  1902,  43,  125,443; 
Pfliiger's  Arch.,  1905,  110,  95.  Burker,  ib..  1904,  105,  480.  Jaquet, 
Arch.  Exp.  Path.  Pharm.,  1900,  45,  i.  Schneider  and  Havens,  Am.  J. 
Phys.,  1915,  36,  380.  Henocque,  Arch,  de  Phys.,  1889,  710.  Gaule, 
Pfliiger's  Arch.,  1902,  89,  119.  Guillemard  and  Moog,  J.  Phys.  Path. 
Gen.,  1907.  9,  17;  ib.,  1910,  12,  869. 

Destruction  of  Erythrocytes  in  the  Body. — Bain,  J.  Phys.,  1903,  29,  352 
(yCle  of  liver  and  spleen).  Findlay,  ib.,  1910,  40,  445  (hcsmolysis  in  the 
liver  ?).  Kyes,  Internal.  Monatsch.  Anat.  Phys.,  1914,  31,  543  [in  birds). 
Rous  and  Robertson,  J.  Exp.  Med.,  1917,  25,  651,  665. 

Variation  in  Number  of  Erythrocytes. — Boothby  and  Perry,  Am.  J.  Phys., 
1915,  37,  378.  Hawk,  jh.,  1904,  10,  384  (effect  of  exercise).  Btjrker, 
Pfluger's  Arch.,  1905,  107,  42O  (technique).  Downs  and  Eddy,  Am.  J. 
Phys.,  1917,43,415  (influence  of  secretin).  HASSELBALCHandHEVERDAHL, 
Skand.  Arch.  Phys.,  1908,  20,  289  [some  physical  causes  of  variation). 
Ward,  Am.  J.  Phj-s.,  1904,  11,  394.  Wheels  (J.  J.)  and  Sutton  (J.  E.), 
Am.  J.  Phys.,  1915,  39,  31  (blood  counts  in  frog,  turtle  and  mammals). 
(For  influence  of  .\drenahn  see  Chapter  XI.) 

Permeability  of  Erythrocytes. — De  Boer,  J.  Phys.,  1917,  51,  211  {influence 
of  respiration  on  exchange  (f  SO^  between  corpjtscles  and  plasma).  Ham- 
burger, Osmotischer  Druck  und  lonenlehre;  Bioch.  Z.,  1915,  71,  464 
[influence  of  osmotic  pressure  and  the  permeability  problem) ;  Z.  f.  Phy^ikal. 
Ch.,  1909,  69,  663  (for  Ca  ions).  Ho-^er,  Pfluger's  Arch.,  1904,  102,  196; 
Oppenheimer's  Handb.  d.  Bioch.,  1908,  2,  i.  Masing,  Pfliiger's  Arch., 
1913,  149,  227  (glucose).  Manwaring  and  Kusama,  Soc.  Exp.  Biol. 
Med.,  1916,  13,  173  (for  protein).  Rohonyi,  Kolloid.  Chem.  Bcihefte, 
I9i^>,  8,  337,  377  (Phy.siol.  Abstracts,  1917,  2,  178,  179).  Spiro  and 
Henderson,  Bioch.  Z.,  1908.  15,  114  [influence  of  CO2). 

Osmotic  Relations  of  Erythrocytes.— Bang,  Bioch.  Z.,  1909,  16,  255. 
EvKMAN,  Pfluger's  .\rch.,  1897.  68,  58  [permeability).  Hedin,  ib.,  68, 
229  (permeability).  Hober,  ib.,  1904,  102,  196  (ion-permeabilitv). 
Gryns,  ib.,  1896,  63,  86;  ib.,  1905.  109,  289.  Hamburger,  Z.  f.  Biol., 
1897,  35,  252,  289  (respiratory  exchange  and  volume  of  erythrocytes). 
KoRANYi  and  Bence,  Pfluger's  Arch.,  1905,  110,  532  (action  of  CO^. 
Koeppe,  ib.,  1897,  67,  189.  Moore  and  Roaf,  Bioch.  J.,  1907,  3,  55. 
Scott  (F.  H.),  J.  Phys.,  1915,  50,  128.  Stewart  (G.  N.),  J.  Phys.. 
1900-1,  26,  470. 

73 


ir5f  BIBLIOGR  \IHY 

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Hfiemolysis.— Akriiicnil'.s,  Bioch.  Z.,  1908,  11,  161;  ICrgcl).  d.  Phys.,  1908, 
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Blood-Platelets. — Brown  (W.  H.),  J.  Exp.  Med.,  1913.  18,  273  {histogenesis). 
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37,  67  {erythrocytic  origin).  Lee  and  Minot,  J.  Am.  Med.  Ass.,  Apr.  21, 
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Tin:  CIRCULATING  LIQUIDS  Of  THE  BOhY  1155 

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519.     Kop.ertson,  ib.,  1909,  6,  313. 

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[volume index).  Fraenckel  (P.),  Z.  1".  Klin.  Med.,  1904,  52,  470 ;  Stewart 
(G.  N.),  J.  Phys.,  1899,  24,  356  [electrical  resistance  method).  Hedin, 
Pflu-;er's  Arch.,  1895,  60,  36o;"Koeppe,  ib..  1905,  107,  187  [hematocrit). 
Larrabee,  J.  Med.  Res.,  1911,  24,  15  [volume  index). 

Electrical  Conductivity  of  Blood. — Brunings,  Pfliiger's  Arch.,  1903,  100. 
303.  H6iu:r,  Physikal.  Chem.  d.  Zelle.  Hamburger,  Osmotischer 
bruck.  Frank,  Am.  J.  Phys.,  1905,  14,  466  [during  coagulation). 
Oker-Blom,  Pfluger's  Arch.,  1900,  81,  167.  Stewart  (G.  N.),  J.  Phys., 
1S99,  24,  211.  Wilson  (T.  P.),  Am.  j.  Phys.,  1905,  13,  139;  Bioch.  J., 
1907,  2,  377  [in  coagulation). 

Blood-Coagulation. — Arthus,  J.  Phys.  Path.  Gen.,  1901,  3,  887  [fluoride); 
ib.,  1902,  4,  I,  281;  Arch,  dc  Phys.,  1890,  22,  79.  Collinvvood  and 
MacMahon,  J.  Phys.,  1912,  45,  119.  Cramer  and  Pringle,  Q.  J.  Exp. 
Phys.,  191 3,  6,  I ;  J.  Phys.,  191 2,  45,  p.  xi.  Delezennk,  J.  Phys.  Path.  Gen., 
1897,  333,  347  [bird's  blood).  Howell,  Am.  J.  Phys.,  1911,  29,  187 
[antithrombin);  ib.,  1914,  35,  143  [ultramicroscope);  ib.,  1916.  40,  526. 
Loeb  (L.).  Hofmeister's  licit..  1907,  9,  185.  Loeb  and  Fleischer,  Bioch. 
Z.,  1910,  28,  169  [coaguiins).  Mellanby,  J.  Phys.,  1908,  38,  28.  Pick 
and  Spiro,  Z.  Physiol.  Ch.,  1900,  31,  235  [proteoses).  Morawitz,  Ergeb. 
d.  Phys.,  1905,  307;  Deut^ch.  Arch.  Klin.  Med.,  1903-4,  pp.  i,  215,  432. 
Reichert,  J.  Exp.  Med.,  1905,  7,  173  [second  coagulation).  Rettger, 
Am.  J.  Phys.,  1909,  24,  406.  Dastre  and  Floresco,  Arch,  de  Phys., 
1896,  402.     Stuebel,  Pfluger's  Arch.,  1914,  156,  361   [ultramicroscope). 

Coagulation  Time. — ^ .Addis,  Q.  J.  Exp.  Phys.,  1908, 1,  305.  Burker,  Pfluger's 
Arch.,  1913,  149,  318.  Cannon  and  Gray,  Am.  J.  Phys.,  1914,  34,  232. 
Cannon  and  Mendenhall,  ib.,  1914.  34,  243  [adrenalin  effect).  Simpson 
and  Rasmussen,  O.  J.  Exp.  Phys.,  iqK).  10,  159. 

Calcium  and  Coagulation.— Arthus,  Arch,  de  Phys.,  1896,  47;  ib.,  1897,  219. 
Austin  and  Pepper,  .\rch.  Int.  Med.,  1913,  11,  305.  Addis,  Q.  J.  Exp. 
Med.,  1909,  2,  149.  Beard,  J.  Phys.,  191 7,  51,  294.  Hess,  Soc.  Exp. 
Biol.  Med.,  1916.  13,  59.  Goddard,  Am.  J.  Phys.,  1914,  35,  333. 
Morawitz,  Hofmeister's  Beit.,  1904,  4,  381.  Rich,  Am.  J.  Phys.,  1917, 
43,371- 

Anticoagulants. — Franz  (F.),  Arch.  Exp.  Path.  Pliarm.,  1903,  49,  342  [hirudin). 
Havcraet,  ib.,  1884,  18,  209  [leech  extract).  Lee  and  Vincent,  J.  Med. 
Res.,  1915,  32,  445  [anaphylaxis  and  leech  extract).  Mellanby  (J.), 
J.  Phys.,  H)09.  38,  441  [venoms).  Minot,  Am.  J.  Phj's.,  1915,  39,  131 
[chloroform).  Pringle  and  Tait,  J.  Phys.,  1910,  40,  p.  x.xxv. ;  ib.,  1911, 
42,  p.  xxxviii.  Shattuck,  .Vrch.  Int.  Med.,  1917.  20,  167  (protein 
intoxication). 


IT56  BIBLIOGRAPHY 

Proteoses  and  Blood-Coagulation. — Arthus  and  HuniiR,  Arcli.  de  Phys.,  1896, 
857.  Dastkk  ami  Fi.oresco,  ih.,  1897,  210.  Dki-Kzknne,  ib.,  1895,  8, 
635;  ib.,  1898,  50S  [relation  of  liver).  Gley  and  Pachon,  ib.,  1896,715 
[iiver).  Pick  and  Spiro,  Z.  Physiol.  Cii.,  1900,  31,  .^},5.  Schmidt- 
MuLHEiM,  Arch.  f.  Phys.,  1880,  33. 

Fibrin,  Fibrinogen. — Howell,  Am.  J.  Phys.,  lyiO,  40,  526  [fibrin-gel  and 
theories  0/  f^d- formation).  MoRAWnz,  Oppcnhcimcr'.s  Handb.  d.  Bioch., 
ii.,2, ')o. 

Origin  of  Fibrinogen. — Goodpasture,  Am.  J.  Phys.,  1914,  33,  70.  Mathews 
(\.  P.),  lb.,  1899,  3,  53.  Meek,  ib.,  1912,  30,  161  [liver).  Opie,  Barker 
and  Dochez,  J.  Kxp.  Med.,  1911,  13,  162.  Whipple,  Am.  J.  Phys., 
igi.).  33,  50- 

Thrombin,  etc.— Coi.linwoou  and  MacMahon,  J.  Phys.,  1913-14,  47,  4  1 
(tlnoDibin  and  antithrombin).  Gasser,  Am.  J.  Phys.,  1917.  42,  378 
[significance  of  protliyo)nbin  and  thrombin  in  serum).  Howell,  Am.  J. 
Phys.,  1914,  35,  474  [firothronibin).  Drinker  (C.  K.  and  K.  R.),  ib., 
1916,  41,  5  [prothrombin  from  bone-marrow).  MiNOT  and  Denny,  Arch. 
Int.  Med.,  1916,  17,  loi  [prothrombin  and  antithrombin  factors  in  coagit- 
latiou).  Rich,  Am.  J.  Phys.,  1917,  43,  549  [nwtathrombin).  Mellanby 
(J.),  J.  IMiys.,  1917,  51,  390  {rate  of  formation  from  prothrombin). 

Antithrombin.— Denny  and  Minot,  Am.  J.  Phys.,  1915,  38,  233.  Hess, 
J.  JCxp.  Med.,  u)i.5,  21,  338. 

Thromboplastic  Substances  in  Coagulation. —  Howell,  Am.  J.  Phys.,  1912, 
31,  I.  MacRae  and  Sciinac  k,  Hi.,  i'ji3.  32,  211  [action  in  clotting). 
McLean,  ib.,  i9i(),  41,  ^30;  ib.,  i<)i7,  43,  586  [crphalin). 

Intravascular  Coagulation.  Davis,  Am.  J.  Phj's.,  191 1,  29,  160.  Halli- 
burton and  Brodi];,  J.  Phys.,  1894,  17,  135.  Mudge,  Proc.  Roy.  See. 
(Lend.),  1907,  B  79,  103.  Pickering,  J.  Phys.,  1896,  20,  310  [albinos). 
Wright  (A.  E.),  J.  Phys.,  1891,  12,  184. 

Coagulation  in  Invertebrates. — Alsberg  and  Clark,  J.  Biol.  Ch.,  1908,  6,  323 
[limuliis).  L()i;b  (L.),  Bioch.  Z.,  1910,  24,  478.  Tait,  Q.  J.  E.\p.  Phys., 
1 910,  3,  I. 

Blood-Proteins. — Briggs,  J.  Biol.  Ch.,  1915,  20,  7.  Cullen  and  Van  Slyke, 
Soc.  Exp.  Biol.  Med.,  1916,  13,  197  (methods).  Epstein,  J.  Exp.  Med., 
1913,  17,  444.  PoRGEs  and  Spiro,  Hofmcister's  Beit.,  1903,  3,  277 
[globulins).  Robertson,  J.  Biol.  Ch.,  1912,  13,  325.  Thompson,  ib.. 
1915,  20,  I-  Wells,  ib.,  1913,  15,  37.  Woolsey,  ib.,  1913,  14,  433. 
Hammarsten,  Ergeb.  d.  PhysT  (Bioch.),  1902,  330.  Mellanby  (J.),  ). 
Phys.,  i.)07-8,  36,288. 

Blood-Lipoids. — Bloor,  J.  Biol.  Ch.,  1916,  25,  577  [man).  Brown  (E.  W.), 
Am.  J.  Phys.,  1899,  2,  306  [cholesterol  in  birds).  Joslin,  Bloor  and 
Gray,  J.  Am.  Med.  Ass.,  1917,  69,  375;  Seo,  Arch.  Exp.  Path.  Pharm., 
1909,  61,  I  {diabetes). 

Cholesterol  in  Blood.— Bloor,  J.  Biol.  Ch.,  1916,  24,  227;  ib.,  1917,  29,  437. 
CsuNKA,  ib.,  1916,  24,  431.  Gorham  and  Mveks,  Arch.  Int.  Med.,  1917, 
20,  399.     Weston  And  Kent,  J.  Med.  Res.,  1912,  26,  531. 

Blood-Fat. — Bloor,  J.  Bioi.  Ch.,  1914,  19,  i.  Terroine,  J.  Phys.  Path.G6n., 
191 4, 16,  212. 

Serum    Ferments. — Bronfenbrenner   and   Scott,    Soc.    Exp.    Biol.    Med., 

1915,  12,  137.     Jobling,  Petersen  and  Eggstein,  J.  Lab.  Clin.  Med., 

1916,  1,  172;  J.  Exp.  Med.,  1915,  22,  129,  5O8.  Sloan,  Am.  J.  Phys.. 
1915,  39,  9.  Carlson  and  Luckhardt,  Am.  J.  Phys.,  1908,  23,  148. 
Gould  and  Carlson,  ib..  1911,  29,  163 ;  Otten  and  Galloway,  ib.,  1910, 
26,  347  [relation  of  pancreas  to  serum  diastase).  King,  ib.,  1914,  35,  301. 
Van  uek  1£rve,  ib.,  1911,  29,  182  [diastatic  enzymes  in  serum). 

Vasoconstrictor  Property  0!  Serum. — .Atkinson  and  Fitzpatrick.  Soc.  Exp. 
r.iol.  Med.,  H)iJ.,  9,  4u.  Ci  shny  and  Gi'NN,  J.  Pharm.  Exp.  Ther., 
1913,  5,  I  [action  of  serum  on  perfused  heart).     O'Connor  (J.  M.),  Arch. 


THE  CIRCULATISC.  LIQUIDS  01'  illl.  IIODY  Ii57 

Hxp.  i'iitli.  Pharni.,  191 2.  67,  i«J5.  Stkwart  (H.  A.)  and  Harvly 
(S.  C).  J.  Exp.  Mod.,  igi.j,  16,  103.  Stewart  (G.  N.)  and  Zuckkr, 
J.  Iixp.  Med..  1913,  17,  152.     Tatum,  J.  Pharm.  Exp.  Ther.,   191  .J, 4,  115. 

Anaphylactic  or  Protein  Shock. — Anderson  and  Schultz,  Soc.  Exp.  Biol, 
.\li  il  ,  i<»ii).  7,  ^j.  Ai'i;k  and  Robinson,  J.  Exp.  Med.,  1913,  18,  450, 
55b.  Eisi-NBRiiY  and  Pearce,  J.  Pharm.  ICxp.  Tlu>r.,  191 2,  4,  21. 
joHLiNr.,  Petkrskn  and  Ec.gstein,  J.  Exp.  Med.,  1913.  22,  401  {ferment 
actions).  Manwakinc;  and  Crowe,  J.  Immnnitv,  K^iy!  2,  517;  Voegtun 
and  Bernheim,  J.  Ph;irm.  Exp.  Thcr.,  191 1,  2,  507;  Weil,  J.  Inununity, 
1<)17,  2,  323  {relation  of  liver  to).  Weil,  ib.,  1917,  2,  429  {the  vasomotor 
(leptes.sion  in). 

HsBmoglobin  and  Derivatives. — Barcroet  and  Hill,  J.  Phys.,  iqio,  39,  411 
{nature  of  oxyhannoglobin,  molecular  weight).  Huener  and  Gansser, 
Arch.  f.  Phys.,  1907,  209  {molecular  weight).  Eischer  (H.),  ICrgeb.  d. 
Phys.,  I9i(),  185,  791  {blood  and  bile  pigments).  Hai.dane,  J.  Phys., 
1900-1,  26,  497  {colorimetric  deiermination);  ib.,  189S,  22,  298  {methcemo- 
globin).  Hartley,  J.  Phys.,  1907,  36,  62  {sulphhcEmoglobin) .  Alsberg 
and  Clark,  J.  Biol.  Ch.,  1910,  8,  i;  Alsberg,  //;.,  1915,  23,  495  {hcsmo- 
cyanin).  Menzies,  J.  Phys.,  1895,  17,  402  {mcthcvmoglobin).  Milroy 
(J.  A.),  J.  Phys.,  1909,  38,  3^4  {hcrmochromogen);  ib.,  1909,  38,  392; 
Menzies,  ib.,  1914,  49,  p.  iv.  {hcematin).  Laidlaw,  ib.,  1904,  31,  464 
{synthesis  of  hcematin).  Keichert,  Am.  J.  Phys.,  1903,  9,  97.  Reichert 
and  Brown,  Soc.  Exp.  Biol.  Med.,  1907-8,  5,  66;  Proc.  Am.  Phil.  Soc. 
(Philadelphia),  1908,  47,  298.  Frieboes,  Pfliiger's  Arch.,  1903,  98,  434 
{hcemoglobin  crystals). 

Quantity  of  Blood. — Douglas,  J.  Phys.,  1905-G,  33,  493;  ib.,  1910,  40,  472. 
Haldane  and  Smith,  J.  Phys.,  1899-1900,  26,  331;  Smith  (J.  Lorrain), 
ib.,  p.  vi.  (CO  method).  Drever  (G.),  Ray  and  Walker,  Skand.  Arch. 
Phys.,  191 3,  28,  290.  Keith,  Rowntree  and  Geraghty,  Arch.  Int. 
Med.,  1913.  16,  547.  Plesch,  Z.  Exp.  Path.  Ther.,  1909,  6,  380.  Zuntz 
and  Plesch,  Bioch.  Z.,  1908,  11,  47. 

Vividiffusion. — Abel,  Rowntree  and  Turner,  J.  Pharm.  Exp.  Ther.,  1914, 
5,  275.  Rohde  (A.),  J.  Biol.  Ch.,  1915,  21,  325  {ammonia  of  the  circulating 
blood) . 

Lymph. — Carlson,  Greer  and  Luckhardt,  Am.  J.  Phys.,  1908,  22,  91 
{chlorides).  Carlson,  Woelfel  and  Powell,  ib.,  1911,  28,  176  (local 
hcBmodynamic  action  of  tissue  metabolites).  Green  (J.  R.),  ib.,  1910, 
26,  68;  Rous,  J.  Exp.  Med.,  1908,  10,  537  {leucocytes).  Davis  and 
Petersen,  J.  Exp.  Med.,  1917,  26,  693  {ferments).  Howell,  Am.  J. 
Ph^-s.,  1914.  35,  483;  LussKY,  ib.,  25,  334  {coagulation).  Hughes  and 
Carlson,  Am.  J.  Phys.,  1908,  21,  236  {hcsmolytic  action).  Luckhardt, 
ib.,  1910,  25,  345  {conductivity  compared  ivith  serum). 

Chyle.— Hall  (W.  S.),  J.  Am.  Med.  Ass.,  1910,  55,  388.  Hamill,  J.  Phys., 
1906-7,  35,  131.  Paton  (D.  Noel),  J.  Phys.,  1890,  11,  iii.  Sollmann, 
Am.  J.  Phj-s.,  1907,  17,  487. 


CHAPTER  III. 

THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH. 

Carlson,  Biol.  Bull.,  1903,8,123  {comparative  physiology  of  invertebrate  heart). 
MacWilliam,  J.  Phys.,  1885,  6,  192  {heart  of  eel);  ib.,  1888,  9,  107 
{rhythm  of  mammalian  heart).  Nukada  (S.),  Die  Automatic  und  Koordi- 
nation  dos  Herzcns,  Tokyo,  191 7  {limulus  heart).  Roy  and  Adami, 
Phil.  Trans.  Roy.  Soc,  1892,  183,  199  [physiology  and  pathology  of  heart). 
Tigerstedt,  Kreislauf.  Wiggers,  The  Circulation  in  Health  and  Disease, 
1915- 


1 1 58  BIBLIOGRAPHY 

Cardiac  Cycle.  -r>ACHMANN,  Am.  J.  Phys.,  1910,  41,  309  {intei auricular 
nitaval).  Wiggers,  ib..  1016,  40,  218  Uiuricular  myogram);  ib.,  igi6, 
42,  i-ii  (events  of  auricular  systole).  Havcraft  and  Paterson,  J.  Phys., 
1895-0,  19,  496  {changes  in  heart's  shape  and  position);  ib.,  -zbz  (papillary 
muscles).     Tunnicliffe,  ib.,  189O,  20,  51  (diastole). 

Heart  Sounds. — Battaerd.  Heart,  1915,  6,  121  {graphic  researches).  Bridg- 
-MAX,  Heart,  1915,  6,  41.  Einthoven,  Pfliiger's  Arch.,  1907,  120,  31. 
Sewall,  Pliila.  Montlily  Med.  J.,  Sep.,  1899  (papillary  muscles).  Thwer, 
Arch.  Int.  Med.,  1909,  4,  297  (third  heart-sound).  Wiggers  and  Dean, 
A7n.   [.  Phy.s.,  1917,  42,  476  (nature  of  time  relations). 

Registration  of  Heart  Sounds.— Ckehore  and  Meaka,  J.  Exp.  Med.,  1911, 
13,  016  (micrograph).  Junthoven,  Pfliiger's  Arch.,  1907,  117,  461. 
HoLowiNSKi,  Arch,  de  Phys.,  1896,  823.  Hurthle.  Pfliiger's  Arch., 
1893.  60,  263.  Weis-s  (O.),  Phono-kardiogrammc  (Jena,  1909).  Wiggers 
and  Dean,  Am.  J.  Med.  Sci.,  1917,  153,  666. 

Heart  Rate. — Bainbridge,  J.  Phys.,  1915,  50,  65  {influence  of  venous  filling  on 
rate).  Buchanan  (F.),  ib.,  1910,  40,  p.  xlii  (i'n  hibernation);  ib.,  1908, 
37,  p.  Ixxix  (in  mouse);  Sci.  Progress,  July,  1910  (in  vertebrates).  Loeb 
and  EwALD,  Bioch.  Z.,  1913,  58,  177  (heart-rate  as  function  of  the 
temperature). 

Function  of  Pericardium. — Barnard  (H.  L.),  J.  Phys.,  1898,  22,  p.  xliiii. 
Kixo  (V.),  ib.,  1915.  50,  I. 

Endocardiac  Pressure:  Auricle. — Wiggers,  Am.  J.  Phys.,  1914,  33,  13. 
ZwAH-WKxr.rKG  and  Ac.ne\v,  Heart,  1912,  3,  343. 

Endocardiac  Pressure:  Ventricle.— Frank  (O.),  /.  f.  Biol.,  1S97,  35,  478. 
Fkan9ois-1'r.\nk,  Arcli.  de  Phys.,  1890,  22,  ^95;  ib.,  189^.  25,  8^ 
Porter.  J.  ICxp.  Med.,  1S96,  1,  296.  Tigerstedt,  Skand.  Arch.  Phvs., 
1912,  28,  37:  ib..  191.),  31,  241.     Wiggers,  Am.  J.  Phys.,  1914,  33,  382. 

Coronary  Circulation. — Barbour  and  Prince,  J.  Exp.  Med.,  1915,  21,  330 
(epinephrin).  Guthrie  and  Pike,  Science,  1906,  24,  52  (coronary  pressure 
and  action  of  heart).  Hyde,  Am.  J.  Phys.,  1,  213  (dilation  of  ventricles 
and  coronary  flow).  Langendorff,  Pfliiger's  Arch.,  1899,  .78,  423 
(isolated  heart).  Magrath  and  Kennedy,  J.  Exp.  ISIed.,  1897,  2,  13 
(coronary  circulation  and  ventricular  beat).  Markwalder  and  Starling, 
J.  Phys.,  1913,  47,  273.     Miller  and  Matthews,  Arch.  Int.  Med.,  1909, 

3,  476  (obstruction  of  left  coronary).     Porter,  J.  Exp.  Med.,  1895,  1»  46 
(closure  of  coronaries);  Am.  J.  Phys.,  1,  145  (influence  of  beat  on  coronary 

flow) . 

PULSE. 

Arterial  Pulse. — Dawson  (P.  M.),  Am.  J.  Phys.,  1917.  42,  613  {pulse  velocitv). 
Frank  (O.),  Z.  f.  Biol.,  1899,  37,  483  (mathematical);  ib.,  1905,  46,  441. 
Hewlett,  Arch.  Int.  Med.,  1914.  14,  609  (reflection  of  primary  wave). 
Hill,  Barnard  and  Sequeira,  J.  Phys.,  1897,  21,  147  (effect  of  venous 
pressure).  Hoorweg,  Pfliiger's  Arch.,  1905. 110,  598  (peri phcral reflection), 
HOrthle,  Pfliiger's  Arch.,  1890,  47,  17  (origin  of  secondary  tvaves). 
Lewis  (T.),  J.  Phys.,  T906,  34,  414.  Lohman,  Pfliiger's  Arch.,  1904,  103, 
632  (dicrotic  wave).     MacWilliam,  Kesson  and  Melvin,  Heart,  1913, 

4,  393  (conduction  of  pulse  wave).    Tigerstedt,  Ergeb.  d.  Phys.,  1909,  593. 
Wiggers,  J.  Am.  Med.  Ass.,  1915,  64,  1483  (contour  of  normal  pulse). 

Venous  Pulse. — Cushny  and  Grosh,  J.  Am.  Med.  Ass.,  1907,  49,  1254. 
Ewing,  Am.  J.  Phys.,  1914.  33,  158.  Eyster,  J.  Exp.  Med.,  1911,  14, 
594;  ib.,  1910,  12,  257.  FREDiiRiCQ,  Zcntralb.  f.  Phys.,  1908,  22,  297. 
McQueen  and  Falconer,  J.  Phys.,  1914.  48,  292  ('  C  '  wave).  Morrow, 
Brit.  Med.  J.,  Oct.  27,  and  Dec.  22,  1906;  Pfliiger's  Arch.,  1900,  79, 
442  (velocity).     Wiggers,  J.  Am.  Med.  Ass.,  1915.  64,  1483. 

Cardiopneumatic  Movements. — Harris,  J.  Phys.,  1903,  32,  495-  Haycraft, 
il'-.  1S91,  12,  \2(<.  Meltzer,  Am.  J.  Phys.,  1S98,  1,  117.  Stewart 
(G.  X.),  Arch.  1'.  Phys.,  1912,  4O0. 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMI'lI        115O 

BLOOD-PRESSURE. 

Arterial  Blood-Pressure.  -  Hkooks,  Heart,  loio,  2,  5  {tmcings  from  quiescent 
tininial).  C.\.Mi'nj-i.r.  (H.),  J.  Phys.,  1898-9,  23,  301  {/ylnce  of  chief  resist- 
ance to  jlow).  Dawson.  Am.  J.  Phys.,  1906,  15,  "^14  {pycssure  at  diff^renl 
points  of  aitcrial  tree).  Frank  (O.).  Z.  f.  iiiol..  1907.  50,  -'81  (elastic 
membranes).  Hukthi.e,  Pfliiger'-s  Arch.,  1903,  110,  421;  //'.,  191^,  147, 
509  (pressure  and  velocity).  MacCraken  and  Wernkss.  J.  Pharm., 
E.\p.  Thcrap.,  191 7.  9,  305  (overcoming clotting).  Pilcher,  Am.  J.  Phys., 
1915.  38,  209  (membrane  manometer  curves).  Riddle  and  Matthews, 
Am.  J.  I'hys.,  1907,  19,  108  (birds).  VVicgers,  it.,  1914,  33,  i  (pressure 
curve  in  pulmonary  artery).  Wood  (H.  C),  ib.,  1899,  2,  352  (traube 
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Action  of  Proteoses  on  Blood-Pressure  (and  Coagulation). — Chittenden, 
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Zunz,  Arch.  Int.  dc  Phj's.,  1911,  11,  73.  See  also  under  Chapter  II. 
(proteoses  and  coagulation). 

Arterial  Blood-Pressure  in  Man. — Borach  and  Marks,  Arch.  Int.  Med.,  1913, 
11,  485;  ib.,  191 4..  13,  648.  Elliott  (B.  L.),  Am.  J.  Phys.,  191 7,  42,  290 
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1907.  RoLLESTON,  Heart,  1912,  4,  83  (in  aortic  incompetence) .  Taussig, 
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Measurement  of  Blood-Pressure  in  Man. — Frank  (O.),  Tigerstedt's  Handbuch 
d.  physiol.  Mcthodik,  2,  Abth.  4,  216.  INIacleod,  J.  Lab.  Clin.  Med., 
1913,  1,  62,  13S  (r^sumi-). 

Auscultatory  Method. — Brooks  and  Luckhardt,  Am.  J.  Phys.,  1916,  40,  49. 
Erlanger,  ib.,  40,  83.  Foley,  Coblentz  and  Snyder,  ib.,  40,  :'54. 
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Oscillatory    Method. — Erlanger,  Johns  Hopkins  Hosp.  Rep.,  1904,  12,  53; 

Am.  J.  Phys.,  1908,  21,  p.  xxiv.    Kilgore,  Arch.  Int.  Med.,  1915,  16,  893. 
Venous  Pressure. — Burton-Opitz,  Am.  J.  Phys.,  1903,  9,  198.     Hooker,  ib., 

1014,  35,  73;  ib.,  1916,  40,  43.     V.  Recklinghausen,  Arch.  Exp.  Path. 

Pharm.,  1906,  55,  470.     Sewall,  J.  Am.  ^Nlcd.  Ass.,  1906,  47,  1279. 

RATE  OF  PERIPHERAL  BLOOD-FLOW. 

Burton-Opitz,  Am.  J.  Phys.,  1914,  36,  64  (carotid);  Quart.  J.  Exp.  Phys., 

1910,  3,  297;  ib.,  1911,  4,  93;  ib-,  191 2,  5,  83   (hcpxtic  artery);  ib..  191 1, 

4,  113;  ib.,  1912,  5,  189;  ib.,  1912,  5,  309  (portal  vein).  Brodie  and 
Russell,  J.  Phys.,  1905,  32,  p.  xlvii. 

Blood-Flow  in  Man. — Edmunds,  Am.  J.  Phys.,  1907,  18,  129  (influence  of 
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ll6o  BIBLIOGRAPHY 

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9,   (33  (arteries  in  ina)i). 

Rate  of  Blood-Flow  in  Veins.— I'ikton-Opitz,  Am.  J.  Phys..  1903,  7,  4351 
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Heart  Output. — Bornstein  (A.),  Z.  Exp.  Path.  Tlier.,  1911,  9,  382  [gaso- 
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ORIGIN  OF  HEARTBEAT. 

Sino-Auricular  Node. — Cohn,  Kessel  and  Mason,  Heart,  1912,  3,  311,  341. 
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41 1  (extra  systoles  caused  by  stimulation  of  node). 

Cause  0!  Heart  Beat. — Carlson,  Am.  J.  Phys.,  1904.  12,  ''?•  471  (Umulus). 
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THE  CIRCULATION  OF  THE  BLOOD  A\D  LYMPH        1161 

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period  and  compensatory  pause). 
Heart  Muscle  Strips. — Erlanger,  Am.  J.  Phys.,  1910,  27,  87  (auricle). 
Martin  (E.  G.),  ib.,  igo.),  11,  103  (terrapin  ventricle). 

CONDUCTION  OF  CARDIAC  EXCITATION  AND  CONTRACTION. 

Atrio  -  Ventricular    Conduction    System  :  Auriculo  -  Ventricular    Bundle.  — 

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Heart-Block. — Bachmann,    Arch.   Int.   Med.,    1909,    4,    238    (strophanthin). 

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ptvssion  of  cardiac  nerves  of  limulus).     Gesell,  ib.,  1916,  40,  2(>7. 

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1887,  8,  296.     Porter,  Am.  J.  Phys.,  1898,  1,  71  (recovery  of  heart  from). 

Influence  of  Temperature  on  the  Heart. — Carlson,  Am.  J.  Phys.,  1906,  15, 

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Phys.,  1907,  18,  14  (relation  of  activity  to  pressure  in  coronary).     Gorham 

and  Morrison,  ib.,  1910,  25, 419  (action  of  blood  proteins).     Langendorff, 

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Locke  and  Rosenheim,  J.  Phys.,  1907,  36,  205  (consumption  of  dextrose). 

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heart) . 


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(G.  N.),  J.  Phys.,  1892.  13,  59)  Z.  f.  Biol.,  1913,  59,  5U  (influence  of 
temperature  of  heart  on  activity  of  heart  nerves);  Am.  J.  Phys.,  1909,  2% 
341  (tortoise  vagus).  Wiggers,  Am.  J.  Phys.,  1916,  42,  133  (influence 
of  vagus  on  "fractionate  "  contraction  of  right  auricle). 

Accelerators. — Cyon,  Pfliiger's  Arch.,  1906.  113,  111.  FKioiiRicQ  (H.). 
Arch.  Intcrnat.  de  Phys.,  1913,  13,  115.  Hering  (H.  E.),  Pfluger  s 
Arch.,  1903,  107,  125  (direct  action  on  mammalian  ventricle). 

Action  of  Accelerated  on  Quiescent  Heart. — Carlson,  Am.  J.  Phys.,  1904, 
12,  35  (molluscs).  Hering,  Pfliiger's  Arch.,  1906,  115,  354  (mammals). 
Stewart  (G.  X.),  J.  Phys.,  1892,  13,  S3,  90  (amphibia). 


Tlir:  CIRCUL.IIIOS  Ol-    the  DLOOD  A.\D  lymph         1163 

Voluntary  Acceleration  of  Heart.  1"avi  1.1.  ;incl  White.  Heart,  19.7,  6,  175- 
\'an  1)K  \'i;i  i>i;,  I'lln-ns  Anli.,  i8<)7,  66,  2^2. 

Cardio-Inhibitory  Centre  and  Reflexes.  Hainbridcie,  J.  Phys.,  1914,  48, 
^32.  Eyster  and  Hooker,  Am.  J.  Phys.,  1908,  21,  373;  Filehne  ;i:ul 
BiBERFiELU,  Pfliigcr's  Arch.,  1909.  128,  443  {rffcci  of  increased  blond- 
pressure).  Hooker,  Am.  J.  Phys.,  1908,  19,  417  [reflex  acceleration 
independently  of  cardio-inhibitory  centre  ?).  Miller  and  liowMAN,  Am. 
J.  Phys.,  1915,  39,  149.  Wertheimer  and  IMeyer,  Arch,  dc  Phys.,  1890, 
284  {influence  of  deglutition  on  hearl-rhytlnn). 

Relation  0!  Salts  to  Inhibition.— Brine  (B.  U.).  Am.  J.  Phys.,  191 7  44,  171; 
l^uRRiU(;i:,  ].  Phvs.,  1917,  51,  .J.5  ((^  "  ""<^  -^^')-  Ho<;an  and  Ormono,  Am. 
J.  Phys.,  191.:,  3d,  105  (Ca).  Howell,  ib.,  1906,  15,  280  (salts  of  blood). 
Howell  and  Duke,  ib..  1908,  21,  51  [output  of  K  in  inhibition) ;  ib.,  1908, 
23,  1 74  [accelerators  and  Ca,  K  and  N  metabolism  of  isolated  heart) ;  J .  Phys., 
1906-7,  35,  131  [isolated  mammalian  heart).  Langendorff  and  Hueck, 
Pflugcr's  Arch.,  1903,  96,  473  [Ca)-  Loeb  (J.),  J.  Biol.  Ch.,  1906,  1, 
427  [Mg  and  Ca  on  contractions  of  jellyfish).  Martin  (E.  G.),  Am.  J. 
Phys.,  1904, 11,  370  (^^'C/). 

VASOMOTOR  NERVES. 

BowDiTCH  and  Warren,  J.  Phys.,  7,  416  [of  limbs).  Drinker  (C.  K.  and 
K.  R.),  Am.  J.  Phys.,  1916,  40,  514  [of  bone-niarroiv) .  Gaskell  (W.  H.), 
J.  Phys.,  1878-9,  1,  262  [vasomotors  of  muscles).  Langley,  J.  Phys., 
189I,  12,  S45.  375  [course  of  sweat  and  vasomotor  fibres  of  cat' s  foot) ;  ib., 
iQii!  41,  .483  [frog's foot). 

Vasomotors  o£  Intestine.— Bunch  (J.  L.),  J.  Phys.,  1899,  24,  72.  Burton- 
Opitz,  Am.  ].  Phys.,  191 5,  35,  203  [duodenum) .  Hallion  and  Fran^ois- 
Franck,  J. "Phys.  Path.  Gen.,  1896,  478,  493. 

Vasomotors  of  Lungs.— Brodie  and  Dixon,  J.  Phys.,  1904,  30,  476. 
Francois-Franck,  Arch,  de  Phys.,  1S96,  178.  Jackson,  J.  Pharm.  Exp. 
Thcr.,'  1913,  4,  291.  Krogh,  Zentralbl.  f.  Physiol.,  20,  802  [tortoise). 
Langlois  and  Desbouis,  J.  Phys.  Path.  Gen.,  1912,  14,282.  Plumier, 
ib.,  1904,  655.  Tigerstedt,  Ergeb.  d.  Phys.  (Bioph.),  1903,  571. 
Tribe  (E.  M.),  J.  Phys.,  1914,  48,  154.  Wiggers,  J.  Pharm.  Exp.  Ther., 
1909,  1,  341- 

Cerebral  Vasomotors. — Baylis.s  and  Hill,  J.  Phys.,  1S95,  18,  334-  Dixon 
and  Halliburton,  Q.  J.  Exp.  Phys.,  1910,  3,  315-  Gulland  (G.  L.), 
J.  Phys.,  1895,  18,  361;  Huber  (G.  C),  J.  Comp.  Neurol.,  1899,  9,  i; 
Hunter  (W.),  J.  Phys.,  igoo-i,  26,  465  [histological).  Hill  and  Macleod, 
ib.  26,  394-  Jensen,  Pfliiger's  Arch.,  1904.  103,  171,  196.  Wiggers, 
Aril.  J.' Phys.,  1905,  14,  ^5^:ib.,  1907,  20,  206;  ib.,  1908,  21,  454;  J.  Phys., 
1914.  48,  109. 

Vasomotors  of  Heart.— Brodie  and  Cullis,  J.  Phys.,  1911,  43,  313-  Dogiel 
and  Archangelsky,  Pfliiger's  Arch.,  1907,  116,  482.  Porter,  Am. 
J.  Phys.,  1912,  29,  p-  x^xi  [method).     Wiggers,  ib.,  1909.  24,  391. 

Vasomotors  of  Veins  (Veno-Motors).— Bancroft,  Am.  J.  Phys.,  1898,  1,  477 
[hind  limb).  Bayliss  and  Starling,  J.  Phys.,  1894,  17,  120;  Burton- 
Opitz,  Q.  J.  Exp.  Phys.,  1913,  7,  57:  Am.  J.  Phys.,  1914,  36,  325; 
Edmunds  (C.  W.),  J.  Pharm.  Exp.  Ther.,  191 5,  6,  5'^9  [portal  vein). 
Francois-Franck  and  Hallion,  Arch,  de  Phys.,  1897,  434  [liver). 
Henderson  (Y.),  Am.  J.  Phys.,  igiq,  ^2,  5^9  ['"eno-pressor  mechanism). 

Vasomotor  Mechanism.— Asher,  Ergeb.  d.  Phys.  (Biophys.),  1902,  346. 
Bayliss,  ib.,  1906,  319.  Cotton,  Slade  and  Lewis,  Heart,  1917,  6,  227 
[contractile  power  of  capillaries).  Edwards  (D.  J.),  Am.  J.  Phys.,  1916, 
35  15  [compensatory  phenomena  during  splanchnic  stimulation).  Hooker, 
Am.  J.  Phys.,  1911,  28,  361  (chemical  regulation  of  vascular  tone).  Porter 
and  Newburgh,  ib.,  1914,  35,  i  [in  pneumonia) .  Porter  and  Turner, 
ib.,  1915,  39,  236  {vasotonic  and  vascreflex  mechanism). 


M64  BIBLIUL.RAI'IIY 

Vasomotor  Centres. Mathison,  J.  Phys.,  loii,  42,  283;  Portlr  (W.  T.), 
Am.  J.  J'hys..  1913,  31,  p.  xxix  {functional  relation  of  nerve  cells  in);  ib., 
19^5.  36,  418  (vasotonic  and  vasorcjlcx  centre).  Poktkk  and  Ci.akk,  ib., 
1908,  21,  p  XV  [difference  between  bulbar  and  spinal  vasomotor  cells). 
PoRTF.R  and  Storey,  ib.,  1907,  18,  181  (effect  of  injuries  of  brain). 
Kanson,  ib.,  191 6,  42,  i  (chief  vasoconstrictor  centre).  Sollmann  and 
PiLCHER,  ib.,  1910,  26,  233  (effect  of  sciatic  stimulation  and  ctirara). 

Vasodilators. — Bayliss,  J.  Phys.,  1900,  26,  173;  ib.,  190.',  28,  27O  (hind  limb. 
antidrfliiiic  impulses).  Bernard  (Cl.),  Liquidcs  do  ror^anisnie,  2,  269 
(chorda).  Carlson  (A.  J.),  Am.  J.  Phy.s.,  1907,  19,  408;  McLean  (!•'.  C), 
ib.,  22,  279  (vasodilators  to  submaxillary  in  cat's  cervical  sympathetic). 
EcKiiARD,  Bcitra2;c,  3,  125;  4,  (>9  (mervi  erigentes).  Kendall  and 
LucHsiNGER,  Pfliigi'i-'s  Arcli.,  1876,  13,  197  (difference  between  dilators 
and  constrictors  after  nerve  section). 

Depressor. — Bayliss,  J.  Phy.s.,  1908,  37,  264.  Cyon,  Plliiger's  Arch.,  1901, 
84,  304.  Porter  and  Beyer,  Am.  J.  Phys.,  1900,  4,  283.  Ranson 
and  BiLLiNc.sLEY,  Am.  J.  Phy.s.,  1916,  42,  9.  Sewall  and  Steiner, 
J.  Phys.,  1885,  6,  162.  Sollmann  and  I'ilchkr,  Am.  J.  Phys.,  1912, 
30,  369  (response  of  vasomotor  centre  to).  Tigerstedt,  Skand.  Arch. 
Phys.,  1908,  20,  330.     TsciiiRwiNSKY,  Zentralb.  f.  Phys.,  9,  777;  10,65. 

Vasomotor  Reflexes. — Henderson  (V.  E.)  and  Loewi  (O.),  Arch.  Exp.  Path. 
Pharm.,  1903,  53,  56  (vasodilator  excitation).  Hunt,  J.  Phys.,  1895,  18, 
381  (fall  of  blood-pressure  on  stimulation  of  afferent  nerves).  Langley, 
J.  Phys.,  191 2,  45,  239  (effect  of  strychnine).  Martin  and  Lacey,  Am. 
J.  Phys.,  1914,  33,  212  (vasomotor  reflex  thresholds).  Martin  and 
Mendenhall,  ib.,  1915,  38,  98  (vasodilator  response  to  sensory  stimulation). 
Martin  and  Stiles,  ib.,  1916,  40,  194  (vasomotor  summations).  Porter, 
ib.,  1907,  20,  399  (uniform  stimuli  with  blood-pressure  at  different  levels); 
ib.,  1910,  27,  276  (relations  of  afferent  impulses  to  vasomotor  centres). 
Porter  and  Marks,  ib.,  1908.  21,  460  (effect  of  hcsmorrhage).  Porter 
and  Richardson,  ib.,  1908,  23,  131.  Stewart  (G.  N.),  Heart,  igii,  3, 
76;  Stewart  and  Laffer,  Arch.  Int.  Med.,  1913,  11,  365;  Stewart  and 
Walker,  ib.,  11,  383  (elicited  by  loarmth  and  cold  in  man).  Vincent  and 
Cameron,  Q.  J.  Exp.  Phys.,  1915,  9,  45. 

Influence  of  Asphyxia  on  Circulation. — Hill  and  Flack,  J.  Phys.,  1908,  37, 
77  (on  circulation  and  respiration).  MacVVilliam,  J.  Phys.,  1901-2,  27, 
337  (asphyxia  and  cardiac  failure).  Mathison,  (7;.,  igii,  42,  283  (medul- 
lary centres);  ib.,  1910,  41,  416.  Sollmann  and  Pilcher,  Am.  J.  Phys., 
191 1,  29,  100  [reaction  of  vasomotor  centre  to  asphyxia). 

Pressor  Amines. — Abelous  andBAROiER,  Compt.  Rend.  Sec.  do  Biol.,  ^hlr.I7, 
1906;  Dale  and  Dixon,  J.  Phys.,  1909,  39,  25  (formed  in  putrefaction). 
Baehr  and  Pick,  Arch.  Exp.  Path.  Pharm.,  1916,  80,  161  (point  of  attack). 
Bain  (W.),  Q.  J.  Exp.  Phys.,  1914,  8,  229  (pressor  bases  in  urine).  Dale 
and  Laidlaw,  J.  Phys.,  1911,  43,  182;  Laidlaw,  Bioch.  J.,  1911,  6,  141 
(action).     Walpole,  J.  Phys.,  1909,  38,  2.^3. 

Depressor  Amine  ("Vasodilation"). — Barger  and  Dale,  J.  Phys.,  1911, 
41,  499;  Mellanby  and  Twort,  ib.,  191 2,  45,  53  (in  intestine  wall). 

Intracranial  Pressure. — Gushing  (H.).  Johns  Hopkins  Hosp.  Bull..  Sep.,  1901. 
IvYSTER,  Burrows  and  Essick,  J.  Exp.  Med.,  1909,  11,  489. 

Influence  of  Gravity  on  Circulation. — Hill  (L.),  J.  Phys.,  1S93, 18,  13.  Hill 
and  Barnard,  ib.,  1897,  21,  323.   SALATiii,  Compt.  Rend.,  1877,  85,  445. 

SHOCK. 

Bainbridge  and  Bullen,  Lancet  (London),  191 7,  2,  51.  Bayliss  (W.  M.), 
Arch.  Med.  Beiges,  191 7.  70,  793  (Physiol.  Abstracts,  1918.  2,  625)  (treat- 
inent  by  intravenous  injections).  Erlanger  and  Wooovatt,  J.  Am.  Med. 
Ass.,  1917,  69,  1410;  Erlanger,  C^esell,  Gasser  and  Elliott,  ib.,  1917, 
69,  2089.     Guthrie,  ib.,  1917,  69,  1394-     Henderson  (V.),  Am.  J.  Phys., 


RESPIRATION  1165 

1908,  21,  126;  16.,  1900,  23,  345:  ih..  If  10.  27,  15-2:  Henderson  and 
ScARHROi  t;n,  ib.,  lyio.  26,  ^ho  (acapnia  and  shock).  Henderson, 
t6..  1910,  25,  310.  385;  Henderson,  Prince  and  Haggard.  J.  Am.  Med. 
Ass..  H)i7.  69,  965.  Janeway  and  Jackson,  Soc.  Exp.  Biol.  Med.,  1915. 
12,  i<)3;  J.  Am..  Sled.  Ass..  Oct.  16.  1915.  371.  Lvon  and  Swartz.  Soc. 
Kxp.  Biol.  Med.,  1910,  7,  I39-  Meltzer.  Arch.  Int.  Med.,  1908,  1,  571, 
Morrison  and  Hooker,  Am.  J.  Phys.,  1915.  37,  «<'>  Pike  and  Coomus. 
J.  Am.  Med.  Ass.,  191 7,  68,  1892.  "  Porter,  Bost.  Med.  Surg.  J.,  191 7. 
177,  320.  Porter,  Marks  and  Swift,  Am.  J.  Phys.,  1907,  20,  44^• 
Porter  and  Quinby.  Am.  J.  Phys.,  1908.  20,  500.  Seelig  and  Joseph, 
J .  Lab.  Clin.  Med.,  1916, 1,  283.     Simonds,  J.  Am.  Med.  Ass.,  191 7,  69, 883. 

Transfusion.— BoTAzzi  and  Japelli.  Bioch.  Z.,  190S,  11,  331  {physico-chemical 
properties  of  blood  and  lymph  after).  Carlson  and  Ginsburg,  Am.  J. 
Phys..  1015.  36,  280  (influence  on  hyperglyceemia  of  pancreatic  diabetes). 
Crile  (C.  \V.),  Soc.  Exp.  Biol.  Med.,  1906,  4,  6.  Haskins  (H.  D.),  J. 
Biol.  Ch.,  1907,  3,  321  (effect  on  N  metabolism).  Ottenberg  and 
Thalhimer,  J.  Med.  Res.,  1915,  33,  213.  Rabens,  Am.  J.  Phys..  1914, 
36,  294  (influence  on  kidneys). 

Lymph  Hearts. — Abel  and  Tunner,  J.  Pharm.  Exp.  Ther..  1914,  6,  Oi 
(action  after  cardiectomy).  Laxgendorff,  Pfliiger's  Arch..  1906,  115, 
533.  Moore  (A.),  Am.  J.  Phys..  1901,  5,  87  (influence  of  ions);  ib.,  5, 
196  (spinal  centres).  Priestley  (J.),  J.  Phys.,  1878-9,  1,  I,  19  [older 
literature).  Tschermak,  Pfluger's  Arch.,  1907.  119,  165  (spinal  in- 
nervation). 

Channels  in  Liver  Cells  communicating  with  Blood  Capillaries. — Schafer, 
Anat.  Anzeig..  190J,  21,  18.  Herring  and  Simpson,  Proc.  Roy.  Soc, 
1906,  B  78,  455- 

CHAPTER  IV. 

RESPIRATION. 

Blood  in  Lungs. — Kino.  J.  Phys..  1917,  51,  154- 

Respiratory  Movements. — Baglioni.  Ergeb.  d.  Phys.,  1911,  526.  Eyster, 
Austrian  and  Kingsley,  Am.  J.  Phys..  1907. 18,  413  (temporary  occlusion 
of  aorta).  Fitz  (G.  W.),  J.  Exp.  Med.,  1896.  1,  677.  DU  Bois-Reymond 
(R.),  Ergeb.  d.  Phys.  (Bioph.).  1902,  377  (mechanics  of  respiration). 
Guthrie  and  Pike.  Am.  J.  Phys.,  1906,  16,  475;  1907.  20,  45  (effect  of 
change  in  blood-pressure  on) .  Lundsgaard  and  Van  Slyke,  J.  Exp.  Med., 
1918.  27,  65  (lung  volume). 

Temperature  of  Expired  Air. — Loewy  and  Gerhartz,  Pfluger's  Arch.,  1914, 
155,  231 

Artificial  Respiration  and  Resuscitation. —Schafer.  Lancet,  May  30,  1903; 
Trans.  Roy.  Med.-Chir.  Soc,  London,  1904,  86;  Proc.  Roy.  Soc.  (Edin.), 
1904,  25,  39  (in  the  apparently  drowned).  Stewart  (G.  N.)  and  Pike 
(F.  H.),  Am.  J.  Ph\'s.,  1907,  19,  328  (resuscitation  of  respiratory  and  other 
bulbar  centres,  n-ith  reference  to  their  atitowatism). 

Respiratory  Dead  Space. — Douglas  and  Haldane,  J.  Phys.,  1912,  46,  235. 
Haldane  (J.  S.).  Am.  J.  Phys.,  1915,  38,  20.  Henderson  (Y.)  et  al.. 
Am.  J.  Phys.,  1915,  38,  i.  Krogh  (A.)  and  Lindhard  (J.),  J.  Phys.. 
iqi7,  51,  59;  ib.,  191 3,  47,  30.  Pearce  (R.  G.)  and  Hoover  (D.  H.), 
Am.  J.  Phys.,  191 7-  44,  391- 

Alveolar  Air. — Hough  (T.),  Am.  J.  Phys..  191 2,  30,  iS  (alveolar  air  in  muscular 
exercise).  Haldane  and  Priestley.  J.  Phys..  1905.  32,  225.  Henderson 
(Y.)  and  Morriss  (\V.  H.),  J.  Biol.  Ch.^  1917,  31,  217.  Krogh  and 
Lindhard,  J.  Phys.,  1914,  47,  43i-  Macleod  (J.  J.  R.),  J.  Lab.  Clin. 
Med.,  1916,  1,  ^22  (clinical  method  for  determination  of  CO2  in  alveolar  air). 
Pearce  (R.  G.).  Am.  J.  Phys.,  1917,  44,  369.  Van  Slyke,  Stillman 
and  CuLLEN,  J.  Biol.  Ch.,  1917,  30,  401  (alveolar  CO^  and  plasma  bicar- 
bonate) . 


Ii66  lillil.IOGRAl'HY 

Respjiatory  Gaseous  Exchange. — Benedict  and  IIomans.  Am.  J,  Phys., 
inii,  28,  -■'».  lii.NKnicT  [V.  G.),  ib.,  1^09,  24,  .;-}5  {a/?  para  I  us).  Bene- 
dict .lud  lOMi'KiNb,  Boston  ftled.  Surg.  J.,  i<jio,  174,  857,  8»jS,  939 
(apparatus  for  clinical  use).  Carpenter,  Carnegie  Inslit.  Pub.,  No.  216, 
lyij  {methods  in  man).  Jaquet,  Ergcb.  d.  Pliy.s,  (Bioch.),  1902,  457. 
Pembrey,  J.  Phy.s.,  1901,  27,  66  {marmot).  *  Wolf  and  Hele,  J.  Phys., 
1914,  48,  1-8  {decerebrate  animal). 

Respiratory  Quotient. — Benedict,  Emmes  and  Riche,  Am.  J.  Phys.  1911, 
27,  i'A?,  [influence  of  preceding  diet  on).  Lusk,  Arch.  Int.  Med.,  1915,  15, 
939  {diabetes). 

BLOOD  GASES. 

Barcroft,  J.  Phys.,  1908,  37,  12;  Barcroft  and  Higgins,  ib.,  1911,  42, 
512;  Barcroft  and  Koukrt.s,  ib.,   1910,  39,  429    {differential  method). 
BucKMASTEK,  J.  Phys.,  1917,  51,  164  {relations  of  CO^  in  blood).     Buck- 
master  and  Gardner,  J.  Phj^s.,  1910,  40,  373  {gas" pumps);  ib.,  1910, 
41,  60  {gases  of  arterial  and  venous  blood);  ib.,  1912,  43,  401   {nitrogen). 
Cooke  and  B.\rcroft,  J.  Phys.,  1914,  47,  p-  xxxv  [percentage  saturation 
of  O2  in  arterial  blood  in  man).     Friedman  (E.  D.)  and  Jackson  (H.  C), 
Arch.  Int.  Med.,  1917,  19,  767  (CO2  of  blood  and  alveolar  air  in  obstructed 
respiration).     Haldank.    J.    Phys."  1898,   22,   465    {analysis).     Krogh. 
Skand.  Arch.  Phys.,  1908,  20,  259  {microtonometer).     Murlin,  Edelmann 
and  Kramer,  J.  Biol.  Ch.,  191 3,  16,  79  {after  clamping  abdominal  aorta 
and  inferior  cava).     Peters   (J.  P.),  Am.  J.  Phys.,  1917,  43,  113  (CO2 
acidosis  and  cardiac  dyspnoea).     Rasmussen,   Am.   J.   Phys.,   1915,  39, 
20;  ib.,  1916,  41,  162  [blood  gases  in  hibernation). 
Oxygen  Tension  of  Arterial  Blood. — Haldane  and  Smith,  (J.  L.),  J.  Phys.. 
1890,  20,  497.      Kkogh,  Skand.  Arch.  Phys.,  1910,  23,  252.     Osborne 
(\V.  A.),  J.  Phys.,  1907,  36,  48.     Scott  (R.  W.),  Am.  J.  Phys.,  1917,  44, 
196  {decerebrate  cat). 
CO2  Tension. — Boothby  and  Sandford,  Am.  J.  Phys.,  1916,  40,  547  {venous 
blood,  rest  and  work).     Christiansen,  Douglas  and  Haldane,  J.  Phys., 
1914,  48,  244.     Henderson  (Y.)  and  Prince,  J.  Biol.  Ch.,  1917,  32,  325 
{venous  blood). 
Oxygen  Dissociation  Curves  (oi  Blood  and  Oxyheemoglobin) . — Barcroft  and 
I'amis,  J.  Pliys.,   ii)Oi),  39,  14,^      I-Sakcroft  and  ORi'.Ki.r,  ib.,   1910,  41, 
355    (influence   of  lactic   acid).     liAKCROFT,    ib..    1911,    42,    44    [altitude). 
Barcroft  and  Kinc;,  ib.,  1907,  39,  374  {tempi  ralure).     Bohr,  Hassel- 
balch  and  KKOc;n,  Skand.  Arch.  Phys.,  190O,  16,  402  {influence  of  CO^)- 
Douglas  and  Haldane  (J.  S.  and  J.  B.  S.),   J.  Phys..   1912,  44,  275 
{combination  of  Hb  with  CO^  and  Oo)-     Hufner,  Arch.  f.  Phj's.,   1901, 
Supp.   Bd.,   187   {dissociation  of  oxylicBmoglobin).     Mathison,   J.   Phys., 

1911,  43,  347  {influence  of  acids  on  reduction  of  arterial  blood). 

Oxygen  Capacity  of  Blood.— Barcroft  and  Burn,  J.  Phys.,  1913,  45,  49.^ 
Burn,  ib..  1913.  45,  482.     Douglas,  ib.,  1910,  39,  453  [efter  hcemorrhage) ; 
ib.,  1910,  40,  472  [total  O2  capacity  and  blood  volume  at  different  altitudes). 
Haldane,  ib.,  25,  295  [ferricyanide  method).     Hufner,  Arch.  f.  Phys., 
1894,  130;  ib.,  1903,  217  {O^-capacity  of  blood  pigment).    I'kters,  J.  Phys., 

1912,  44,  131. 

Carbon  Monoxide. — GuiiiANT,  Arch,  dc  Phys.,  1898,  315.  434  (absorption). 
Haldane,  J.  Phys.,  18,  201,  430  (action).  Nasmith  and  Graham,  ib., 
35,  32  (poisoning).  Nkloux.  J.  Phys.  Path.  Gen.,  1914,  6,  145,  164 
(absorption). 

Chemical  Regulation  of  Respiration.— Bayliss  and  Starling,  Ergeb.  d. 
Phys.,  1906,  6O9.  Campi'-ell,  Douglas,  Haldane  and  Hobson,  J. 
Phys.,  1913,  46,  301.  Gasser  and  Loevenhart,  J.  Pharm.  E.\p.  Ther., 
1914,  5,  239  (decreased  O^.  Gordon  and  Haldane,  J.  Phys.,  1909, 
38,  420.  Haldane  and  "Poulton,  ib..  1008,  37,  y)o  (O^-defuiency). 
Haldane  and  Priestley,  ib.,   1905,  32,  225.     Hough.   Am.   j.  Phys., 


RESPIRA  riOyj  I167 

1911,  28,  .K>o  (hreaihing  a  confined  volume  of  air).  Hill  and  Flack, 
J.  Phys.,  1908,  37,  77  (excess  of  COn  und  uuuit  of  O.^).  Peters,  Am.  J. 
I'hys..  i>)i7,  44,  >S4  (H-ion  comoilrolion  of  blood).  ijcoTT  (R.  W.),  Am. 
J.  riiys.,  11)17,  44,  T<)(">  {COo  and  H-ion  concentiation  in  decerebrate  cat). 

Nervous  Mechanism  of  Respiration. — Barry,  J.  Phys.,  i<ji.?,  46,  473  (afferent 
niiprcisuois).  Bokl:it.\ii,  Jirgcb.  d.  Phys.  (Biophys.),  1902,  403. 
Deason  and  Kobb,  Am.  J.  Phys.,  1911,  28,  57  (paths  in  cord).  Gad, 
Arch.  1.  Phys.,  1880.  i.  Gruber,  Am.  J.  Phys.,  1917,  42,  450.  Nice, 
Am.  J.  Phys.,  1914,  33,  -304  (thresholds  for  respiratory  reflex).  Frohlich. 
Pfliiger's  Arch.,  1906,  113,  433  (elimination  of  vagus  without  stimulation). 
Haldane  and  Mavrogordato,  J.  Phys.,  ii)i<^>,  50, p.  xh  (vagus  regulation) . 
LoKWv  (A.),  Pfliiger's  Arch.,  1888,  42,  .^73.  Lewandowsky,  Arch.  1. 
Phys.,  189G,  195.  Meltzek,  Arch.  f.  Plus.,  1892,  340.  Nicolaide.s, 
Arch.  f.  Phys.,  1907,  68.  Porter  (\V.  T".),  J.  Phys.,  1S94-5,  17,  455 
(phrenic  path).  Porter  and  Turner,  Am.  J.  Phys.,  1913,  32,  95  (reflex 
respiratory  movements).  Stewart  (G.  N.),  ib.,  1907,  20,  407.  Stewart 
and  Pike,  //;.,  1907,  19,  328;  ib.,  20,  61  (resuscitation  (f  nervous  respira- 
tory Dit'chanisni). 

Respiratory  Centre. — Baglioni,  Ergeb.  d.  Phys.,  191 1,  58S  (automatism  of). 
Boruttau,  lb..  1904,  89.  Brown  (T.  G.),  J.  Phys.,  1914,  48,  p.  xxxii 
(a  respiratory  tract  in  mid-brain).  Hooker,  J.  Pharm.  Exp.  Ther.,  1913, 
4,  443  (perfusion  in  frog).  Laqueur  and  VerzAr,  Pfliiger's  Arch.,  191 2. 
143,  395  (specific  action  of  CO^,  on).  Loewy,  ib.,  1888,  42,  245  (repetition 
of  Marckwald's  experiments  on  paraffin  injection  [Z.  f.  Biol.,  1890  26, 
259]). 

Bronchi. — Abbott,  J.  Med.  Res.,  1912,  26,  513.  Dixon  and  Brodie,  J.  Phys., 
1903,  29,  97;  Dixon  and  Ransom,  J.  Phys.,  1912,  45,  413  (innervation). 
DU  Bois-Reyaiond  (R.),  Ergeb.  d.  Phys.  (Bioph.),  1902,  396  (alterations 
in  calibre).      Henderson  (V.  E.)  and  Taylor,  J.  Pharm.  Exp.  Ther., 

1910,  2,  153  (secretion).     Jackson,  ib.,  1914,  6,  479  (drugs). 
Dyspncea. — Athanasiu  and  Carvallo,  Arch.  d.  Phys.,  1898,  95  (heat  dyspnoea). 

Lewis,  Ryffel,  Wolf,  Cotton  and  Barcroft,  Heart,  1915,  5,  45 
(dvspncea  in  cardiac  and  renal  patients).     Moorhouse,   Am.   J.   Phj's., 

1 91 1,  28,  223  (lieat  dyspnoea). 

Apncea. — Bqothby,  J.  Phys.,  1912,  45,  328.  FoA.,  Arch.  di.  Fis.,  1911,  9, 
453.  Githens  and  Meltzer,  See.  Exp.  Biol.  Med.,  1914,  12,  64. 
:\iiLROY,  Q.  J.  Exp.  Phys.,  1913,  6,  373.  Mosso,  Arch.  Ital.  do  Biol., 
40,  I.  Pembrey  and  Pitts,  j.  Phys.,  1899,  24,  305  (respiration  in 
hibernation).  Scarbrough  and  Henderson,  Am.  J.  Phys.,  1910,  25, 
p.  xiii. 

Cheyne-Stokes  Respiration.— Barbour,  J.  Pharm.  Exp.  Ther.,  1914,  5,  393 
(morphine).  Clark  (A.  J.)  and  Hamill,  ib.,  357  (circulatory  changes  in). 
Douglas,  J.  Phys.,  1910,  40,  454  (at  high  attiiudes).  Eyster,  J.  Exp. 
Med.,  1906,  8,  5G5.  Fulton,  Heart,  1915,  6,  77.  Gordon  and  Haldane, 
J.  Phys.,  1909,  38,  401.  Mackenzie  and  Cushny,  ib..  1907,  36,  p.  xiii. 
Pembrey,  Beddard  and  French,  ib.,  1906,  34,  p.  vi.  Pembrey  and 
Allen,  J.  Ph3'-s.,  1905,  32,  p.  xviii.  Pollock,  Arch.  Int.  Med.,  1912, 
9,  406. 

Mechanism  of  Gas  Exchange  in  Lungs. — Boothby  and  Berry,  Am.  J.  Phys., 
1913,  37,  433;  Christiansen  and  Haldane,  J.  Phys.,  1914,  48,  273 
(influence  of  distension  of  lungs).  Dixon  and  Ransom,  J.  Pharm.  Exp. 
Ther.,  1914,  5,  539  (effect  of  altered  vascular  conditions  in  lungs) .  Douglas 
and  Haldane,  J.  Phys.,  1912,  44,  305  (causes  of  O2  absorption  in  lungs). 
Evans  and  Starling,  J.  Phys.,  1913,  46,  413  (oxidation  in  lungs). 
Haldane  and  Lorrain  Smith,  ib.,  189S,  22,  231,  307.  Hartridge, 
ib.,  T912,  45,  170  (O2  secretion  ?).  Krogh  (M.),  ib.,  1915,  49,  271  (diffusion 
throvgh  lungs). 

Swim  Bladder. — Baglioni,  Z.  allg.  Phys.,  1970,  11,  145.  Jafcer,  Pflflger's 
Arc'-i.,  1903,  94,  65. 


1 1 68  BIBLIOGRAPHY 

Tissue  Respiration.— Batti.lli  and  Stern,  J.  Phvs.  Path.  G6n.,  1907,  9,  i, 
34.  Burrows,  Am.  J.  Phys.,  1917,  43,  i-^'  (02-pyessiire  necessarv  for 
tissue  activity).  Fletchkr,  J.  Phys.,  1898,  22,  10;  1902,  28,  54  {survival 
respiration  of  muscle).  Jackson  (D.  E.),  J.  Lab.  Clin.  Med.,  1916,  2, 
145  {action  of  drugs  on  rate  of  Oz-consumption) .  Mann  and  Gage,  J. 
Phys.,  1912,  45,  p.  ix  {nuclei  and  metabolism,  particularly  in  blood). 
Newman.  Am.  J.  Pliys.,  1906,  15,  371  {limulus  heart).  Vhknon,  J.  Phys., 
1909,  39,  149  (action  of  poisons);  ib.,  1907,  36,  8r  {perfusion  experiments): 
ib.,  1910,  40,  2g^  {tortoise  heart).  Harris  (D.  F.),  J.  BioJ.  Ch.,  1915, 
23,  469  {time  required  for  reduction  of  o.xyhcs>noglobin  in  vivo).  Lesser, 
ErgL-b.  d.  Phys..  1909,  742  {life  without  oxygen).  Packard.  Am.  J.  Phys., 
1907.  18,  164,  ib.,  1908.  21,  210  {resistance  to  lack  of  oxygen). 

Reducing  Power  of  Tissues.— Hj^rris  and  Irvine.  Bicch.  J.,  190G.  1,  355. 
Hekthk,  Am.  J.  Phys.,  1904,  12,  128.  457. 

Gaseous  Metabolism  of  Organs. — Barcroft  and  Brodie.  J.  Phj^.,  1903.  32, 
i^  :  "''.,  33,  .52  [kidney).  Harcroft  and  Di.xon,  ib.,  1906-7,  35, 182  {heart). 
Bakckoit  and  Shore,  ib.,  1912.  45,  296  {liver).  Barcroft  and  Starling, 
ib.,  1904,  31,  496  {pancreas).  Barcroft  and  Muller,  ib.,  1912,  44,  259 
{subma.xillary  gland).  Boycott,  ib..  1905,  32,  343  {intestine).  Evans. 
ib.,  1912,  45,  213  {heart  and  lungs).  Hill  and  Nabarro,  ib.,  1895,  18, 
218  {brain  and  muscle).  Langley  and  Itagaki,  ib.,  1917,  51,  202 
{oxygen  use  of  denervated  muscle).  Neuman.  ib.,  1912,  45,  188  {supra- 
renal). Pearce  and  Carter.  Am.  J.  Phys.,  1915,  38,  350  {influence  of 
vagus  on  gaseous  metabolism  of  kidnev).  Verz>Cr,  J.  Phys.,  1912,  44, 
243;  Krgcb.  d.  Phys..  1916.  i  {muscle). 

Experiments  Bearing  on  Mechanism  of  Oxidations  in  the  Body. — Bunzel, 
J.  Biol.  Ch.,  1909,  7,  1.57  [mechanism  of  oxidation  of  glucose  by  bromine). 
Cu-SHNY,  Arch.  E.xp.  Path.  Ther.,  Supp.  Bd.,  1908,  126  {action  of  oxidizing 
salts).  Dakin,  J.  Biol.  Ch..  1907,  3,  57  {simple  aliphatic  substances). 
Guthrie  (F.  V.).  Soc.  Exp.  Biol.  Med..  1910.  7,  152  {modification  of 
tissue  oxidation  in  vitro).  Harden  and  Maclean,  J.  Phys.,  1911,  43,  34 
{oxidation  of  isolated  tissues).     Mathews  and  McGuigan,   Am.  J.  Phys.. 

1907,  19,  199  {oxidizing  power  of  cupric  acetate  solutions).  McClendon, 
J.  Biol.  Ch.,  1915.  21,  275  {oxidizing  power  of  oxyhesmoglobin  and 
erythrocytes).  Uxderhill  and  Closson.  Am.  J.  Phys.,  1905,  13,  35S 
{methylene  blue,  etc.).  Usui.  Pfliiger's  Arch.,  1912.  147,  100  {measure- 
ment of  tissue  oxidations  in  vitro). 

Oxidiling  Ferments. — Abel^us  and  Biarn£s,  Arch,  de  Phys.,  1896,  311; 
ib.,  I8<j8,  664;  ib.,  1897,  277.  Battelli  and  Stern,  Ergeb.  d.  Phys.. 
1910.  10,  531;  ib.,  1912.  12,  96.  197.  Bertrand.  Arch,  de  Phj-s.,  1896. 
23  (laccase).  Bunzel.  J.  Biol.  Ch.,  1916,  24,  91  {mode  of  action) ;  ib.,  1916, 
28,  ii5  {relation  to  H-ion  concentration);  ib.,  24,  103  {plants).  Kastle. 
Hyg.  Lab.  Bull.,  No.  59,  Dec,  1909.     Kastle  and  Porch,  J.  Biol.  Ch., 

1908,  4,  301  {peroxidase  reaction  of  milk).  Lillie,  J.  Biol.  Ch.,  1913,  15, 
237  {formation  of  indophenol  at  nuclear  and  plasma  membranes  of  frogs' 
blood-corpuscles).  Loevenhart  and  Grove.  J.  Pharm.  Exp.  Ther..  1911, 
3,  loi.  Moore  and  Whitley,  Bioch.  J..  1909,  4,  136.  Reed,  J.  Biol. 
Ch.,  1915,  22,  99  (r6le  in  respiration);  ib.,  1916,  27,  299  {relation  to  H-ion 
concenitation). 

Catalases. — Amberg  and  Winternitz.  J.  Biol.  Ch.,  1911,  10,  295  {sea-urchin 
eggs).  Arkin,  Am.  J.  Phys..  1917,  42,  603.  Battelli  and  Stern,  Ergeb. 
d.  Physiol.,  1910,  5?i.  Burge,  Am.  J.  Phys..  191 7,  43,  545'.  44,  75,  290; 
ib.,  1916,  41,  isi  {>i"iscles).  Burge.  Kennedy  and  Neill,  Am.  J. 
Phys.,  1917,  43,  433  {effect  of  thyroid  feeding).  Evans.  Bioch.  J..  1907. 
2,  133  {blood).  LoEW,  Pfliiger's  Arch..  1909,  128,  560;  U.  S.  Dept.  Agric. 
Rep.,  No.  68.  1901.  Mendel  and  Leavenworth,  .\m.  J.  Phys..  1908, 
21,  85  {tissues).  Shaffer,  Am.  J.  Phys.,  1905,  14,  299.  Winternitz 
and  Meloy,  J.  Exp.  Med..  1908,  10,  759  {blood).  Winternitz  and 
Pratt,  J.  Exp.  Med.,  1910,  12,  i,  115  {blood).  Winternitz  and  Rogers. 
ib..  1910,  12,  12,  755  {eggs). 


RESPlkATtON  1109 

Reductases.  —  Harris    (D.   l-".).   J.   Biol.   Ch..    i«ji5,   22,   533.     Harris  and 

Cki  ir.inoN,  ih.,  21.  '■."> :  20,  170;  Bioch.  J.,  1914,  8,  585. 
Bioluminescence  (Phosphorescence).— Harvey,  Am.  J.  Phys.,  1915,  37,  230; 

ib..   1916,  41,44'),  454;  'b-.  1917.42,  318;  J.  Biol.  Ch.,  1917.  31,    311. 

Kastle  and  McDermott,  Am.  J.  Phys.,  1910,  27,  122.     Moore,  Bioch. 

J.,  1908,  4,  I. 

COMPRESSED  AND  RAREFIED  AIR. 

Caisson  Illness. — Boycott  and  Damant,  J.  Phys.,  1907-8,  36,  p.  xiv.  Ham 
and  Hill,  ib.,  1905-6,  33,  pp  v,  vi,  vii.  Hill  and  Macleod,  ib.,  1903, 
29,  382,  492.  Hill  and  Greenwood,  Proc.  Roy.  Soc,  1906,  B  77,  442; 
1907,  B  79,  21,  284;  1908,  B  80,  12.  TwoRT  and  Hill,  J.  Phys.,  1910, 
41,  p.  \-. 

Effects  of  Atmospheres  Rich  in  Oxygen. — Benedict  and  Higgins,  Am.  J. 
Phys.,  191 1,  28,  I  (effect  of  O.^-yich  mixtures  on  man).  Bullott,  J.  Phys., 
1904.  31,  359  {action  of  O^  at  low  and  high  pressure  on  the  cornea).  Hill 
and  Macleod,  Proc.  KoyT  Soc,  B  70,  455,  465  {effects  of  an  atmosphere  of 
O2  on  respiratory  exchange  and  circulation  in  mouse  and  frog).  Hill  and 
Flack,  J.  Phys.,  1910,  40,  347  {effect  of  oxygen  inhalation  on  muscular 
work).  Karsner,  J.  Exp.  Med.,  1916,  23,  149.  Karsner  and  Ash, 
J.  Lab.  Clin.  Med.,  1917,  2,  254.  Lorrain  Smith,  J.  Phys.,  1899,  24,  19 
{pathological  effect  of  increased  O^  tension).  Mosso,  Arch,  de  Phys.  et 
Path.,  1878,  10,  76  {action  of  compressed  air) . 

Influence  of  High  Altitudes. — Barcroft,  J.  Phys.,  1911,  42,  44;  ib.,  1913, 
46,  p.  XXX.  Bartlett,  Am.  J.  Phys.,  1904,  10,  149.  Boycott  and 
Haldane,  J.  Phys.,  1908,  37,  355  {low  atmospheric  pressures) .  Cohnheim, 
Ergeb.  d.  Phys.  (Bioch.),  1903,  612.  Douglas,  Haldane,  Henderson 
and  Schneider,  Proc.  Roy.  Soc.  (Lond.),  1913,  B  85.  Durig  and 
Zuntz,  Arch.  f.  Phys.,  1904,  Supp.  Bd.,  417.  Hueppe,  Pfliiger's  Arch., 
1903,  95,  447.  Mosso  and  Marro,  Arch.  Ital.  Biol.,  1903,  39,  387. 
Schneider  et  al..  Am.  J.  Phys.,  1908,  23,  90;  ib.,  1914,  34,  29;  ib.,  1916, 
40,  380  {circulation).  Tissot,  J.  de  Phys.  Path.  Gen.,  1910,  12,520;  ib., 
1911,  13,  75  {mountain  sickness).  Ward,  J.  Phys.,  1908,  37,  378.  Zuntz 
and  V.  ScHRorTER,  Arch.  f.  Phj's.,  1902,  Supp.  Bd.,  430,  436  {balloon). 

Influence  of  Respiration  on  Circulation. — Golla  and  Symes,  J.  Phys.,  1916, 
50,  p.  xxxii  {cerebrospinal  pressure  and  respiratory  movements).  Hender- 
son and  Barringer,  Am.  J.  Phys.,  1913,  31,  399  {respiration  and  heart 
output).  Snyder,  Am.  J.  Phys.,  1915,  1^7,  104  {causes  of  respiratory 
change  in  heart  rate) .  3 

Respiratory  Waves  in  Blood -Pressure. — Erlanger  and  Festerling,  J.  Exp. 
Med.,  1912,  15,  370.  Lewis  (T.).  J.  Phys.,  1908,  37,  213,  233.  Snyder, 
Am.  J.  Phys.,  1915,  36,  430.  Wiggers,  Am.  J.  Phys.,  1911,  35,  124  {in 
pulmonary  artery). 

Cutaneous  Respiration. — Barratt,  J.  Phys.,  1897,  21,  192  {CO^and  H^O); 
ib.,  24,  II  {varnished  skin).  Bohr,  Skand.  Arch.  Phys.,  1900,  10,  74 
{frog).     Reid  and  Hambley,  J.  Phys.,  1895,  18,  411  (C"6.^  in  frog). 

CHAPTER  V. 

VOICE  AND  SPEECH. 

Fleeming  Jenkin  and  Ewing,  Trans.  Roy.  Soc.  (Edin.),  1879,  28,  745  {vowe 
sounds).  GRiJrzNER,  Ergeb.  d.  Physiol.  (Bioph.),  1902,  466  {voice  and 
speech).  Hermann,  Pfliijer's  Arch.,  1901,  83,  i,  S3  {consonants);  ib.,  86, 
92  {vowel  sounds).  McKendrick,  Trans.  Roy.  Soc.  (Edin.),  37,  Pt.  4. 
Meyer,  The  Organs  of  Speech.  Paulsen,  Pfliiger's  Arch.,  1895,  61, 
407  {the  singing  voice  of  children);  ib.,  1899,  74,  570  {pitch  of  the  voice). 
Russell  (J.  S.  R.),  Proc.  Roy.  Soc,  1892,  102  {innervation  of  glottis). 
.  Scripture,  Study  of  Speech  Curves,  Carnegie  Instit.  Pub.,  Wasliington, 
1906. 

74 


1170  BlBLlOGh'.U  HY 

CHAPTER  VI. 
D  I  G  E  S  IM  O  N  . 

MOVEMENTS  OF  ALIMENTARY  CANAL. 

Cannon,  Mechanical  I'actois  of  Digestion,  New  York,  1911;  J.A.ISl.A.,  1903, 
40,  749- 

Deglutition. — Botazzi,  J.  Phys.,  iSgg,  25,  157  (nerves).  Cannon,  Am.  J. 
Pliys.,  1907,  19,  436  {oesophageal  peristalsis  after  vagototiiy).  Cannon 
and  MusEK,  ib.,  i8y8,  1,  435.  Kahn,  Arch.  f.  Phys.,  1903,  Supp.  Band., 
386  (nerves);  ib.,  1906,  355,  362.  Kaiser,  Arch.  Ncerland  do.  Phys., 
191 7,  1,  148.  Meltzer,  J.  Exp.  Med.,  1897,  2,  453;  See.  Exp.  Biol.  Med., 
1906,  S,  52  (reflexes);  Brit.  Med.  J.,  Dec.  22,  1906  (vagus  reflexes);  Soc. 
Exp.  Biol.  Med.,  1907,  4,  35  (secondary  peristalsis  of  cesophagus).  Miller 
and  Sherrington,  Q.  J.  Exp.  Phys.,  1913-16,  9,  147  (reflex  deglutition 
in  decerebrate  animal).  Stiles,  Am.  J.  Phys.,  1901,  5,  338  (rhythmic 
activity  of  cesophagus).  Stuart  (T.  P.  Anderson),  J.  Phys.,  1907,  35, 
44G  (epiglottis). 

Stomach  Movements.— Auer  (J.),  Am.  J.  Phys.,  1908,  23,  165  (rabbit). 
Cannon  (\V.  B.),  ib.,  1911,  29,  250  (nature  of  gastric  peristalsis);  ib.,  29, 
2G7  (receptive  relaxation).  Carlson,  ib.,  1912,  31,  151;  ib.,  1913,  32, 
245  (enifty  stomach  of  man).  Hertz,  Q.  J.  Med.,  1910,  3,  373  (man). 
RofX  and  Balthazard,  Arch,  de  Physiol.,  1897,  85  (x-rays). 

Innervation  of  Stomacb. — Auer  (J.),  Am.  J.  Phys.,  1910,  25,  334-  Brune- 
MKiER  and  Carlson,  /6.,  1913,  36,  191  (reflexes  from  intestinal  mucosa  to 
stomach).  Cannon,  ib.,  190O,  17,  429.  Lamgley.  J.  Phys.,  1898-9, 
23,  407  {inhiliitorv  fibres  in  vagu.i).  .AIay  (W.  P.),  J.  Phys.,  1904,  31,  260. 
Rogers,  Atn.  J.  Phy->.,  191 7.  42,  605  (y.^flex  control  of  gastric  vagus  tone). 

Sensibility  of  Stomach. — Carlson  and  Braaflaadt,  Am.  J.  Phys.,  1915,  36, 
153.  Hertz,  Cook  and  Schlesinger,  J.  Phys.,  1908,  37,  481  (stomach 
and  intestines).     Miller,  J.  Phys.,  1910,  41,  409. 

Pylorus  Control. — Boldyreik,  Pfluger's  Arcli.,  1907,  121,  13.  Cannon, 
Am.  J.  Phys.,  1904,  12,  387;  ib.,  1907,  20,  283;  ib..  1908,  23,  105  (acid 
control).  Cathcart,  J.  Phys.,  1911,  42,  433.  Morse,  Am.  J.  Phys.. 
1916,  41,  439  (acid  control).  Hedblom  and  Cannon,  Am.  J.  Med.  Sci., 
(Xt.,  1909. 

Movements  of  Intestines. — Alvarez,  Am.  J.  Phys.,  1914,  35,  177;  ib.,  1915, 
37,  207  (rhythm  of  segments  from  different  parts  of  intestine);  J.  Am.  Med. 
Ass.,  1913,  65,  383.  Bayliss  and  Starling,  J.  Phys.,  1900,  26,  107,  123. 
Cannon,  Am.  J.  Phys.,  1902,  6,  251;  1911,  29,  2;^ii;  1912.  30,  114  (tonus 
and  anti peristalsis);  J.  Am.  Med.  Ass.,  1912,  59,  i  (large  intestine);  Arch. 
Int.  Med.,  1911,  8,  417  (importance  of  tonus).  Elliott  and  Barclay- 
Smith,  J.  Phys.,  1904,  31,  272;  Hertz  and  Newton,  J.  Phys.,  1913-14, 
47,  57;  Lyman,  Am.  J.  Phys.,  1913.  32,  Gi  (colon).  Hambleton,  Am. 
J.  Phvs.,  1914,  34,  44O  (movements  of  villi).  Hertz,  J.  Phys.,  1913,  47, 
54  (il'eo-colic  sphincter).  Magnus,  Pllii^er's  Arch.,  1904.  102,  123,  349; 
ib.,  103,  513,  523;  ib.,  1906,  111,  152  (surviving  intestine).  Meltzer 
and  AiKR.  .\m.  j.  Phys.,  1907,  20,  239  (peristaltic  rush). 

Innervation  of  Intestine.— Bunch,  J.  Phys.,  1898,  22,  337;  'b-.  1899,  25,  22. 
Cannon,  Am.  J.  Phys.,  1906,  17,  429.  Langley  and  Magnus,  J.  Phys., 
1903-6,  33,  34- 

Defsecation.-  Charles,  Brit.  Med.  J.,  Sept.  30,  1899;  Frankl-Hochwart  and 
liOHi.icH,  Pfiiger's  Arch.,  1900,  81,  420  (tonus  and  iiinrrvntion  of  anal 
.sf^liinclcrs).     Hertz,  Sensibility  of  llic  Alimentary  Canal.  191 1. 

Vomiting:  Emetics. —  Brooks  and  Luckhardt,  Am.  J.  Phys.,  1915,  36, 
104  (blood-pressure  during  vomiting).  Eggleston  and  Hatcher.  J.  Pharm. 
Exp.  Ther.,  1913.  7,  225.  Magnus,  Ergeb.  d.  Physiol.,  1903.  643. 
Miller  (F.  K.),  "Pr.ii^'er's  Arch.,  1912,  143,  i;  Am.  J.  Phys.,  1915.  38, 
240  (cardiac  inhibition  during  vomiting). 


DIGESTION  iijt 

CHEMICAL  PHENOMENA  OF  DIGESTION. 

BoLUVRKFF,  O.  J.  I  xp  IMiys  ,  Km".  10,  17',  * .  Kii  n  \s  oou  and  Saunders, 
J.  I'hys..  i8i)|,  16,  .(41  (f>roto:.0(in  digestion).  London,  Z.  Physiol.  Ch., 
1005.  46,  ,1^1;  ib..  1906,  47,  3O8  {prolein  digeslioti);  ib.,  1907.  61,  241; 
ib..  190S.  58,  .512  (caiboliydrate  digestion).  Pawi.ow,  Work  of  the 
Digestive  Gliimis,  London,  1910;  Ergeb.  d.  Physiol.  (Bioch.),  1902, 
2.\h  (l^h.ysiologicul  surgery  of  digestive  canal).  Shaw,  Am.  J.  Phys., 
lui  ^  31,  ■\},9  {in  birds— chick). 

Catalysis,  Catalysers.  -Bredig,  Anorganische  Fermeutc;  Bioch.  Z.,  1907, 
6,  ^bi;.  liicRc;  and  Gies,  J.  Biol.  Ch..  1906,  2,  489  {ions  and  catalysis). 
Brown  (O.  H.).  Am.  J.  Phys.,  1905.  13,  427.  Euler.  Z.  f.  Physiol.  Ch., 
1905,  45,  4-!o.  Kasti.e  and  Loevknmart,  Am.  Clicm.  J.,  1903,  29,  397, 
503.  LoEVENHART,  Am.  J.  Phys.,  1903,  13,  171  {H.2p,^.  Neilson  and 
Terry,  Am.  J.  Phys.,  1905,  14,  248.  Dakin,  J.  Biol.  Ch.,  1909,  7,  49 
{catalytic  action  of  amino-acids,  etc.).     T.wlor,  ib.,  7,  49;  ib.,  1910,  8,  503. 

ENZYMES  OR  FERMENTS. 

Armstrong  (H.  E.  and  E.  i".),  Proc.  Ivoy.  Soc.  (Lond.),  1907,  B  79,  360 
{nature  of  enzymes).  Armstrong  and  Ormerod,  ib.,  B  78,  376  {lipase). 
Bayliss,  Nature  of  Enzyme  Action,  1908;  J.  Phys,  1913.  46,  236;  ib., 
1915,  50,  85  {enzyme  action).  Bearn  and  Cramer,  Bioch.  J.,  1907,  2, 
174  {zymoids).  Bredig,  Ergcb.  d.  Phys.  (Bioch.),  1902,  134.  Bunzel, 
J .  liioi.  Ch.,  1915.  20,  697  (alfalfa  laccase).  Buchner,  Arch.  f.  Phys.,  1906, 
548  [in  micro-oi'ganisms).  Croft  Hill,  Brit.  Med.  J.,  June  '20,  1903 
{reversibility  of  maltase  action).  Cole  (S.  W.),  J.  Phys.,  1904,  30,  281; 
Mathews  and  Glenn,  J.  Biol.  Ch.,  1911,  9,  29;  Osborne  (W.  A.),  Z.  f. 
Physiol.  Ch.,  1899,  28,  399  {invertase).  Falk  (K.  G.),  J.  Biol.  Ch.,  1917, 
28,  389;  Van  Slvke  and  Cullen,  J.  Biol.  Ch.,  1914.  19,  141  {mode  of 
action  of  urease  and  of  enzymes  in  general).  Fischer  (E.),  Ber.  Deutsch. 
Chem.  Ges.,  28,  1429;  Zcntralb.  Physiol.,  10,  117  {configuration  and 
enzyme  action).  Euler,  Ergeb.  d.  Phys.,  1907,  239  {synthesis  by  ferments) ; 
ib..  187  {chemistry).  jNIutch,  J.  Phj's.,  1912,  44,  176  {histozym). 
MiCHAELis  and  Eiirenreich,  Bioch.  Z.,  1908,  9,  283  {adsorption  analysis 
of  ferments).  Pavy  and  Bywaters,  J.  Phj's.,  1910,  41,  168.  Peters, 
J.  Biol.  Ch.,  1908,  5,  367  {adsorption  of  diastase  and  catalase).  Porter 
(A.  E.),  Q.  J.  Exp.  Phj^s.,  1910,  3,  375  {inactivation  of  enzymes).  Oppen- 
HEIMER,  Ferments  and  their  Actions,  translated  by  Mitchell.  Sorenson, 
Bioch.   Z.,   1907,   7,  45;  ib.,   1909,  22,   352. 

Action  of  Substances  on  Ferments. — Bierry,  J.  Phys.  Path.  Gen.,  1912,  14, 
253  (electrolytes  in  diastatic  actions).  Cole  (S.  W.),  J.  Phys.,  1904,  30,  202 
(acid  on  saliva).  Morse,  J.  Biol.  Ch.,  1915,  22,  125  (halogens).  Neilson 
and  Brown,  Am.  J.  Phys.,  1904,  10,  225,  335  (ions).  Quinan,  J.  Biol. 
Ch.,  1909,  6,  53  (hydroxyl-ion  concentration  and  diastatic^hydrolysis). 

Enzyme  Syntheses. — Bradley  and  Kellersberger,  J.  Biol.  Ch.,  1912,  13, 
425  (diastase  and  starch).  Bradley,  ib.,  1912, 13,  431  (lactase  of  mammary 
gland).     TAYLtiR  (A.  E.),  ib.,  1908,  3,  87  (trypsin  and  protein). 

Proteolytic  Enzymes.— Cathcart,  J.  Phys.,  1905,  32,  299  (spleen  enzyme)- 
Dakin,  ib.,  1903,  30,  84  (kidney  enzyme).  Effront,  Biochemical  Cataly- 
sis in  Life  and  Industry,  Proteolytic  Enzymes  (translated  by  Prescott), 
1917-  Frankel,  J,  Biol.  Ch.,  1916,  26,  31  (action  on  purified  proteins)'. 
Hedin,  J.  Phys.,  1904,30,  155,  195.  LEVENEandSTOOKEY,  Am.  J.Phys., 
1904.  12,  I  (interaction  of).  Kober,  J.  Biol.  Ch.,  1911,  10,  9  (method)'. 
Opie  and  Barker,  J.  Exp.  Med.,  1907,  9,  207  (leucoprotease).  Shackles 
and  Meltzer,  Am.  J.  Phys.,  1909.  25,  81  (effect  of  shaking).  Roaf,  Bioch. 
J.,  1908,  3,  188  (colorimetric  method).  Sloan,  Am.  J.  Phys.,  1917,  48, 
568  (origin  of  proteolytic  ferments). 

Lipases.— Arthus,  J.  Phys.  Path.  Gen.,  1902,  4,  56,  455  (lipase  of  blood). 
BoLDYREFF,  Z.  Physiol.  Ch.,  190O-7,  50,  394  (lipase  of  intestinal  juice). 
Bradley,   J.   Biol.   Ch.,   1910,   8,   251    (lipase   reactions).      Connstein, 


tl72  BIBLIOGRAPHY 

Krgcb.  d.  riiys.  (Bioch.).  1904,  194.  Falk,  J.  Biol.  Oh..  1917.  31,  07- 
Hull  and  Ki;i;i'on,  J.  Bi(jl.  Cli.,  191  7.  32,  1^7  {gailric  lipase).  I.okven- 
HAKT,  J.  Biol.  Ch.,  1906,  2,  391;  KosKNHiiiM,  J.  Phys.,  1910,  40,  p.  xiv 
(co-cnzyme  of  lipase).  Loevenhart,  J.  Biol.  Ch.,  1906,  2,  427  (identity 
of  lipases) ;  Am.  J.  Plays.,  1902,  6,  331  [lipase  and  fat  metabolism).  London, 
Z.  f.  Phys.  Ch.,  1906-7,  60,  125.  Jobling,  Eggstkin  and  Pktersen, 
J.  E.\p.  Med.,  1915,  22,707  [serum  esterase).  Mendel  and  Leavenworth, 
Am.  J.  Phys.,  1908,  21,  95  [lipase  in  embryonic  tissues).  IMkllanuy  and 
WooLLKY.  J.  Phys.,  1914,  48,  -;S7;  Shaw-Mackenzii;,  J.  Phys.,  1915, 
49,  216;  Di:  SouzA,  Jiioch.  J.,  191G,  10,  108  [pancreatic  lipase).  QuiNAN, 
].  .Mod.  Kcs.,  1915,  32,  45  [tissue  esterases),  von  Hess,  J.  Biol.  Ch.,  1911, 
10,  3S1  [rclalion  of  pancreas  to  blood  and  lymph  lipase). 
An'iiJerments. — Bayliss,  J.  Phys.,  1912,  43,  455  [anti-emulsin) .  Cathcakt, 
J.  l^Jiys.,  1904,  31,  497  ;  Jobling  and  Petersen,  J.  Exp.  Med.,  1914,  19, 
459;  Weil.  Arch.  Int.  Med.,  1910,  5,  109  [serum  antitrypsin).  Euler, 
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and  Petersen,  J.  Exp.  Med.,  1914,  20,  452  [bacterial).  LangenskjSld. 
Skand.  Arch.,  1914,  31,  i.  Weinland,  Z.  f.  Biol.,  1902,  43,  86;  44,  i 
[tape-worm). 

SALIVARY  DIGESTION. 
Cannon  and  Day,  Am.  J.  Phj-s.,   190:;,  9,  396    [in   slotnach).     Maxwell. 

Bioch.  J.,  1915,  9,  323  [salivary  and  gastric  digestion). 
Diastase  in  Saliva. — Carlson  and  Ryan,  Am.  J.  Phys.,  1908,  22,  i  [cat). 
Evans,  J.  I'hys.,  1912,  44,  191  [amylo-clastic  action  of  saliva).  Chitten- 
den and  KicHARDS,  Am.  J.  Phys.,  i8g8,  1,  461  [iiian).  Mendel  and 
Undekhill,  J.  Biol.  Ch.,  1907,  3,  135  [dog).  Palmer,  Am.  J.  Phys., 
1916,  41,  483  [ox).  Seymour,  Am.  J.  Phys.,  1917,  43,  577  [horse). 
Secretion  oJ  Saliva. — Asher  and  Cutter,  Z.  f .  Biol.,  1900.  40,  535.  Barcroft, 
J.  Phys.,  1900,  25,  479  [movement  of  ivater  in  secretion).  Bunch,  J.  Phys. 
1907,  36,  I  [changes  in  volume  of  submaxillary  during  activity).  Carlson 
and  McLean,  Am.  J.  Phys.,  1908,  20,  457  (Og  supply  and  secretion). 
Carlson,  Greer  and  Becht,  Am.  J.  Phys.,  1907,  20,  180  [blood-supply 
and  character  of  saliva).  Carlson  and  Crittenden,  ib.,  1910,  26,  169; 
Kyan  (J.  G.),  ib.,  1909,  24,  234  [ptyalin  concentration).  Demoor,  Arch. 
Intcrnat.  de  Phys.,  1913,  13,  187.  Grunbaum  (O.  F.  F.),  J.  Phys., 
189S,  22,  385  {resistance  to  secretion  and  percentage  of  salts).  Hender- 
son (V.  E.),  J.  Pharm.  Exp.  Ther.,  1910,  2,  i  [action  of  drugs).  L.\ngley, 
J.  Phys.,  1885,  6,  71,  ib.,  1888,  9,  55;  ib..  1890,  11,  123  [paralytic  secre- 
tion); 1916,  50,  p.  xxvi  [trophic  secretory  fibres).  Japelli,  Z.  f.  Biol., 
1906,  48,  398  [physico-chemical  conditions).  Latimer  and  Warren, 
J.  Exp.  Med.,  1897,' 2,  465  [zymogen  of  ptyalin).  Mathews  (.\.  P.),  Am. 
J.  Phys.,  1901,  4,  482  [atropiti).  Pawlow,  Ergeb.  d.  Physiol..  1904, 
177  [psychical  secretion);  Arch.  Internat.  de  Phj-s..  1904,  1,  119. 
Wi.rthi;imi:r  and  Battez,  J.  Phys.  Path.  Gen.,  1914,  6,  438. 
Salivary  Glands  and  Gastric  Juice. — Hemmeter,  Bioch.  Z..  1908,  11,  238. 
Swanson,  Am.  J.  Phys.,  1917.  43,  205.  Hyde,  Z.  f.'Biol.,  1897,  35,  459 
[Octopus  macropus). 

GASTRIC  DIGESTION. 
Gastric  Juice. — Carlson,  Am.  J.  Phys.,  1915.  37,  50  [secretion  in  man). 
Carlson,  Hagar  and  Rogers,  ib..  1915,  38,  248  [chemistry  of  normal 
human  gastric  juice).  Cohnheim  and  Soetheer,  Z.  f.  Physiol.  Ch.,  1902-3, 
37,  467;  Gmelin,  Pfliigcr's  Arch..  1904,  103,  618  [secretion  of  new-borti). 
Edkins,  J.  Phys.,  1906,  34,  133;  Edkins  and  Tweedy,  ib..  1909,  38,  263 
[chemical  mechanism  of  gastric  secretion).  Hamburger  (W.  W.),  J.Exp. 
Med.,  191 1.  14,  535  [pepsin  and  so-called  antipepsin).  Harvey  (B.  C.  H.), 
Am.  J.  Anat.,  1907,  6,  207  [gastric  glands).  Porter  (A.  E.),  J.  Phys., 
191 T,  42,  389  [pepsin  and  rennet  are  independent).  Rogers,  ]^\HE, 
Eawcett  and  Hackett,  Am.  J.  Phys.,  1916,  39,  345  [effect  of  organ  ex- 
tracts on  gastric  secretion). 


DIGESTION  1 1 73 

Quantitative  Relations  o!  Pepsin  Action.—  Huppert  (and  SftcHTz).  Pfliiger's 
Arch.,  lyoo,  80,  470.  Neilson  and  Bonnot,  Arcli.  Int.  Med.,  1913. 
11,  305.     SpRir.cs,  Z.  f.  Physiol.  Ch.,  igoi,  36,  4O5. 

HCl  of  Gastric  Juice.-  I'leio,  J.  Phys.  Path.  G<Sn.,  1908,  10,  toog  {reactions 
for).  LusK  and  I'erris,  Am.  J.  Pliy.s.,  1898,  1,  277  (inversion  of  cane 
sugar  by).  Pai.mi  k,  Bioch.  J..  1906,  1,  398  (in  carcinoma).  SjSjVisT. 
Skand.  Arch.  Phys.,  18^3,  5,  277.  Weinland,  Z.  f.  Biol..  1910,  65,  58 
(in  shar/i).  Widdicombe  (J.  H.),  J.  Phys.,  1902,  28,  175  (digestion  of 
cane  sugar). 

Acidity  of  Gastric  Juice. — Mf.nten,  J.  Biol.  Ch.,  191 5,  22,  341  (in  wan). 
Michaelis  and  Da\id.soiin,  Z.  Exp.  Path.  Ther..  1910,  8,  398.  Tan-gl, 
Ptliigcr's  Arch.,  I90(j,  115,  64. 

Formation  of  HCl  of  Gastric  Juice. — Bensley  and  Harvey,  Trans.  Chicago 
Path.  Soc,  igi^  9,  -:-'i.  Bergeim,  Soc.  Exp.  Biol.  Med.,  1914,  12,  21. 
Benrath  and  Sach.s,  Pfliiger's  Arch.,  1905,  109,  466.  Koeppe,  PflUgcr's 
Arch.,  1896,  62,  567.  Liebermann,  Pfliiger's  Arch.,  1891,  60,  25. 
Osborne  (T.  B.),  Am.  J.  Phys.,  1901,  5,  180.     Monti,  Archivio  di  Fisiol., 

1913,  11,  155  (function  of  the  delomorphic  cells),     von  Rhorer,  Pfluger's 
Arch.,  1905,  110,  416.     Wesener,  ib.,  1899,  77,  483. 

Acidity  of  Gastric  Contents. — Fowler,  Bergeim  and  Hawk,  Soc.  Exp. 
Biol.  Med.,  1916,  13,  58  (indicators).  JNIcClendon,  Am.  J.  Phys.,  1915, 
38,  191  (adults  and  infants,  acidity  in  stomach  and  duodenum) .  Moore, 
Alexander,  Kelly  and  Roaf,  Bioch.  J.,  1906,  1,  274. 

Protein  Digestion  in  Stomach. — Tobler,  Z.  f.  Physiol.  Ch.,  1905,  45,  185. 
ZuNz  (E.),  Ergcb.  d.  Phys.,  1906,  622,  663.  Chittenden,  Mendel 
and  Jackson,  Am.  J.  Phys.,  1898,  1,  164  (action  of  alcohol  on  digestion). 

Proteoses,  Albumoses. — Chittenden  and  Hartwell,  J.  Phys.,  1891.  12,  12. 
Haslam,  ib.,  1907,  36,  164  (deutero-albuinose) .  Kuhne  and  Chittenden, 
Z.  f.  Biol.,  18S4,  20,  II,  409. 

Digestion  of  Nucleins. — Amberg  and  Jones,  J.  Biol.  Ch.,  191 1.  10,  81. 
Levene  and  Medigreceanu,  ib.,  9,  375. 

Chymase  (Rennin). — Bang,  Z.  f.  Physiol.  Ch.,  1904-5,  43,  358.  Bosworth, 
J.  Biol.  Ch.,  1913,  15,  231  ;  ib.,  1914,  19,  397.  Burge,  Am.  J.  Phys.,  1912, 
29,  330.  Edmunds,  J.  Phys..  1896,  19,  466.  Fuld.,  Ergeb.  d.  Physiol. 
(Bioch.),  1902,  468.  Hawk,  Am.  J.  Phys.,  1903,  10,  37.  Kent,  J.  Phys., 
1911,  43,  p.  xxiv.  Leary  and  Sheib,  J.  Biol.  Ch.,  1917,  28,  393.  Locke, 
J.  Exp.  Med.,  1897,  2,  493.  Loevenhart,  Z.  f.  Physiol.  Ch.,  1904,  41, 
177.  Mellanby,  J.  Phvs.,  1912,  45,  345.  Pawlow  and  Parastschak, 
Z.  f.  Phj^siol.  Ch.,  1904,  42,  415.  Porter  (A.  E.),  J.  Phys.,  1911,  42,  389. 
Taylor  (A.  E.),  J.  Biol.  Ch.,  1908,  5,  399-  Warren  (J.  W.),  J.  Exp. 
Med.,  1897,  2,  475. 

PANCREATIC  JUICE. 

Bayliss  and  Starling,  J.  Phys..  1904,  30,  61.     Boldyreff,  Q.  J.  Exp.  Phys., 

1914,  8, 1 ;  Jb.,  1916, 10, 175 ;  Ergeb.  d.  Physiol.,  1911,  121,  156.  Bradley, 
J.  Biol.  Ch.,  1909,  6,  133  (hitman).  De  Zilwa,  J.  Phys.,  1904,  31,  230 
(composition).  Fischer  (E.)  and  Abderhalden,  Z.  f.  Physiol.  Ch.,  1907, 
61,  264  (action  on  polypeptides).  Welker  and  Falls,  J.  Biol.  Ch.,  1917, 
32,  509  (influence  of  pancreatic  digestion  on  non-colloidal  N-content  of 
S(riim). 

Enzymes  of  Pancreas. — Bayliss,  J.  Phys.,  1907,  36,  221  (causes  of  rise  of 
electrical  conductivity  in  trypsin  action).  Edkins,  ib.,  1891,  12,  218 
(action  on  casein).  Hedin  (S.  G.),  ib.,  1905,  32,  468;  ib.,  1906,  34,  370 
(trypsin  action).  Magnus,  Z.  f.  Physiol.  Ch.,  1906,  48,  376  (synthetic  bile 
acids  and  pancreatic  fat-splitting).  M.\Ys  (K.).  ib.,  1907,  61,  182. 
Mellanby  and  Worley.  J.  Phys.,  1913,  47,  338  (trypsin,  trypsinogen, 
enterokinase);  ib.,  1913,  46,  159  (Ca  and  generation  of  trypsin  from  tryp- 
sinogen). Robertson  (T.  B.),  J.  Biol.  Ch.,  1908,  5,  31  (r6le  of  alkali  i:i 
hydrolysis  of  proteins  by  trypsin).     Terroine  and  Schaeffer,  J.  Phys. 


"74 


BIBLIOGRAPHY 


Path.  Gen.,  1910.  12,884,  065  (trypsin  anderepsin).     Terroine,  ib.,  1911, 

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J.  Phys.,  1^99,  25,  165  (influence  of  bile);  Am  J.  Phys.,  1899,  2,  483. 

Secretion  of  Pancreatic  Juice. — Von  Anrep,  J.  Phys..  1914,  49,  i;  ib.,  1916, 
50,  421  (vagus).  C.A.MUS  and  Gley,  Arch.  Internat.  Phys.,  1913,  13,  102 
(pilocarpin) .  Herring  and  Simpson,  Q.  J.  IC.xp.  Phy.s..  1909.  2,  100 
(secretory  pressure).  May  (O.),  J.  Phys.,  1904.  30,  400  (secretion  and 
blood  supply).  Rogers,  Rahe,  Fawcett  and  Hackett,  Am.  J.  Phys., 
1916,  40,  12  (effect  of  organ  extracts).  Werthkimer  and  Boulet,  Arch. 
Internat.  Phys.,  191 2,  12,  247. 

Secretin.- — Bayliss  and  Starling,  Ergeb.  d.  Physiol.,  1906,  G70;  ib.,  693 
(chemical  nature  of  hormones);  J.  Phys.,  1903.  28,  325;  ib.,  29,  174. 
Bainbridge  and  Beddard,  ]5ioch.  J.,  1906,  1,  429;  Evans.  J.  Phys., 
191 2,  44,  461  (secretin  and  diabetes).  Delezenne,  J.  Phys.  Path.  Gen., 
1912,  521,  540.  Dixon  and  IIamill,  J.  Phys.,  1909,  38,  314.  HiooN, 
Arch.  Internat.  Phys.,  1912,  12,  485.  Wertheimer  and  Lepage, 
J.  Phys.  Path.  Gen.,  1901,  3,  O89,  708. 

Adaptation  in  the  Digestive  Juices. — Bayliss  and  Starling,  Ergeb.  d.  Physiol., 
lyoO,  681;  J.  Phys.,  1904,  30,  O4.  Plimmer  (R.  H.  A.),  J.  Phys.,  iyo6, 
84,  93;  i^-'  1906,  35,  20  (adaptation  of  pancreas  to  lactose). 

BILE. 

Chemistry  oJ  Bile. — Brand,  Pfliiger's  Arch.,  1902,  90,  491;  Rosenbloom, 
J.  Biol.  Ch.,  1913,  14,  241  (human  bile).  Fischer  (H.),  Ergeb.  d.  Phj's., 
1916,  185  (bile  and  blood  pigment).  Heynsius  and  Campbell,  Pfliiger's 
Arch'.,  1871,  4,  497;  Haycraft  and  Scofield,  Z.  f.  Physiol.  Ch.,  1890, 

14,  73;  Stewart  (G.  N.),  Studies  Physiol.  Lab.,  Univ.  Manchester,  1891, 
201  (bile- pigment  spectra).  Hammarsten,  Ergeb.  d.  Physiol.,  1905.  1. 
Okada,  J.  Phys..  1915,  60,  114  (reaction).  Gardner  and  Knox,  J.  Phys., 
1907,  36,  p.  ix  (cholesterol  in  bile).  Hammarsten,  Z.  f.  PhysioJ.  Ch.. 
1904-5,  43,  127;  Lewis,  Bioch.  J.,  1908,  3,  119;  Schryver,  J.  Phys.,  1912, 
44,  2O5  (bile-salts).  Sellards,  J.  Exp.  Med.,  1909,  11,  786  (reaction  with 
blood-serum). 

Bile  and  Bile-Pigment  Formation.— Whipple  and  Hooper,  Am.  J.  Phys., 
1916,  40,  332;  ib.,  191 7,  42,  256,  544;  ib.,  191 7.  43,  258,  275,  290;  J.  Exp. 
Med.,  1913,  17,  612  (from  hemoglobin  mitside  the  liver). 

Bile  and  Bile  Pigment  Secretion.— Barbera,  Arch.  Ital.  Biol.,  1902,  38,  447. 
liAYLiss  and  Starling,  Ergeb.  d.  Physiol.,  1906,  677.  DovoN  and 
Di-FOURT,  Arch,  de  Phvs.,  1896,  587;  ib..  1897,  562.  Dastre,  ib.,  1890, 
800.  Eiger,  Z.  f.  Biol.,  191 5,  66,  229  (vagus  influence).  Hooper  and 
Whipple,  Am.  J.  Phys.,  1917,  42,  264,  280  (influence  of  bile).  Okada, 
J.  Phys.,  19x5,  49,  457.  Pfaff  and  Balch,  J.  Exp.  Med.,  1897,  8,  49- 
Pugliese,  Arch.  Ital.  Biol.,  1902,  38,  257.  Simpson  (S.),  Soc.  Exp.  Biol. 
Med.,  1910,  7,  8. 

Eck's  Fistula. — Bernheim  and  Voegtlin,  J.  Pharm.  Exp.  Ther.,  1909,  1,  463. 
Carrel  and  Guthrie,  Compt.  Rend.  Soc.  Biol.,  June  30,  1906,  1104 
(simple  method).  Hawk,  Am.  J.  Phys.,  1908,  21,  259.  Herrick  (F.  C), 
J.  Exp.  Med.,  1905,  7,  751-     Sweet,  J.  Exp.  Med.,  1905.  7,  163. 

Absorption  of  Bile,  Icterus.— Harley,  Proc.  Roy.  Soc.  1892,  (paths). 
Harold,  Pepper  and  1'erry,  J.  Exp.  Med.,  1915,  22,  675.  Herring 
and  Simpson,  Proc.  Roy.  Soc,  1907,  B  79,  517  (secretory  pressure  and 
absmption).  Pearce  (R.  M.)  et  al.,  J.  Exp.  Med.,  1912,  16,  758,  769. 
7S0  (hemolytic  jaundice  and  the  spleen).  Sutherland,  Bioch.  J.,  1906. 
1,  364.     Voegtlin  and  Bernheim,  J.  Pharm.  Exp.  Ther.,  191 1,  2,  455- 


DIGESTIOX  1175 

Wertheimer  and  Lepage,  Arch,  de  Phys.,  1897.  y>i  (paths  of  absorp- 
tion); ib.,  1S08.  334:  J.  I'hys.  Path.  Gen..  1899,  1,  259.  Whipple  and 
Hooper,  J.  E.\p.  Med.,  i>,ni.  17,  593 ;  191O,  23,  137.  Whipple  and  Kino, 
ib..  1911,  13,  115. 

Toxicity  of  Bile.  -Krothingham  and  Minot,  J.  Med.  Kcs.,  1912.  27,  79- 
Kaks.nkk  iiiul  EisENisREY,  lb.,  1912,  26,  357  (antibodies).  King  and 
Stewart  (H.  A.),  J.  Exp.  Med.,  1909,  11,  573.  Meltzek  and  Salant, 
ib.,  1906,  8,  127.     Tatum,  J.  Biol.  Ch.,  191O,  27,  243  (itijhtencc  on  autolysis). 

Bile  Circulation. — Stadelmann,  Z.  f.  Biol.,  1897.  34,  i.  Wektheimkk,  Arch. 
dc  riiys.,  iS()2,  577. 

Innervation  of  Gall-BIadder.— Bainbridge  and  Dale,  J.  Phys..  1905.  33,  138. 
Fkeicsk,  Johns  llopk.  Hosp.  Bid!.,  16,  June,  1905.  LiEBand  McWhorter, 
Soc.  Exp.  Biol.  Med.,  1913,  12,  102. 

Bile  and  Bile-Salts  in  Digestion. — Chittenden  and  Albro,  Ain.  J.  Pliys., 
189S,  1,  307  [iuflnoicc  on  pancreatic  proteolysis).  De  Jonge,  Arch. 
Neerland.  Physiol.,  1917,  1,  182.  Kingsbury,  J.  Biol.  Ch.,  1917,  29, 
367.  Loevenhart  and  Sol'der,  ib.,  1906-7,  2,  415.  Pfluger  (E.), 
Pfliiger's  Arch.,  1902,  90,  i.     Kachi-ord,  J.  Phys.,  1891,  12,  93. 

INTESTINAL  JUICE. 

Bayliss  and  Starling,  Ergeb.  d.  Physiol.,  1906,  678  (chemical  reflexes). 
Hamburger  and  Hekma,  J.  Phys.  Path.  Gen.,  1902,  4,  805;  ib.,  1904,  6, 
40  (man).  Mendel,  Pfliiger's  Arch.,  1896,  63,  425  (paralytic  secretion). 
Mosenthal,  j.  Exp.  yied.,  191 1.  13,  319.  Pregl,  Pfliiger's  Arch.,  1895, 
61,  359  (sheep).     Salaskin,  Z.  Physiol.  Ch.,  1902,  35,  419  (dog). 

Ferments. — Blood  (A.  P.),  J.  Biol.  Ch.,  1910,  8,  215;  Cohnheim,  Z.  Physiol. 
Ch.,  igo6,  47,  286;  1902,  35,  134;  36,  13,  244;  Reed  and  Stahl,  J.  Biol. 
Ch.,  1911,  10,  109;  Vernon,  J.  Phys.,  1905,  33,  81  (erepsin).  Hamill, 
J.  Phys.,  1905-6,  33,  476;  Mellanby  and  Woolley,  ib.,  1912,  45,  370 
(enterokinase) . 

Reaction  of  Intestinal  Contents. — McClendon,  Shedlov  and  Thomson, 
J.  Biol.  Ch.,  1917,  36,  269  (ileum).  Moore  and  Bergin,  Am.  J.  Phys., 
1900,  3,  316. 

Digestibility  of  Foods.— Bryant  and  Milner,  Am.  J.  Phys..  1903.  10,  81 
(vegetables).  Frank.  J.  Biol.  Ch.,  191 1,  9,  463  (egg-white).  Langworthy 
and  Holmes,  U.  S.  D_'pt.  Agric.  Bull.,  1917.  505,  507;  Langworthy,  ib., 

1915,  310;  Smith,  Miller  and  Hawk,  J.  Biol.  Ch.,  1915,  23,  505  (fats). 
RocKwooD,  J.  Biol.  Ch.,  1910,  8,  327  (flour). 

Bacteria  of  Alimentary  Canal. — BALowaN,  J.  Ciol.  Ch.,  1909,  7,  37.  Gushing 
and  Livingood,  Johns  Hopkins  Hosp.  Rep.,  9,  543.  Gerhardt,  Ergeb. 
d.  Physiol.  (Bioch.),  1904,  107.  Herter,  Harvey  Lect.,  Xew  York, 
Nov.  3,  1906.     Herter  and  Kendall,  J.  Biol.  Ch.,  1909,    6,  499;.  16., 

1909,  7,  203  (influence  of  diet  on  intestinal  flora).  Kendall,  J.  Med.  Res., 
191 1,  25,  117.     KiANiziN,  J.  Phys.  Path.  Gen.,   191 1,  13,  689;  J.  Phys., 

1916,  50,  391;  XuTTALL  and  Thierfelder,  Arch.  f.  Physiol.,  1895,  559; 
Schottelius,  Arch.  f.  Hygiene,  34  (aseptic  digestion). 

Fseces. — Ellis  and  Gardner,  Proc.  Roy.  Soc,  191 2,  B  86,  13  (excretion  of 
cholesterol). 

CHAPTER  VIL 

ABSORPTION. 

Adsorption. — Barrett  and  Edie,  Bioch.  J.,  1907,  2,  44.V  Bayliss,  ib.,  1906, 
1, 175.     Hedin,  ib.,  1907,  2,  112  (of  enzymes).     Hofmann,  Zentr.  f.  Phys., 

1910,  24,  805.  Michaelis  and  Rona,  Bioch.  Z.,  1908, 15,  i9*i-  Robert- 
son, J.  Biol.  Ch.,  1908,  4,  35.     Van  Slyke,  ib.,  190S,  4,  259. 

Diffusion.— Denis  (W.),  Am.  J.  Phvs.,  1906,  17,  35  (siiUs  of  blood).  Flexner 
and  Xoguchi,  Soc.  Exp.  Biol.  Med.,  1906,  3,  66.  Hedin,  Pfluger's  Arch., 
1899,  78,  205.     Hober,  ib.,  1898,  71,  624  {in  intestinal  absorption);  ib., 


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tectomy). Greene  and  Skaer,  Am.  J.  Phys.,  1913,  32,  358.  Greene, 
ib.,  1912,  30,  278  (salmon).  Mendel  and  Baumann,  J.  Biol.  Ch.,  1915, 
22,  165  (fro)n  stomach).  McClure,  Vincent  and  Pratt,  Am.  J.  Phys., 
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Ch.,  1909,  62,  448. 


FORMATION  OF  LYMPH  1177 

Albumoscs  in  Tissues  and  Blood. — Abel.  Pincoffs  and  Rouillkr,  Am.  J. 

Phys.,  191 7,  44,  3^0.     liMnuiiN  and  Knoop,  Hofmeister's  Beit.,  1903,  3, 

120.     Langstein.  ib..  3,  373.     Schumm,  16.,  1904.  4,  453. 
Absorption  of  Sugars.    Hfino>f,  Arch,  de  Pharmacod.,  1900,  7,  163.     MUNK, 

Arch.  f.  Phys.,   ivSgo.  370  {paths  for  sugar,  protein,  fat).     Reach.  Arch. 

E.vp.  Path.   Pliarni.,  47,  ^31  (i>y  rectum).     Reid.  J.  Phys.,  1901.  26,  427; 

190J,  28,  241.     RoiiMANN  and  Nacano.  Pfluger's  Arch.,  1903.  95,  533. 
Absorption  0!  Iron. — Ahuerhalden.  Z.  f.  Biol.,  1900,39,113,  rgv     Bunge, 

Z.  f.   Physiol.   Ch..  1898.   25,   36.     Hall  (W.  S.).  .\rch.  f.  Phys.,   1896. 

49;  ib.,  1894,  435.     Meyer,  Ergeb.  d.  Phys..  1906,  698.     Sattler,  Arch. 

Hxp.  Path.  Pharm.,  1905,  52,  320. 

CHAPTER  VHI. 

FORMATION  OF  LYMPH. 

Lymphatic  System. — Job,  Anat.  Record,  1915,  9.  JMacCallum  (W.  G.),  Arch, 
f.  Anat.  (u.  Physiol.),  1902,  273  {relation  of  lymphatics  to  connective  tissue). 
Sabin  (F.  R.),  Ergeb.  d.  Anat.  u.  Entwick.,  1913;  Am.  J.  Anat.,  1904, 
3,  183  {origin  of  lymphatic  system). 

Lymph  Formation. — Asher  and  Barbera,  Z.  f.  Biol.,  1898.  36,  154.  Asher 
and  BuscH,  Z.  f.  Biol.,  1900,  40,  333.  Asher,  Z.  f.  Biol.,  1899,  37,  261. 
Asher  and  Gies,  Z.  f.  Biol.,  1900,  40,  180.  Baixbridge,  J.  Phys.,  1906, 
34,  275  {post-mortem);  J.  Phys.,  1900-1,  26,  79  {submaxillary  gland); 
ib.,  28,  204  {liver);  ib.,  32,  i  {pancreas).  Brande  and  Carlson,  Am.  J. 
Phys.,  19,  221  {lymphagogues  and  agglutinins  in  serum  and  lymph). 
Cuttat-Galizka,  Z.  f.  Biol.,  191 1,  56,  309  {post-mortem).  Cohnstein, 
Pfluger's  Arch.,  1895,  59,  350,  508;  ib.,  1895,  62,  58;  Arch.  f.  Phys.,  1896, 
379.  Carlsox,  Greer  and  Becht,  Am.  J.  Phys.,  1907,  19,  360  {salivary 
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Exp.  Med.,  igi2,  16,  139.  Ellinger,  Ergeb.  d.  Phys.  (Bioch.).  1902, 
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9,  75- 

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Amer.  Medicine,  1904,  8-  Miller  (J.  L.)  and  Matthews  (S.  A.),  Arch'. 
Int.  Med.,  1909,  4,  356  {pulmonary).  Moore  (A.  R.),  Pfluger's  Arch. 
191 2,  147,  28;  Am.  J.  Phys.,  1915,  37,  220.  Pearce  (R.  M.),  Arch. 
Int.  Med.,  1909,  3,  422.  Woolley,  J.  Lab.  Clin.  Med.,  1916,  1,  267 
{nervous  influences  and). 

CHAPTER  IX 
EXCRETION. 

COMPOSITION  OF  URINE. 

BoucHEZ,  J.  Phys.  Path.  Gen.,  1912,  14,  46,  74.  Camerer,  Z.  f.  Biol., 
1904,  45,  i;  FoLiN,  Am.  J.  Phys..  1905.  13,  45,  66  {normal  urines). 
Cathcart,  Bioch.  Z.,  1907,  6,  109  {in  starvation). 


1 1 78  BIBLIOGRAPHY 

Total  Nitrogen  Excretion  in  Normal  Persons. —  BARRi.sr.tR  (T.  B.  and  B.  S.), 
Am.  J.  Phys.,  mio,  27,  ii9- 

Urea  in  Urine. — Marshall,  J.  Biol.  Ch.,  1913, 14,  283  ;  ib.,  15,  495;  Van  Slyke 
uiul  C'l'LLKN,  ib.,  1914,  19,  211.  Van  Slykk,  ib.,  1916,  24,  117  {deter- 
}iii nation  by  urease  method). 

Ammonia  in  Urine. — Folin  and  Bell,  J.  Biol.  Ch.,  1917,  29,  329  [colorimeiric 
itttcnm nation).     Folin  and  Macallum,  ib.,  1912,  11,  323  {determination). 

Acidity  of  Urine. — Henderson  (L.  J.)  and  Palmer,  J.  Biol.  Ch.,  1912,  13, 
3>is;  "''■,  14,  81.     Henderson  and  Spiro,  Bioch.  Z.,  1908,  15,  105. 

Phenols. — Dubin,  J.  Biol.  Ch.,  1916,  26,  f>9  (physiology  of).  Folin  and  Denis, 
'''■.  5f'7  {relative  excretion  of,  by  Sidneys  and  iittesiine). 

Uric  Acid  Excretion.  Benedict  and  Hitchcock,  J.  Biol.  Ch.,  1915,  20,  C19; 
Folin  and  Denis,  ib.,  1912,  13,  363,  469  (colorimeiric  estimation  of  uric 
acid  in  xirine).  Hanzlik  and  Hawk,  ib.,  1908,  5,  355  (normal  men). 
Leathes,  J.  Phys.,  iyo6,  35,  125  (diurnal  and  nocturnal  variations). 
Mendel  and  Brown,  J.  Am.  .Med.  Ass.,  1907,  49,,  89*)  (rate  in  man). 
Mendel  and  Stehle,  J.  Biol.  Ch.,  1915,  22,  215  (role  of  digestive  glands  in 
excretion  of  endogenous).  Rockwood,  Am.  J.  Phys.,  1904,  12,  38 
{endogenous).  Wells  (H.  G.),  J.  Biol.  Ch.,  1916,  26,  319  (acciimtilalion 
in  tissues  in  suppression  of  urine). 

Alkaptonuria. — Dakin,  J.  Biol.  Ch.,  1911,  9,  151.  Garrod  and  Hartley, 
J.  Phys.,  1907,36, 136.  Garrod  and  Hele,  ib.,  1905-6,  33, 198.  Garrod 
and  Clarke,  Bioch.  J.,  1907,  2,  217.  R  a  wold  and  Warren,  J.  Biol. 
Ch,,  1909,  7,  465.     ScHULZ,  1-rgeb.  d.  Physiol.  (Bioch.),  1903,  180. 

Bile-Salts  in  Urine. ^ — Allen,  J.  Biol.  Ch.,  191 5,  22,  505  (Hay's  surface  tension 
method).     Grtjnbaum,  J.  Phys.,  1904,  30,  p-  xxvi. 

Bile-Pigments  in  Urine. — Hammarsten,  Skand.  Arch.  Phj's.,  9,  313.  Jolles 
(A.),  ib.,  10,  338;  Pfliiger's  Arch.,  1899,  75,  446.  Munk,  Arch.  f.  Phys., 
1898,  361.     ScHULz,  Ergcb.  d.  Physiol.  (Bioch),  1903,  174. 

Proteinuria. — Cameron  and  Wells,  Arch.  Int.  Med.,  1915,  15,  74;  Cloetta, 
Arch.  Exp.  Path.  Pharm.,  1S99,  42,  453  (origin  of  the  proteins).  Folin 
and  Denis,  J.  Biol.  Ch.,  1914,  18,  273;  Marshall,  Banks  and  Graves, 
Arch.  Int.  Med.,  1916, 18,  250  (estimation  of  the  proteins).  Sikes,  J.  Phys., 
1905-6,  33,  loi  (the  globulin  of"  albuminous  "  urine). 

Amino-Acids  in  Urine. — Benedict  and  Murlin,  J.  Biol.  Ch.,  191 3,  16,  365 
(determination  of  amino-acid  nitrogen).  Forssner,  Z.  f.  Physiol.  Ch., 
1906,  47,  15-  Hall  (I.  W.),  Bioch.  J.,  1906,  1,  241.  Levene  and  Van 
Slyke,  J.  Biol.  Ch.,  1912,  12,  301;  Van  Slyke,  ib.,  1913,  16,  125  (estima- 
tion).    Mutch,  J.  Phys.,  1914,  49,  p.  ii- 

Pentosuria. — Levene  and  La  Forge,  J.  Biol.  Ch.,  1913,  16,  4S1 ;  ib.,  1915, 18, 
319  (note  on  a  case).  Neuberg,  Ergcb.  d.  Physiol.  (Bioch.),  1904,  373 
(physiology  of  pentoses  and  glycuronic  acid). 

Heematoporphyrin  in  Urine. — Garrod,  J.  Phys.,  1892,  13,  598;  ib..  1894,  15, 
108;  ib.,  1894-5,  17,  349.     Schulz,  Ergeb.  d.  Physiol..  1903,  162. 

SECRETION  OF  URINE. 

CusHNY,  The  Secretion  of  Urine,  London,  191  7;  J.  Phys.,  1901-2,  27,  429; 
J.  Phys.,  1917,  51,  36  (excretion  of  urea  and  sugar).  Bainrridge  and 
Bedd.\rd,  Bioch.  J.,  1906,  1,  255  (secretion  by  renal  tubules  in  frog). 
Bainbridge,  Mrnzies  and  Collins,  J.  Phys.,  1914,  48,  233  (urine  forma- 
tion in  frog).  Barcroft  and  Straub,  ib.,  1910,  41,  145.  Barcroft  and 
Piper,  ib..  1915,  49,  p.  xiii  (in  decerebrate  animals).  Beddard,  ib.,  1902, 
28,  20  (ligation  of  renal  arteries  in  frog).  Boyd,  ib.,  1902,  28,  76  (extirpa- 
tion of  renal  medulla).  Brodie  and  Cullis,  ib.,  1906,  34,  224.  Brodie 
and  Mackenzie  (J.  J.),  Proc.  Roy.  Soc,  191 4.  B  87,  594  {changes  in 
glomentli  and  tubules  accompanying  activity).  Brodie,  ib.,  87,  571 
(glomerular  function).  Cow  (D.),  J.  Phys.,  19x4.  48,  i-  Cullis  (C.), 
J.  Phys.,  1906,  34,  250;  ib.,  1908,  37,  P-  xvi  (frog).     Folin  and  Denis, 


EXCRETION  1 1 79 

J.  Biol.  Ch.,  1915,  22,  321  {selective  activity  of  human  kidney).  Haskins, 
Am.  J.  Phys.,  1904,  10,  302;  Hatcher  and  Sollmann,  ib.,  1903,  8,  139 
(in  sttll-hiniger).  von  I'ukth,  Ergeb.  d.  Physiol.  (Hioch.).  1902,  395 
{urine  secntton  of  loivvr  animals).  Knowlton  (F.  P.),  J.  Phys.,  191 1, 
43,  219  {influence  of  colloids).  Isaacs  (R.),  Am.  J.  Phy.s.,  1917,  45,  71 
{reaction  of  kidney  colloids  and  renal  function).  Lindemann,  Z.  f.  Biol., 
1901,  42,  161  {elimination  of  glomeruli).  Gesell,  Am.  J.  Phys.,  1913, 
32,  70.  Hooker,  ib.,  1910,  27,  24  {relation  of  pulse  pressure  to  renal 
secretion).  Macallim  and  Benson,  J.  Biol.  Ch.,  1909.  6,  87  {composition 
of  dilute  renal  e.xcrctions).  Magnus,  Arch.  Exp.  Path.  Pharm.,  1901,  45, 
201  (in  plethora).  Quinby,  Am.  J.  Phys.,  1917,  42,  593;  J.  Exp.  iMt-d., 
1910,  23,  535  (denervated  kidney).  Richards  and  Plant,  Am.  J.  Phys., 
1017,  42,  592  (blood-pressure  and  urine  formation).  Sollmann,  Am.  J. 
Phys.,  1902,  8,  155.  Sollmann  and  Brown,  J.  Exp.  Med.,  6,  207 
(injection  of  egg-albumin,  etc.).  Sollmann,  Am.  J.  Phys.,  1905,  9,  425 
(chlorides  of  urine).  De  SotJZA,  J.  Phys.,  1900,  26,  139  (effects  of  venous 
obstruction).  Spiro  and  Vogt,  Ergeb.  d.  Physiol.  (Bioch.),  1902.  414. 
Spiko,  Arch.  Exp.  Path.  Pharm.,  1898,  41,  148  (action  of  artificial  concen- 
tration of  the  blood).  Sharpe,  Am.  J.  Phys.,  1912,  31,  75  (in  birds). 
Starling,  J.  Phys.,  1S99,  24,  317  (glomerular  function).  Underhill, 
Wells  and  Goldschmidt,  J.  Exp.  Med.,  1913.  18,  347  (renal  secretion 
during  tartrate  nephritis). 
Perfusion  of  Excised  Kidneys. — Richards  and  Plant,  J.  Pharm.  Exp.  Ther., 

1915.  7,  4S5.      Sollmann  (T.),  Am.  J.  Phys.,  1905,  13,  241;  ib.,  1907, 
19.  -53'.  '*-.  1908,  21,  37.     WiLLiATkis,  ib..  1907,  19,  252. 

Excretion  of  Pigment  by  the  Kidney. — Carter  (W.  S.),  J.  Am.  Med.  Ass., 
Nov.  21,  1903,  p.  1248.  GuKWiTSCH,  Pfluger's  Arch.,  1902,91,  71.  Hober 
and  Kempner,  Bioch.  Z.,  1908,  11,  105.  Hober  and  Konigsberg, 
Pfliiger's  Arch.,  1905,  108,  323.  Shaffer  (G.  D.),  Am.  J.  Ph3's.,  1908, 
22,  355-     Sobieranski,  Pfluger's  Arch.,  1903,  98, 135. 

Acid  Secretion  of  Kidney. — Cushny,  J.  Ph^'s.,  1904,  31,  188.  Dreser, 
Hofmeister's  Beit.,  1905,  6,  178.  Henderson  and  Palmer,  J.  Biol.  Ch., 
1914.17,305.     Henderson  (L.  J.),  i6.,  1911,  9,  403.     Trevan,  J.  Phys., 

1916,  50,  265. 

Reabsorption  from  Kidney. — Addis  and  Shevky,  Am.  J.  Phys.,  191 7,  43, 
363  (return  of  urea  from  kidney  to  blood).  Henderson  (V.  E.),  J.  Phys., 
1905-6,  33,  175- 

Saline,  Diuresis. — Cushny,  J.  Phys.,  1902,  28,  431.  Sollmann,  Am.  J.  Phj^s., 
1903,  9,  454.  Thompson  (W.  H.),  J.  Phys.,  1899-1900,  25,  487.  Win- 
field,  ib.,  1912,  45,  182  (osinotic  pressure  of  blood  and  urine  during  diuresis 
by  Ringer's  fluid).     Yagi  and  Kuroda,  ib.,  1915,  49,  162. 

Tests  of  Renal  Function. — Mosenthal,  J.  Am.  Med.  Ass.,  1916,  67,  933; 
Arch.  Int.  Med.,  1915,  16,  733.  Pepper  and  Austin,  Am.  J.  Med.  Sci., 
1913,  145,  254.  Rowntree  and  Geraghty,  J.  Pharm.  Exp.  Ther.,  1910, 
1,  579;  Arch.  Int.  Med.,  1912,  9,  284  (phenolsul phone phthalein  test). 

Urea  Excretion. — Ambard,  J.  Phys.  Path.  Gen.,  1910,  12,  209;  Ambard  and 
Weill,  ib.,  1912, 14,  753  ;  McLean.  J.  Exp.  Med.,  1915,  22,  212  (numerical 
laws  of  renal  secretion  of  urea  and  NaCl).  Addis  and  Watanabe,  J.  Biol. 
Ch.,  1916,  24,  203;i6.,  27,  249;i6.,  1917,29,  381.  399  (rate  of  urea  excretion) . 
Mendel  and  Lewis,  J.  Biol.  Ch.,  1913.  16,  19,  37,  55  (rate  of  nitrogen 
excretion  as  influenced  by  diet  factors). 

Nephrectomy,  etc. — Herter  and  Wakeman,  J.  Exp.  Med.,  1899,  4,  177. 
Jackson  and  Saiki,  Arch.  Int.  Med.,  1912,  9,  79.  MacNider,  J.  Med. 
Res.,  1911,24,425  (ligationof  one  branch  of  renal  artery).  Pilcher  (J.D.). 
J.  Biol.  Ch..  1913,  14,  3S9  (K-excretio*i  after  ligation  of  branches  of  renal 
arteries). 

Innervation  of  Kidney. — Asher  and  Pearce,  Z.  f.  Biol.,  1913,  63,  83 ;  Zentralb. 
f.  Physiol..  1913,  27,  584  (secretory  fibres).  Burton-Opitz,  Am.  J.  Phys., 
1916.  40,  437;  J.  Exp.  Med.,  191 1,  13,  308.     Burton-Opitz  and  Lucas, 


II60  BIBLIOGRAPHY 

Pfluger's  Arch.,  1909,  127,  143,  148.  Bradford  (J.  R),  J.  Phys.,  1889. 
10,  358  (vasomotors).  JosT  (W.),  Z.  f.  Biol.,  1914.  64,  441.  De  Souz.\, 
J.  Phys.,  1900,  26,  139- 

Innervation  of  Bladder.— B.\rrington,  Q.  T.  Kxp.  Phys.,  1913.  9,  -o. 
l-^LMOTT,  J.  Phys.,  1905-0,  33,  p.  xxix.  Knowlton.  ib.,  it^ii,  43,  'ii 
F.xc.GE,  ib.,  190V  28,  304.  L.\NGLEY.  ib.,  1901-2,  27,  -5-:;  ib..  1910.  40, 
p.  Ixii;  ib.,  1911,  43,  125.  Ott,  Zentralb.  f.  Physiol.,  189.5.  335  (centre). 
Stewart  (C.  C),  Am.  J.  Phy.s.,  1899,  2,  182;  ib..  1900,  3,  i.  Waddell, 
J.  Pliarm.  Exp.  Ther.,  191  7,  10,  243  (drugs). 

Excretion  by  Skin. — Benedict  (F.  G.).  J.  Biol.  Ch.,  1905,  1,  263  (nitrogenous 
matter).  Schwenkenbecher  and  Spitta,  Arch.  Exp.  Path.  Pharm., 
1907,  56,  2S4  (.VaC7  and  A).  Taylor  (A.  E.),  J.  Biol.  Ch.,  191 1,  9,  21 
(nitrogen,  sulphur,  phosphorus). 

Sweat. — Biggs,  J.  Med.  Res.,  1911,  24,  285;  Camerer,  Z.  f.  Biol.,  1901,  41, 
271  (chemistry  of  sweat).  O'Connor  (J.  M.),  J.  Phys.,  1915,  49,  113  (in- 
fluence of  temperature  on  sweat  secretion).  Wende  and  Bvsch,  J.  Am. 
Med.  Ass.,  1909,  53,  207  (localized  facial  sweating  following  olfactory 
stimuli) . 

CHAPTER  X. 

METABOLISM,  NUTRITION  AND  DIETETICS. 

LusK  The  Science  of  Nutrition.  Schryver,  Bioch.  J.,  1906.  1,  123  (chemical 
dynamics  of  animal  nutrition). 

CARBOHYDRATE  METABOLISM. 

Dakin  and  Dldlev,  J.  Biol.  Ch.,  1913,  14,  555.  Johannson,  Skand.  Arch. 
Phys.,  1908,  21,  I.  Woodyatt,  Harvey  Lecture,  New  York,  1915-16 
(intermediate  carbohydrate  metabolism). 

Dextrose. — Davis.  Am.  J.  Phys.,  191 7.  43,  514  (intravenous  injection). 
Macleod,  J.  Lab.  Clin.  Med..  1917,2,112  (utilization).  Kleiner,  J.  Exp. 
Med.,  1911,  14,  274  (excretion  in  stomach  and  intestine).  Janney  and 
CsONKA,  J.  Biol.  Ch.,  1915,  22,  203  (glucose  formation  from  body  proteins). 
Mathews  (A.  P.),  J.  Biol.  Ch..  1909,  6,  3  (spontaneous  oxidation  of  sugars). 
LusK,  Am.  J.  Phys.,  1908,  22,  174.  Ringer,  J.  Biol.  Ch.,  1912,  12,  511; 
Stiles  and  Lusk,'  Am.  J.  Phys.,  1903,  9,  380  (formation  from  amino-acids). 
Macleod  and  Fllk,  Am.  J.  Phys.,  191 7.  42,  193  (retention  of  dextrose  by 
liver  and  muscles). 

Glycogen. — Botazzi  and  d'Errico,  Pfluger's  Arch.,  1906,  115,  159  (physico- 
chemical  experiments).  Cremer,  Ergeb.  d.  Phys.  (Bioch.),  1902,  803 
(physiology  of  glycogen).  Huber  and  Macleod.  Am.  J.  Phys.,  1917,  42, 
619;  Macleod,  Soc.  Exp.  Biol.  Med.,  191 7.  14,  124;  Kalkmann,  Compt. 
Rend.  Soc.  Biol.,  1895,  317  (glycogen  in  bloodvessels  of  liver).  Langstein, 
Ergeb.  d.  Phys.  (Bioch.),  1904.  453  (formation  of  carbohydrate  from  protein). 
Lusk,  Am.  J.  Phys.,  1911.  27,  427  (cold  baths  and  glycogen  content). 
Macleod  and  Pearce,  Am.  J.  Phys.,  1911,  27,  341:  ^f>--  1915.  88,  425 
{sugar-retaining  power  and  glycogen  content  of  liver).  Pfluger  (E.). 
Pfluger's  Arch.,  1902,  91,  119;  ifc.,  1903.  96,  i  (monograph  on  glycogen): 
ib.,  1903,  93,  165  (directions  for  estimation);  ib.,  1904.  103,  169  (abbreviated 
method).  Rusk,  Soc.  Exp.  Biol.  Med.,  1912,  12,  21  (comparison  of 
chemical  and  microchemical  methods). 

Glycogenesis. — Epstein  and  Baehr.  J.  Biol.  Chem.,  1916,  24,  17  (influence 
ofphlorhiziyi).  Hatcher  and  Wolf,  ib..  1907.  3,  25  (formation  of  glycogen 
in  muscle).  Macleod,  Soc.  Exp.  Biol.  Med.,  1916,  13,  169  (influence  of 
alkali).  McGuigan,  J.  Pharm.  Exp.  Ther.,  1916,  8,  407  (influence  of 
atropin  and  pilocarpin).  McDanell  and  Underbill,  J.  Biol.  Ch.. 
191 7,  29,  255  (relation  of  diet  to  glycogen  content  of  liver).  Pfluger  (E.). 
Pfluger's  Arch.,  1907.  120,  2^1  (in  starvation) 


METABOLISM.  KUTRinON  AND  DIETETICS  ii8t 

Glycogenolysis. — Bang,  Bioch.  Z.,  1913,  49,  40,  81 ;  Macleod  and  Ruh,  Am.  J. 
Phys.,  1908.  22,  397  (splanchnic  stimulation).  Macleou,  ib.,  22,  3  73 
{glycogenolytic  fibres  in  splanchnic  ?).  Macleod  and  Pearce,  16.,  1911,  2i8, 
403  (glycogenase).  Neilson  and  Terrv,  ib..  1905,  14,  105.  Paw,  J. 
Phys..  1898,  22,  391.  Paton  (D.  N.),  J.  Phys.,  1899,  24,  36  {sugar 
formation  in  liver).     Taylor,  J.  Biol.  Ch.,  1908,  5,  315- 

Blood-Sugar  Content  Methods.— Fitz  (R.),  Arch.  Int.  Med.,  1914,  14,  133 
(Bang  and  Btiliund  ,net)iods  compared).  Lewis  and  Benedict  (S.  R.), 
J.  Biol.  Chein..  1915  20,  61.  Macleod,  J.  Lab.  Clin.  Med.,  1916,  1,  445 
{rtsumi).  McGuiGAN  and  Ross,  J.  Biol.  Ch.,  191 7.  31,  533  (Benedict 
and  Bertrand  methods  compared).  Morris,  J.  Lab.  Clin.  Med.,  191 6,  1, 
208,  252.  Myers  and  Bailey,  J.  Biol.  Ch.,  1916,  24,  147.  Pearce,  ib., 
1915,  22,  525.  Scott  (E.  L).  Am.  J.  Phys.,  1914,  34,  271.  Shaffer, 
J.  Biol.  Ch..  1914,  19,  285,  297. 

Blood-Sugar  Content. — Epstein  and  Aschner,  J.  Biol.  Ch.,  1916.  25,  151. 
{psychic  and  sensory  stimuli).  Graham,  J.  Phys.,  1916,  50,  285. 
Kramer  and  Coffin,  J.  Biol.  Ch.,  1916,  25,  423  (psychic  and  sensory 
stimuli).  Macleod  and  Wedd,  ib.,  1914,  18,  447  (in  hepatic  vein). 
McGuigan,  Am.  J.  Phys.,  1916,  39,  4S0.  Lee  and  Scott,  ib..  1917,  40, 
486.  Macleod,  ib.,  1909,  23,  278  (asphyxia).  Macleod  and  Pearce, 
ib.,  1915,  38,  415.  McDanell  and  Underhill,  J.  Biol.  Ch.,  1917,  29, 
227,  233,  265  (alkali).  RoNA  and  Michaelis,  Bioch.  Z..  1908,  14,  476; 
ib.,  1909,  16,  60  (partition  between  corpuscles  and  plasma)  Ross  and 
McGuigan,  J.  Biol.  Ch.,   1915,  22,  407  (ether  ancssthesia). 

Glycolysis. — Cohnheim,  Z.  Physiol.  Ch.,  1903.  39,  336;  ib.,  1904,  42,  401;  ib., 
1905.  43,  547;  ib..  190O.  47,  253;  TucKETT,  J.  Phys.,  1910,  41,  89;  Claus 
and  Embden,  Hofmeister's  Beit.,  1905.  5,  214;  ib.,  1906,  6,  343;  Levene 
and  Meyer,  J.  Biol.  Ch..  1911.  9,  97;  ib..  1912,  11,  347;  McGuigan,  Am. 
J.  Phys.,  1908,  21,  351  (muscle  and  pancreas).  Levene  and  Meyer,  J. 
Biol.  Ch.,  1912,  11,  353  (action  of  tissues  on  glucose);  ib.,  1912,  11,  361 
(leucocytes) . 

Blood  Glycolysis. — Arthus,  Arch.  dePhys..  1891,  425.  Lupine,  J.  Biol.  Ch.. 
1913.  16,  559.  ;\LvcLEOD,  J.  Biol.  Ch..  1913,  15,  497-  Macleod  and 
Pearce,  Am.  J.  Phys.,  1914,  33,  378.  Pavy  and  Siau,  J.  Phys.,  1901-2, 
27,  451.     AL-vckenzie  (G.  M.),  J.  Exp.  Med..  1915.  22,  757. 

HYPERGLTCSIMIAS  AND  GLYCOSURIAS. 

Brown  (O.  H.),  Am.  J.  Phys.,  1904,  10,  378  (effect  of  Ca  on  glycosuria). 
Edie.  Bioch.  J.,  1906.  r,  455  (excess  of  CO^  in  air).  Henderson  and 
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Salt  Glycosuria.— Burnett.  J.  Biol.  Ch..  1908,  5,  35i-  Fischer  (M.), 
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Adrenalin  Glycosuria. — Blum,  Pfluger's  Arch..  1902,  90,  617.  Herter  and 
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1182  BIBLIOGRAPHY 

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1912,  45,  470;  Patterson  and  Starling,  ib.,  1913.  47,  137;  Knowlton 
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human  heart). 


METABOLISM,  KUlRlllUS  A.\D  DILTETILS  il8j 

Diabetes  Mellitus.— Allkn.  Studies  concerning  Glyco.siuia  and  Diabetes. 
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Diabetes  Insipidus. — Christie  and  Stewart.  Arch.  Int.  Med.,  191  7.  20,  10. 
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1184  BIBLIOGRAPHY 

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METABOLISM  OF  FAT. 

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growth) . 


MLIAUOIISM,    SllUlllOS   ASP   I)H:ILT1CS  il8s 


METABOLISM  OF  PROTEINS. 

CATHCARTundClKi;,  N  lii.uli  I  i.ii  ;.7,  I  [Kil<  <if  /■niliinciiltibalisni):  }.  Pliys.. 
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491.  Foster  (X.  B.),  Arch.  Int.  .Med.,  1913.  15,  35<i.  Pepper  and 
Austin,  J.  Biol.  Ch.,  1915,  22,  Si.  Greenwalu,  J.  Biol.  Ch.,  1916,  21, 
61.  Welker  and  Falls,  ib..  1910.  25,  5O7.  Taylor  and  Hulton, 
ib.,   1913,  22,  63. 

Amino-Acids.  Dakin,  J.  Biol.  Ch.,  1905,  1,  171;  ib..  1908,  4,  63;  Denis, 
J.  liiul-  Ch.,  1911,  9,  j!b5 ;  ib.,  1911,  10,  73  (oxidation  of  aniino-acid's).. 
Folin,  J  .  Am.  Med.  Ass.,  191  7,  69,  1209  (resume).  Abderhaloen  et  al., 
Z.  Phys.  Ch.,  1906,  47,  391;  lb..  48,  357;  //'.,  51,  311,  323  (decomposition 
of  amino-acids  in  the  body).  Hardinc;  and  Maclean,  J.  Biol.  Ch.,  1916, 
25,  337  {ninhydrin  reaction).  Folin  and  Denis,  J.  Biol.  Ch.,  1912,  12: 
141 ;  Wishart  (M.  B.),  ib.,  1915,  20,  533  (amino-acids  in  blood  and  tissues). 
Harding  and  Maclean,  ib.,  1916.  24,  503;  Van  Slyke,  ib.,  1912.  12, 
273;  ib.,  1913.  16,  121;  ib.,  1913,  23,  407  (amino-acids,  amino-nitrogen, 
estimation  of).  Osborne  and  Jones,  Am.  J.  Phys.,  1910,  26,  212 
(amino-acids  in  proteins).  Osborne  and  Mendel,  J.  Biol.  Ch.,  1914,  17, 
325  (amino-acids  in  nutrition  and  growth).  Van  Slyke,  Arch.  Int.  Med., 
IQ17,  19,  56  (amino-acids  in  physiology  and  pathology,  resumi).  Van 
Slyke  and  Meyer,  J.  Biol.  Ch.,  1912.  12,  399;  ib.,  1913,  16,  197,  231 
(amino-acid  nitrogen  of  blood).  Gyoroy  and  Zunz,  J.  Biol.  Ch.,  1913, 
21,  511  (amino-acid  nitrogen  in  blood). 

Intermediary  Metabolism  of  Amino-Acids. — Dakin,  J.  Biol.  Ch.,  1913,  14, 
3JI.  Greenwald,  J.  Biol.  C'h..  im<),  25,  Si ;  Lusk,  Z.  Physiol.  Ch.,  1910, 
66,  106;  KiNGER,  J.  Biol.  Ch..  1912,  12,  223  (production  of  dextrose  from 
amino  acids).  Janney,  J.  Biol.  Ch.,  1913,  22,  191 ;  Csonka,  J.  Biol.  Ch., 
1913,  20,  339  (rate  of  metabolism  of  amino-acids).  Levene  and  Meyer, 
Am.  J.  Phys.,  1909,  25,  214  (elimination  of  nitrogen,  etc.,  after  administra- 
tion of  some  amino-acids).  Macleod,  J.  Lab.  Clin.  Med.,  1915,  1,  112 
(resume).  Lusk,  J.  Am.  Chem.  Soc.  1910,  32,  671  (fate  of  amino-acids  in 
organism).  Matthews  (S.  A.)  and  Nelson,  J.  Biol.  Ch.,  1914,  19,  229 
(fate  in  muscular  tissue).  Wakeman  and  Dakin,  ib..  1911,  9,  139.  Van 
Slyke  and  Meyer,  J.  Biol.  Ch.,  1913,  16,  213;  Woelfel,  Am.  J.  Phys., 
iqij.  29,  p.  xxxviii  (locus  of  transformation  of  absorbed  amino-acids). 

Arginine  Metabolism.— Dakin,  J.  Biol.  Ch.,  1907,  3,  433;  Kossel  and  Dakin, 
Z.  Physiol.  Ch.,  1904,  41,  321  (arginase).  Thompson,  J.  Phys.,  1903,  82, 
137;  ib.,  1905-6,  33,  106;  ib..  1917,  51,  III,  347- 

Tryptophane. — Hopkins  and  Cole,  J.  Phys..  1903,  29,  431  (constitution). 
WiiLCocK  and  Hopkins,  J.  Phys.,  1906  35,  88  (m  nutrition).  Dakin, 
J.  Biol.  Ch.,  1906,  2,  289;  Hopkins  and  Cole,  Proc.  Roy.  Soc.  (Lond.), 

75 


Iib(*  BlBLlOGliAPHY 

1901,    n  68,   23    [glyoxylic  acid  teacttou  for).      L'M'EKHILL,    Vale    Univ. 
l^iL-^h.  iiri)    PhVMology  of  Aniiuo-acjds. 
Cystiu.   Cystein. — .Mathhws  and  Walkkk,  J.  Biol.  Ch..  lyoy,  6,  21,  29,  289. 
^it<)  [iffontunecnis  oxidation  of  cystein).     Kotheka.  J.  Phys.,  I905,  32,  175; 
Lewis  (H.  B.).  J-  BioI.Ch.,  1917,31,  3O3  (cystxn  and  metabolism) .     Abder- 
HALDEN  and  ScHiTTENHELM.  Z.  Physiol.  Ch.,  1903.  45,  468;  Garrod  and 
Hurtley,  J.  Phys.,  lyoO,  34,  217.     Alsberg  and  Folin,  Am.  J.  Phys., 
1905,  14,  34;  Hele,  J.  Phys.,  1909,  39,  52;  Simon,  Z.  Physiol.  Ch.,  1905, 
45,  357,   Williams  and  Wolf.  J.  Biol.  Ch.,   1909,  6,  337;  Wolf  and 
Shaffer,  J.  Biol.Ch.,  iqoH,  ^, .^T^g  (protein  metabolism  in  cystinuria) . 
Hippuric   Acid   Synthesis. — Epstein  and  Bookman,  J.   Biol.   Ch..    191 1,  10, 
^33  ;  (^..  H(i  2.  13,  117;/^.,  1 91 4,  17,  455  [formation  of  glycocoll  in  the  body). 
KiNt.sBiRY  and  Bell,  ib.,  1915,  20,  73  (in  tartrate  nephritis);  ib.,   1915. 
21,  297  [after  nephrectomy).     Lewis  (h.  B.),  ib..  1914,  17,  503  (on  glyco- 
coU-free diet) ;  ib.,  1914, 18,  223  [after  benzoate in  ma7i).     PARKERand  Lusk. 
Am.  J.  Phys.,  1900,  3,  402;  Kinger,  J.  Biol.  Ch.,  1911,  10,  327  (maximum 
production).      Kaiziss  and  Dl  bin.  J.  Biol.  Ch.,  1913,  21,  331. 
Lactic  Acid  in  Intermediary  Metabolism  — Asher  and  Jackson,  Z.  f.  Biol., 
i\ioi.   41,   393       Levkne  and  Mevkk,   J.  Biol.  Ch.,    1913.  14,  149.   551 
(lactic  acid  from  carbohydrates).     Macleod  and  Hoover   (D.   H.),   Am. 
J.  Phys.,  191 7,  42,  460  (lactic  acid  prodtution  in  blood  after  injection  of 
aikali).     Macleod  and  Wedd,  J.  Biol.  Ch.,  1914.  18,  447  [sugar  and  lactic 
acid  in  liver  blood).     Mandel  and  Lusk,  Am.  J.  Phys.,  1906,  16,  129; 
Ryffel,  J.  Phys.,  1909,  39,  p.  xxix  (lactic  acid  formation  in  man). 
Urea  in  Blood. — Folin  and  Denis,  J.  Biol.  Ch.,  191 2,  11,  527;  ib.,  1916,  26, 
305.     Lewis  and  Karr.  ib.,  1916.  28,  17-     McLean  and  Selling,  ib.. 
1914.  19,  31.     Marshall,  ib.,  1913,  15,  487. 
Ammonia  in  Blood. — ^Fiske  and  Karsner.  J.  Biol.  Ch.,  1914. 18,  381  (destruc- 
tive lesions  of  liver  and  reduced  ammonia  in  blood).     Folin  and  Denis, 
ib.,  1912.  11,  161.  527.     Jacobson  (C.),  ib..  1914,  18,  133;  Am.  J.  Phys  . 
1910.  26,  407.     Salaskin  et  al..  Z.  Physiol.  Ch.,  1902.  35,  246.  552. 
Taylor  and   Ringer,  J.  Biol.  Ch.,  1913,  14,  407  (ammonia  in  protein 
metabolism). 
Urea  Formation. — Bostock  (G.  D.),  Bioch.  J.,  191 1,  6,  388  (deamidization). 
Djyon  and  Dufox'RT.  Arch,  de  Phys..  1898.  322  [ligation  of  hepatic  artery 
and  portal  vei.i).     Fiske  and  Karsner,  J.  Biol.  Ch.,  191  3,  16,  399  [per- 
fusion of  liver  with  ammonium  carbonate  and  with  glycocoll).     Fiske  and 
Summer,  ib.,  1914.  18,  285;  Jansen,  ib.,  1913,  21,  557;  Salaskin.  Z.  f. 
Physiol.  Ch.,  1898,  25,  128  (from  amino-acids  in  liver).     Folin  andDENis, 
J.  Biol.  Ch..  1912,  12,  141.     HoAGLAND  and  Mansfield,  ib.,  191 7,  31, 
487    (muscular    tissue    and   urea  formation).     Macleod    and    Haskins, 
16..  1906,  1,  319  [carbamates) .     Matthews  and  Miller,  ib.  1913.  15,  87 
(liver  circulation  and  nitrogen  metabolism).     Halsey,  Z.  Physiol.  Ch.,  1898, 
25,   325    (prjcursors  of  urea).     Jacoby   (M.).   Ergeb.   d.   Phys.    (Bioch.), 
1902,  332.     Taylor  and  Lewis.  J.  Biol.  Ch.,  1915.  22,  17  (predominance 
of  liver).     Wakeman  and  Dakin.  J.  Biol.  Ch.,  1911.  9,  327  (relationship 
hetiv&en  urea  and  ammonium  salts).     Van  Slyke.  Cullen  and  McLean, 
Soc.  Exp.  Biol.  Med.,  1915.  12,  93  (liver). 
Purin  Metabolism. — AcKROVoand  Hopkins,  Bioch.  J.,  1916.  10,  551  (arginin 
and   hislidin    as   possible   precursors    of  purins).     Burian    and    Schur, 
Pfliiger's  Arch.,  1900,  80,  241;  ib.,  1901,  87,   239;  ib.,    1903,   94,   273   (tn 
man).     Hunter  (A.),  J.  Biol.  Ch.,  1914.  18,  107;  Hunter  and  Givens, 
ib.,   1912,  13,  371;  lb.,   1914,  17,  37  [monkey).     Hunter.  Givens  and 
GuioN,  ib.,  1914, 18,  387  (marsupials,  rodents  and carnivora) .     Kennaway. 
J.  Phys..  1908.  38,  I  (effect  of  muscular  work).     Macleod  and  Haskins. 
J.  Biol.  Ch..  190G,  2,  231  (man).     Wells  (H.  G.).  J.  Biol.  Ch..  1909.  7, 
171  (monkey);  J.  Lab.  Clin.  Med.,  1916.  1,  164. 
Poiin  Enzymes. — Jones  (W.),  Z.  Physiol.  Ch.,  1905,  45,  84  iguanase  in  spleen). 
Caldwell  and  Wells,  J.  Biol.  Ch.,  1914,  18,  137:  '''     19,  2-9.     Long. 
ib..  191  \.  15,  449  (adenase).     Rohde  and  Jones,  ib.,  1909,  7,  237. 


MliT.lIiOl.lSM.   MTh'iriOS'  AMJ  DUiTI'.TICS  1187 

Allantoiu. — Huntek  (A.).  J.  Biol.  Ch  .  KJ17.  28,  3<»'j  (in  hlood).  Givens, 
('' .  I'M  J.  18,  ji;  Mkndel  and  Whitk.  Am.  J.  Phys..  iwo^.  12,  85 
(fni'i/iicliun  in  the  body). 

Uric  Acid  in  Blood,  -liiiNKDicT  {S.  K.),  J.  Biol.  Ch.,  1915,  20,  533  (ox  and 
chickiu).  Dknis,  J.  Biol.  Ch.,  1915,  23,  147  (effect  of  ingested  purins). 
I'INE  and  CiiALE,  J.  Pharm.  iCxp.  'Ihcr.,  1914,  6,  219;  I-olin  and  Denis, 
J.  Biol.  Ch.,  1913.  14,  29  (uric  acid,  urea  and  non-prolein  nitrogen  in 
blood).  FoLiN  and  Denis,  Arch.  Int.  Med.,  1915,  16,  },i.  Slemons  and 
BoGERT,  J.  Biol.  Ch.,  i«>i7,  32,  03  (maternal  and fcetal  blood). 

Uric  Acid  Metabolism.  Cathcakt  and  Leathes.  Prcic.  Roy.  See.  (Lond.), 
IQ07,  H  79,  341  [relation  between  uric  acid  output  and  heat  production). 
Ckoftan,  I'tliiger's  Arch.,  1908,  121,  377.  Benedict  (S.  R.).  J.  Lab. 
Clin.  -Med..  1916,  2,  i.  Raiziss,  Duuin  and  Rin(;er.  J.  Biol.  Ch..  1914, 
19,  473  (endogenous).  Wiener,  Ergeb.  d.  Phys.  (Bioch.),  1902,  555; 
;/'..  11)03.  377  [in  pathology). 

Uric  Acid  Formation.^ — Cathcakt,  Kennaway  and  Leathes,  Q.  J.  Med.,  1908, 
1,  410;  Stehle,  Soc.  Exp.  Biol.  Med.,  1915,  12,  148  (origiri  of  endogenous). 
Jerome,  J.  Phys.,  1898,  22,  146  (influence  of  diet).  Milroy  (T.  H.), 
J.  Phys..  1903,  30,  47  (in  birds).  Plimmer,  Dick  and  Lieb,  ib.,  1909,39, 
98  (origin).  Taylor  and  Ross,  J.  Biol.  Ch.,  1914,  18,  519  (influence  of 
protein  intake). 

Uricolysis. — Fine  (M.  S.),  J.  Biol.  Ch.,  1915,  23,  471  (non-destructibiliiy  of 
uric  acid  in  man).  Schittenhelm,  Z.  Physiol.  Ch.,  1905,  45,  161  (urico- 
lytic  ferments).  Taylor  and  Adolph,  J.  Biol.  Ch.,  1914,18,521.  Taylor 
and  Rose,  J.  Biol.  Ch.,  1913,  14,  419;  Wiechowski,  Arch.  Exp,  Path. 
Pharm.,  1909,  60,  185  (in  man). 

Metabolism  of  Nucleins. — Abderhalden  and  Schittenhelm,  Z.  f.  Physiol- 
Ch.,  1906,  47,  452  (formation  and  decomposition  ofmichic  acids  in  the  body). 
Jones  (W.),  J.  Biol.  Ch.,  1908,  5,  i  (identity  of  nucleic  acids  of  thymus, 
spleen  and  pancreas) .  Jones  and  Austrian,  Z.  Physiol.  Ch.,  1906,  48, 
no;  Schittenhelm  and  Schmid,  Z.  Physiol.  Ch.,  1906-7,  50,  30  (ferments 
of  nuclein  metabolism).  Jones  (W.),  J.  Biol.  Ch.,  1911,  9,  169  (des 
amidases).  Jones,  ib-,  1911,  9,  129;  Levene  and  La  Forge,  ib.,  1912, 
13,  507;  Levene  and  Medigreceanu,  ib.,  1911,  9,  65,  389  (nucleases). 
McCollum,  Am.  J.  Phys.,  1909,  25,  120  (nuclein  synthesis  in  the  body). 
Milroy  and  Malcolm,  J.  Phys.,  1898-9,  23,  217  (metabolism  of  nucleins) ; 
ib.,  1899,  25,  105  (in  leucocythcBmia).  Sweet  and  Levene.  J.  Exp.  Med., 
1907,  9,  229  (nuclein  metabolism  with  Eck's fistula).  Givens  and  Hunter, 
J.  Biol.  Ch.,  1913.  23,  299  (sodium  nucleate). 

Creatin  and  Creatinin  Metabolism. — Folin,  J.  Biol.  Ch.,  1914,  17,  469  (deter- 
mination in  urine);  ib.,  19x4,  17,  47.5  (determination  in  blood,  milk,  and 
tissues).  Folin  and  Denis.  i6.,  igi:{.  17,  ^8j  (content  of  blood);  ib.,  1914, 
17,  493  (in  relation  to  metabolism).  Foster  (N.  B.)  and  Fisher,  ib.. 
191 1,  9,  359  (with  Eck's  fistula).  Mellanby  (E.),  J.  Phys.,  1907-8,  36, 
447.  Mendel  and  Rose,  J.  Biol.  Ch.,  1911,10,213  (rdle  of  carbohydrates)'. 
Graham  and  Poulton,  J.  Phys.,  1914,  48,p.liii  (in  starvation).  Shaffer, 
Am.  J.  Phys.,  1908,  23,  i  {in  health  and  disease)  ;  J.  Bil.  Ch.,  1914,  18, 
525.  TowLES  and  Voegtlin,  J.  Biol.  Ch.,  1911,  10,  479  (function  of 
liver).     Wolf,  ib.,  1911,  10,  473. 

Creatinin. — Benedict  and  Myers,  Am.  J.  Phys.,  1907,  18,  377;  Tracy  and 
Clark,  J.  Biol.  Ch.,  1914,  19,  115  (elimination  in  woman).  Amberg  and 
Morrill,  J.  Biol.  Ch.,  1907,  3,  311  (in  new-born  infant).  Levene  and 
Kristellar.  Am.  J.  Phys..  1909,  24,  45  (factors  regulating  output  in  man). 
Myers  and  Fine,  J.  Biol.  Ch.,  1914,  17,  65;  ib..  1915,  21,  383;  Scott 
(E.  L.)  and  Spohn,  Am.  J.  Phys.,  191 7,  42,  600  (in  muscles).  Palmer, 
J.  Biol.  Ch.,  1914,  19,  239  (basal  metabolism  and  creatinin  elimination). 
Ringer  and  Raiziss,  J.  Biol.  Ch.,  1914,  19,  487  (excretion  of  creatinin  ivith 
creatin-free  diet).  Rockwood  and  Van  Epps,  Am.  J.  Phys.,  1907,  19 
97  (influence  of  drugs  on  elimination  of  creatinin). 


1 1 88  Illlil.KX.RAl'llY 

Creatin:  CreatiD  Content  of  Muscle. — Brown  and  Cathcart,  Bioch.  J.,  i90y, 
4,  420  [work).  Dknis.  J.  Biol.  Ch.,  1916,  26,  379.  Folin  and  Blckman, 
J.  Biol.  Oil.,  u>i.i,  17,  |«3  MiNOKL  and  KosE.  ih..  utix.  10,  255; 
Mykrs  and  Fink,  /7^.,iyi  ^  13,  2S3  [starvation);  ib.,  lyij,  14,  9.  1  homi'- 
SON,  J  .  Phys.,  i9i(),  50,  p  liii  (excitation  of  motor  nerve). 

Creatin:  Creatin  Estimation.  -Baumann  and  Hinks,  J.  Biol.  Ch..  191O,  24, 
.431).  li.M  .MA.NN  aiul  1n*.valdsen,  ib..  19K),  26,  195.  Benedict  (S.  K.), 
ib..  191 4.  18,  iMi  J.vNNEYand  Blatherwick,  ib.,  1915,21,  5O7.  Kose, 
ib.,  1912,  12,  73.      Walpole,  J.  Phys.,  1911,  42,  301. 

Creatin:  Creatinuria.  Dhms  and  Minot,  J.  Biol.  Ch.,  1917,  31,  561  {normal 
adults).  Foi.iN  and  Denis,  ib..  191 2,  11,  253  (children).  Kral'se  and 
Cramer,  (j.  J.  Exp.  Phys.,  1910,  3,  289;  tb.,  1911,  4,  293  (m  women). 
Rose,  J.  Biol.  Ch.,  1917,  32,  i  (women).  McCrvdden  and  Sargent, 
ib.,  1916,  24,  423.     Taylor  (A.  E.),  ib.,  1915,  21,  663. 

Creatin  :  Creatin  Metabolism. — Balmann  and  Marker,  J.  Biol.  Ch.,  1915,  22, 
49  (origni  uj  cifutin).  Benedict  (S.  K.)  and  Osterberg,  ib..  1914,  18, 
195  (origin  of  urinary  creatin).  AIcCollcm  and  Steenbock,  ib.,  1912, 
13,  209  (growing  pig).  Myers  and  Fine,  ib.,  1915,  21,  377  (file  of  creatin 
administered  to  )nan).  Paton  and  Mackie,  J.  Phys.,  1912,  45,  115 
(liver).  Koss,  Dimmitt  and  Cheetham.  J.  Biol.  Ch.,  191O,  26,  339  {pro- 
tein feeding  and  creatin  elimination  in  fasting  man).  Kowe,  Am.  J.  Phys., 
1912.  31,  i'><(  (creatin-splitting  enzyme).  Twort  and  Mellanby,  J. 
Phys.,  1912,  44,  43  (creattn-destroying  bacilli  in  intestine). 

Autolysis. — BosTocK,  Bioch.  J.,  1912,  6-  Bradley,  J.  Biol.  Ch.,  1916,  25, 
joi.  Bradley  and  Taylor,  ib.,  25,  261  (effect  of  reaction);  ib.,  191 7, 
29,  281  (effect  of  bile).  Jackson  (H.  C),  J.  Exp.  Med.,  1909,  11,  55. 
Dochez,  J.  Exp.  Med.,  1910,  12,  666  (liver).  Jacoby,  Ergeb.  d.  Phys. 
(Bioch.),  1902,  213.  Levene,  Am.  J.  Phys.,  1904,  11,  437;  ib.,  1904,  12, 
276.  Lane-Clay'ton  and  Schryver,  J.  Phys.,  1904,  31,  169.  Benson 
and  Wells,  J.  Biol.  Ch.,  1910,  8,  61;  Stewart  (G.  X.).  J.  Exp.  Med., 
1899,  4,  235.  (aittolysis  studied  by  physico.-chemical  methods).  Mendel 
and  Leavenworth.  Am.  J.  Phys.,  1908,  21,  69  (embryo).  Morse,  J.  Biol. 
Ch.,  1916.  24,  163 ;  191  7.  30,  197  (reaction) ;  1917.  31,  303  (spleen) ;  Am.  J. 
Phys.,  1915,  36,  143  (in  involution);  J.  Lab.  Clin.  Med..  1917,  2,  506 
(resume).  Tatvm,  j.  Biol.  Ch.,  1916,  27,  243.  Schryver,  Bioch.  J.. 
1906,  1,  123.  Schryver,  J.  Phys..  1905,  32,  150;  Wells  and  Benson, 
J.  Biol.  Ch..  11)07,  3,  35  (influence  (f  thyroid). 

Protein  Metabolism  after  Removal  of  Portions  of  Intestine. — Carrel,  Meyer 
and  Levene,  Am.  J.  Phys.,  1910,  25,  439;  »''  .  26,  369.  Erlanger  and 
Hewlett,  ib..  1902,  6,  i-  Levin,  ^Manson  and  Levene,  ib.,  1909,  25, 
231.     Underhill,  ib..  1911,  27,  366. 

Assimilation  of  Protein.^ — Abderhalden,  Funk  and  London,  Z.  Physiol.  Ch., 
i<>o7.  51,  2()<).     Pkin(,i-k  and  Cramer,  J.  Phys.,  1908,  37,  158. 

Parenterally  Introduced  Substances. — Austin  and  Eisenbrey,  Arch.  Int 
Med.,  1912, 10,  305  (utilization  of  serum).  Michaelis  and  Rona,  Pfliiger's 
Arch.,  1907,  121,  163  (protein).  Hogan,  J.  Biol.  Ch..  igi4.  18,  4S3: 
Kuriyama,  ib.,  1916,  25,  521;  Am.  J.  Phys.,  191  7.  43,  343;  Mendel  and 
Kleiner,  Am.  J.  Phys.,  1910,  26,  396  (utilization  of  sucrose). 

INORGANIC  SALTS. 

Calcium. — Bergeim,  Stewart  and  Hawk,  J.  Exp.  Med.,  1914.  20,  225  (Ca 
metabolism  after  thyroparathyroidectomy).  Lyman.  J.  Biol.  Ch.,  1013.  21, 
531  (estimation  in  urine  and fcBces) ;  ib.,  191  7.  29,  i<)9:  '''  .  30,  i  (in  blood). 
Malcolm  (J.),  J.  Phys.,  1903,  32,  183  (Ca  and  Mg  relationship).  Mendel 
and  Benedict  (S.  R.1.  Am.  j.  Phys.,  1909.  25,  i},  (Ca  r.xcretion).  Nelson 
and  Williams,  J.  Biol.  Ch.,  1916,  28,  231  (Ca  in  urine  and  faces).  Patter- 
son, Bioch.,  j.  1908,  3,  39  (Ca  metabolism). 


METABOLISM.  i\'UTHllIO\  A.\U  DIETETICS  1189 

Phosphorus. — Hart.  McCollum  and  Filler.  Am.  J.  Phys.,  i<)oy.  23,  ^4'' 
\toif  of  inorganic  I'  in  nutrition).  Lisk  Am.  J.  I'hys..  1907,  19,  \*>i 
(infiuence  on  tueluhnlisni).  Nasmiih  and  Fiulkk,  J.  I'hy.s.,  iyo,s.  37,  -7^- 
Paton.  DiNLop.  Ckawforu  and  ArrcjiisoN.  J.  Phys.,  ibyu,  26,  J«^ 
(P  metaholism).  Scott  (F.  H.).  ib..  lyoO-j,  86,  iiy  (histo-chemical 
methods  for  detection).  Weber,  Ergeb.  d.  Phys.  (Bioch.).  1904.  284 
(infiuence  on  metaholism). 

Iron.— Abdekhaluen.  Z.  f.  Biol..  1900,  39,  487;  Kinkel,  Pflijger's  Arch., 
1895.  61.  595  (blood -formation).  Di'bin  and  Pearce.  J.  Exp.  Med.. 
1917.  26,  075  (distribution  in  anccmia).  Macalli.m  (A.  B.).  J.  Phys.. 
1897.  22,  y^  {micro-chemical  reaction).  Stock.man,  J.  Phys..  1895,  18, 
484  (in  fond).     Stockman  and  Gkeu;.  ib.,  iSij-,  21,  35. 

Metabolism,  Qaantitative  Data.— Benedict  and  Hom.  J.  Biol.  Ch.,  Kjij. 
20,  ^u  (vegetarians).  Benedict  and  Smith,  ib..  njij.  20,  -:43  (athletes). 
DiNLoi'.  J.  Phys.,  i8yO,  20,  82  (action  of  acids).  Goodhouv,  Bardswell 
and  Chapman,  J.  Phys.,  lyoj.  28,  ^57  (ordinary  and  forced  diets).  Krim- 
HACHEK,  Ergcb.  d.  Phys..  lyoo.  74O.  Pflugek  (E.),  Pfluger's  Arch..  1899. 
77,  4-5  (influence  of  quantity  and  kind  of  food).  Rubner.  Gesetze  des 
Energieverbrauchs.  Speck.  Ergeb.  d.  Phys.  (Bioch.),  1403.  i.  Weber. 
ib..  1904.  21^  (influence  of  various  substances  on  metabolism).  Zuntz. 
Pfliiger's  Arch.,  1903.  95,  192;  Arch.  f.  Phys.,  1895.  378  (work  and 
metahnlisni). 

Basal  Metabolism. — Alb  and  Di  Bois,  Arch.  Int.  Med.,  191 7,  19,  840  (dwarfs 
and  legless  men)  ;  ib..  1917,  19,  823  (old  men).  Benedict,  Emmes,  Roth 
and  Smith,  J.  Biol.  Ch.,  1914,  18,  139.  Benedict  and  Emmes.  ib.,  1915. 
20,  253  (men  and  women).  Gephart  and  Du  Bois.  Arch.  Int.  Med., 
1915,  15,  836  (effects  of  food).  Means,  J.  Med.  Res.,  1915,  32,  121;  Arch. 
Int.  Med.,  1916,  17,  704  (obesity). 

DIETETICS. 

Benedict  (F.  G.),  Am.  J.  Phys.,  iyo6.  16,  409.  McCay,  The  Protein  Element 
in  Nutrition.  Chittenden,  The  Nutrition  of  Man,  N.  Y..  1907;  Physio- 
logical Economy  in  Nutrition,  1905.  Macleod.  J.  Lab.  Clin.  Med., 
191 7,  2,  743  (resume,  economic  readjustment  of  dietaries).  Mendel, 
Changes  in  Food  Supply  and  their  Relation  to  Nutrition.  Vale  Univ. 
Press,  1916.  Knigt,  Pratt  and  Langworthy,  U.S.  Dept.  Agric. 
Bull.,  22i3,  1910  (dietary  studies  in  public  institutions).  Pembrey  and 
Parker,  J.  Phys.,  1907-8,  36,  p.  xlix  (food  of  the  soldier).  Voit  (C), 
Physiologie  des  Stofiwechsels,  1881 .  Wilson  and  Rathbun.  J .  Am.  Med. 
Ass.,  191b,  66,  1 760  (dietary  at  .V.  Y.  Municipal  Sanitarium).  Siven.  Skand. 
Arch.  Phys..  igoi,  11,  308;  Caspari,  Arch.  f.  Phys.,  1901,  ^2^  (minimum 
protein  requirement).  Taylor  (A.  E.),  Univ.  of  Calif.  Pub.,  July  30, 
1904  (ash-free  diet).  Rlbner,  Z.  f.  Biol.,  1901.  42,  261  (energy  value  of 
food  of  human  beings).  Little  and  Harris,  Bioch.  J.,  1907,  2,  230 
(vegetarians). 

Inanition. — Benedict,  N.  Y.  Med.  J.,  Sept.  11.  1907;  Proc.  Nat.  Acad.  Sci., 
1915,  1,228.  Cathcart  and  Fawcett.  J.  Phys.,  1907,  36,  27.  Givens. 
See.  Exp.  Biol.  Med..  191  7,  14,  149  (Ca  and  Mg  metabolism).  Greene. 
Ani.  J.  Phys.,  191  7,  42,  Ooy  (changes  in  composition  of  muscle).  Hoover 
and  Sollmann,  J.  PIxp.  Med..  1897.  2,  405  (hypnosis).  Howe,  Mattill 
and  Hawk,  J.  Biol.  Ch.,  1912,  11,  103.  Kalfmann,  Z.  f.  Biol.,  1901, 
41,  75.  Lewis  (H.  B.),  J.  Biol.  Ch.,  1916.  26,  61  (S  and  N  elimination). 
Meyers,  J.  Med.  Res.,  191 7,  36,  51  (morphological changes).  Sherwin  and 
H.\WK,  J.  Biol.  Ch.,  1912,  11,  169  (putrefaction  in  intestine).  Voit,  Z.  f. 
Biol.,  1901,  41,  1O7,  502  ;  ib..  1905.  46,  167  (diminution  in  weight  of  organs). 
Weber,  Ergeb.  d.  Phys.  (Bioch.),  1902,  702.  Woelfel,  J.  Biol.  Ch., 
1909,  6,  189  (transfer  of  protein). 
Milk  and  the  Suckling. — Abderhalden.  Z.  Physiol.  Ch..  1898-y.  26,  498 
(ash  of  suckling  tnd  ash  of  milk).  Camerer.  Z.  f.  Biol.,  1900,  39,  ^7 
(physiology  of  suckling).     Langstein,  Ergeb.  d.  Phys.,  1905,  851  (energy 


Iiyo  blBLlOGUAPllY 

halawc  oj  suckling).  Oppenheimer,  Z.  f.  Biol.,  imoi,  42,  1(7  (food 
requireiucnt  and  hodv  surface  of  suckling).  Kihner  and  Heubner, 
Z.  f.  Biol.,  i8.)8,  36,'  I  (feeding  of  suckling).  Sikes  (A.  W.),  J.  Phys.. 
i')o»i,  34,  .}04  (Ca  and  P  of  Ininian  milk). 
Influence  of  Diet  on  Growth  and  Nutrition. — Gardner  and  Laider,  Proc. 
Roy.  See,  1914.  B87,  22(r.  Mikli-ek,  J.  Biol.  Ch..  1913.  21,  -'3  (cholesterol 
and  growth).  Mendel,  Krgeb.  d.  Physiol  ,  mK),  102;  Harvey  Lecture, 
New  York,  1914-15.  McCollum,  Simmonds  and  Vn/.,  J.  Biol.  Ch., 
1916.  27,  33  (fat-soluble  A  and  water-soluble  li  and  the  growth-promoting 
properties  of  milk).  Mendel  and  Osborne,  J.  Lab.  Clin.  Med.,  191b, 
1,  211  (resume).  McCollim  and  Davis,  J.  Biol.  Ch.,  1915,  23,  231 
(essential  factors  in  diet  during  growth).  O.sborne  and  Mendel,  J.  Biol. 
Ch.,  1912,  12,  Si  (growth  on  fat -free  food) ;  ib..  12,  473  (gliadin  in  nutrition) ; 
ib.,  13,   ~ii   (maintenance  experiments  with  isolated  proteins);  ih.,   1914, 

18,  95  (suspension  of  growth) ;  ib..  1915,  20,  331  (comparative  value  of 
certain  proteins  in  growth,  and  the  problem  nf  the  protein  minimum) ;  ib., 
1913,  23,  439  (resumption  of  growth) ;  ib.,  191b,  25,  1  (amino-acid  minimum 

for  maintenance  and  growth).  Robertson  (T.  B.),  J.  Biol.  Ch.,  1916,  25, 
(133  (cholesterol  and  growth);  ib..  25,  t>.\~  (lecithin).  Watson  (C),  Lancet 
(Lond.).  July  21,  1906,  145;  Dec.  8,  1585  (excessive  meat);  Proc.  Roy. 
Soc.  (Edin.),  1905-6,  26,  87  (varying  diets).  Watson  and  Hunter, 
J.  Phys.,  1906,  34,  III. 

Vitamines,  Accessory  Factors  in  Dietaries.^-DRUMMOND  and  Halliburton, 
J.  Phys.,  1917,  51,  235  (nutritive  value  of  margarine  and  butter  substitutes). 
Funk  (C.),  Ergeb.  d.  Phys.,  1913.  124;  J.  Biol.  Ch.,  1916,  25,  409  (exclusive 
diet  of  oats)  ;  J .  Phys.,  1913,  46,  i  73  (chemistry  of  vitamine  from  yeast  and 
rice  polishings);  Funk  and  Macallum,  J.  Biol.  Ch..  1916,  27,  51  (lard 
and  butter-fat  in  growth);  ib.,  1915,  23,  413  (nature  of  growth- promoting 
substances).  Hopkins  (F.  G.),  J.  Phys.,  1912,  44,  425.  McCollum, 
Simmonds  and  Fitz,  Am.  J.  Phys.,  1916,  41,  361  (fat-soluble  A).  Osborne 
and  Mendel,  J.  Biol.  Ch.,  1916,  24,  37  (butter-fat) . 

Polyneuritis,  Beriberi.— Funk  and  Douglas,  J.  Phys.,  1914,  47,  475  (relation 
of  beriberi  to  endocrine  glands).  McCollum  and  Kennedy,  J.  Biol.  Ch., 
1916,  24,  491 ;  ib.,  1912,  45,  73-  Steenbock,  Am.  J.  Phys.,  191  7,  42,  610 
(antineuritic  substances  from  egg-yolk). 

Pellagra.^ — Chittenden  and  Underbill,  Am.  J.  Phys.,  1917.  44, 13.  McCol- 
lum and  Simmonds,  J.  Biol.  Ch.,  1917,  32,  181.  Vedder,  Arch.  Int. 
Med.,  191O,  18,  137- 

Experimental  Scurvy. — Jackson  (L.)  and  Moore  (J-  J.).  J-  Infect.  Dis.,  X916, 

19,  478. — McCollum  and  Fitz,  J.  Biol.  Ch.,  '^91  7,  31,  229. 

CHAPTER  XI. 

INTERNAL  SECRETION. 

Biedl,  Innere  Sekretion.  Schafer,  The  Endocrine  Organs,  1916.  Vincent 
(S.),  Internal  secretion  of  the  ductless  gland.s,  Ergeb.  d.  Phys.,  1910, 
451;  ib..  1911,  218.  KojiMA  (M.),  Q.  J.  Exp.  Phys.,  1917.  11,  255 
(relations  between  endocrine  glands).  Mann  (F.  C),  Am.  J.  Phys.,  191G, 
41,  173  (ductless  glands  and  hibernation). 

PANCREAS. 
Islets. — Bensley,  Am.  J.  Anat.,  1911-12,  12,  297.  Cecil,  J.  Exp.  Med.,  X912, 
16,  I.  Homans,  Proc.  Roy.  Soc,  1913,  B  86,  73;  J.  Med.  Res.,  1914 
30,  49-  Milne  and  Peters,  J.  Med.  Res.,  1912,  26,  405  (atrophy  of 
pancreas  after  occlusion  of  duct).  MacCallum  (W.  G  ),  Johns  Hopkins 
Hosp.  Bull.,  Sep.  19,  1909.  Pratt  and  Murphy,  J.  ICxp.  Med.,  1913.  17, 
232  (transplantation  of  pancreas  in  spleen).  Vincent  and  Thompson, 
|.  Phys.,  1900,  34,  p.  xxvii.     DeWitt,  J.  Exp.  Med.,  190')   8,  193. 


/.V/7.7v'.V.lL  SLCJiLTlO.V  Ilgt 

Internal  Secretion  of  Pancreas.  Drennan.  Am.  J.  IMiys  ,  i<jii,  28,  396 
{presence  of.  m  Uood).  Hbdon.  Arch.  Intornat.  de  P'liys.,  lyn.  13,  255 
(pancreatic  diabetes).     (For  additional  references  sec  Chapter  X.) 

SEXUAL  ORGANS. 
Bayliss  and  Starlinc.  Ergeb.  d.  I'hys.,  lyoo,  684  [chemical  correlations  of 
sexual  organs).  Carmichael  and  Marshall,  I.  Phys.,  njoH,  36,  431 
(compensatory  hypertrophy  of  ovary).  Dixon  (\V.  K.),  J.  Phys.,  1900-1. 
26,  ^44  (action  of  orchilic  extracts):  ib.,  1900.  25,  350;  Rosenheim,  ib., 
191  7.  51,  p.  vi  (spermine).  Hanes,  J .  Exp.  Med.,  191 1,  13,  338 ;  Steinach, 
Pfluger's  Arch.,  1912,  144,  71  (interstitial  cells  of  I.rydig  and  internal 
secretion  of  testicle).  Lipschutz,  J.  Phys.,  191 7.  51,  283.  Loewy, 
Ergeb.  d.  Phys.  (Bioch.),  1903,  130.  Marshall  and  Jolly,  Q.  J.  Exp'. 
Phys.,  1908,  1,  115  {heteroplastic  transplantation  of  ovaries).  Oliver 
{]■)•  J-  Phys.,  1912,  44,  3.5,5  (internal  secretion  of  ovary).  Wheelon  and 
Shipley,  Am.  J.  Phys.,  191O,  39,  394  (effects  of  testicular  transplants  on 
vasomotor  irritability). 

Castration.— Henderson  (J.),  J.  Phys.,  1904,  31,  222  (castration  and  the 
thymus).  Livin(.ston,  Am.  J.  Phys.,  iqit>,  40,  153  (effect  on  pituitary). 
Marshall  and  Hammond,  J.  Phys.,  1914.  48,  171  (effect  on  horn  growth). 
McCrudden.  J.  Biol.  Ch..  1901).  7,  185  (effect  on  metabolism).  Morc;an. 
See.  Exp.  Biol.  Med.,  1915,  13,  31  (ejfect  on  feathers).  Simpson  and 
Marshall,  Q.  J.  Exp.  Phys.,  1908,  1,  257  (stimulation  of  nervi  erigentes 
after  castration). 

THYMUS. 

GooDALL,  J.  Phys.,  1905,  32,  191  (effect  of  castration).  Hewer,  J.  Phys.,  1914, 
47,  479  (effect  of  thymus  feeding  on  reproductive  organs).  Marine  and 
Manley,  J.  Lab.  Clin.  Med.,  191 7,  3,  48  (grafting  ;  relation  of  thymus  to 
sexual  maturity).  Paton,  J.  Phys.,  1905,  32,  2S  (thymectomy  and  growth 
of  sexual  organs);  ib.,  191 1,  42,  267  (relation  of  thymus  and  sexual  organs 
to  growth).  Paton  and  Goodall,  ib.,  1904,  31,  49.  Pappenheimer, 
J.  Exp.  Med.,  1914,  19,  319;  ib.,  1914,  20,  477;  Park  (E.  A.),  ib.,  1917,  25^ 
129;  Vincent  (S.),  J.  Phys.,  1904,  30,  p.  xvi.  (results  of  extirpation). 
Seemann,  Ergeb.  d.  Phys.  (Bioch.),  1904,  45.  Vincent  (S.),  ib.,  1911, 
303- 

PARATHYROID. 

Arthus  and  Schafermann,  J.  Phys.  Path.  Gen.,  1910,  177  (parathyroidectomy 
and  Ca  salts  in  rabbit).  Camis,  J.  Phys.,  1909,  39,  73  ;  Meigham.  J.  Phys.. 
1917,  51  (action  of  giianidin  on  muscle).     Cooke  (J.  V.),  J.  Exp.  Med.! 

1910.  12,  45  (<^"«  and  Mg  excretion) ;  i6.,  191 1,  13,  439  (N  metabolism  after 
parathyroidectomy).  Halsted.  Am.  J.  Med.  Sci..  1907,  134,  i;  J.  Exp. 
Med.,  1909.  11»  175;  >b-.  1912,  15,  205  (grafts).  Hoskins  and  Wheelon, 
Am.  J.  Phys.,  1914.  34,  2b^^  (vasomotor  irritability  after  parathyroidectomy). 
Joseph  and  Meltzer.  J.  Pharm.  Exp.  Ther..  igii,  2,  361  (action  of  NaCl 
after  parathyroidectomy).  Koch  (W.  P.),  J.  Biol.  Ch.,  1912,  12,  313 
(methyl  guanidin  in  urine);  ib.,  1913,  15,  43  (toxic  bases  in  urine  after 
parathyroidectomy);  J.  Lab.  Clin.  Med.,  1916,  1,  299  (physiology  of  para- 
thyroid). Marine  (D.),  Soc.  Exp.  Biol.  Med..  1914.  H,  117  (hyperplasia 
in  fowls).  Paton  et  al..  Q.  J.  Exp.  Phys.,  1917,  10.  Thompson  (F.  D.). 
Phil.  Trans.  Koy.  Soc.  (Lond.).  1910.  \\  201,  91  (thyroid  and  parathyroid 
in  vertebrates) .  \Vil.son,  Stearns.  Thornton  and  Jannev,  J.  Biol.  Ch., 
1015.  23,  123  (excretion  of  acids  and  ammonia  after  parathyroidectomy). 

Parathsrroid  Tetany. — Carlson,  Am.  J.  Phys.,  191 2,  30,  309  (digestive  tract  in). 
Carlson  ;;nd  Jackson,  ib..  191 1,  28,  133  (nature  of  tetany).  Greenwald, 
J.  Biol.  Ch.,  191b,  25,  223.     Haskins  and  Gerstenberger,  J.  Exp.  Med., 

191 1,  13,  314  (Ca  metabolism  in  infantile  tetany).  Keeton,  Am.  J.  Phys., 
1914,  33,  25  (secretion  of  gastric  juice  during  the  tetany).  MacCallum 
(W.  G.),  Med.  News,  Oct.  31,  1903;  ih..  1^03.  86,  625  (gastric  and  duodenal 
dilatation  in);  Soc.  Exp.  Biol.  Med.,  1912,  9,  2^  (seat  of  action  in  tetany). 


1192  BJULJUURAPHY 

MacCalli  M  ami  \oi:(.tlin,  J.  Exp.  Mod..  1909.  11,  118  {Ca  in);  J. 
Pharm.  Exp.  Ther..  lyii,  2,  421  {influence  of  various  sails  tn).  Mac- 
Calli'm  and  V'o<;ei..  J.  Exp.  Med.,  uii  .^  18,  018.  MacCallvm.  Lambert 
and  VoGKL.  J.  Exp.  Med..  1914.  20,  149  (retuoval  of  L  a  from  the  blood  by 
dialysis).  Marine  (]).),  ib..  191.},  19,  89.  Stoland,  Am.  J.  Phys.,  1914. 
33,  -^83  (influence  of  the  tetany  on  liver  and  pancreas).  Underhill  and 
Blatherwkk.  J.  Hiol.  Ch..  1914,  19,  119  (influence  of  dextrose  and  Ca 
lactate  on  blood-sugar  and  tetany). 

THYROID. 

AsHER,  Pfluger's  Arch.,  k^ii,  139,  5()i  (history  and  methods).  Bayliss  and 
Starling,  Ergeb.  d.  Phys.,  1900,  683  (chemical  correlations  of  thyroid). 
V.  EiJRTH.  ib..  1909.  9,  5^4;  Oswald,  Pfliigcr's  Arch.,  i9i().  164,  500 
{thyroid  and  the  circulation).  Vincent  (S.),  Ergcb.  d.  Phys.,  1911,  in; 
Vincent  and  Jolly,  J.  Phys.,  190b,  34,  295  (functions  of  thyroid  and 
parathyroid) . 

Results  of  Thyroidectomy. — Gley,  Arch,  do  Phys.,  1893,  467  (rabbit);  ib., 
ji-ih  (dog).  1  Iai.phnny  and  Gi'NN,  Q.  J.  Exp.  Phys..  1911.  4,  237  (monkey). 
HosKlNS  and  Morris,  Soc.  Exp.  Biol..  Med,  191 7.  14,  74  (amphibia). 
Palmer,  Am.  J.  Phys..  1917.  42,  572  (pig)-     Simpson.  ().  J.  Exp.  Phys., 

1913,  6,  119  (sheep).  Smith  (J.  L.),  J.  Phys..  1894,  16,  378  (heat  regula- 
tion).    Tatim  (A.  L.).  J.  Exp.  Med.,  1913.  17,  i>3<>  (experimental  cretinism). 

Morphological  Changes  in  Thyroid. —  Halsted  (\V.  S.).  Trans.  Ass.  Amer. 
Physicians.  19x3;  If)hns  Hopkins  Hosp.  Rep..  1896.  1  (compensatory 
hypertrophy).  Marine  (D.),  J.  Exp.  Med.,  1914,  19,  37O  (involution  of 
active  hyperplasia  in  brook  trout).  Marine  and  Lenhart.  Arch.  Int. 
Med.,  1909,  4,  253,  440;  Marine  and  Willl-^ms,  ib.,  1908,  1,  349  (relation 
of  iodine  to  thyroid  structure).  \V.\tson  (C),  J.  Phys.,  1905,  32,  p.  xvi; 
io.,  1906,  34,  p-  xxix ;  ib..  1907,  36,  p.  i  (changes  in,  on  meat  diet). 

Influence  of  Thyroid  on  Metabolism. — Carlson  and  Jacobson.  Am.  J.  Phys,, 
1910,  25,  403;  Jacobson  (C).  J.  Biol.  Ch..  1914.  17,  133  (blood-ammonia 
after  thyroidectomy).  Cramer  and  Krai^se,  Proc.  Roy.  Soc,  1913,  B  86, 
550  (carbohydrate  metabolism  and  the  thyroid).  Hinter  (.\.),  Q.  J.  Exp. 
Phys.,  1914,  8,  23  (thyro-parathyroidectomy  and  A'  metabolism  in  sheep). 
King  (J.  H.),  J.  Exp.  Med.,  1909, 11,  6O5  ;  Underhill  and  Hilditch,  Am. 
J.  Phys.,  1909,  25,  66;  Kuriyama.  Am.  J.  Phys.,  191  7,  43,  481  (carbo- 
hydrate metabolism  after  thyroidectomy).  McCtrdy  (J.),  J.  Exp.  Med., 
1909,  11,  798  (thyroidectomy  and  alimentary  glycosuria). 

Thyroid  Feeding. — Carlson,  Rooks  and  McKie,  Am.  J.  Phys.,  1912.  30,  129 
(attempts  to  produce  hyperthyroidism).  Cramer  and  McCall,  O.  J.  I-lxp. 
Phvs.,  191  7.  11,  59  (effect  on  gaseous  metabolism).  Ci'nningham  (H.  H.|, 
J.  Exp.  Med.,  1898,  3,  147  (experimental  thvroidism).  Guderxatsch, 
Am.  J.  Phys.,  1913.  36,  370  (in  rats).     Hewitt  (J.  A.),  Q.  J.  Exp.  Phys.. 

1914,  8,  113.  297  (influence  of  small  amounts  of  thyroid  and  anterior  lobe  of 
pituitary  on  metabolism).  Kuriyama.  J.  Biol.  Ch.,  191  7.  33,  193  (storage 
and  moiiilization  nf  I ivri  glycogen  in). 

Active  Constituents  of  Thyroid.— Baimann.  Z.  f.  Physiol  Ch..  1895-6.  21, 
;i9  (thyroidin).  Caldwell,  Am.  J.  Phys.,  1912,  30,  42  (intravenous 
injection  of  thyroid  pressure  liquid).  Carlson  and  Woelfel,  ib..  1910. 
26,  ^^  (internal  secretion  of  thyroid).  1'\\wcett.  Rogers,  RAHEand  Beebe, 
lb..  i<»t4.  36,  113;  Eenger,  J.  Biol.  Ch..  i()i2.  11,  4^59:  ili..  12,  r,^  (active 
principle  in  thyroid  and  suprarenal  before  and  after  birth).  Graham  (A^, 
J.  Exp.  Med.,  1916.  24,  343;  Lenhart,  ib.,  1915.  22,  739;  Rogoff  and 
Marine,  J.  Pharm.  Exp.  Ther.,  1916,  9,  57  (relation  of  effect  on  tadpoles 
to  amount  of  iodine).  Giderna tsch.  Arch.  Entwick.  Niech.  d.  Org.. 
1912-13,  35,  437;  Am.  J.  Anat.,  1913.  15,  431  (effect  on  tadpoles).  Hi'NT 
and  Seidell,  J.  Pharm.  Exp.  Ther.,  i<)io.  2,  15  (thyreotropic  iodine 
compounds).  Hunt  (U.).  J.  Biol.  Ch..  1905.  1,  .vV.  Lussky  (H.  O.). 
Am.  J.  Phys.,   1912,  30,  63  (acelo-nilrile  test).     Kendall,  J.  Biol.  Ch., 


IM  KhWAL  SliCJUiTJON  ii'J3 

I«ii3  20,  .501  (product  of  (ilUalme  hydrolysis  of  thyroid).  Koch  (F.  C). 
J.  Hiol.  C\\..  i<»i  |,  U)i  (nutitre  of  the  lodine-containing  lonif^le.x  lu  thyreo- 
f;lol>ulin).  Marixk.  il>..  i'»i  s,  22,  31  7  ((»  t'/T'o  absorption  of  K I  hv  thyroid). 
Marink  ;iiul  I'kiss.  J.  I'hjiriu.  JCxp.  Ther.,  n»t3,  7,  537  Uihsorption  of  Kl 
by  perfused  thyroid).  Makink  and  !<()(. okk,  ib..  i<)i<>.  9,  1  Untie  required 
for  elaboration  of  the  iodme-ioutaining  substance).  Mousk  (M),  J-  Biol. 
Ch..  IQ14.  19,  .JJI  (the  principle  accelerating  involution  m  tadpoles). 
Oswald.  Arch.  Jixp.  P.ith.  Pharm.,  lyog,  60,  115  (iodolhyrin).  Pick 
and  riNELEs.  Z.  Kxp.  Path.  Ther.,  190Q,  7,  518.'  Kocioj-i-  (J.  M),  J. 
Pharm.  Exp.  TIut.,  191 7,  10,  199  (tadpole  method  for  standardization 
of  thyroid  prepnyations. 

Iodine  Content  of  Thyroid.  -Aldrich,  Am.  J.  Phys.,  1912,  31,  r^S-  Fenger, 
J.  Biol.  Ch.,  i.)i.;,  14,  397  (/  and  P  in  fecial  thyroids).  Hunter  (A.), 
lb..  1910,  7,  .1-11  (estimation).  Hinter  and  Si.mp.son,  ib.,  IQI3,  20,  119 
(influence  of  diet  of  marine  algcr).  W'atis,  Am.  J.  Phys.,  1913,  38,  35O 
(iodine  co)itrnt  and  bloodfloiv  through  thyroid). 

Innervation  of  Thyroid. — Secretory  Nerves  ? — Asher  and  Plack,  Z.  f.  Biol.. 
1911.  56,  83.  BuRGET.  Am.  j.  Phys.,  1917,  44,  4q-:.  Cannon,  Bingep. 
and  Pnz,  ib..  1914,  36,  363.  Levy,  ib..  i<)i().  41,  iM--  Manley  and 
Marine,  Soc.  Exp.  Biol.  Med.,  1915,  12,  2.01.  IMarine,  Rogoff  and 
Stewart,  Am.  J.  Phys.,  1918,  45,  2b8.  Kahe,  Rogers,  Fa wcett  and 
Beebe,  (7).,  19K).  34,  72. 

Vasomotors  of  Thyroid. — Fran^ois-Franck  and  Hallion,  J.  de  Phys. 
Path.  Gen.,  1908,  10,  442.     Stewart  (G  N.),  J.  Phys.,  1893.  15,  79- 

Thyroid  Grafts. — Hesselberg  (C),  J.  Exp.  Med..  1913.  21,  i'm  ian'o-  and 
homoco-grafls  in  guinea  pig).  Manley  and  Marine,  J.  Am.  Med.  Ass., 
1916,  67,  260. 

ADRENALS. 

Epinephrin  (Adrenalin,  Suprarenin). — Abel  (J.  J.).  Am.  J.  Phys.,  1901,  5, 
p.  v;  lb..  1903,  8,  p.  xxix  ;  Alurich,  ib..  190 1,  5,  437;  ib..  7,  3391  v.  FiJrth, 
Hofmeistcr's  Beit.,  1902,  1,  243:  Takamine.  J.  Phys.,  1901-2,  27,  P-  xxix 
(isolation).  Abel  and  Macht,  J.  Pharm.  Exp.  Ther.,  1912,  3,  327,  334 
(in  toad's  venom).  Embden  and  v.  Fijrth,  Hofmeister's  Beit.,  1904,  4, 
421.  Weiss  and  Harris,  Pfluger's  Arch.,  1904,  103,  510  (destruction 
in  the  body).  Ewins  and  Laidlaw,  J.  Phys.,  1910,  40,  275  (formation). 
Funk,  J.  Phys.,  1911,  43,  p.  iv;  Greer  and  Wells,  Arch.  Int.  Med., 
1909,  4,  2qi  (absent  in  hvpernephroma). 

Action  of  Suprarenal  Estract  and  Adrenalin. — Aler  and  Gates,  J.  Exp. 
Med..  1917,  26,  201:  Jackson.  J.  Pharm.  Exp.  Ther..  1912,  4,  59  (on 
lungs).  Bainbridge  and  Trevan,  J.  Phys.,  1917,  51,  460  (on  liver). 
Barbour  and  Kleiner,  J.  Pharm.  Exp.  Ther.,  1915,  7,  341  ion  vagus). 
Barcroft  and  Piper,  J.  Phys.,  1912,  44,  339  (on  gaseous  metabolism  of 
submaxillarv).  Botazzi,  D'Enrico  and  Japelli,  Bioch.  Z.,  1908,  7,  431 
(on  saliva  and  urine  secretion).  Brown  (E.  D.).  J.  Pharm.  Exp.  Ther., 
1916,  8,  195.  BuRKET.  Am.  J.  Phys.,  191 2,  30,  382  (on  blood-pressure). 
Cannon  and  Gray,  Am.  J.  Phys.,  1914.  34,  2}i:  Grabfield,  Am.  J. 
Phys..  191(5,  42,  4'}  (on  coagulation).  Cannon  and  Nice,  ib..  1913.  32,  44; 
Gruber,  77).,  1914.  33,  333;  ib.,  1917.  43,  330  (on  muscular  fatigue). 
Cannon  and  Lyman,  (7*.,  1913.  17,  37'i;  Hoskins  and  ^IcClure,  ib..  1912, 
30,  192;  Moore  and  Purinton,  Pfluger's  Arch.,  1900,  81,  483;  Am.  J. 
Phys..  1900,  3,  p.  XV  (depressor  action  of  minimal  doses).  Cushny,  J. 
Phys.,  1908,  37,  130:  it>..  1909,  38,  239  (adrenalin  isomers).  Evans  and 
Ogawa,  ib..  191 4,  47,  44'>  (on  gaseous  metabolism  of  heart).  Edmunds, 
Am.  J.  Phys..  18,  129  (on  blood-velocity).  Elliott,  J.  Phys.,  1903. 
32,  401.  F^LEISHER  and  Loeb.  J.  Exp.  Med..  1910,  12,  288  (on  absorption). 
GiTHENs,  J.  Exp.  Med.,  191 7,  25,  !t,27i.  Golla  and  Symes,  J.  Pharm. 
Exp.  Ther.,  1913,  5,  87  (on  bronchioles).  Gunn.  C_).  J.  Exp.  Phys.,  1913, 
7,  75  (f'"  heart).  Gunn  and  Chavasse,  Proc.  Roy.  Soc,  1913,  (on  veins). 
Harold,  Xierenstein  and  Roaf,  J.  Phys..  1910,  41,  308.     Hartmann 


1194  BIBLIOGRAPHY 

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Eyster,  Am.  J.  Phys.,  1915,  38,  62  (heart  rate).  Meltzer  (S.  J.  and  C), 
Am.  J.  Phys.,  1903,  9,  252  (subcutaneous  injection).  Meltzer  and  Auer, 
j6.,  1904,  11,  28,  40  (paradoxical  pupil  dilatation);  ib.,  11,  449  (frog's 
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1915.  6,  339  (on  vasomotor  centre).  Takayasu,  Q.  J.  Exp.  Phys.,  1916, 
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Determination  o!  Epinephrin. — Folin,  Cannon  and  Deni.s,  J.  Biol.  Ch,, 
1912,  13,  477;  Seidell,  ib.,  1913,  15,  197  (colorimetrtc).  Elliott, 
J.  Phys.,  191 2,  44,  374  (pithed  cat) ;  ib.,  1913,  46,  p.  xv. 

Epinephrin  Content  of  Adrenals.^ — Elliott,  J.  Phys.,  191 2,  44,  374  McCord, 
J.  Biol.  Ch.,  1915,  23,  435  (foettts).     Ritchie  and  Bruce,  Q.  J.  Exp.  Phys., 

191 1,  4,  127  (effect  of  diphtheria  ioxine).  Seidell  and  Eenger,  U.  S. 
Hyg.  Lab.  Bull.,  100,  1914,  p.  57.     Stewart  and  Rogoff,  J.  Exp.  Med., 

1916,  24,  709. 

Epinephrin  in  Blood  (and  Tests  for). — Barbour  and  Prince,  J.  Exp.  Med., 
1915,  21,  330;  Barbour,  ib..   1912,  15,  403;  Janeway  and  Park,  ib., 

1912,  16,  541 ;  Park,  ib.,  1912,  16,  532  (coronary  artery  test).  Dale  and 
Laidlaw,  J.  Phys.,  1912,  45,  i  ;  J.  Pharm.  Exp.  Ther.,  1912,  4,  75  (guinea 
pig  uterus  test).  Jackson  (D.  E.),  Am.  J.  Phys.,  1909,  23,  226  (disappear- 
ance after  injection).  Lawen,  Arch.  Exp.  Path.  Pharm.,  1904,  51,  415 
(frog  perfusion  test).  Meyer,  Z.  f.  Biol.,  1906,  48,  352;  Park  and  Jane- 
way,  Soc.  Exp.  Biol.  Med.,  191 2,  9,  31  (artery  ring  test).  Schultz  (W.  H.), 
J.  Pharm.  Exp.  Ther.,  1909,  1,  291  (critique  of  tests).  Stewart  (G.  N.), 
J.  Exp.  Med.,  1911,  14,  377  (biological  tests — rabbit  intestine  and  uterus 
segments);  ib.,  1912,  15,  347  (absence  of  detectable  epinephrin  in  venous 
blood);  ib.,  1912,  16,  302  (comparison  of  plasma  and  serum  on  intestine 
segments).  Stewart  and  Rogoff,  J.  Pharm.  Exp.  Ther.,  1917.  9,  393 
(partition  between  corpuscles  and  plasma).  Stewart  and  Zixker,  J. 
Exp.  Med.,  1913,  17,  152,  174  (artery  ring,  frog  perfusion,  rabbit  intestine 
and  uterus  coynpared).  Trendelenburg,  Arch.  Exp.  Path.  Pharm., 
1913.79,  134- 

Epinephrin  Secretion  and  Adrenallnnervation. — Asher.  Z.  f.  Biol.,  1912,  58, 
274;  Pfluger's  Arch.,  1917,  166,  372.  Cannon,  Aub  and  Binger,  J. 
Pharm.  Exp.  Ther..  1912,  3,  379  (nicotine).  Dreyer.  Am.  J.  Phys.,  1899, 
3,  203.  Elliott,  J.  Phys.,  1912,  44,  374;  ib.,  1913,  46,  283  (innervation); 
ib.,  1914,  49,  38  (some  results  of  excision  of  adrenals).  Hoskins  and 
McPeek,  J.  Am.  Med.  Ass.,  1913,  60,  1777  (massage  of  adrenals).  Joseph 
and  Meltzer,  .\m.  J.  Phvs.,  ii)i2,  29.  p.  xxxiv  (splanchnic  stimulation). 
O'Connor,  Arch.  Exp.  Path.  Pharm.,  1912.  67,  193:  'b..  68,  383. 
Stewart,  Rogoff  and  Gibson,  J.  Pharm.  K\p.  Ther.,  1910,  8,  203 
(splanchnic  stimulation).  Stewart  and  Rogoif,  ib..  191b,  8,  479 
(spontaneous  liberation);  ib..  1917.  10,  49  (asphyxia);  J.  Exp.  Med.,  191  7, 
26,  637  (effect  of  sensory  stimulation) ;  ib.,  191  7.  26,  613  (spinal  centre  for 
epinephrin  secretion);  J.  Pharm.  Exp.  Ther.,  191 7,  10,  i  (indispensa- 
bility  of  epinephrin  ?);  Am.  J.  Phys.,  191  7.  44,  149  (relation  of  liberation 
of  epinephrin  and  adrenal  blood- flow). 

Adrenals  and  Metabolism.— Edmunds.  J.  Pharm.  Exp.  Ther..  191 1,  2,  359; 
Mann,  Arch.  Int.  Med.,  1915,  16,  781 ;  Pemberton  and  Sweet,  ib.,  1912, 


INTERNAL  SECRETION  iuj5 

10,  169  {relation  to  pancreas).  Li'sK  ;iiul  KiCHE,  tb.,  l<n\.  13,  673; 
KiNUKK,  I    V.\\<   Med     Ki'.o.  12,  103  (diahetfs). 

Disseminated  Chromaffin  Tissue.  Hikui.  and  WiEshi..  PHiiKer's  Arch.,  ujoz. 
91,  434.  tii.K  ami  Macleou,  Am.  J.  Phys.,  i<;i(i,  40,  n.  Gaskell 
(J.  F.),  J.  Phys.,  i<>iJ.  44,  59  (distribution  of  medullary  tissue  in  petro- 
myzon). 

PITUITARY. 

Blair  Bell.  Q.  j.  Ilxp.  Phys  .  191  7, 11,  77  [fxperuuental  operatums).  Cu.shin<". 
(H.).  The  pituitary  body  and  its  disorders,  I'hiladelphia.  iqi2:  Johns 
Hopkins  Hosp.  Bull.,  1910,  21,  1^7  (experi}tietital  hypnphysectomy). 
V.  Cyon,  Pfliiger's  Arch.,  1900.  81,  .;'>7;  J-  Phys.  Path.  Gen.,  1909,  il, 
J59.  GoETscH  (E.),  Q.  J.  Med.,  1914,  7,  173  (review).  Herring  (P.  T.). 
y.  J.  Exp.  Phys..  1908.  1,  111  (histology);  ib..  1913,  6,  73  {comparative 
anatomy  and  physiology):  ib.,  1914,  8,  267  (activity  of  pars  intermedia  and 
pars  nervosa);  ib..  1914,  8,  .245  (origin  of  active  material  of  posterior  lobe). 
Pai'lesco,  J.  Phys.  Path.  Gen.,  1907,  9,  441.  Schaker.  Proc.  Roy. 
Soc.  1909,  B81,  442  (functions).  Simpson  and  Hunter,  Q  J.  E.\p.  Phys., 
1910,  8,  i.:i  {relation  bettveen  thyroid  and  pituitary).  Vince.nt  (S.), 
Ergeb.  d.  Phys.,  iqii,  3ot>;  Practitioner,  Jan.,  1915  (general  review). 

Influence  on  Growth  and  Metabolism,  .\lurich.  Am.  J.  Phys.,  191J,  31, 
94  (feeding  to  rats).  Bi.nedict  ;ind  Homans,  J.  Med.  Res.,  1912,  25,  409 
(metabolism  after  hypophysectomy).  Gushing  and  Goetsch,  J.  Exp. 
Med.,  1915,  22,  25  (hibernation  and  the  pituitary).  Malcol.vi  (J.),  J. 
Phys.,  1903,  30,  270.  Maxwell.  Univ.  of  Calif.  Pub..  1916,  5,  5;  Pearl 
(R.),  J.  Biol.  Ch.,  1916,  24,  123  (feeding  pituitary  to  fowl).  Miller  and 
Lewis.  Arch.  Int.  Med.,  1912,  9,  601  (glycosuria  after  injection  of  extracts). 
Robertson  (T.  B.),  J.  Biol.  Ch.,  1916,  24,  397,  409;  Robertson  and 
Delprat,  ih.,  191 7,  31,  567;  Schmidt,  J.  Lab.  Clin.  Med.,  1917.  2,  719 
(tethelin).  Schafer  (E.  A.),  Q.  J.  Exp.  Phys.,  1912,  5,  203  (effect  of 
ovarian,  pituitary,  and  thyroid  tissue  on  growth  of  rats).  Wulzen  (R.), 
Am.  J.  Phys.,  1914,  34,  127  (growth  in  birds). 

Action  of  Extracts. — Addis  and  Barnett,  Soc.  Exp.  Biol.  Med.,  1916,  14,  49 
(on  urea  secretion  by  kidney).  Auer  and  Meltzer,  J.  Pharm.  Exp.  Ther.. 
1913,  4,  359  (pituitrin  on  depressor  action  of  vagus).     Dale,   Bioch.  J., 

1909,  4,  427.     Hamburger  (W.  W.),  Am.  J.  Phys.,   1904,  H,  282;  ib., 

1910,  26, 1  78  (anterior lobe).  Howell,  J.  Exp.  Med.,  1898,3,  245  (posterior 
lobe).  HosKiNs  and  Means.  J.  Pharm.  Exp.  Ther.,  191 3,  4,435  (pituitrin 
diuresis).  Kin(.  and  Stoland,  Am.  J.  Phys.,  1913,  32,  405  (action  on 
renal  activity).  Xice,  Rock  and  Courtright,  Am.  J.  Phys.,  1914,  35, 
194  (on  respiration).  Paton  and  Watson,  J.  Phys..  1912,  44,  413  {on 
circulation  of  bird).  Pilcher  and  Sollmann,  J.  Pharm.  Exp.  Ther., 
191 5,  6,  405  (on  vasomotor  centre).  Schafer  and  Herring,  Phil.  Trans. 
Roy.  Soc.  (Lond.),  1906,  B  199,  i  (on  kidney).  Waddell,  Am.  J.  Phys., 
i<»i6,  41,  529  {on  frog's  cesophagus). 

Formation  and  Secretion  (?)  of  Active  Substance.— Carlson  and  Martin, 
Am.  J.  Phys.,  1911,  29,  64  (question  of  infundibular  secretion  in  cerebro- 
spinal fluid).  Cow  (D.).  J.  Phys.,  1915,  49,  367.  Fencer,  J.  Biol.  Ch.. 
1915,  21,  283;  ib.,  1916,  25,  417  (composition  and  activity  of  pituitary). 
Keeton  and  Becht.  Am.  J.  Phys.,  1915,  29,  109  (stimulation  of  pituitary). 
McCord,  J.  Biol.  Ch..  191 5.  23,  435  (active  substance  in  fcetus).  Rabens 
and  LiFSCHlTZ,  Am.  J.  Phys..  191 4,  36,  47  (innervation).  Weed  and 
Gushing,  ib..  191,5  36,  77  (effect  of  pituitary  extract  on  its  secretion). 
(For  action  of  pituitary  extract  on  milk  secretion,  see  Chapter  XIX.) 

SPLEEN. 

Splenectomy.^ — Goldschmidt  and  Margot,  J.  Exp.  Med.,  1913,  22,  319; 
Mendel  and  Gibson,  .\m.  J.  Phys.,  1907.  18,  201  (.V  metabolism  in  man). 
RicHET,  J.  Phys.  Path.  Gen.,  1912,  14,  089;  ib.,  1913,  15,  579  {effects  on 
nutrition). 


1196  BlliUOGRAPHY 

Blood  Changes  after  Splenectomy. —KARsNiiR  and  Pkarck,  J.  Kxp.  Med., 
lyi-:,  16,  7<->»j.  PiiARCE,  AisriN  and  MirssER.  ib..  n)ii.  16,  758  (hanio- 
lylic  jaundice).     Orr,  J.  Lab.  Clin.  Med..  1917,  2,  093. 

Spleen  and  Blood  Formation.  Do.nhauskr,  J.  Kxp.  Med.,  kjoH,  10,  559. 
MoKKis,  ///.,  nil  |.  20,  3  7<».  Paton,  CiuLLAND  and  Fowler,  J.  Phys., 
i')o;,  28,  ."^-:       Si  KMANN.  Ergeb.  d.  Phy.s.  (Bioch.),  1904,  30. 

Spleen  and  Haemolysis. — Levin,  J.  Med.  Res.,  8,  iio.  Krumbhaar  and 
Mus.sER,  J.  Kxp.  Med.,  1916,  23,  07.  Krumbhaar.  ib..  1914,  20,  108. 
Paton  and  Goodall,  j.  Phys.,  1903.  29,  411.  Pearce,  Austin  and 
Krumbhaar,  [.  Exp.  Med.,  1912,  16,  S'^v  Pearce  and  Peet,  J.  Exp. 
Med.,  1013.  18,    l-M. 

Relation  of  Spleen  to  Pancreas. — Herzen,  J.  Phys.  Path.  Gen..  1902,  4,  625; 

Pfliiger's  Arch.,   1901,  84,  115.     Mendel  and  Kettger,  Am.  J.  Phys., 

1902,  7,  387- 
Spleen    Innervation. — Langley,    J.   Phys.,    1896,   20,   223.    bcHiFER   and 

.MUOKK.    lb..   20,    I. 

Spleen  Grafts. — Manley  and  Marine,  J.  Exp.  Med.,  191 7,  25,  619;  See.  Exp. 
Biol.  .Med.,  IQ17.  14,  123. 

Effects  of  Reduction  of  Kidney  Substance. — Bainbridge  and  Beddard, 
Proc.  Koy.  Soc,  H)<J7,  \i  79,  73-  Barrington.  Heart,  1915,  6,  163. 
Bradford  (J.  K.),  J.  Phys.,  189S-M.  23,  415.  Kar.sner,  Bunker  and 
Grabfield,  J.  Exp.,  Med.  1915,  22,  344.  Pearce  (R.  M.),  ib.,  1908, 
10,  ()32.     Sampson  and  Pearce,  ;//..   i()«h.  10,  743. 

Effect  of  Kidney  Extracts  on  Blood-Pressure.— Pearce  (1^  M.),  J.  Exp.  Med.. 
i90tj,  11,  430;  Arch.  Int.  Med.,  1912,  9,  3'j2.  Tigerstedt  and  Bergman, 
Skand.  Arch.  Phys.,  189S,  8,  223  {pressor  substance  in  kidney  extracts). 

Pineal  Body. — v.  Cyon,  Pfliiger's  Arch.,  1903,  98,  327.  Dandy,  J.  Exp.  Med., 
1915,  22,  237  {extirpation).  Fenger,  J.  Am.  Med.  Ass.,  1916,  17,  183O 
{composition  and  activity).  Horrax,  Arch.  Int.  Med.,  1916,  17,  607- 
McCoRD,  J.  Am.  Med.  Ass.,  1915,  65,  517.  Jordan  and  Eyster,  Am.  J 
Phys.,  1911,  29,  113  {extracts).  Orr  and  Scott,  See.  Exp.  Biol.  Med., 
1012,  9,  O.f  {extracts). 

Salivary  Glands  (Removal). — Schafer  and  Moore,  J.  Phys.,  19,  p.  xiii. 

Organ  Extracts.  -  Broun  and  Joseph,  J.  Phys.,  i<jo6.  34,  282.  Campbell 
(J.  A.),  ().  J.  Ex]).  Phys.,  1911,  4,  I  {on  bloodvessels).  Kawcett,  Rahe, 
Hackett  and  Ro(,ers,  Am.  J.  Phys.,  1915,  39,  154  {on  smooth  muscle). 
Joseph  (D.  R.),  ].  Exp.  Med.,  i<)07,  9,  606  {on  blood-pressure).  Miller 
(J.  L.  and  E.  M.)",  J.  Phys.,  1911,  43,  242. 

Bone-Marrow  Extracts. — Brown  and  Guthrie,  Am.  J.  Phys.,  1905,  14,  328; 
Brown  and  Josicph,  ib.,  1906,  16,  no. 

Extracts  of  Nervous  Tissue. — Halliburton,  J.  Phys.,  iqoo-i,  26,  229. 
Osborne  and  Vincicn  1 ,  ib.,  1899-1900,  25,  283.  Schafer  and  Moore,  ib., 
189O,  20,  I.  Schafer  and  Vincent,  25,  87.  Vincent  and  Cramer,  ib., 
1904,  30,  143. 

CHAPTER  XII. 

ANIMAL  HEAT. 

Calorimetric  Observations. — Atwater,  lugcb.  d.  Phys.  (iiioch.).  1904,  41^8. 
Benedict,  and  Carpenter,  Carnegie  Instil.  Pub.,  123,  i<>io  (respiration 
calorimeters  for  man);  ib.,  Pub.  128,  1910  {mctaliolism  of  normal  men). 
Du  Bois,  J.  Am.  Med.  .\ss.,  1914,  63,  827,  830  {total  cnrrpy  requirement 
in  disease);  Arch.  Int.  Med..  1916,  17,  887  {children).  dWrsonval,  Arch, 
de  Phys.,  1890,  ()io,  781.  Hill  (.\.  V.),  J.  Phys.,  191 1,  43,  379  {cold- 
blooded animals);  ill..  1912-13,  45,  2()i  {micro-calorimeter).  Hill  (A.  V. 
and  A.  M.),  ib.,  IQ13,  46,  81  {warm-blooded  animals).  Langworthy  and 
MiLNER,  yparbook,  U.S.  Dept.  Agric,  1910  (respiration  calorimeter). 
Lefevre    j.  Phys.    Path.  Gen.,  1900,  2,  259.     Lusk,  Arch.  Int.  Med., 


AM  MAI.  HEAT  1 197 

IMI3, 16,  7i»3  (respiration  calorimeter  for  study  of  disfase) ;  J.  Biol.  Cli.,  iyi2. 
13,  -7  (ingestion  of  dextrose  and  fat).  McCri'UUEN  and  LisK,  J.  Biol. 
Cli..  iMiJ.  13,  447-  Macdonald  (J.  S.).  J.  Phys..  lyij,  44,  p.  iv  (man). 
Mi'KLiN  ami  HooBLEK,  Am.  J.  Dis.  Childn-n,  It^i3,  9,  91  (infants). 
MuRLiN  anil  LusK,  J.  Biol.  Ch.,  191 3.  22,  13  (ingestion  of  fat).  Pkauody, 
Meyer  and  Du  Bois.  Arch.  Int.  Med.,  19K),  17,  980  (hasal  metabolism 
in  cardio-renal  disease).  KicuE  and  Sooekstrom,  Arch.  Int.  Med.. 
1913.  15,  903.  Williams,  J.  Biol.  Ch.,  lyi.*,  12,  J17  (small  calorimeter). 
Williams,  Kichk  and  Li'sk.  (/>.,  1912,  12,  349  (ingestion  of  meat). 

Specific  Dynamic   Action  of  Foodstuffs. — Lusk.  J.  Biol.  Ch.,  1915.  20,  555. 

Surface  Area.-  Benkdu  r  (!•.  C).  \m.  J.  IMivs-,  1916,  41,  275.  Du  Bois 
iD.  Hiul  1-:.  F.),  Arch.  Int.  Med.,  1913,  15,  .S()8;  ib.,  1910,  17,  80^ 

Surface  Area  and  Metabolism  (Heat  Production).  I^e.neukt  (F.  G.),  Am.  J. 
Phys..  mil),  41,  .i'U.  C.icpilxkt  and  Dr  Hois.  .\rch.  Int.  Med.,  1916, 
17,  00.'.      Mi;.\Ns  I  J.  111.  J.  Biol.  Ch.,  H)i3,  21,  ^''3. 

Heat  Production  in  Various  Organs  (and  Functions). — Bayliss  and  Hill  (L.). 
J.  Phys.,  iiS<j4,  16,  331  [salivury  glands).  Chauveat,  Arch,  de  Phys., 
1887,  2.49  (thermodynamics  of  muscular  work).  Herlitzka,  Archivio  di 
Fis..  1912,  10,  301;  Snyder,  Am.  J.  Phys.,  1917,  44,  421  (heart).  Hill 
(A.  v.),  J.  Phys.,  1912,  43,  433;  Rolleston  (H.  D.),  ib.,  1890,  11,  208; 
Stewart  (G.  N.),  ib..  iSyi,  12,  409  (nerve).  Mosso  (A.),  Proc.  Roy.  Soc, 
1892,  B  51,  83  (brain).  Reichert  (E.  T.),  Am.  J.  Phys.,  1900,  4,  397 
(digestion).  Reid  (W.),  J.  Phys.,  1893,  18,  p.  xx.xi  (glands).  Vernon, 
ib..  1894,  17,  277  (relation  of  respiratory  exchange  to  temperature). 

Effect  of  Various  Conditions  on  Heat  Production  and  Loss  (Climate). — Lee, 

Edmi'nds,  et  al.,  Soc.  E.xp.  Biol.  Med..  1913,  12,  72  (humidity,  etc.). 
Lefevre,  Arch,  de  Phys.,  1898,  683  (death  by  cold) ;  J .  de  Phys.  Path.  G^n., 
1903.  5,  783  (radiation).  Macleod  (J.  J.  R.),  Am.  J.  Phys.,  1907,  18, 
I  (humidity).  Masje,  Virchovv's  Arch.,  1887,  107;  Stewart  (G.  N.), 
Studies,  Phj'siol.  Lab.  Univ.  Manchester,  1891,  1,  loi  (loss  by  radiation). 
McClure  and  S.^uer,  Am.  J.  Dis.  Children,  1913,  9,  490  (effect  of  clothing). 
Osborne  (W.  A.),  J.  Phys.,  1910-11,  41,  343;  ib..  1913,  49,  133  (climate). 
Pembrey  and  Pitts,  J.  Phys.,  1899,  303  (hibernating animals).  Rubner, 
Arch.  f.  Hygiene,  1891.  11,  208;  Nature,  May  28,  1891,  666  (dry  and 
moist  air);  Die  Gesetze  des  Energieverbrauchs,  1902.  Waller  (A.  D.). 
J.  Phys.,  1893,  14,  p.  XXV  (calorimetry  by  surface  thermometric  and 
hygrometric  data) . 

Varnishing  the  Skin. — BabXk,  Pfliiger's  .\rch.,  1903,  108,  389.  LAULAxifi, 
Arch,  de  Phys.,  1897,  302.  Stewart  (G.  N.),  Studies,  Physiol.  Lab. 
Univ.  Manchester,  1891,  1,  122.  Winternitz,  Arch.  Exp.  Path.  Pharm., 
1894, 33, 286. 

Effect  of  Cold  (Hibernation). — Cameron  and  Brownlee,  Q.  J.  Exp.  Phys.. 
1913,  7,  113;  Cameron  (A.  T.),  ib.,  1913,  8,  341;  Harris,  J.  Phys.,  1910. 
40,  p.  liii  (on  frog).  Merzbacher,  Ergeb.  d.  Phys.  (Bioph.),  1904,  214 
(general  physiology  of  hibernation).  Simpson  (S.),  Soc.  Exp.  Biol.  Med., 
191 3.  10,  180  (hibernation  and  external  temperature).  Simpson  and 
Herring.  J.  Phys.,  1903.  32,  303  (cold  narcosis) . 

Heat  Paralysis. — Becht,  Am.  J.  Phys.,  1908,  22,  456  (heat  paralysis  in  nerve 
tissue).  Cameron  and  Brownlee,  Q.  J.  Exp.  Phys.,  1915,  9,  247  (death 
temperature  in  frog).  Eve,  J.  Phys.,  1900-1,  26,  119  (superior  cervical 
sympathetic  ganglion).  Halliburton,  Q.  J.  Exp.  Physiol.,  1915-16, 
9,  193  (death  temperature  of  nerve).     Mayer,  Am.  J.  Phys.,  1917,  44,  581. 

Body  Temperature. — Damant  (G.  C.  C),  J.  Phys.,  1906,  35,  p.  v  (goat). 
F'ROTniNc.HAMand  MiNOT,  Am.  J.  Phys.,  1912,  30,  430  (rabbit).  Lazarus- 
Barlow.  Lancet  (London),  1893,  Oct.  26  (mouth).  Pembrey  and  Xicol, 
J.  Phys.,  1898-9,  23,  386  (deep  and  surface  temperatures).  Simpson  (S.), 
Proc.  Roy.  Soc.  (Edin.).  1912,  32  (i).  no  (seasonal  changes);  ib.,  1907-8' 
28  (2),  661  (fishes).  Woodhead  (G.  S.),  J.  Phys.,  1898-9,  ^,  p.  xv  (rest  and 
ivork.  in  horse).     Young  (W.  J.),  ib.,  1913,  49,  202  (Europeans  in  tropics). 


ii.>8  BIIiI.I()(,RAl'H\ 

Diurnal  Variation  of  Body  Temperature. — Benedict  (F.  G.).  Am.  J.  Phys.. 
l^>t>^.  11,  145-  JouANSsu.N,  Sk.iiul.  Arch,  i'hys.,  lSm-**.  8,  >>  >  SiMpsnv 
(S.),  J.  Phys.,  1902,  28,  p.  xxi  [monkey).  Si.mpson  ;inii  G.XLbKAliii. 
ib..  1905,  33,  225  {nocturnal  birds,  etc.).  Toulouse  arnl  PifcKos,  J.  Phys. 
Path.  G<jn.,  1907,  9,  425  {inversion  of  dAily  routine). 

Temperature  Topography. — Heidenhain  and  K6rner,  PHuger's  Arch.,  1871. 
4,  .t.t!^  (*'S^'t  tind  h-ft  ventricles).  Kunkel  (A.).  Deutscli.  Med.  Zc-it.,  1887; 
Stewart  (G.  N.).  Studies,  Physiol.  Lab.  Iniv.  Manchester,  1,  1891,  104 
(surface  temperatures  in  man).  Lefevrk,  Arch,  de  Phys.,  1898,  254  {ther- 
mal topography  iti  cooling  by  baths).  Kancken  and  Tic.erstedt,  Skand. 
Arch.  Phys.,  1909,  21,  80  {stomach). 

Thermotaxis. — BabXk,  Pfliiger's  Arch.,  1902,  89,  154  {new-born).  Boycott 
and  Haldane,  J.  Phys.,  1905-6,  33,  p.  xii  {high  external  temperature). 
Chauveau,  Compt.  Rend.,  136  (13),  p.  792;  ib.  (14),  pp.  847,  852  {animal 
thermostat) ;  Zentralb.  f.  Phys.,  1903, 17,  391.  Colosanti,  Pfliiger's  Arch., 
1871),  14,  92.  Hale  White,  Lancet  (London),  1897  (June  19,  26;  July  3, 
10).  HXri,  Pfliiger's  Arch.,  1909,  130,  90  {chemical  regulation  in  mam- 
mals). Johansson.  Skand.  Arch.  Phys.,  1904,  16,  88.  LEFivRE,  J. 
Phys.  Path,  Gen.,  1901,  3,  p.  i.  Pembrey  and  Hale  White,  J.  Phys., 
189.5-6,  19,  477  {hibernation).  Pembrey,  Gordon  and  Warren,  ib.. 
1894-5,  17»  331  {chick  before  and  after  hatching).  Pembrey,  ib.,  1895, 
18,  363  {young animals).     Richet,  Arch,  de  Phys.,  1893,  25,  312  {shive:-ing) 

Heat  Centres. — Aronsohn,  Virchow's  Arch.,  169,  505;  Aronsohn  and 
Citron,  Z.  Exp.  Path.  Ther.,  1910,  8,  13  {puncture  fever).  Barbour  and 
Wing,  J.  Pharm.  Exp.  Ther.,  1913,  5,  105  {application  of  drugs  to  centres) ; 
Barbour  and  Prince,  ib..  1914,  6,  i  ;  Cloetta  and  Waser,  Arch.  Exp. 
Path.  Pharm.,  1914,  77,  16  {local  heating  of  centres).  Kennaway  and 
Pembrey,  J.  Phys.,  191 2,  45,  82  {effect  of  section  of  spinal  cord  on  tem- 
perature and  metabolism).  Means,  Aub  and  Du  Bois,  Arch.  Int.  Med., 
191  7,  19,  832  {effect  of  caffein  on  heat  puncture).  Ott  (L),  J.  Nerv.  Ment. 
Dis.,  N.  Y.,  1884.  Pembrey,  Brit.  Med.  J.,  1897  (2),  883.  Reichert, 
Univ.  Pann.  Med.  Mag.,  Mar.,  1893,  Feb..  1894;  J.  Am.  Med.  Ass.,  1902, 
38,  143.  Sachs  and  Green,  Am.  j.  Phys..  1917,  42,  6o^  Hale  White 
J.  Phys..  1890,  11,  i;  lb.,  1891,  12,  233.' 
Fever. — Babak,  Pfliiger's  Arch.,  1904,  102,  320.  Burnett  and  Martin. 
Soc.  Exp.  Biol.  Med.,  1916,  13,  141.  Carpenter  and  Benedict,  Am. 
J.  Phys.,  1909,  24,  203.  Coleman  and  Du  Bois,  Arch.  Int.  Med.,  1914, 
14,  168  {high-caloric  diet  in  typhoid).  Leathes,  J.  Phys..  1907,  35,  205 
{nitrogen,  creatin,  and  uric  acid  excretion).  Loewi,  Ergeb.  d.  Phys. 
(Bioch.),  1904,  339.  Mandel,  Am.  J.  Phys.,  1907.  20,  439  {xanthin); 
ib.,  1904,  10,  452  {alloxuric  bases  in  aseptic  fever).  Ott  and  Collmar, 
J.  Phys.,  1887,  8,  216  {pyrexial  agents);  Ott  and  Scott.  J.  Exp.  Med., 
1907,  9,  671  {metabolism).  Rosenthal,  Zentralb.  f.  Phys.,  1888,  635; 
Deutsch.  Med.  Woch..  1888,  No.  8.  Sharpe  and  Simon,  J.  Exp.  Med., 
1914,  20,  282  {nitrogen  excretion).  Stewart  (G.  N.),  ib.,  1913,  18,  372 
{bloodflow  in  extremities  in  fever). 

CHAPTER  XIII. 

THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES. 

Cilia. — LiLLiE  (R.  S.),  Am.  J.  Phys.,  1901.  5,  5^.  '^o-^.  7,  25:  1906,  16,  89 
{influence  of  ions).  Maxwell,  j6..  1905.13,154-  Meyer,  Soc.  Exp.  Biol. 
Med.,  1909,  7,  13.  Parker.  Am.  J.  Phys.,  1905.  13,  i:  14,  i.  Pitfter, 
Ergeb.  d.  Phys.  (Bicrph.),  1903,  i.  Schafer,  Anat.  Anzeig.,  1904.  24, 
Xos.  iM  and  20;  1905,  26,  517- 

Smooth  Muscle.  -BoTAZZi,  Pfliiger's  Arch..  1906,  113,  136.  Botazzi  and 
(.iKUNBAUM.  ].  Phys.,  1899,  24,  51  (cesophagus  of  toad  and  auricle  of 
tortoise).  Grutzner,  Ergeb.  d.  Phys.,  1904.  12.  Lewis  (M.  R.  and 
W.   H.),   Am.   J.   Phvs..   igi7,   44,  57  {smooth  muscle  cells  in  cultures). 


THE  I'liySI()JA)GY  or  THE  COSTRALTll.i:  TISSUES       II.J9 

LiNc.LU   (D.   J.).    Am.   J.   Fhys..   igio.   28,  3O1   (tone  in  smooth  mvsrle), 
iliiiL.s    Am.  J.  Phys..   igi-j.  29,  317  {tttuyoscopic  study  of  living  ■.iinxiHt 
muscle).     Stewakt" (C.  C),  ih.,  U)Oo,  4,  1S5  (cat's  blad,der).     WuouwuRTii, 
lb..  iSoo.  3,  .'<). 
General  PhysioIoRical  Properties  of   (Diaphragm)    Muscle. — Lee.  Guknther 
,nicl  Mi'Mi'MN  ,  .\m    J     I'hys.,  Kji'),  40,    ( i')       Hotazzi,  Rend.  Acud.  dei 
Liiuci,   n)i3  [mittiiititis  papers). 
Elasticity  0!  Animal  Tissues.  -  Haycraft,  J.  I'hy.s.,  1904.  31,  39^- 
Muscle  Contraction     Theories.  -Bernstein.  PfltiKcr's  Arch.,   1909,128,  136; 
'/'..    1413.    162,    1.      Hkki,   (\V.).    tb..    1913,   149,    195    [Zuntz's    theory). 
Enoelmann,  Arch.  I.  I'hys.,  1907,  25  (contractility  and  double  refraction). 
Burnett  (T.  C),  J.  Biol.  Ch..   1907.  2,  193  (influence  of  temperature  on 
contractility,    and    its    relation    to    chemical    reaction    velocity).     Ewalu, 
Pfluger's  Arch.,  1S87,  41,  ^13  (volume  unaltered  in  contraction) .     Garrey, 
Am.    J.    Phys..    1903,    13,    1H6    (t7vitchinf;s   produced   by   salt   solutions). 
Lanc.ley,  J".  Phys.,   1907-S,  36,  347;   h»".S,  37,  i(>5.  285;   1909,  39,  .;35 
(receptive  substances).     Lombard   and   Aishott,  Am.  J.  Phys.,   1907.  20, 
I  (contraction  of  individual  muscles  of  frog's  thigh).     Lucas  (K.),  J.  Phys., 
1905-b,  33,  125  (graduation  of  activity  in   skeletal  muscle);  ib.,  1904.  30, 
443  (influence  of  tension).     McDougall.  J.  Anat.  and  Phys.,   1897,  31, 
410;  ib.,  1898,  32,  187.     Macdonald  (J.  S.),  J.  Phys.,  1908,  37,  p.  xxv. 
Meigs,  Am.  J.   Phys.,  1905,  14,  138.     Schafer,  Q.  J.  Exp.  Phys.,  1910, 
3,63. 
Action  of  Substances  on  Muscle  -Permeability  of  Cells. — Asher,  Bioch.  Z., 
190S,   14,    I.     Carliek,    Brit.    Med.    J.,    Sept.    16,    1911    (various   salts). 
Hamburger  (H.  J.),  Bioch.  Z.,  1908,  11,  443;  Osmotischer  Druck,  etc. 
Harvey  (E.  N.),  J.  Exp.  Zool..  1911,  10,  507;  Am.  J.  Phys.,  1913,  31, 
335-     Joseph  and  Meltzer.  Am.  J.  Phys..   1911,  29,   i   (A'a  and  Ca). 
Kite,   ib.,    1915,   37,   282   (permeability  of  internal  cytoplasm).     Lillie 
(R.  S.),  ib.,  191 1.  28,  197  (relation  of  stimulation  and  conduction  to  per- 
meability changes).     Locke  (F.  S.),  Pfliiger's  Arch.,  1893,  54,  501  (NaCl 
solutions):  J.  Exp.  Med.,  1893,  1.  ^3°  (ether).     Loeb  (J.),  see  J.  Biol.  Ch., 
23  to  32,  for  numerous  papers.     Mathews  and  Loniifellovv,  J.  Pharm. 
Exp.  Ther.,  1910,  2,  201  (dyes).     McClkndon,  Am.  J.  Phys.,  1912,  29, 
302  (increased  permeability  of  muscle  to  ions  during  contraction) ;  ib.,  1915, 
38,  173  (ancssthetics  and  permeability).     Meigs  and  Atwood,  ib.,  1916, 
40,  31  (KCl).     MiLLiKiN  and  Stiles.  Am.  J.  Phys.,  1905,  14,  359  (Na  or 
Li  ions).      Mines  and  Dale  (D.),   J.  Phys.,   191 1.  42.  p.  xxix  (acids). 
Osterhout.  J.  Biol.  Ch..   1914,  19,  335,  493  (effect  of  alkali  and  acid). 
Overton,   Ergeb.  d.  Phys.   (Bioch.),   1902,    749  (anilin  dyes);  Pfluger's 
Arch.,  1902,  92,  115  (osmotic  properties  of  muscle);  ib..  92,  340;  ib.,  1904, 
105,   170  (.Vfl  or  Li  ions  in  contraction).     Roaf.   Bioch.   J..   1906.  1,  88 
(tadpole).     Robertson  (T.  B.).  J.  Biol.  Ch.,  1908,  4,  i.     Stiles,  Am.  J. 
Phys..  1903,  8,  269  (Ca  and  K  on  smooth  muscle  tone).     Zoethout,  ib., 
1902,  7,  199  (K  and  Ca  on  striated  muscle) ;  ib.,  1904,  10,  373  (electrolytes), 

EXCITATORY  PROCESS  IN  MUSCLE  (AND  NERVE). 

Biedermann,  Ergeb.  d.  Phys.  (Bioph.),  1902,  121;  ib..  lyog,  26  (the  excitable 
tissues).  Erlanger  and  Garrey,  Am.  J.  Phys.,  H)i4,  35,  377;  Martin 
(E.  G.j,  Am.  J.  Phys.,  1908,  22,  6i,  116;  ib..  191 1,  28,  49;  1910,  27,  226 
(faradic  stimulation) ;  Measurement  of  Induction  Shocks,  New  York, 
1912.  Hill  (A.  V.),  J.  Phys.,  1910,  40,  170.  Lapicque,  J.  Phys.  Path. 
Gen.,  1903,  6,  843,  991;  ib.,  1907.  9,  368,  O19;  ib.,  1909,11,  1009,  1035; 
tb.,  1910,  12,  t)oi,  624;  ib..  1911,  13,  42.  Lillie  (R.  S.),  Am.  J.  Phys., 
1916,  41,  126.  Lucas  (K.),  J.  Phys.,  1908,  37,  459  (rate  of  development 
of  excitation);  ib.,  1907,  36,  253;  ib..  1910,  40,  223;  ib..  1909,  39,  331 
(refractory  period);  ih..  1908,  37,  P-  xxx  (Nernst's  Theory  applied);  Proc. 
Roy.  Soc.  (Lond.),  191 2,  B  85,  493  (process  of  excitation  in  nerve  and 
muscle).     Lucas  and  Mines,   J.   Phys.,   1907-8,  36,   334   (temperature). 


I200  iubliography 

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conduction).     Zoethout,  Am.  J.  Phys.,  1902,  7,  3^o  {contact  irritability). 

Threshold  Stimuh. — Graufielu  and  Martin,  Am.  J.  Phys.,  191 3,  31,  300. 
Gruber,  ib.,  1915,  37,  -259  {cervical  sympathetic).     M.\rtin,  Grace  and 
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denhall,  .\m.  J.  Phys..  m\\.  36,  57  (aittonnmic). 
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•All  or  None'  in  Muscular  Contraction.^ — Eisenherger,  Am.  J.  Phys.,  1917, 
45,   44    {yninimal  contraction).     Lucas    (K.),    J.    Phys.,    1909,   38,    113. 
Pratt,  Am.  J.  Phys.,  1917,  44,  517. 
Summation. — Adrian  and  Lucas,  J.  Phys.,  1912,  44,  (j8  {of  propagated  dis- 
turbance in  nerve  and  muscle).     Lucas  (K.),  ifc.,  1910,  39,4'ji  {of  inadequate 
stimuli).     Mines  (G.  K.),  (6.,  1913,  46,  i  {of  contractions). 
Staircase   Phenomenon    (' Treppe'). -Lie  (F.  S.),  Am.  J.  Phys.,  1907,  18, 

j()7.     Lee  and  Harvey,  Soc.  Exp.  Biol.  ^f<^d.,  1910,  7,  135- 
Tetanus. — Basler,  Pfluger's  Arch.,   1904,  105,  344-     Hofmann,  ib..  1903,  93, 
18O;  ib.,  95,  484  ;  ib..  1904, 103,  291.     Kronecker  and  Stirling,  J.  Phys.. 
1878-9,  1,  384.     Sewall  (H.),  J.  Phys.,  1888,  9,  92. 
Tonus  Rhythms  in   Striated   Muscle. — Cannon  and  Gruber,  Am.  J.  Phys.. 
191b,  42,   >•)      Samojloff,  Arch.  f.  Phys.,  1907,  145.     Storey,  Am.  J. 
Phys,,  1904,  12,  75.      Wedensky,  Arch,  de  Phys.,  1891.  23,  59- 
Voluntary  Contraction. — Cleghorx  and  Stewart  (C.  C),  Am.  J.  Phys.,  1901, 
5,  281  {inhibition  lime).     FoA,,  Z.  f.  AUg.  Phys.,  191 1,  13,  35  {rhythm  of 
motor  impulses).     Haycraft,  J.  Phys..   1890.  11,  352;  ib..   1898,  23,   i 
(rapid  voluntary  movements).     Harris,   J.   Phys.,    1894-5.  17,   315   {time 
relations   in    man).     Griffiths,    ib.,    i888.    9,    39    {rhythm).     Lombard 
(W.  P.),  J.  Phys.,  1892,  13,  I. 
Fatigue. — Burridge,  J.  Phys.,  1910,  41,  285  {chemical  factors).     Crider  and 
KoBiNsoN,  Am.  J.  Phys.,   1916.  41,  37t'  if^'og's  muscle).     Forbes  (A.). 
Am.  J.  Phys.,  1912,  31,  102  (reflex  fatigue).     Franz  (S.  L),  ib.,  1900,  4, 
348.     Gruber,  ib.,  1913,  32,  221.  438.     Lee  (F.  S.),  ib..  1907,  20,  170 
(fatigue  substances);  J.  Am.  ?»Ied.  Ass..  May  19,  1906.     Lee  and  Arono- 
viTCH,  Soc.  Exp.  Biol.  Med.,   1917,  14,  153  {fatigue  toxin?).     Lee  and 
ElvERiNGHAM,    Am.    J.    Phys.,    1909,    24,    384    {pseudo-fatigue  of  cord). 
Lombard  (W.  P.),  J.  Phys.,  1893,  14,  97-     Pipkr.  Arch.  f.  Phys.,  1909. 
491.     Ryan  and  Agnew,  Am.  J.  Phys.,  191 7.  42,  5W      Storey,  Am 
J.  Phys..  1903,  8,  355-     Schenck,  Pfluger's  Arch.,  1900.  82,  3S4.     Wood- 
worth.  Am.  J.  Phys.,  1901,  5,  p.  iv. 
Ergograph,  Ergometer.     Benedict  and  Emmes,  Am.  J.  Phys.,  1915,  38,  52. 
Hall  (\V.  S.).  ib..  1902,  6,  p.  xxiii.     Houcm  (T.),  ib.,  1901,  5,  240;  ib., 
1902,  7,  76.     Lombard,  ib.,  1902,  6,  p.  xxiv.     Martin  (C.  J.)    J.  Phys., 
1914.  48,  p.  XV. 
Lactic  Acid  and  Muscular  Work.— Feldman  and  Hill  (L.),  J.  Phys.,  191 1. 
42,  43-9  {influence  of  oxygen).     Fletcher,  ib.,  1911,  43,  286;  ib.,  1911-12, 
45,  28O;  ib.,  1913,  47,  3f)i-     Fletcher  and  Hopkins,  ib.,  1906-7,  35,  247. 
Hill  (A.  V.),  ib.,  1914,  48,  p.  ix  {oxida:ive  removal).     Kwanjitsuji,  ib., 
1916,  60,  T,i2  {isolated  heart).     Roaf.  ib.,  1914,  48,  380.     Winfield  and 
Hopkins,  ib..  191 5,  50,  p.  v  {influence  of  pancreatic  extracts). 
Source  of  Energy  of  Muscular  Contraction.— DuNLOP,  Paton,  Stockman  and 
Macadam     J.   Phys.,    1898,   22,   08   (muscular  exercise  and  metabolism). 
Frentzel    Pfluger's  Arch.,  1897,  68,  191-     Krummacher.  Z.  f.  Biol., 


ini.  PllVSlOLOGY  or  the  COSriiACltLE  TISSUES      liol 

iSyo,  33,  io8;  Pettenkofer  and  \oit,  ih..  1866,  2,  538  (protein  metab- 
olism not  increased).  Pflui;er  (E.).  Pfluger's  Arch..  1891,  50,  98. 
SEEf.EN,  Arch.  f.  Phys..  i8yO.  383,  4O5.  Shaffer,  Am.  J.  IMiys.,  1908. 
22,  m5  {diminished  muscular  activity  and  protein  metabolism).  Speck, 
Arch.  f.  Phys.,  1895.  4O3. 

ENERGY  TRANSFORMATIONS  IN  MUSCULAR  WORK. 

Anderson  and  Lisk,  J.  Biol.  Ch.,  1917.  32,  4^1  (diet  and  body  condition  and 
heat  production  in  muscular  work).  Benedict  and  Cathcart,  Carneg. 
Instil.  •Pixh..  191 3.  Benedict  and  Murschacser,  Carneg.  Pub.,  No.  231, 
1915  (horizontal  walking).  Bkoca  and  Kichet.  Arch,  de  Phys.,  1898, 
JJ3.  Berg,  dv  Bois-Keymond  (R.)  and  Zlnz.  Arch.  f.  Phys.  Supp. 
Bd.,  1904,  20  (bicycling).  Chauveau,  Arch,  de  Phys.,  1897,  229.  261. 
JoHANNsoN,  Skand.  Arch.,  Phys.,  1901,  11,  273  ;  ib..  1903, 14,  60  (CO.,  out- 
put). Lee  and  Scott,  Am.  J.  Phys.,  1916,  40,  486  (action  of  temperature 
and  huutidity  on  working  power  of  muscles).  Macdonald  (J.  S.),  J.  Phys.. 
1914,  48,  p.  xxxiii  (efficiency  in  man).  Reach  (F.),  Bioch.  Z.,  1908,  14, 
43°- 

Heat  Production  in  Muscular  Contraction. — Blix,  Skand.  Arch.  Phys.,  1902, 
12,  52.  Evans  and  Hill.  J.  Phys..  1914,  49,  10  (relation  of  length  to 
tension  and  heat  production).  Frank  (O.),  Ergeb.  d.  Phys.,  1904,  348 
(thermodynamics  of  nim^.ilar  contraction).  Hill  (A.  V.),  J.  Phys.,  1911, 
42,  I  (position  of  heat  production  in  the  sequence);  ib.,  1912,  44,  46O;  ib.. 
1913,  47,  305;  ib..  1913,  46,  435  (mechanical  efficiency);  ib.,  1910.  40,  389 
(contracture  and  tonus).  Peters,  J.  Phys.,  1913,  47,  243  (in  fatigue  and 
relation  to  lactic  acid);  ib.,  1913,  46,  28  (recovery  processes).  Snyder, 
Am.  J.  Phys.,  1914,  35,  340  (smooth  muscle).  Weizsacker,  J.  Phys.,  1914, 
48,  396. 

Eff^ts  of  Muscular  Exercise. — Barach,  Arch.  Int.  Med.,  1910,  5,  382  {severe 
exertion,  Marathon  race).  Cook  and  Pembrey,  J.  Phys.,  1913,  45,  429. 
Gasser  and  Meek,  Am.  J.  Phys.,  191 4.  34,  48  (mechanism  of  heart  accelera- 
tion). Hill  (L.)  and  Flack,  J.  Phys.,  1910,  40,  347  (O2. inhalation). 
Hough,  Am.  Phys.  Educ.  Rev..  April,  1909.  Hyde,  Root  and  Curl, 
Am.  J.  Phys.,  191 7,  43,  371  (athlete  and  non-athlete).  Krogh  and  Lind- 
hard,  J.  Phys.,  1913,  47,  112  (regulation  of  respiration  and  circulation 
in  work).  Lowsley,  Am.  J.  Phys.,  1911,  27,  446  (blood-pressure  and 
heart-rate).  Martin,  Gruber  and  Lanman,  Am.  J.  Phys.,  1914,  35,  211 
(body  temperature  and  pulse-rate).  Schneider  and  Havens,  ib.,  1915,  36, 
239  (blood  changes) . 

Denervated  and  Regenerating  Muscle. — Langley,  1917-  51,  377. 

Rigor  Mortis. — Folin  (O.),  Am.  J.  Phys.,  1903,  9,  374  (cold  rigor).  Latham. 
Bioch.  J.,  1908,  3,  193  (lactic  acid  and  CO.,  formation).  Joseph  and 
Meltzer,  J.  Exp.  Med.,  1909,  11,  10.  314;  Am.  J.  Phys.,  1909,  25,  113; 
MacWilliam,  J.  Phys.,  1901-2,  27,  33(>  (rigor  of  heart).  Meltzer  and 
Auer,  J.  Exp.  Med.,  190S,  10,  45  (influence  of  Ca  and  Mg).  Winter- 
stein.  Pfluger's  Arch.,  1907.  126,  225. 

Heat  Rigor. — Burridge  and  Scott.  J.  Phys.,  1912,  44,  p.  iii.  Fletcher  and 
Brown,  ib.,  1914,  48,  177  (CO2  production).  Vernon,  ib.,  1899,  24,  239. 
Vrooman,  Bioch.  J.,  1907,  2,  363. 

Water  Rigor. — Brooks  (C),  Am.  J.  Phys..  1906,  17,  218  (conduction  ana 
contraction  in).     Meigs,  J.  Phys.,  1909,  39,  3S5. 

CHEMISTRY  OF  MUSCLE. 

Botazzi  (F.).  Bioch.  Bull.,  1913,  2,  379  (physical  chemistry  of  muscle-plasma). 
BoTAZZi  and  Quagliariello,  Arch.  Internat.  Phys.,  191 2.  12,  234,  289, 
409  (proteins) ;  Arch.  Ital.  deBiol.,  19x3.  60,  255.  Halliburton.  J.  Phys.. 
1887.  8,  133  ;  Biochemistry  of  Muscle  and  Nerve,  von  Furth.  Ergeb.  d. 
Ph^'^.  (Bioch.),  1902,  no;  ib.,  1903,  575;  Arch.  Exp.  Path.  Pharm.,  1895, 

76 


120  J  hlBLlOORAPHV 

36,  -31.  jANNbv,  J.  Biol.  Cli.,  1910,  25,  177,  1S5  {total  pyoieim).  Lee, 
Scott  and  Colvin,  Am.  J.  Phys.,  kjiO,  40,  176.  Mek.s.  Am.  J.  Phys., 
1909,24,  1.  i-j"/  {protein  Lixigidatiori  (indheat  shortening).  MKK.sand  Ryan, 
J.  Biol.  Ch.,  i»)iJ,  11,  401  [ash  of  smooth  muscle).  ObBORNK  and  Zobel, 
J.  Phys.,  1903.  29,  I  (sugars).  Ransom  (F.),  J.  Phys.,  1910,  40,  i  [enzymes). 
Saiki,  J.  Biol.  Ch.,  1908,  4,  483.  Stewart  and  Sollmann,  J.  Phys., 
1899,  24,  4^7  [proteins).  Urano,  Z.  f.  Biol.,  1908,  51,  483  [salts). 
Vincent  (S.)  and  Lewis,  J.  Phys.,  1901,  26,  445  [proteins  and  heat 
shortening) . 

CHAPTER  XIV. 
NERVE. 

The  Nerye  Impulse  or  Propagated  Disturbance. — Bramwell  and  Llcas, 
J.  Phys.,  1911,  42,  495  (refractory  period  and  propagated  disturbance). 
Mathews  (A.  P.),  Science,  1902.  15,  492;  ib..  1903,  17,  729;  Maxwell 
(S.  S.),  J.  Biol.  Ch.,  1907,  3,  359;  Strong,  J.  Phys.,  1899-1900,  25,  427; 
Sutherland,  Am.  J.  Phys.,  1905,  14,  112;  ib.,  1906,  17,  297;  ib.,  1909, 
23,  113  (theories). 

Chemistry  0!  Nerve. — Alcock  and  Lynch,  J.  Phys.,  1907,  38,  93;  ib.,  1910, 
39,  402  (saits).  Halliburton,  Ergeb.  d.  Phys.,  1903.  24.  Macallum 
(A.  B.),  Proc.  Roy.  Soc,  1906,  B  77,  163.  Macdonald  (J.  S.),  J.  Phys., 
1907,  36,  pp.  iii,  xvi  (chlorides).  Tashiro,  Am.  J.  Phys.  1913,  32,  107, 
137;  Tashiro  and  Adams,  Am.  J.  Phys.,  1914,  34,  405 ;  J.  Biol.  Ch.,  1914, 
18,  329;  Waller  (A.  D.),  J.  Phys.,  1896,  19,  p.  i  {CO.,  production  in  nerve). 
Tkornlk.  I'fluger's  Arch.,  1914,  156,  253  (O.^  requirement  of  nerves). 

Fatigue  of  Nerve. —Brodie  and  Halliburton,  J.  Phys.,  1903.  28,  181  (non- 
medullated).  Scott  (F.  H.),  J.  Phys.,  1906,  34,  145.  Tait  (J.)  and  Gunn 
(J.  A.),  Q.  J.  Exp.  Phys.,  1908, 1,  191  (vohi  mbini  zed  nerve) .  Tait,  J.  Phys., 
T906,  34,  p.  xxxv.  (cooli)ig  and  fatigue). 

Excitation  and  Conduction  in  Nerve. —Adrian,  J.  Phys.,  i9i4.  47,  460; 
lb.,  1913.  46,  3<S4  (all-or-Hone  principle);  ib.,  191b,  50,  345  (recovery). 
BiEDERMANN.  Ergob.  d.  Phys.  (Bioph.),  1902,  141.  Cardot,  J.  Phys. 
Path.  Gen.,  1912,  14,  737.  Gau  and  Sawyer,  Arch.  f.  Phys.,  1889,  350 
(CO2  and  alcohol).  Gruber,  Am.  J.  Phys.,  1913,  31,  413  (nerve  block). 
Lan'oley,  J.  Phys.,  1901,  27,  226;  Proc.  Roy.  Soc.  190O,  B  78,  170  {nerve 
endings).  Lillie  (R.  S.),  Am.  J.  Phys.,  i<)i3.  37,  348.  Lucas  (K.), 
J.  Phys.,  1911,  43,  4f>  [transference  of  impulse  from  nerve  to  muscle);  ib., 

1913,  46,  470  (alcohol).  Li'CAS  (K.),  Conduction  of  the  Nervous  Impulse 
(revised  by  E.  D.  .\drian),  London,  1917.  Meek  and  Leeper.  Am.  J. 
Phys.,  191 1,  27,  308  [pressure).  Mayer,  Am.  J.  Phys..  igib.  39,  375; 
ib.,  1917.  42,  469.  Symes  (\V.  L.),  J.  Phys.,  191  7,  51,  p.  xix  [survival 
of  mammalian  nerve).  Waller,  J.  Phys.,  1917,  18,  p  xlv  (ancBsthetics). 
Wedensky,  Pfliiger's  Arch.,  1900,  82,  134  [fundamental  properties  of 
nerves  under  certain  poisons). 

Temperature  and  Excitability  of  Nerve,  .\drian,  J.  Phys.,  1914.  48,  453 
(temperature  coefficient  of  refraclnrv  period).  Boycott,  ib..  190J,  27,  488. 
GoicH  and  Macdonald,  //;.,  189(1,  20,  247.  Tait,  Q.  J .  Exp.  Phys.,  iqio. 
3,  221  [refractory  phase  and  electrical  change);  ib.,  1909,  2,  157  [refractory 
phase  in  yohimbini::ed  nerve). 

Electrotonus.— LoEB  (J.),  Pfliiger's  Arch.,  1907,116,  193;  Univ.  of  Cj,lif.Pub. 
1905,  3,  9.  Hermann  and  Tschitschkin,  Pfliiger's  Arch.,  1899.  78, 
^3  (inexcitabilitv  of  kathode  with  certain  current  strengths).  Pfluc;er  (E). 
Electrotonus.  "Stewart  (G.  N.),  J.  Phys..  1888.  9,  2b;  ib.,  1889,  10, 
458  (depression  of  conductivity  at  kathode  as  compared  with  anode  ivith 
certain  current  strengths).  Werigo  (B.).  Pfliiger's  Arch.,  1901,  84,  547 
(depressive  action  at  ka'hode). 

'  Chemical '  Stimulation  of  Nerves. — Guthrie  and  Lee,  Soc.  Exp.  Biol.  Med., 

1914.  11,    !.('>    (sensory).     Gr^tzner,    Pfliiger's    Arch.,    1894,    58,    69. 


NERVE 


1203 


Mathews  (A.  P.).  Am  J.  J'liys.,  lyo.j,  11,  435;  t^.,  1.J05,  14,  ^oj.  Lillil. 
Soc.  Exp.  Biol.  Med  .  u>io,  7,  lyo.  Loku  and  Ivwalu,  J.  Biol.  Ch.,  1916, 
28,  377.  Si'iniiRi.AND.  Am.  J.  Phys.,  ii>o(>,  17,  20b. 
Velocity  of  Nerve  Impulse.  Adrian,  J.  Phys.,  1914,  48,  43.  Carlson,  Ami. 
I  I'hys  i>io-\.  10,  401.  Hermann,  PHiiger's  Arch.,  1002,  91,  189. 
Jenkins  and  Caki.son,  J.  Comp.  Neurol..  1903,  13,  239;  Am.  J.  Phys., 

1903.  8,  231.  LiM.iE,  Am.  J.  Phys.,  1914,  34,  414.  Lucas  (K.),  J.  Phys.. 
1908.  37,  112;  Snvder  (C.  D.),  Am.  J.  Phys.,  1908,  22,  179  (tenipeyature 
coefficient  0/  velocity  of  nerve  conduction);  ib.,  191 1,  28,  i()7  {temperature 
coefficients  of  velocities  of  various  physiological  actions).  McClendon, 
J.  Biol.  Ch..  1917.  82,  275  (effect  of  stretching).  Nicolai,  Pfliiger's  Arch., 
1901.  86,  <>5  {olfactory  nerve  of  pike).  Piper,  ib.,  1908,  124,  59;  ib.,  1909. 
127,  4  74  {in  vuin). 

Degeneration  0!  Nerves. — I-'eiss  and  Cramer,  Proc.  Roy.  Soc,  1912-13,  B  86, 
119.  Langley,  J.  Phys.,  1909,  38,  304  (nerve  endings).  Tuckett. 
J.  Phys..  1896.  19,  2'>7  (non-medullated  fibres). — Van  Gehuchten,  Le 
Nevraxe,  i<)o^  1,  i.  263  ;  ib.,  1905,  7,  203. 

Regeneration  of  Nerve.    -Baer,  Dawson  and  Marshall,  J.  Exp.  Med..  1899. 

4,  29  [dorsal  root-fibres  in  cord).  Bethe,  Pfliiger's  Arch..  1907,  116,  385! 
Bruce  and  Dawson,  Trans.  Roy.  Soc,  J-:dinburgh,  1913,  48,  697.  Cajal, 
Compt.  Rend.  Soc.  de  Biol.,  1903,  420  {against  autoregeneration).  Clark 
(E).,  J.  Comp.  Neurol.,  1914,  24,  Oi.  Feiss.  Q.  J.  Exp.  Phys.,  1913,  7, 
31.  Harrison  (R.),  Anat.  Record.,  Dec,  1908;  Ingebrigtsen,  J.  Exp. 
Med.,  1913,  17,  182;  ib.,  1913,  18,  412  (in  vitro).  Head,  Brit.  Med.  J.. 
May  27,  1903.  Huber,  J.  Lab.  Clin.  Med.,  1917.  2,837  (operative treat- 
ment of  peripheral  nerves);  Am.  J.  Phys..  1900.  3,  339  (degeneration  and 
regeneration  of  nerve  endings  in  nniscle).  Langley  and  Anderson,  J. 
Phys.,  1904,  31,  418  (on  autogenetic  regeneration);  ib.,  31,  365  (union  of 
different  kinds  of  fibres).  Langley,  J.  Phys.,  1900,  26,  417  (preganglionic 
fibres);  ib.,  1898,  22,  213;  Kilvington  and  Osborne,  J.  Phys.,  1906,  34, 
267  (postganglionic  fibres).  Meek,  Am.  J.  Phys..  1910.  26,  367;  1911, 
28,  352  (myenteric  nerves).  Mott,  Halliburton  and  Edmunds,  Proc 
Roy.  Soc,  1906,  B  78,  239,  329,  (no  autoregeneration).  Osborne  and 
Kilvington,  J.  Phys.,  1908.  37,  i;  ib.,  1909.  38,  268  (axon  bifurcation); 
Brain,  1910,  33,  261  (central  nervous  response  to  peripheral  nervous  dis- 
tortion). ScaiFER  and  Feiss,  Q.  J.  Exp.  Phys.,  1916,  9,  329  (cervical 
sympathetic  and  vagus).     Tuckett,  J.  Phys.,  1903,  29,  303  (vagus). 

Anastomosis  of  Nerves. — Budgett  and  Green,  Am.  J.  Phys.,  1900,  3,  115 
(vagus  and  hypoglossal).  Cunningham,  ib.,  1898,  1,  239.  Erlanger, 
ib.,  1903,  13,  372  (spinal  nerve  and  vagus).     Feiss,  Q.  J.  Exp.  Phys.,  1912, 

5,  I,  399-  Howell  and  Huber.  J.  Phys.,  1892^  13,  333.  Kennedy! 
Proc.  Roy.  Soc,  1914,  B  87,  331  (nerve  anastomosis).     LANtiLEY,  J.  Phys., 

1904,  31,  363  (phrenic  and  cervical  sympathetic);  ib.,  1898,  23,  240  (vagus 
and  cervical  sympathetic).  Langley  and  Anderson,  J.  Phys.,  1904,  30, 
439  (union  of  a  cervical  nerve  with  superior  cervical  ganglion). 

Trophic  Nerves. — Bikeles  and  Jasninski,  Zentralbl.  f.  Phys.,  12,  343. 
Jacobson  (C).  Am.  J.  Phys.,  1910,  26,  413.  ]Marinesco  and  Serieux, 
Arch,  de  Phys.,  1893.  26,  453-  Turner  (W.  A.),  Brit.  Med.  J.,  Nov.  23 
1895. 

CHAPTER  XV. 
ELECTRO-PHYSIOLOGY. 

Biedermann,  Elecktrophysiologie ;  Ergeb.  d.  Phys.  (Bioph.),  1902,  120;  ib., 
1903,  103.     Du  Bois-Reymond,  I'ntersuch.  iibcr  thierische  Elektricitat. 

Relation  of  Permeability  of  Cell  Envelopes  to  Ions  and  Electrical  Phenomena 
of  Tissues.— Bernstein,  Pfliiger's  Arch.,  1902,  92,  321.  Br^nings,  ib., 
1903.  98,  241;  100,  367.  Hober,  ib..  1903,  106,  399-  Lillie  (R.  S.), 
Am.  J.  Phys.,  1914,  34,  414;  t6.,  1913,37,  34^;  ib.,  1916,  41,  126  (conditions 


I204  BIBLIOGRAPHY 

of  physiological  coudiicliun  in  iiiilable  tis:>itis).  Macuonalu  (J.  S.), 
Thompson  Vates  Lub.  Kep.,  I'niv..  Liverpool,  njo-',  4,  ^i,?.  Nernst, 
Go.tingcM-  Xachrichte  Math.  Phys.  Kl.,  1899,  llvli  1  (resume  in  Hojer's 
Physikal.  Cheni.  tl.  Zell.  u.  Gewcb.  3rd  Edit.,  lyii,  454  )  (theory  oj  stimu- 
lation). Stewart  (G.  N.),  J.  Bost.  Soc.  Med.  Sci.,  June  3,  1897;  J-  Phys.. 
iS(»').  24,  JiJ. 

Electrolytes  and  Cells.-  Ckoziek,  Am.  I.  Phys.,  lyiO,  39,  297  {sensory  stimu- 
lation). LoHB  and  Cattell,  J.  Biol.  Ch.,  1915.  23,  41  {diffusion  of 
potassium).  Loeb  (J.),  Am.  J.  Phys.,  lyoj,  6,  411;  Pflii^er's  Arch., 
1902,  88,  OS;  ib.,  1902,  91,  248;  ib. ,'igo^,  107,  25 j;  Bioch.  Z.,  1907,  6, 
351 ;  Mathews  (A.  P.),  Am.  J.  Phys.,  1904,  12,  419  ('  toxic  and  antitoxic  ' 
effects  of  ions). 

Current  of  Injury  (Demarcation  Current,  Resting  Current). — Bernstein  and 

TbCHERMAK,  PUiiger's  Arch.,  1904,  103,  07.  Bernstein,  ib..  1906,  113, 
605.     Bru.n'ings,  ib..  1904, 101,  201.     Cybulski,  Arch.  Internal,  de  F'hys.. 

1912,  11,  418.  Hexze,  Pfliiger's  Arch.,  1902,  92,  451-  Hermann,  Z.  f. 
Biol.,  1912,  58,  281.  Hardy,  J.  Phys.,  1913,  47,  108.  Ho3er,  Pfliiger's 
Arch.,  1909,  126,  331;  ib..  1910,  136,  333;  Stewart  (G.  N.),  Am.  J. 
Phys.,  1903,  9,  75  {effect  of  saponin  on  resting  current  of  muscle  and  nerve). 
Loeb  and  Beutner,  Science,  1912,  35,  912;  Bioch.  Z.,  1912,  44,  303;  ib., 
1914.  59,  195-  Macdonald  (J.  S.),  Proc.  Roy.  Soc,  1900,  B  67,  310,  315, 
325;  SowTON  and  Macdonald,  ib..  B  71,  282,  472  {nerve).  Mathews 
(A.  P.),  Am.  J.  Phys.,  1903,  8,  294  {electrical  polarity  in  hydroids). 

Action  Current  of  Muscle. — Bernstein,  Pfluger's  Arch.,  1902,  89,  289  {relation 
to  work).  Buchanan,  J.  Phys.,  1901-2,  27,  95  {persistent  contractions). 
HoFFM.\NN,  Arch.  f.  Phys..  1909,  341  {voluntary  contraction).  Ll'c.\s  (K.), 
J.  Phys.,  1909,  39,  207  {relation  to  propagation  of  excitation).  Sanderson 
(J.  B.),  J.  Phys.,  1898-9,  23,  i^5-  Snyder,  Am.  J.  Phys.,  1913,  32,  336 
{twitch) . 

Action  Cujrrent  of  Nerves. — Bernstein,  Pfluger's  Arch.,  1897,  67,  349- 
Alcock  and  Sekmann,  Pfluger's  Arch.,  1903.  108,  426;  J.  Phys.,  1905,  32, 
p.  XXX ;  Lewandowsky,  Pfluger's  Arch.,  1898,  73,  288  (vagus  in  respira- 
tion). Macdonald  (J.  S.),  J.  Phys.,  1899,  24,  p.  xxvi  {vagus).  Mac- 
don.\ld  and  Keid,  J.  Phys.,  1898,  23,  100  {phrenic).  Waller  and 
Sowton,  Proc.  Roy.  Soc,  Oct.  31,  1903;  J.  IMiys.,  189S,  22,  1  {effect  of 
poisons  on).     Wedensky,  J.  de  Phys.  Path.  Gen.,  1903,5,  1042  {telephone). 

Polarization   of   Nerves. — Du  Bois-Reymond,   Sitzungsber.  d.   Kgl.  Preuss. 

Akad.,  1883,  1  {secondary  electromotive  phenomena).  Herm.\nn.  Pfluger's 
Arch.,  1879,  19,  416;  ib..  1881,  26,  246;  ib.,  1884,  33,  103;  Handbuch. 
d.  Physiologie,  Band  2,  1878.  Lapicque  and  Petetin,  j.  Phys.  Path. 
Gen.,  1910,  12,  696.  Locke  (F.  S.),  J.  Exp.  Med.,  1896.  1,  630  {effect 
of  ether).  Schwartz,  Pfluger's  Arch.,  1911,  138,  487.  Stewart  (G.  N.), 
Proc  Roy.  Soc  (Edin.),  Jan.  21,  1889;  J.  Phys.,  1889.  10,  458.  Waller 
(A.  D.),  J.  Phys.,  1895,  19,  p.  vii;  ib..  20,  p.  xi;  ib..  21,  p-  vi;  ib..  22,  p.  i 
(electrotonic  currents). 

String  Galvanometer. — ^Einthoven,  Pfluger's  Arch.,  1909,  130,  287.  Samo- 
JLOFF,  Arch.  f.  Phys.,  1910,  477.  Snyder,  Am.  J.  Phys.,  1913.  32,  329 
{use  of).  Williams  (H.  B.),  Am.  J.  Phys.,  1916,  40,  230  {protection 
against  external  electrical  disturbances). 

Action  Current  of  Heart  (Electrocardiogram). — Dale  and  Mines,  J.  Phys., 

1913,  46,  319  {nerve  stimulation).  Fkaser,  J.  Exp.  Med.,  1915.  22,  292. 
GoTCH,  Heart,  1910,  1,  235.  Jolly,  (,).  J.  Exp.  Phys.,  1915,  9,  9.  Meek 
and  Eyster,  Am.  J.  Phys.,  1912,  30,  271  {vagus  stimulation);  ib..  1912. 
31,  31.  Mines,  J.  Phys.',  1914,  47,  419  {vagus).  Pike  (F.  H.),  Am.  J. 
Phys.,  1916,  40,  433  {stimulation  of  phrenic  by).  Sanderson  and  Page, 
Proc.  Roy.  Soc,  1878,  401.  Symes,  J.  Phys.,  1905,  32,  p.  Ixxi  {heart- 
nerve  stimulation).  Waller.  Phil.  Trans.  Roy.  Soc,  1889,  B  189. 
Wiggers,  Arch.  Int.  Med.,  1917,  20,  93. 


ELECTRO-PHYSIOLOGY  1205 

Human  Electrocardiogram.  Barker  (L.  F.),  Johns  Hopk.  Hosp.  Bull..  1910, 
}^6  (ifsiinie).  Hi  i.L,  J.  Phys..  1911,  43,  p.  v;  Fahr  (G.),  Heart,  1912,4, 
147  (electro-  and  phono-cardiograms) .  Einthovkn  et  al.,  Pfliiger's  Arch., 
1900.  80,  139:  lb-.  1903,  99,  47^;  ib..  1913,  149,  48,  05;  ib.,  1913,  150, 
EYSTERanil  Mei:k.  Arch.  Int.  Mod.,  191 3. 11,  204;  Forbes  and  H  apple  ye, 
Am.  J.  Phys..  11(17.  42,  228  (effect  of  temperature).  Goddard,  Arch.  Int. 
Med.,  1915,  16,  033.  Krl'mbhaar  and  Jenks,  Heart,  1917,  6,  189 
(children).  Lewis  (T.),  Heart,  1910,  2,  23.  HoniNsoN  (Canby),  J. 
Exp.  Med.,  1912.  16,  291:  Arch.  Int.  Med.,  i9i(>.  18,  830.  Waller, 
Lancet,  1913.  May  24  and  31  (general  review):  .^rch.  d.  Pliys,  1890,  22, 
14ft;  J.  Phvs.,  11)14,  48,  pp.  x\ii,  xl.  \Villl\ms,  Am.  J.  Phys.,  1914, 
35.  2QJ. 

Gland  Currents.— Bradford  (J.  R.),  J.  Phys.,  iSSS. 9,  287  (submaxillary  gland). 
Cannon  and  Cattell,  Am.  J.  Phys.,  1916,  41,  74.     Gesell,  ib..  1917,  42, 

Eye  Currents.— Day,  Am.  J.  Phys.,  1915,  38,  369.  Einthoven  and  Jolly, 
().  J  .  JIxp.  Phys..  190S,  1,  373.  GorcH.  J.  Phys.,  1903,  29,  388;  ib.,  1904, 
31,  I.  Jolly,  Q.  J.  Exp.  Phys.,  1909,  2,  363.  Trendelenblrg,  Ergeb. 
d.  Phys.,  191 1,  21.     Waller,  Q.  J.  Exp.  Phys.,  1909.  2,  401. 

Electric  Fishes.-  Du  Bois-Reymond,  Ges.  Abhand.,  2,  001  (Malapterurus) ; 
Sitz.  d.  Berl.  .\kad.,  March  13,  1883  ;  July  it),  1885  (torpedo).  Gotch  and 
Birch,  Phil. Trans.  Roy.Soc,  1896,  B1S7,  3  .{J  (Malapterurus) .  Sander- 
son and  Gotch,  J.  Phys.,  1888,  9,  137  (skate). 

Galvanotropism. — Abbott  and  Life.  .\m.  J.  Phys.,  1908,  22,  202  (bacteria). 
Bancroft  (F.  W.).  l.'niv.  Calif.  Pub.,  1904,  1905,  1906  (paramoecium). 
Dale  (H.  H.).  J.  Phys.,  1900-1.  26,  291 ;  Garrey  (W.  E.),  Am.  J.  Phys., 
1900,  3,  291  :  Pearl  (R.),  Am.  J.  Phys..  1900.  4,  96  (infusoria).  Hadley 
(P.  B.),  ib.,  1907,  19,  ^9  (lobster  larvcB).  Loeb  and  Budgett,  Pfluger's 
Arch.,  1897.  65,  518  (theory).  Miller  (F.  R.),  J.  Phys.,  1906-7,  35,  215 
(crayfish).  Moore  and  Goodspeed,  Univ.  Calif.  Pub.,  191 1.  Moore 
and  Kellogg,  Biol.  Bull.,  iqK)  30,  131. 

CHAPTER  XVI. 
THE  CENTRAL  NERVOUS  SYSTEM. 

Von  Bechterew,  Funktionen  der  Xervencentra,  Jena,  191 1.  Do.valdson 
(H.  H.),  The  Rat,  191 5  (statistical  data).  Van  Gehuchten,  Anatomie 
du  Systeme  Xerveux.  Schafer  and  Symington,  Quain's  Anatomy.  3, 
Pt.  I  (numerous  references).  Sherrington,  Integrative  Action  of  the 
Xervous  System,  Xew  York,  1906.  Van  Rijnberk,  Arch.  Xeerland.  de 
Phys.,  191  7,  1,  198  (organization  of  nervous  system). 

Nerve-Cells. — Donaldson  (H.  H.).  J.  Comp.  Xeurol.,  1899,  9,  141;  Am.  J. 
Phys.,  1900,  4,  p.  vi  (size  of  cell  body  and  axon).  Gomez  and  Pike,  J.  Exp. 
Med.,  1909,  11,  25;  TucKETT,  J.  Phys.,  1905,  33,  77  (effects  of  ancemia). 
KiLviNGTON,  J.  Phys.,  1903,  28,  426  (snake  venom).  Stewart  (C.  C), 
J.  Exp.  Med.,  1896,  1,  623  (alcohol  poisoning).  Warrington,  J.  Phys., 
1898-9,  23,  112;  24,  464;  1 899-1900,  25,  462  (alterations  after  section  of 
nerve  fibres). 

Spinal  Ganglia.— Kramer  (S.  P.),  J.  Exp.  Med.,  1907,  9,  314  (function). 
Steinach.  Pflii.c^er's  .\rch..  1809,  78,  291  (centripetal  conduction). 

Enumeration  of  Fibres  in  Spinal  Roots. — Dale,  J.  Phys.,  1899,  25,  198  (dorsal 
roots,  cat).  Dvnn,  J.  Comp.  Xeurol.,  1909,  19,  6S5;  Hardesty,  ib..  1899, 
9,  64.  Ingbert,  16.,  1903,  13,  53;  ib.,  1904,  14,  209  (man).  Hatai,  ib.', 
13,  177  ('"  growing  rats). 

Paths  in  Central  Nervous  System. — BRowN-StguARo,  Arch,  de  Phy^.,  1889, 
484  (sensory).  Brice  (X.),  O.  J.  Exp.  Ph^'s..  1910,  3,  391  (Ci07ver's  tract). 
Eraser  (E.  H.),  J.  Phys.,  1901-2,  27,  37-;  1902,  28,  }C>C->  (Monakow's 
bundle).     Ranson  and   Billingsley,    Am.   J.   Phys.,    1916,    40,     571; 


I206  BIBLIOGRAPHY 

Ranson  and  Von  Hess,  ib..  191 5,  38,  1^8  [pain  and  affitent  vasomotor 
paths).  ScHAFER,  Q.  J.  Exp.  I*tiy.s.,  lyio.  3,  355  [paths  for  volitional 
impulses).  Simpson  and  Jolly,  Proc.  Roy.  Soc.  (Edin.),  1906-7,  27, 
281  (degenerations  after  lesions  of  motor  cortex  in  monkeys). 

SPINAL  CORD. 

Donaldson  and  Davis,  J.  Comp.  N'eurul.,  1903,  13,  19  {area  of  cross-sections). 

Fkiedenthal,  Arch.  f.  Phys.,  1905,  127;  Goltz  and  Ewald,   Pfluger's 

Arch.,  ibgO,  63,  362  (exciston  of  part  of  cord).     Sherrington,  J.  Phys., 

1897,  21,  209;  Dale,  ib.,  1901-2   '27,  30°  {efferent  fibres  in  dorsal  roots). 

Sherrington,    ib.,    27,    360    {spirial  roots   and  dissociative  aneesthesia). 

Trendelenburg,   Ergeb.  d.   Phys.,    1910,   454   [comparative  physiology 

of  cord) . 
Spinal  Preparation. — Guthrie  (C.  C),   Z.  biol.  Tech.    Meth.,  1911,  2,  138 

{}}ia»i»ial  and  bird).     Roaf  and  Sherringto.n,  Q.  J.  Exp.  Phys.,  1910, 

3,  209.     Sherrington,  J.  Phys.,  1909,  38,  375  [cat). 

Decerebrate  Preparation. — Brown  (T.  G.),  Q.  J.  Exp.  Phys.,  1914,  7,  293, 
345  [reflexes).  Forbes  and  Sherrington,  Am.  J.  Phys.,  191 4,  35,  367 
[acoustic  reflexes).  Miller  and  Sherrington,  Q.  J.  Exp.  Phys.,  1916, 
9,  147  [decerebrator) .  Weed,  Am.  J.  Phys.,  1917,  48,  131  [reactions  in 
decerebrate  kittens) . 

Reflexes.  -Baglioni,  Z.  f.  Allg.  Phys.,  1912,  40,  160  [cutaneous  reflexes). 
Brown  (T.  G.),  Ergeb.  d.  Phys.,  1913,  279;  Q.  J.  Exp.  Phys.,  1914,  8, 
"^ob'  193  [progression).  Brooks,  Am.  J.  Phys.,  1910,  27,  212  [effect  of 
lesions  of  dorsal  roots).  Forbes  and  Gregg,  Am.  J.  Phys.,1915,  39,  172 
[strength  of  stimulus  and  reflex  response) ;  ib.,  1915,  37,  118  [flexion  reflex). 
Langley,  J.  Phys..  1900,  25,  3t)4  {axon  reflexes).  Mayhew,  J.  Exp.  Med., 
1897,  2,  35  [time  of  reflex  winking).  Moore  and  Oertel.  Am.  J.  Phys., 
1900,  3,  45  [reflexes  after  high  section  of  cord).  Pamlow,  Ergeb.  d.  Phj-s., 
1911,  345  [conditioned  reflexes).  Porter  (E.  L.),  .\m.  J.  Phys.,  1913. 
31,  223  [reflex  arc  in  asphyxia) ;  ib.,  191 7,  43,  497  [variations  in  irritability 
of  reflex  arc).  Sherrington  and  Laslett,  J.  Phys..  1903,  29,  58  [inter- 
connection of  spinal  segments).  Sherrington,  Ergeb.  d.  Phys.,  1905. 
797  [co-ordination  of  reflexes,  common  path);  J.  Phys.,  1904,  30,  37  [spinal 
reflex  and  quality  of  cutaneous  stimulus);  ib.,  1910,  40,  28  [flexion  reflex, 
crossed  extension  reflex);  ib.,  1900,  34,  i  ;  Q.  J.  Exp.  Phys.,  1910,  3,  213 
[scratch  reflex);  Proc.  Roy.  Soc,  1907,  B' 79,  337;  1908,  80,  53;  1909. 
81,  249;  1913,  86,  219  (reciprocal  innervation  of  antagonistic  muscles). 
Simpson  and  Herring.  J.  Phys.,  1905.  32,  305  [cold  narcosis  and  reflexes). 

Knee-Jerk. — Bowditch  and  Warren,  J.  Phys.,  1890,  11,  25.  Franz,  Am. 
J.  Insanity,  1909,  65,  471.  Jolly,  Q.  J.  Exp.  Phj's..  191 1,  4,  07. 
Lombard,  J.  Phys.,  1889.  10,  122.  Sherrington,  J.  Phys.,  1892.  13, 
669  [posterior  roots  concerned).  Snyder,  Am.  J.  Phys.,  1910,  26,  474. 
Stewart  (P.).  J.  Phys..  1898.  22,  oi.     Waller,  ib.,  1890,  11,  384. 

Reversal  of  Reflexes. — Brown  (T.  G.),  Ergeb.  d.  Phys.,  191 3,  430.  Knowl- 
TON  and  Moore,  Am.  J.  Phys.,  1917.  44,  490  (reversal  of  reciprocal  inhibi- 
tion in  earth-worm).  Sherrington  and  Sowton,  J.  Ph\-s.,  1911,  42, 
383  [chloroform  and  reversal) ;  Proc.  Roy.  Soc,  1911,  B  83,  435. 

Inhibition  in  Nervous  Reactions. — BRowN-SfiQUARO,  Arch,  de  Phys..  1889, 
21,  751.  Hering.  Ergeb.  d.  Phys.  (Bioph.).  1902,  50V  Forbes  (A.), 
Q.  J.  Exp.  Phys.,  191 2,  5,  149  [reflex  inhibition).  McDoug.^ll,  Brain, 
1903,  102  (2),  p.  153.  Pawlow,  Richet's  Livre  Jubilaire,  1912.  325. 
Yerkes,  J.  Comp.  Neurol.,  1904,  14,  124  [frog).     Sherrington,  J.  Phj-s., 

1907,  36,  185  [effect  of  strychnin);   ib.,  1913.  47,  196;  Q.  J.  Exp.  Phys.. 

1908,  1,  67  (combination  of  excitation  with  inhibition). 

Spinal  Shock.— Pike  (F.  H.),  1912.  Am.  J.  Phys.,  1912,  30,  436;  Q.  J.  Exp. 
Phys  .  iyi3,  7,  i-  Porter  and  Mihlberg,  Am.  J.  Phys.,  1900,  4,  334 
(inhibition  after  injury  of  cord?). 


THE  CENTRAL  NERVOUS  SYSTEM  1207 

CEREBELLUM. 

Herrick  (C.  J.).  J.  Comp.  Xeurol.,  1895,  6,  66  (histogenesis) ;  ib.,  1914,  24, 
I  {S'ecturus).  Luciani,  Ergcb.  d.  Phys.  (Bioph.),  1904,  259.  Wilson 
and  Pike.  Am.  J.  Phys..  1916.  41,  571  {lesions). 

Localization. — BakX.ny.  Wicn.  Klin.  Woch.,  191  2,  No.  52.  Black,  J.  Lab. 
C~lin.  Med.,  iqK),  1,  407  (risti)ne).  Bradley,  J.  Anat.  and  Phys.,  I903, 
37,  -i-!!  (fissures).  Lkwandowsky,  Arch.  f.  Phys,,  1903,  129.  Meyers, 
J.  .\m.  Mfd.  .\ss..  i9i<>,  67,  1745.  Mills  and  \Veisenbir(;.  ih.,  1914, 
Nov.  21.  I  Si  3.      \an  Kynhekk,  Ergcb.  d.  Phys.,  1908,  653. 

Labyrinth  and  Equilibration. — Alexander  and  Kreidl,  Pfliiger's  Arch., 
1902,  89,  473  {galvanic  reaction  in  deaf  vmtes).  Beritoff,  Q.  J.  Exp. 
Phys.,  11)10.  9,  ig9  [labyrinthine  reflexes  in  decerebrate  preparation).  Bak- 
Any,  Z.  f.  Sinnesphysiol.,  1906,  41  (2),  37.  Cyon,  Pfltiger's  Arch.,  1900. 
79,  211  ;  Arch.  f.  Phys.,  1897.  29  (vestibule  and  space  perception).  Ewald 
(J.  K.),  Pfliiger's  Arch.,  1896,  521  (labyrinth  and  rigor).  Fisher  and 
Muller,  Am.  J.  Phys..  1916,  #1,  267  (cats).  Golla,  Proc.  Koy.  Soc. 
Med.,  1912,  5,  123.  Hensen,  Pfluger"s  Arch.,  1899,  74,  22  (statocysts). 
Kreidl,  Ergeb.  d.  Phys.,  1906,  572  (vestibular  apparatus).  Lee  (F.  S.), 
Am.  J.  Phys.,  1898,  1,  128  (ear  and  lateral  line  in  fishes).  Lyon  (E.  P.), 
ib.,  1900.  3,  86;  4,  77  (compensatory  movements  in  fishes).  Maxwell, 
(S.  S.),  ib.,  1912.  29,  367.  Mills  and  Jones,  J.  Am.  Med.  Ass.,  1916, 
67,  1296.  Parker,  Bull.  I'.S.  Bur.  Fisheries,  1909,  29,  45  (influence 
of  eyes,  ears,  etc..  on  movements  of  dog  fish).  Prince,  Am.  J.  Phys.,  1917, 
42,  308  {kittens).  Wilson  and  Pike,  Phil.  Trans.  Roy.  Soc'  (Lond.), 
1 91 2,  B203,  127;  Arch.  Int.  Med.,  191 4,  14,  911.  'S'erkes.  Am.  J.  Phys., 
1907.  10,  p.  xviii.  ZoTH,  Pfliiger's  Arch.,  1901,  86,  147  (ear  of  dancing 
»wuse) . 

Postural  Reflexes,  Decerebrate  Rigidity. — Brown  (T.  G.),  J.  Phys.,  191 5,  49, 
180  (plastic  flexor  tonus  in  monkey).  Cobb,  Bailey,  and  Holtz,  .\m.  J. 
Phys.,  191 7,  44,  239  (extensor  rigidity).  Frohlich  and  Sherrington, 
J.  Phys..  1903,  28,  14  (path  of  inhibitory  impulses).  Maonvs  and  de 
Kleijn,  Pfluger's  Arch.,  1913,  164,  163,  178;  ib..  1915,  160,  429  (postural 
reflexes);  ib.,  1914,159,  2i8(frog).  Mills  (C.  K.),  J.  Am.  Med.  Ass.,  1916, 
67,  1485  (problems  of  cerebral  tone) .  Roaf,  Q.  J.  Exp.  Phys.,  1913,  5,  31 
{CO2  output  in  decerebrate  rigidity).  Sherrington,  Brain,  1913,  38,  191 
(postural  activity  of  muscle  and  nerve);  O.  J.  ]*-xp.  Phvs..  1909,  2,  109. 
J.  Phys.,  1898,  22,  319  (decerebrate  rigidity  and  reflex  co-ordination  of 
movements).  Van  Kijnberk.  Arch.  Neerland.  de  Phys.,  1917,  1,  762 
(muscular  tonus  and  decerebrate  rigidity).     Weed.  J.  Phys.,  1914,  48,  205. 

Muscular  Tonus. — Burnett  (T.  C),  Soc.  Exp.  Biol.  Med.,  1915,  12,  177 
[skeletal  muscle).  Hooker,  Am.  J.  Phys.,  1912,  31,  47  (influence  of 
CO.y  and  O^  on  tone  in  bloodvessels  and  alimentary  canal).  Lingle  (D.  J.), 
Am"*.  J.  Phys.,  1910,  26,  361  {plain  muscle).  Mott  and  Sherrington, 
Proc.  Koy.  Soc,  1895,  57,  481  (influence  of  sensory  nerves  on  movements 
and  nutrition  of  limbs).  Sherrington,  J.  Phys.,  1894-5,  17.  -JH  (nerves 
of  muscles). 

Co-ordination  of  Movements. — Beevor,  Ergeb.  d.  Phys.,  1909,  326.  Dv  Bois- 
Kevmond  (  K.).  Arch.  f.  Phys.,  Supp.  Bd.,  1900, '327;  ib.,  1902,  Supp.  Bd.. 
27.  Hering  and  Sherrington,  Pfluger's  Arch.,  1897,  68,  211  {inhibition 
of  voluntary  muscles  from  corte.x:).  M.\gnl's,  ib..  1909,  130,  219,  2^^;  ib., 
191a,  134,  545;  Sherrington,  Proc.  Koy.  Soc,  1905,  B  76,  160,  269 
(reciprocal  innervation). 

Basal  Ganglia  and  Mid-Brain. - -Brown  (T.  g.),  J.  Phys.,  1915,  49,  195,  208 
(is  progression  learnt  ?).  Herrick  (C.  J.),  J.  Comp.  Xeurol..  1917,  28, 
215  (mid-brain  and  thalamus  of  Xccturus). 

CEREBRUM. 

Baglioni,  Zentralb.  f.  Phys.,  1901,  14,  97;  Maxwell  (S.S.),  J.  Biol.Ch.,  1907, 
2,  183  (chemical  stimulation),  von  Bechterew,  Arch.  f.  Phj-s.,  1902, 
264  (cortical  secretory  centres);  ib.,   1905,   297   (urine  and  sweat  centres)'; 


t2o8  BIDfJOGRAPHY 

ib.,  1005.  5-25  (injluencc  of  cortex  on  sexual  glands).  Brown  (T.  G.),  Q.  J. 
Exp.  Pliys.,  1910,  3,  1,^9  {removal  of  cortex  of  one  hemisphere);  J.  Phys., 
1914,  48,  pp.  XXX,  xxxiii  (post-central  gyrus).  Campbkll,  Hrit.  Med.  J.. 
Feb.  6,  1904  (histological  differentiation,  summary).  Flechsk;,  Lancet, 
Oct.  19,  igoi,  1027;  Vogt.,  J.  Phys.  Path.  Gtin.,  1900,  525  (myelination). 
Fran(;:ois-Franck  and  Pitres,  Arch,  de  Phys.,  1885,  7,  My  (exciiahility). 
Franz  (S.  I.),  Psychol.  ]iull.,  191 1,  8,  m  ;  ib.,  1914,  11,  131  ;  ib..  1916,  13, 
149  (review  and  summary);  J.  Am.  IVlcd.  Ass.,  190O,  47,  M^M  (association 
areas  in  monlieys).  Golt/:,  PHiiger's  Arch.,  189J,  51,  370;  ih.,  1899,  76, 
411  (brain  extirpations,  monkey).  Hkrrick  (C.  J.),  J.  Animal  Behav., 
1913,  3,  222  (origin  of  cerebral  cortex).  Holmks  (G.),  J.  Phys.,  1901,  27, 
I  (histology  of  Goltz's  'brainless  dog').  Karpi.us  and  Kreidl,  Arch.  f. 
Phys.,  1914,  155  (extirpation  of  hemispheres  in  monkeys),  von  Monakow, 
Krgeh.  d.  Phys.  (Bioph.),  1902,  534;  ib.,  1904,  100  (localization).  Mott, 
ScHi'STKR  and  Hai.libiirton,  Proc.  Roy.  Soc,  1910,  B  82,  124  (cortical 
lamination).  Rollett,  Pfliiger's  Arch.,  1900,  79,  303;  80,  O38  (historical, 
especially  on  Gall's  doctrines). 

Frontal  Lobes.  Bolton,  Brain,  26,  215.  Franz,  Am.  J.  Phys.,  1902,  8,  i 
(frontal  lobes  and  sensori-motor  habits);  Arch,  of  Psychol.,  Mar.,  1907, 
No.  2  (functions) .  Herrick  (C.  J.),  Science,  1910,  31,  7  (intelligence  and  its 
organs).  McDougall,  Brain,  1901,  24,  577  (seat  of  psycho-physical 
processes) . 

Motor  Areas. — von  Bechterew,  Arch.  f.  Phys.,  1899,  Supp.  Bd.,  543  (man); 
lb.,  1900,  22  (sensory  functions  of  motor  area).  Brown  and  Sherrington, 
J.  Phj's.,  1911,  4S,  209  (baboon);  ib..  1913,  46,  p.  xxii  (recovery  after 
lesions).  Brown  (T.  G.),  Q.  J.  Exp.  Phys.,  1915,  9,  82.  loi,  117,  131 
(^facilitation  '  in  motor  cortex  in  monkey).  Ci'nnin<;ham,  J.  Phys.,  1898. 
22,  2(14  (opossum).  Franz  (S.  I.),  Psychol.  Monographs.  April,  1915. 
Gru.nraum  and  Sherrington,  Proc.  Roy.  Soc,  190 1,  B  69,  206;  ib..  72, 
152  (higher  apes).  Hitzig,  Brit.  Med.  J.,  Dec.  i,  1900.  Levton  and 
Sherrington,  Q.  J.  Exp.  Phys.,  1917,  11,  135  (excitable  cortex  of  chim- 
panzee, orang-utan  and  gorilla).  Russell  (J.  R.),  J.  Phys.,  1894-5,  17, 
378  (eye-movements).  Simpson  and  Kin<;,  y.  J.  Exp.  Phys.,  1911,  4, 
53  (sheep).  ScHAEER,  J.  Phys.,  1898-9,  23,  310  (sensory  function). 
Ziehen,  .\rch.  f.  Phys..  1899,  138  (relation  between  position  and  function 
in  motor  region). 

Sensory  Localization  in  Cerebral  Cortex.^ — Dusser  de  Barenne  (J.  G.), 
(.).  J.  Exp.  Phys.,  1910.  9,  333;  Arch.  Neerland.  de  Phys.,  1916,  1,  15. 
von  Bechterew,  Arch.  f.  Phys.,  1905,  53;  1912,  t,},;  Black,  J.  Comp. 
Neurol.,  1913,  23,  193;  Hitzig,  Arch.  f.  Psychiat.,  35,  383;  Sharkey, 
Lancet,  May  22,  1897,  1399;  Vitzou,  Arch,  de  Phys.,  1893,  ^7^  (visual 
centres).  Franz,  Am.  j.  Phys.,  191 1,  28,  308  (occipital lobes).  Larionow, 
Pfliigcr's  Arch.,  1899,  76,  608  (auditory  centre,  music).  Munk,  Zentralb. 
f.  Phys.,  9,  770  {tactile  sensibility). 

Fatigue  of  Nerve  Cells  (Centres). —Carlson,  Am.  J.  Phys.,  1903,  2,  341 
(retina).  Dollev,  ib..  1909,  25,  151  ;  J-  Med.  Res.,  1909,21,95;  ib.,  1911, 
25,  283  (Purkinje  cells);  ib.,  1913,  29,  65.  Eve,  J.  Phys.,  1896,  20,  334. 
Hodge,  J.  Phys.,  1894-5,  17,  129.  Kocher,  J.  Am.  Med.  Ass.,  1916, 
67,  278.  Legendre  and  PitRON,  J.  Phys.  Path.  Gen.,  191 1,  13,  519. 
Lew,  J.  Phys.,  1900-1,  26,  210;  ib.,  1903,  28,  i.  Pugnet,  J.  Phys.  Path. 
Gen.,  1 90 1,  3,  183. 

Sleep.  Bri'.sh  and  Fayerweather,  Am.  J.  Phys.,  1901.  5,  i9<)  (changes  in 
blood- pressure).  Brodmann,  J.  Psych.  Neurol.,  1,  10;  Zentralb.  f. 
Physiol.,  16,  310.  Goddard,  J.  Comp.  Xcurol.,  i8g8,  8,  245  (movements 
of  nerve  cells).  Howell,  J.  Exp.  Med.,  1897,  2,  313  (plethysmograms  in). 
Walokn.  Am.  J.  Phys.,  1900,  4,  124  (hypnotic  sleep). 

Cerebral  Circulation. — Brown  (E.  D.),  J.  Pharm.  Exp.  Ther.,  i9i<>,  8,  185. 
Cannon  (W.  B.),  Am.  J.  Phys.,  1902,  6,  91  (cerebral  pressure  after  trauma). 
Grunbaum  and  Sherrin(;ton,  Brain,  25,  270  (apes).  Hill  (L.),  Phil. 
Trans.  Roy.  Soc,   1900,   B  193,  '>9  (ligation  of  cerebral  arteries).     Mott 


THE  CF.XTRAL  NERVOUS  SYSTEM  1209 

and  Hill.  J.  Phys..  i8ij8-<j.  23,  p.  xix;  H'-.  i<)o(».  34,  p.  iv  (histological 
changes  after  cerel>ral  anceniia).  Howkll,  Am.  J.  IMiys.,  1808,  1,  57 
(effect  of  high  arterial  pressure).  Kkamkk.  J.  Mxp.  Med.,  nji^.  15,  348 
(function  of  circle  o/'  II  illis).     Jf.nskn,  PHiigcr's  Arch.,  1905.  107,  81. 

Resuscitation  of  Central  Nervous  System. — Pike.  Guthkik  and  Stewart, 
;.  llxp.  yivd..  ii)oS.  10,  .)wo;  Am,  J.  Phys.,  igo8.  21,  339  (reflex  excita- 
bility after  cerebral  aucBtiiia).  Stewart,  Guthrie,  Burns  and  Pike, 
J.  lixp.  Med.,  H)Of),  8,  ^8(). 

Chemistry  0!  Central  Nervous  System.  c;n:s,  J.  Biol.  Ch.,  1907,  2,  159 
(crrel>ron).  H.mai,  .\m.  J.  I'livs.,  190^,12,  lid  (effect  of  partial  starvation). 
Koch  (W.).  Z.  i.  Physiol.  Ch.,  1902.  36,  134  (lecithin,  hephalin  andcerebrin). 
Koch  (W.  and  M.  L.),  J.  Biol.  Ch..  n)i.<,  15,  4-23  (yat) ;  ib..  1917.  31,  595- 
Koch  and  Mann,  J.  Phys..  1908.  36,  p.  xxxvi  (human  brains).  Lkvenk. 
j.  Biol.  Ch..  191J,  13,  463  (sulphatide).  Lkvkne  and  West,  J.  Biol. 
Ch.,  191 7,  31,  633,  (>49;  Levene,  ib.,  1913,  15,  339  (cerebrosides) ;  tl>.,  191O, 
24,  41  (kephalin).  Rosenheim,  Bioch.  J.,  1913,  7,  604;  if^-,  I9i4'  8,  no 
igalactosides).     Tebb,    J.    Phys.,    1906,    34,    loO    (cholesterol). 

Cerebrospinal  Fluid.— Blumenthal,  Ergeb.  d.  Phys.  (Bioch.).  1902,  285. 
Caktek  (W.  S.),  Arch.  Int.  Med.,  1912,  10,  425  (intraspinal  injection  of 
Ringer's  solution).  Dixon  and  Halliburton,  J.  Phys.,  1913.  47,  ^15 
(secretion) ;  ib.,  1914,  48,  12S,  317  (pressure) ;  ib.,  1916,  50,  198  (circulation). 
Frazier  and  Peet,  Am.  J  .  Phys..  1914,  35,  268  (formation  and  circulation) ; 
ib.,  1915,  36,  4(>4.  Kramer  (S.  P.),  New  York  Med.  J.,  Mar.  16,  1912 
(circulation).  Spina,  Pfliiger's  Arch.,  1899,  76,  204;  ib.,  1900,  80,  370; 
ib..  1901.  83,  120.  415.  Thomson.  Hall  and  Halliburton.  Proc.  Roy. 
Soc.  ii  64,  343  (man).     Weed  and  Gushing.  Am.  J.  Phys..  1915.  36,  77. 

Chemistry  of  Cerebrospinal  Fluid. — Carlson  and  Martin,  Am.  J.  Phys..  1911. 
29,  64  {pituitary  secretion  in?).  Felton,  Hussey  and  Bayne-Jones. 
Arch.  Int.  Med.i  1917,  19,  1085.     Fine  and  Myers,  Soc.  Exp.  Biol.  Med.. 

1916.  13,  126  (non-protein  N).     Halverson  and  Bergeim.  J.  Biol.  Ch.. 

1917.  29,  337  (calcium).  Hurwitz  and  Tranter.  Arch.  Int.  Med.. 
1916,  17,  828.  Kahn  and  Neal,  Soc.  Exp.  Biol.  Med.,  1916,  14,  26. 
Kramer  (S.  P.),  Brain.  1911,  34,  39.  Krause  and  Corneille.  J.  Lab. 
Clin.  Med,,  1916,  1,  685;  Xawratski,  Arch.  t.  Phys..  1897.  156  (sugar  in). 
Myers.  J.  Biol.  Ch.,  1909,  6,  115:  Rosenbloom.  Arch.  Int.  Med.,  1914. 
14,  536  (potassium).  Weston,  J.  Med.  Res..  191 7,  35,  367  (reaction). 
Woods,  Arch.  Int.  Med.,  1915,  16,  577  (nitrogen). 

CHAPTER  XVII. 

THE  AUTONOMIC  NERVOUS  SYSTEM. 

Autonomic  System.^ANOERSoN  (H.  K.).  J.  Phys.,  1902,  28,  499  (regeneration 
of  sympathetic).  Brown  and  Sherrington.  Q.  J.  Exp.  Phys..  1911,  4, 
i9i  (pilomotor  system).  Burton-Opitz  (R.).  Am.  J.  Phys..  1916,  41, 
103  ;  ib.,  1917,  42,  498  (depressor  function  of  thoracic  sympathetic).  Dastre 
and  MoRAT,  Arch.de  Phys.,  1S82,  ^t,-j (vasodilatators in  cervical sym pathetic) . 
Edwards  (D.  J.).  Am.  J  .Phys.,  1914.  33,  220  (sympathetic  nervous 
system  in  the  turtle).  Gaskell,  J.  Phys.,  1886,  7,  i-  Herring  (P.  T.), 
J.  Phys.,  1903,  29,  282  (spinal  origin  of  cervical  sympathetic).  Langley, 
Ergeb.  d.  Phys.  (Bioph.),  1903,  818  (autonomic  system  of  vertebrates). 
Langley,  J.  Phys.,  1894-5,  17,  296  (secretory  and  vasomotor  fibres  of  cat's 
foot) ;  ib..  1896,  20,  33  (medullated  fibres  of  the  sympathetic  system).  Lang- 
ley, J.  Phys.,  1899-1900,  25,  468;  ib.,  1904,  3i,  244  (commissural  fibres  in 
sympathetic  system).  Langley  and  Anderson,  J.  Phys.,  1895-6,  19,  71. 
372  (innervation  of  pelvic  and  adjoining  viscera);  ib.,  17,  177  (hypogastric 
nerves).  Langley  and  Orbeli.  J.  Phys.,  1910,  41,  450;  ib.,  1911,  42, 
113  (sympathetic  and  sacral  autonomic  system  of  amphibia).  ^Ieltzer 
(S.  J.  and  C).  Am.  J.  Phys.,  1903.  9,  57  {vasomotor  nerves  of  rabbit's  ear). 


1210  BIBLIOGRAPHY 

CHAPTER    XVIII. 
THE  SENSES. 

Helmholtz,  Physiologische  Optik.  Helmholtz.  Tonempfindungen  (trans- 
lated by  Kills).  Mi'LLER.  Ergeb.  d.  Phys.  (Bioch.j,  1903,  2O7  {psycho- 
phvsical  methods). 

VISION. 

Eye  Liquids. — Henderson  (E.  E.)  and  Starling,  J.  Phys.,  1904.  31,  305; 
Proc.  Roy.  Soc,  IQ06,  B  77,  294  [intraocular  pressure  and  secretion). 
Hill  and  Flack,  ib.,  \q\z.  B  85,  439  [secretion  of  aqueous).  Wessely. 
I>£;i-h.  d    Phys.,  1903,  365. 

Accommodation.  -Barrett,  J.  Phys.,  1885,  6,  46.  Beer,  Pfliiger's  Arch., 
kS'M,  58,  323;  ib.,  1897,  67,  541;  69,  507;  Science,  Nov.  18,  1904.  Ein- 
thovex,  Ergeb.  d.  Phys.  (Bioph.),  1902,  680.  Hess,  Arch.  f.  Ophthal., 
42,  288  [velocity  of  accommodation).  Schoen.  Pfluger's  Arch.,  1893.  S9, 
427.  Snellen.  Ergeb.  d.  Phys.  I  Bioph.),  1904,  339  (sAmsco/>v).  Stuart 
(T.  P.  Anderson),  J.  Phys.,  1904,  31,  38.  Tscherning,  Arch,  de  Phys.. 
1892,  158;  ib..  1894,  40;  1893,  15^'  181;  J.  Phys.  Path.  Gen.,  1899,  312. 

Iris. — Anderson  (H.  K  ),  J.  Phys.,  1906,  33,  150,  414;  ib.,  1904,  30,  15.  290; 
Meltzer  and  Auer,  Am.  J.  Phys.,  1904,  11,  28  [paradoxical  dilatation 
of  pupil).  Cobb  (P.),  Am.  J.  Phys.,  1914,  36,  335  [pupil  diameter  and 
visual  acuity).  Guthrie  and  Ryan,  Science,  1910,  31,  395  [effect  of 
asphyxia  on  pupil).  Grunert,  Zenlralb.  f.  Phys.,  1899,  12,  406. 
ScijiFER,  O.  J.  Exp.  Phys..  1908,2,  287  [dilator  pupillcs in  man). 

Eye  Movements  and  Innervation. — Dodge,  Am.  J.  Phys.,  1903,  8,  307- 
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J.  Phys.,  1896,  17,  27;  ib.,  1916,  50,  p.  xlvi  [apparatus  to  illustrate 
Listing-Bonders  law).     ZoTH,  Xagel's  Handbuch  der  Physiologic. 

Retina. — Dittler,  Pfliiger's  Arch.,  1907,  117,  293  [contraction  of  cones). 
Ferree  nd  Rand,  Am.  J.  Phys.,  1912,  29,  398;  Hansell,  Philadelphia 
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Laurens  and  Williams,  Soc.  Exp.  Biol.  Med.,  1916,  13,  183  [movements 
of  retinal  elements).  Trendelenburg,  Ergeb.  d.  Phys.,  191 1,  i. 
TscHERMAK,  Ergeb.  d.  Phys.  (Bioph.),  1902,  693  [functions  of  rods  and 
cones). 

Colour  Vision. — Calkins,  Arch.  f.  Phys.,  1902,  Supp.  Bd.,  244.  Edridge- 
Green,  J.  Phvs.,  1913,  49,  263.  Exner,  Zentralb.  f.  Phys.,  1903,  17, 
24  [Young-Helmholtz  system).  Franklin  (Mrs.  C.  L.).  Z.  f.  Psych,  u. 
Phys.  d.  Sinn.,  1892,  4;  Psychol.  Review,  1894,  1896,  1899.  Hartridge. 
J.  Phys.,  1912.  45,  p.  xxix  [vellow  sensation).  Hering  (E.),  Pfluger's 
Arch.,  1888,  42,  3.iO- 

Contrast— After-images.— Edridge-Green,  J.  Phys.,  1912.  43,  p  xxviii; 
45,  p.  XIX  {simultaneous  colour  contrast):  ib.,  1913.  46,  180;  47,  p.  vi 
{after-images).  Hartridge,  J.  Phys..  1915.  50,  .ij  {contrast).  Tscher- 
MAK,  Ergeb.  d.  Phys.  (Bioph.),  1903.  726  [contrast  and  irradiation). 

Colour-Blindness.-  Collin  and  Xagel,  Z.  f.  Sinncsphysiol.,  1906,  41,  74 
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Intermittent  Stimulation  0!  Retina.  -Charpentier,  Arch,  de  Phys.,  1896. 
077  [retinal  oscillations).  Schenck  (F.),  Pfluger's  .^rch.,  i90h.  112,  292. 
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THE  SENSES  '^ii 

phenomena  afterwards  described/or  lienham's  top).     Bidwul:.,  I'roc   Roy. 

Soc.  (Lond  ),  June  7.  i8.,4;  Nature.  Sept.  6,  1894.  4^6;  Percival,  Trans. 

Ophthal.  Soc.  n»oi>,  29,  1 1'>- 
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(O.  V.  F.),    |.  Phvs.,  1898.  22,  ■\.U-     Makuk,  Pfliiger  s  Arch..  iW.  87, 

U=i      i'AKKKK  .uifl  PAirFN.  Am.  J.  Phys..  1912.31.  z^.     Stewart  (G.  N.), 

Trans.  Kov.  S...  .  ii:clin.).  July  lO,  1888,  441  (for  very  short  stimuli). 
Heliotropism  (Phototropism).  -Davenport  and  Cannon.  J.  P^ys    J897  ^ 

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J.  Exp.  Zool.,  1913,  19,  2.^;  20,  -:i7;  ih..  1917.  22,  187. 

HEARING,  SMELL.  TASTE. 

Hearing.— Bkrnouilli,  Prii.ger's  Arch..  1910,  134,  b^.^EwAi^D  (J.  R.j.  ih 
i":,s  59  -SS-  ib.  190,,  93,  485;  Wundt,  tb..  1895.  61,  .U9  (labyrinth  and 
hearings  EwAi-u.  ib'..  1899.  76,  i47  (sound  picture  theory).  ^}^^^^- 
Frgeb  d  Phys  (Bioph.).  1902,  847.  Kol^iak.  ib.. 1911.  H^  (end apparatus 
of  eighth  nerve  and  its  significance) .  E.  ter  Kuile.  Pfluger's  Arch  1900. 
79  M(>  484;  Meyer  (M.),  ib..  1900.  81,  61  (theory  of  hearing)  McKen- 
DRiCK.  Nature.  June  15.  1899.  i(>3  (perception  of  musical  tone)  Parker 
(G  H  )  U  S.  Fish  Commission  Bull.,  1903,  451  Am.  Naturalist.  37,  185 
(hearing in  fishes).  Wittemaack.  Pfliiger's  Arch..  1907,  120,  249  (support 
of  Helmhoitz's  resonance  theory).  Zwaardemaker.  Arch.  f.  Fhys.,  190^, 
bupp   Bd     124  (sound-pressure  in  Corti's  organ  as  the  stimulus). 

Smell  and  Taste.-CusHiNo  (H.),  Am.  J.  Phys  1903.  8,  p.  xxvii;  Gowers, 
T.  Phys.,  190^  28,  ^,00;  Harris  (W.),  J.  Am.  Med.  Ass  1914.  63,  i/2o 
(course  of  taste  fibres).  Parker  and  Stabler,  Am.  J.  Phys..  1913.  «JA 
2^0  (distinctions  between  smell  and  taste).  Zwaardemaker  Ergeb.  d. 
Phys.  (Bioph.),  1902,  896  (smell);  ib..  1903.  699  (taste);  Arch.  f.  Phys., 
1907,  Suppl.  Bd.,  59;  ib..  1908.  51. 

COMMON  SENSIBILITY. 

Cutaneous  Sensations.— Barker  (L.  F.),  J.  Exp.  Med.,  1896,  1,  i  (localized 
sfnZypValysi:) .  Borino,  Q.  J .  Exp.  Phys  1916,  10,  i .  Head  Rivers 
and  Sherren.  Brain.  110,  100;  Head  and  Sherren,  Bram  110  116. 
Trotter  and  Davies.  J.  Phys.,  1909,  38.  134:  (Brodmann  s)  J.  f.  Psych. 
Neurol  iQi  ?  20.  102  (section  of  cutaneous  nerves  tn  man).  Buck  (Ai.). 
Arch  f:'Phys  .  1901.  i.  Lombard  (W.  P.).  Am.  J.  Phys..  1913.  31.  p.  xv; 
Stanley  Hall  and  Albin.  Am.  J.  Phys.,  1897,  9.  10  (tickle-sense). 
Carr  Psychol.  Review.  IQ16,  23.  252  (Head's  theory).  Elo  and  Nicolai, 
Skand  Arch.  Phys.,  1910.  24,  22b  (warmth  sense).  Franz  and  Ruediger. 
Am.  J.  Phys..  1910,  27,  45  (effect  of  local  anesthetics).  Fr.^nz  J  Comp. 
Neurol.  Psvchol.,  190Q,  19,  107  [pressure  sense).  xo>;  FRey.  Z.  f-  BioJ- 
I9IVI4  63  -07  3^5;  J.  Am.  Med.  Ass.,  1906,  47,  O45 ;  Ergeb.  d.  Ph>-^., 
iQi'^  96;  May  (P.),  i6.,  1909,  657  (cutaneous  sensations).  Nac.el, 
Handbuch  d.  Physiol.,  3.  7^3  (tickling  and  itching).  \eRKES  R  M.  . 
Pfluger's  Arch.,  1905,  107,  207  (facilitation  and  inhibition  oj  tactile 
stimuli  in  the  frog). 
SensibUity  of  Internal  Organs.-HERTZ.  The  Sensibility  of  the  Alimentary 

Canal    igii.     Kast  and  Meltzer,  Med.  Rec,  Dec.  29,  1906. 
Muscular  Sense.-voN  Frey,  Z.  f.  Biol.,  1914.  63,  129;   64,  203.     Lashley, 
Am.  J.  Phys.,  1917.  43,  169  (accuracy  of  movement  ui  absence  of  e.rcita- 
tion  from  moving  organ). 
Localization  of  Sensations.-BRows  (T.  G.)  and  Stewart  (R.   M.).    Bram, 
1916,  39,  348.    Lani.stroth.  Arch.  Int.  Med.,  191 5,1%,  i^g  (referred pain. 
Head's  zones  of  hyperalgesia) . 
Hunger  and    Appetite.— Cannon  and  Washburn    Am.  J.  Phys.,  191 1.  29, 
441 ;  Carlson  (A.  ].).  .\m.  J.  Phys.,  1912-13,  31    131.  i7.=5.  212;  »fc.    1913. 
32    ^,69-  ib     191 4   33,  «)V.  34,  155  {nervous  control  of  hunger  contractions). 
Carlson,   Control  of   Hunger  in   Health  and  Disease,   Chicago.    191b. 


IM2  BIBLICGRAPHY 

Carlson  and  Lewis.  Am.  J.  I'liys.,  1^14,  34,  149  {influence  of  smoking). 
Carlson.  Orr  and  McGrath.  ib.,  33,  119-  Ginsburi,,  Tlmpowski  and 
Carlson,  J.  Am.  Med.  Ass.,  1915,  64,  182.2  (hunger  tn  infants  after  feeding). 
Luckhardt,  Am.  J.  Phys.,  1915,  39,  335  {dreaming).  Lickhardt  and 
Carlson,  16.,  1914,  36,  37  {chemical  control).  Meyer  and  Carlson,  ib., 
1917,  44,  222  [in  fever).  Patterson,  ib.,  1915.  37,  3i<>;  I9if>.  42,  56. 
Rogers  and  Hardt,  ib.,  1914,  38,  274. 

CHAPTER  XIX. 

REPRODLXTION. 

BiRiAN,  Ergeb.  d.  Phys.  (FSioch.).  1904,  84;  ib..  1906,  768  {chemistry  of  sperma- 
tozoa).    Marshall  (F.  H.  A.),  Physiology  of  Heproduclion,  London,  1910. 

Ovary. — Carmichael  and  ^LJkRSHALL,  Proc.  Koy.  Soc,  1907,  B  79,  387 
[correlation  of  ovary  and  uterus).  Gi-thrie  (C.  C),  J.  Exp.  Zool.,  1906, 
3.  5<i}  (transplantation  of  ovaries  in  chickens) ;  Science,  Nov.,  1909  [guinea- 
pig  graft  hybrids):  ib..  191 1,  33,  816  (influence  on  offspring  of  engrafted 
ovarian  tissue).  Loeb  (L.),  Soc.  Exp.  Biol.  Med.,  19K.,  13,  162  [cyclic 
changes);  J.  Am.  Med.  Ass..  1917,  69,  236  {relation  of  ovary  to  uterus  and 
mammary  gland).  Rosenbloom.  J.  Biol.  Ch.,  1912,  13,  511  (I'pms  of 
ovary  and  corpus  luteum). 

Corpus  Luteum. —  Ancel.  J.  de  Phys.  Path.  Gen.,  191 1.  13,  31.  Bolin  and 
Ancel,  lb..  1910.  12,  16.  Itagaki.  Q.  J.  Exp.  Phys.,  1^17,  11,  i  [influence 
of  extracts  on  plain  muscle).  Loeb  (L.),  J.  Am.  Med.  As.s..  1906,  Feb.  10, 
1906;  Anat.  Record.  1908,  2,  240.  Marshall,  Q.  J.  Exp.  Micros.  Sc, 
1905,  49,  189  [development,  review).  Novak,  J.  Am.  Med.  Ass.,  1916, 
67,  1285.  Ott  and  Scott,  Soc.  Biol.  Exp.  Med..  1912,  9,  64  [extracts);  ib., 
1914,  12,  47  (action  on  mammary  glands).  Pearl  and  Surface.  J.  Biol. 
Ch.,  1914,  19,  263  {effect  on  ovulation). 

Uterus. — Barry  (D.  T.),  J.  Phys.,  1915,  50,  259  (uterus  contractions  and 
ovarian  extract).  Cl'shny,  J.  Phys.,  1906,  35,  i  [movements).  Barbour 
and  CoPENHAVER,  Soc.  Exp.  Biol.  Med.,  1916,  13,  139  (cerebral  control 
of  uterus  .^).  Kurdinowski,  Arch.  Internat.  de  Phys.,  1904. 1,359;  Arch, 
f.  Phys.,  1904,  Supp.  Bd.,  "^2^  {isolated  uterus  movements).  Loeb  (L.), 
J.  Am.  -Med.  Ass..  1908.  50,'  1897;  Arch.  f.  Entwick.  d.  Org.,  1909,  27, 
89  [production  of  deciduomata).  Ott  and  Scott,  J.  Exp.  Med.,  1909.  11, 
326  [actioti  of  glandular  extracts  on  uterus  contractions). 

Menstruation — (Estrus.— Hammond  and  Marshall.  Proc.  Roy.  Soc,  1914. 
B  87,  422  {correlation  between  ovaries,  uterus,  and  mammary  glands). 
Heape,  Brit.  Med.  J.,  Dec.  24,  1898  (monkeys).  King  (J.).  Am.  J.  Phys., 
1914.  34,  203  (cardio-vascular  and  temperature  variations  in  women), 
Loeb  (L.).  Biol.  Bull.,  1914,  27,  i  (correlation  between  cyclic  changes  m 
uterus  and  ovaries).  Marshall  and  Runciman.  J.  Phys..  191 4.  49,  17 
(ovarv  and  (gslrus).  Marshall  and  Jolly.  Phil.  Trans.  Roy.  Soc,  1903. 
198,  99  {dog). 

Fertilization.— Fischer  and  Ostwald.  Pfluger's  Arch..  1905.  106,  229 
iphvsico-chemical  theory).  Gorham  and  Tower,  .\m.  J.  Phys.,  1903, 
8,  173.  Loeb  (J.).  Pfluger's  Arch.,  1904,  103,  257;  )7;.,  104,  325;  I'niv. 
of  Calif.  Pub.,  1903-7;  Harvey  Lecture,  New  York,  1911  ;  .\m.  Naturalist, 
1913,  49,  257  (conditions  determining  entrance  of  spermatozoon);  Arch.  f. 
Entw.  d.  C)rg.,  1914,  11,  ^01;  Science,  Nov.  6,  1914  [ultraviolet  light). 
Lyon  (E.  P.).  Am.  J.  Phy.s..  1909,  25,  199  (catalasc).  Morgan  (T.  H.), 
Science,  Feb.  18.  1S98.  Nemec,  Fertilization  Processes,  Berlin,  1910. 
Mathews  (\.  P.),  Am.  J.  Phys..  1902.  6,  216;  ib.,  1907.  18,  89.  Robert- 
son (T.  B.),  Soc.  Exp.  Biol.  Med..  1912,  9,  90  (oocylase);  J.  Biol.  Ch.. 
1912.  11,  339;  ib.,  12,  I,  163.     ScHijcKiNG,  PflQgers  Arch.,  1903,  97,  58. 

Artificial  Parthenogenesis.— Fischer  (M.  H.),  Am.  J.  Phys..  1902,  7,  301: 
K*'"*^,  9,  100.  Greeley,  ib.,  1902.  6,  296  {produced  by  lowering  of  tem- 
perature).    Harvey  (E.  N.),  Biol.  Bull..  1910.  18,  260  (methods).     Lillie 


UEl'kODLLTlOS  1213 

(K.  S.),  Am.  J.  Phys.,  1907,  18,  p.  xvi  (by  raising  leniptralurc).  Loeb 
(J.),  Am.  J.  Fliys..  itioo,  4,  178,  |^.^;  Die  Chemischc  Entwickclungserre- 
j;img  dcs  Tieiischon  ICics,  Berlin,  i^otj;  Arch.  f.  ICiitwick.  d.  Org.,  1902, 
13,  -tlSi  (fiitt/iods) ;  I'lliim-r's  Arcli.,  1907,  118,  iSi  [osmotic  excitation 
of  development  in  sea-urchin  eggs);  Proc.  Nat.  Acad.  Sci.,  i9i(>,  2,  313 
(sex  of  parthenogenetic  frogs).  i\lATnii\vs  (A.  P.),  Am.  J.  Phys.,  1900,  4, 
343;  ib..  190J,  6,  14.!  (by  mechanical  excitation).  McClendon.  Am.  J. 
Phys.,  191  _•,  29,  29S  (in  vertebrates).  Morgan  (T.  H.),  J.  E.xp.  Zool., 
1904.  1,  135  [self-fertilization  induced  by  artificial  means). 
Sex.  -DoNCASTER,  Determination  of  Sex,  Cambridge,  1914.  Kiddle,  Science, 
191 7,  46,  19.     Wilson  (E.  B.),  Soc.  Exp.  Biol.  Med.,  1905-6,  3,  19. 

Pregnancy.  -Hasselbalch,  Skand.  Arch.  Phys.,  1912,  27,  i  (respiratory 
exchange).  Miklin,  Am.  J.  Phys.,  1910,  26,  134  (energy  metabolism  of 
fregnant  dog);  ib.,  1910.  27,  177  [nitrogen  balance).  Murlin  and  Bailey, 
Arch.  Int.  Med.,  1913,  12,  .2i)8  [protein  metabolism). 

Abderhalden  Reaction. —BoLDYREFF,  J.  Phys.,  1917,  51,  p.  xxii.  Bronfen- 
HRENNER,  J.  Lab.  Clin.  Med.,  1915,  1,  79.  Wells  (H.  G.),  ib.,  1,  175. 
Williams  and  Pearce,  Soc.  Exp.  Biol.  Med.,  1913,  10,  73.  Van  Slyke 
ET  al.,  J.  Biol.  Ch.,  1915.  23,  377- 

Development  of  Egg. — Abderhalden,  Pfliiger's  Arch.,  1915,  147,  99  (com- 
pounds which  influence  development) .  Babak,  Pfliiger's  Arch.,  1905,  109, 
70  (central  nervous  system  and  metamorphosis  of  frog).  Brown  (O.  H.), 
.\m.  J.  Phys.,  1905,  14,  354  (permeability  of  egg).  Eaves,  J.  Phys.,  1910, 
40,  451  (fat  transformations  in  eggs  in  development) .  Harvey,  J.  Exp. 
Zool.,  1910,  8,  355  [monbrane  formation).  Hulton,  J.  Biol.  Ch.,  1916, 
25,  227  [ferment  production  in  response  to  introduction  of  placenta).  Hyde 
(1.  H.),  Am.  J.  Phys.,  1904,  12,  241  [differences  of  potential  in  developing 
eggs).  Krogh,  Z.  f.  AUg.  Phys.,  1914,  16,  it>3  (temperature  and  rate  of 
embryonic  development).  Loeb  (J.),  Biol.  Bull.,  1915.  29,  103  [membrane 
formation).  Loeb  and  Wasteney's,  Bioch.  Z.,  1911,  37,  401 ;  J .  Biol.  Ch., 
1913,  14,  S^5.  459;  ib.,  1915,  21,  153  (influence  of  bases  on  development 
and  oxidations  in  sea-urchin  eggs).  Lillie  (R.  S.),  Am.  J.  Phys.,  1916, 
40,  249;  ib.,  1917,  43,  43  (permeability).  Lyon,  Am.  J.  Phys.,  1904,  11, 
3J  (rhythms  in  cleavage).  Ly'on  and  Shackell,  J.  Biol.  Ch.,  1909,  7,  371- 
(autolysis  of  fertilized  and  unfertilized  eggs).  Mathews  (A.  P.),  J.  Biol. 
Ch.,  1913,  14,  465  [chemical  difference  between  sea-urchin  and  starfish  eggs), 
McClendon,  Am.  J.  Phys.,  igiz,  31,  131  (effect  of  alkaloids);  ib.,  1915, 
38,  163  (development  and  permeability).  Meltzer,  Am.  J.  Phys.,  1903, 
9,  246  (effect  of  agitation).  Moore  (A.  R.),  J.  Biol.  Ch.,  1917,  30,  5 
(cytolysis  in  echinoderm  eggs).  Malcolm  (J.),  J.  Phys.,  1901,  27,  356 
[composition  of  egg-yolk).  Mendel  and  Leavenworth,  Am.  J.  Phys., 
ii»o8,  21,  77  (changes  in  purin,  cholesterol,  etc.,  content  in  development). 
Riddle  (O.),  Am.  J.  Phys.,  1916,  41,  409  (metabolism  of  egg-yolk  in 
incubation).  Riddle  and  B.\ssett,  ib.,  41,  425  (effect  of  alcohol  on  size 
of  egg-yolk).  Robertson,  Soc.  Exp.  Biol.  Med.,  19x2,  9,  61  (sea-urchin 
eggs).  Shackell,  Science,  191 1,  34,  573  (phosphorus  metabolism  in 
nliinodcrm  eggs). 

Metabolism  of  Embryo. — Jones  and  Aisiriax.  J.  Biol.  Ch.,  1907.  3,  227 
[nuclein  ferments).  Loghead  and  Cr.^mer,  Proc.  Roy.  Soc,  1908,  B  80, 
263  (glycogenic  changes  in  placenta  and  foetus).  Mendel  and  Leaven- 
worth, Am.  J.  Phys.,  1907,  20,  117  [glycogen  in  embryo).  Mendel  and 
Mitchell,  ib..  20,  81  (inverting  enzymes  of  alimentary  tract  in  embryo); 
ib..  20,  97  (enzymes  in  purin  metabolism).  Wells  and  Corper,  J.  Biol. 
Ch.,  1909,  6,  469  (purin  metabolism  of  foetus  and  placenta).  Zintz  and 
Hasselbalch.  Skand.  Arch.  Phys.,  1900,  10,  149  (COo  production  in 
embryo) . 

Placenta. — Charrin,  Arch,  de  Phys..  1898,  703  [transmission  of  toxins  from 
foetus  to  mother).  Famulener,  J.  Infect.  Dis.,  1912,  10,  332  (transmission 
of  inimunity  from  mother  to  offspring).     Fenger,  J.  Biol.   Ch.,  191 7,  29, 


I2I.1  UiBLlOGRAPllY 

11)  {compoiitwn).  Llueker  and  Pribram,  PHuger's  Arch.,  it>io,  134, 
.531  (relation  of  placenta  and  mammary  gland).  l6b  and  Higuchi.  Bioch. 
Z..  1909,  22,  310  {enzymes).  Loeb  (L.),  J.  Am.  Med.  Ass.,  1901),  53,  1471 
(maternal  placenta  and  function  of  corpus  luleum).  Rosenheim,  J.  Phys., 
1901).  38,  337  (pressor  principles  from  placenta).  WERTHEiMERund  Meyer, 
Arch,  de  Phys.,  1890,  193;  1891,  204  (exchanges  between  mother  and 
feet  us). 

Parturition.  —Healy  and  Kastle,  Soc.  Exp.  Biol.  Med.,  1912,  9,  48  (internal 
.accretion  of  mammary  gland  as  a  factor). 

Chemistry  of  Milk. — Milroy,  Bioch.  J.,  iyi5,  9,  217  (reaction).     Olson,  J. 

Biol.  Ch..  1908,  5,  261  (proteins).     Osborne  and  Wakeman,  ib.,  1915,  21, 

539;  i^-.  1916,  28,  1  (phosphatids).     Raudnitz,  Ergeb.  d.  Phys.  (Bioch.), 

1903,  193.     Van  Slyke  and  Bosworth,  J.  Biol.  Ch.,  1914, 19,  73  (casein) ; 

ib.,  1915,  20,  135;  ib.,  1916,  24,  173  (goat's  milk). 
Human  Milk. — Bosworth,  J.   Biol.  Ch.,  1915,  20,  707;  Bosworth  and  Van 

Slvke,  ;7).,  1910,  24,  187.     Hammett,  ib.,  1917.  29,  381  (after  parturition). 

Holt,  Courtney  and  Fales,  Am.  J.  Dis.  Child..  1915,  10,  229  (salts). 

MEiGsandMARSH,  J.  Biol.  Ch.,  1913,  16,  147  (human  and  cow's).     Sikes, 

j.  Phys.,  1906,  34,  404  (P  and  Ca). 

Colostrum. — St.  Engel,  Ergeb.  d.  Phys.,  1911,  41.  Kastle  and  Healy.  Soc. 
Exp.  Biol.  Med.,  1912.  9,  44;  Woodward,  J.  E.xp.  Med.,  1897,  2,  217 
(chemistry). 

Secretion  of  Milk. — Basch,  Ergel).  d.  Phys.  (Bioch.),  1903,  320. — Caspaki. 
.\rch.  1.  Phys.,  1899,  Supp.  Bd.,  207  (source  of  milk  fat).  Bowen,  J.  Biol. 
Ch.,  1915,  12,  II  {passage  of  food  and  fatty  acids  into  mammary  glands). 
Campbell  (J.  A.),  O.  J.  Exp.  Phys.,  191 3,  7,  35  (chemistry  of  mammary 
gland).  Gaines,  Arn.  J.  Phj's.,  1915,  38,  285  (lactation).  Ha.mmond  (J.), 
Q.  J.  Exp.  Phys.,  1913,  6,  311 ;  Hill  and  Simpson,  ib.,  1914-15,  8,  103,  377 
(pituitary  extract).  Hammett  and  McNeile,  J.  Biol.  Ch.,  1917,  3i0,  145 
(effect  of  placenta).  Hill  and  Simpson,  Am.  J.  Phys.,  1914.  35,  361 ;  ib., 
1915,  36,  347  (effect  of  pituitary  extract).  Marshall  and  Kirkness, 
Bioch.  J.,  1906,  2,  i;  Paton  and  Cathcart,  J.  Phys.,  1911,  42,  179; 
PoRCHER,  Arch.  Internat.  Phys.,  1909,  8,  356  (lactose  formation).  Mac- 
kenzie (K.),  O.  J.  Exp.  Phys.,  191 1,  4,  305;  Schafer  and  Mackenzie. 
Proc.  Roy.  Soc.  1911,  B  84,  lO  (action  of  animal  extracts).  Moore  and 
Parker,  Am.  J.  Phys.,  1900,  4,  2.y)  (lactose  formation).  Ott  and  Scott, 
Soc.  Exp.  Biol.  Med.,  1912,  9,  63;  Schafer,  Q.  J.  Exp.  Phys.,  1913,  6,  17 
(effect  of  pituitary  and  corpus  luteum);  ib.,  1915,  8,  379  (pituitary  extract). 

Correlation  of   Mammary   Gland   with   Other  Sexual   Organs. — Biedl    and 

Ko.sii.sTKiN,  Z.  Exp.  Path.  Tlicr.,  1910,  8,  338  (honuone  which  exciies 
matnmary  gland  in  pregnancy).  He.\pe,  J.  Phys.,  1900.  34,  p.  i.  Lane- 
Claypon  and  Starling,  Proc.  Roy.  Soc,  1906,  B  77,  .S05.  Loeb  (L.) 
and  Hesselberg,  J.  Exp.  Med.,  i<)i7,  25,  285.  305  (correlation  in  cycle  of 
uterus,  ovaries,  and  mammary  gland).  O'Donoghue,  J. Phys.,  1911,  48, 
p.  xvi  (corpus  luteum  and  mammary  gland). 

Rrowth. — -Cramer,  J.  Phys.,  1916,  50,  322  (the  biochemical  mechanism  of 
growth).  Hatai,  Am.  J.  Phys.,  1907,  18,  ^09  (rat).  Loeb  (J.),  Science, 
191 5,  41,  169  (simplest  constituents  required  for  growth  in  an  insect). 
Robertson  (T.  B.).  Am.  J.  Phys.,  1915,  37,  i.  74  (pre-  and  post-natal 
grouth  of  )U(ni).     Osborne  and  Mendel,  sec  Chapt.  X. 

Anastomosis  of  Bloodvessels. —Carrel  (A.)  and  Guthrie  (C.  C),  J.  Am.  Med. 
Ass.,  1906,  Nov.  17,  p.  164S  (kidney  transplantation);  Surg.  Gyn.  Obst., 

1906,  2,  266  (veins).  Carrel,  J.  Exp.  Med.,  1910,  12,  139;  ib.,  19x2,  15, 
388;i6.,16,  i7(aorta).  Guthrie,  Heart,  1910,2,115  (survival  of  engrafted 
organs).     Carrel,  J.  Exp.  Med..  1907,  9,  226:  Guthrie,  Am.  J.  Phys.. 

1907,  19,  482  (hetero-transplantation  of  bloodvessels).  Guthrie,  Blood- 
vessel Surgery,  London,  1912.  Carrel,  Johns  Hopk.  Bull..  1900.  17, 
^^h  (surgery  of  bloodvessels) .     Guthrie,  J.  Am.  Med.  Ass.,  1908,  60,  1035. 


REFRODUCTWS  1^15 

Transplantation  0!  Organs. — Qakrel.  J-  Exp.  Med..  1910,  12,  i4<»  {remote 
re^ulti.  of  rtj-'liDitation  of  kidney  and  spleen).  Giihku;,  ib.,  12,  ^^>^  {sur- 
vival of  engrafted  ovaries  and  testiiies).  Githkik  ami  Li;t,  J.  Am.  Med. 
Ass.,  191.5.  64,  i8-'3  {ovarian  transplantation).  GiiUKit,  Arch.  Int. 
Med.,  1910,  5,  ^3^  {kidney ,  perfused  or  not) .  Murphy  (J.  H.),  J  .  I'xp.Med., 
1913,  17,  •I'^.J  (transplantability  of  tissues  to  the  embryo  of  foreign  species); 
ib.,  1914, 19,  513  ;  ib..  19,  181  {ultimate fate  of  mantmalian  tissue  implanted 
in  chick  embryo).  Lokb  and  Aduison,  Arch.  f.  Entwick.  d.  Org.,  1909,  27, 
73  {hetero-plastic  skin  transplantation).  I^eb  (L.),  J.  Am.  Med.  Ass.. 
1915.  64,  7.25  (changes  in  chemical  environment  and  growth  of  tissues) ; 
J.  Med.  Res.,  1917,  37,  229  (kidney  tissue).     (Sec  also  Chapter  XI.) 

Tissue  Cultures.  Baitsell,  J.  Exp.  Med.,  1915,  21,  455  (origin  of  a  fibrous 
tissue  in  cultures  of  adult  frog  tissues).  CarREL  and  Burrows,  J.  Exp. 
Med.,  1911.  13,  387;  Lambert,  ib.,  1916,  24,  367  (technique);  ib..  13,  416 
(thyroid).  Carrel,  J.  Exp.  Med..  1913,  18,  287  (connective  tissue) ;  ib.,  17, 
14  (activation  of  grotvth  of  connective  tissue);  ib.,  1912,  15,  51^1;  J-Ibeling, 
ib.,  1913,  17,  273  (permanent  life  of  tissues  outside  of  the  organism). 
Inc;ebrigt.sen  (R.),  J.  Exp.  Med..  1913,  18,  412  (regeneration  of  axis 
cylinders  in  vitro);  ib.,  1916,  23,  251  (life  of  peripheral  nerves  in  plasma). 
LoEB  (L.),  Unte.such.  iibcr  Umwandlungen  u.Thaligkeitenin  d.Geweben, 
Chicago,  1897.  LosEE  and  Ebelin(.,  J.  Exp.  Med.,  1914,  19,  593  (human 
tissue).  Laubt  (R.  A.),  J.  Exp.  Med.,  1913.  18,  400  (influence  of  tempera- 
ture and  medium  on  survival  of  embryonic  tissue  in  vitro).  Lewis  (M.  R. 
and  W.  H.).  Am.  J.  Phys.,  1917,  44,  57  (contraction  of  smooth  muscle  cells 
in  tissue  cultures).  Newmann  and  Burrows,  Am.  J.  Phys.,  1917.  42, 
397  (effect  of  amino-acids  and  peptones  ongrovuth  of  cells  in  vitro) .  Walton  , 
J.  Exp.  Med.,  1915,  22,  194  (production  of  substances  inhibiting  cell-growth) ; 
ib.,  1914,  20,  .5.54  (effect  of  tissue  extracts  on  growth  in  vitro).  Weil,  J  .  Med. 
Res.,  1912,  26,  159  (tissue  cultures  in  vitro).  Uhlenhuth,  J.  Exp.  Med., 
1915,  22,  76  (skin);  ib.,  1914,  20,  614. 

Parabiosis.  -Rous,  Soc.  Exp.  Biol.  Med.,  1909.  7,  8  (test  for  circulating  anti- 
bodies in  cancer). 


INDEX 

References  to  the  Practical  Exercises  are  in  black  figures. 


Abdominal  breathing,  230 

muscles  in  expiration,  229 
Abducens,  or  sixth  nerve.  926 
Aberration,  chroniatir,  1027.  1063,  II06 

spherical,  1027.  1063,  1106 
Absorption,  426 

and  lipoid  solubility,  437 

coefi&cient  of  gases,  247 

comparative  physiology  of,  431 

factors  concerned  in,  435 

from  the  peritoneal  cavity,  439 

from  the  stomach,  433 

gas  exchange  in  intestine,  436 

in  large  intestine,  451 

intra-  and  inter-epithelial,  446 

of  bile-constituents  in  jaundice,  384 

of  cane-sugar,  436,  464 

of  carbo-hydrates,  445 

of  fat,  path  of,  443.463 

of  gases  in  blood.  250 

of  iron,  447 

of  light,  1012 

of  proteins,  447 

of  the  food, 431 

physical  introduction  to,  426 
theories  of,  433-436 

of  water  and  salts.  422,  446 

osmosis  and  diffusion  in,  435 

parenteral,  446 
Acapnia  and  blood-pressure,  184 

and  mountain  sickness,  298 

and  shock,  192 
Acceleration  of  heart  by  sipping  water, 

171,210 
Accelerator  nerves  of  heart,    157,    162, 

166, 197,  199 
Accessory  auditory  nucleus,  928 

dietetic  factors,  617 

vagus  nucleus,  929 
Accommodation,  1020 

mechanism  of,  1022 

pupil  in,  1023 
Acerebral  tonus,  942,  955 
Acetaldehyde.  544,  562 
Acetone,  562 

and  katabolism  of  fatty  acids,  567 


]    Acetone  in  diabetes,  529,  555 
in  urine,  529 
Aceto-acetic  acid,  562,  567 

in  diabetes,  555 
A.C.E.  mixture,  63 
Acetic  acid,  556 
Acid  albimiin,  352, 458 
Acidity  of  gastric  juice,  350,  417 
Acidosis,  24,  282,  555 
Acrolein,  12 
Action  currents,  823,  824,  830, 842 

and  functional  activity,  825 

diphasic.  825 

double  conduction  of,  792 

electromotive  force  of.  827 

in  polarized  nerves.  831 

in  voluntary  contraction,  762 

monophasic,  825 

of  central  nervous  system,  838 

of  eye,  839 

of  glands,  83S 

of  heart,  88,  833-838, 844 

of  muscle,  823,  843 

of  phrenic  nerves,  827 

of  skin,  838 

of  spinal  cord,  838.  849,  895 

of  vagus,  828 

of  veratrinized  muscles,  829 

propagation  of,  824 

rate  of  propagation   of  vai-ia- 
tion,827 

reflex,  913 

theories  of,  828 
Adamkiewicz's  reaction  of  protein,  8 
Adaptation  of  digestive  juices  to  food. 
371,  398,  405.  400.  414 
of  retina,  1047,  1058 
Addison's  disease  and  adrenals,  655 
Adenin.  481,  592,  593 
Adequate  stimuli,  901,  1007 
Adipocere,  564 
Adii'osophilia,  569 
Adnnal  b*jdics,  655 

ci>inephTin  content  of.  664 

relation  of,  to  coagulation,  45 

secretory  nerves  of,  661 

1216 


IS  DFX 


I  21  7 


A'renal  cortex,  function  of.  665 
Adrenalin,  action  of.  01  artiry  rin^s.  66, 
216 
on  coagulation  linjc.  45.  656 
on  heart.  655 

on  nerve -endings,  182,  635 
on  pupil.  636. 
on  sympathetic,  655.  1005 
on  vaso-motors,  173,  179,  655 
on  veins.  181 
action  of  stnall  doses  of,  660 
arterio-sclerosis.  660 
artiticial.  665 
assay  of.  453.  636 
biological  tests  for.  46,  656 
chemistry  of.  664 
formation  of.  665 
function  of,  657 
glycosuria,  550 

secretorv    influence   of   nerves    on, 
661 
Adsorption,  430 
Aerotonometer.  258 
.fiisthesiometer.  compasses.  11 15 

Fray's  hair.  1080,  1114 
Afferent  impulses,  decussation  of,  894 
paths,  892 

scheme  of,  880 
After -brain  (rayelencephalon),  850 
After-images,  1055,  llll 
Agglutination,  30,71 

by  foreign  serum,  71 
Agglutininogens,  31 
Agraphia.  970 
Alanin,  2,  360,  574.  590 

formation  of  dextrose  from.  538 
Alanyl-glycyl-tyrosin,  449 
Albinos,  intravascular  clotting  in.  43 
Albuminates  or  derived  albumins.  9 
Albuminoids.  2 
Albumins,  2.9 

heat -coagulation  of,  9 
in  urine.  488.  497.  499,524,  525 
Albumoses,  3 

action  of.  on  blood -pressure,  173,215 

on  coagulation.  37,  45 
in  peptic  digestion,  352 
tests  for,  in  urine.  525 
Albumosuria.  489.  525 
Alcohol,  630 

action  of,  on  respiratory  centre,  191, 
631 
on  gastric  secretion,  630 
in  diet,  630 
poisoning,  blood -pressure  curve  in, 

191 
precipitation  of  proteins  by,  8 
Alcohols,  relation  of.  to  carbohydrates,  3 
Aldehydase.  272 
Aldehydes,  relation  of.  to  carbo-hydrates, 

.1.  543-  544-  545-  S^i 
Aldohexoses.  543 


Aldol,  362 
.\lgometer.ioS<) 

.Alimentary  canal,  anatomy  of.  319 
length  of.  320 

time  of  pa>.sa!;e  through.  334 
glycosuria.  3  jn.  717 
.Mkali-albuniin.  10,  461 
Alkalinity  of  bio  jd.  etc..  titratabie.  2S 
.Alkaptonuria.  483.  3.'^I 
.\llantoin.  excretion  of.  596 
Allantois.  1128 
'  All-or-nothing  "  law.  154 
Alloxuric  bodies.  48 1 
.\lveolar  air,  partial  pressure  of  gases  in. 

241.  263 
Amblyopia  after  occipital  lesion.  966 
Amboceptors.  28,73 
Amide-nitrogen  in  proteolysis,  360 
Amino-acetic  acid,  2 
Amino-acids,  i,  360,  352,  417,  562 
absorption  of.  449,  450 
changes  in  liver.  384 
chemical  nomenclature  of.  360 
conversion    of.    into  glycogen    and 

dextrose.  536.  538.  590 
formation  of.  from   tissue-proteins. 
578 
of  urea  from.  582.  584.  586, 588. 
624 
in  blood.  574 
in  liver  diseases.  586 
in  phosphorus  poisoning,  563 
in  urine.  481,  488 
metabolism  of.  582 
synthesis  of.  by  bacteria,  618 
Amino-bodies.  deaminization  of,  588 
Amino-succinic  acid.  360 
Amino-valerianic  acid,  360 
Ammonia,  action  of.  on  muscle.  759 
impermeability  of  lungs  for,  240 
in  proteolysis.  360 
in  the  blood,  source  of,  585.  588 

after  Eck's  fistula.  585 
in  urine.  480.521 

reflex  in  hibition  of  heart  by.  170. 
210 
Ammonium    salts,    fomation    of    urea 
from.  384.  588 
sulphate,    precipitation  of  proteins 
by.  8,  525 
Amnesia.  970 
Amnion.  1128 
Amniotic  fluid.  1128,  1134 
Amoeba,  6.  16.  732 
Amoeboid  movements.  732 
Ampl^re,  725 
Amylase.  345.  346 

pancreatic.  358.  362. 461 
salivary.  346,  417.455 
Arayl  nitrite,  action  on  pulse.  106 

formation    of    met  haemoglobin 
by,  33 

77 


I2l8 


INDEX 


Ainylolytic   stage    of  sastric    digestion. 

34S.  356.  417 
Amylopsin.  358.  362,461 

intlucncc  (if  bile  on.  370 
Anatiolic  liiaiiKcs  in  living  matter.  6 
Anacrotic  [nilse,  106 
An.i'Sthesia  by  A.C.J'".  mixture,  63 

by  chloral.  217 

by  chloroform   (fir6hant's  method). 
202 

by  morphia.  63,  201 

by  pressure  on  brain,  985 

by  nrethane.  217 

for  animals.  63 
Anaphylaxis.  32 
Anastomosis  of  nerves.  o75 

of  bloodvessels.  1145 
Aneleotrotonus.  7S6.  844,  845, 
Angular  gyrus  and  vision,  066 
.\nimal  board.  201,  214 
Animal  heat.  674 

Animals,  localization  in  different,  980 
.Anions.  429 
Ankle-clonus.  915 

Annulus  of  Vieussens,  157,  162,  179 
.Anode,  429.  724 
.Anterior  commissure.  922.  893 

horn,  cells  of.  858.  864.  876 
connections  of,  876 

roots,  797,  876 
Antero-lateral  ascending  tract,  866,  S73, 
886 
connections  of,  87^? 

descending  tract,  867 

connections  of,  884 

ground  bundle,  867 
Antibodies,  31,  648 
Antidiabetic  diet,  554,  356 
'  .Antidromic  '  nerve  impulses.  181,  792, 

807 
.Antiferments.  339.  390.  343 

in  intestinal  parasites.  390 
Antigens,  31 
Antikinase,  44.  391 
Antilytic  secretion,  398 
Antimony  and  protein  metabolism,  563 
Antiperistalsis.  330,  332,  421 
Antipyretics.  704 
Antithrombin.  38,  39,  42.  44 
Antitrypsin,  343.  390 
Antrum  pylori.  326.  327 
Aorta,  effect  of  compression  of.  204 
Aortic  insufficiency,  efifect  of,  on  pulse, 
106 

notch, 96 

stenosis,  effect  of,  on  pulse,  107 

valves,  87,96.206 

and  dicrotic  wave.  104 
Apex-beat,  90,201,  207 
Apex  preparation  of  heart,  143,  194 
Aphasia,  c)68 
,Aphasia.  Broca's.  970 


Aphasia,  motor.  o7o 

sensory,  370,  972 

subcortical,  972 

temporary,  972 

Wcrnickes-,  971 
Aphemia.  971 
Apno-a.  2H3,  300 

vagi.  284 

vera,  283 
.Apocodeine,  action  of,  on  vaso-raotors, 

173 
.Appetite,  1099 
juice,  1099 
Aqueduct  of  Sylvius.  874 
Aqueous  humour.  58 

composition  of.  466 
secretion  of.  1016 
Arachnoid,  861 
Arachnolvsin,  action  of,  on  ervthrocytes, 

28 
Arcuate  fibres,  internal,  873 
Arginase,  587 
Arginin,  360,  587 
Argyll-Robertson  pupil,  1025 
Arhythmia.  respiratory.  287 
Aromatic  sulphates  in  urine.  484,  517 
Arsenic  and  protein  metabolism.  563 
Arterial  blood -pressure,  amount  of.  112 
.Arteries,  blood -pressure  pulse  in.  100 
structure  of,  82 
to  insert  cannuUe  into,  63 
tone  of,  185,  918 
.Artery  rings,  action  of  adrenalin  on.  216 

action  of  serum  on,  46 
Arterioles,  resistance  in,  129 
.Arteriosclerosis,  velocity  of  pulse  in,  109 
.Artificial  respiration.  202,  230 

with  oxygen.  204 
.Ascending  degeneration,  866 
.Aspartic  acid.  360 
.Asphyxia.  178,  283,  1S7 

condition  of  ha-moglobin  in,  51 
effect  of,    on  circulation.    172.   187, 

213 
glycosuria  caused  by.  548 
in  the  fu?tus,  1137 

inlhience  of.  on  bl<x)d-pressure,  213 
Assimilation  limits  for  carbohydrate,  540, 

551.637 
Association  areas.  973 
centres,  962,  973 
fibres,  883.  885 
.Asthma,  spasmodic,  and  bronchial  mus- 
cles. 287 
Astigmatism,  irregular.  1028 

regular,  1031,  1062,  1105 
Astrospheres.  1122 
.Atrio-ventricular  bundle.     See  .Auriculo- 

ventricular  bundle 
.Atropine,  action  of.  on  heart.  166.  199 
on  nerve-cells.  i,S2 
on  pupil.  1026 


iNi)i:.\' 


1219 


Atropine,  action  of,  on   salivarv  secre- 
tion. 392,  306.  457 
Attraction  sph«rc,  5.  851,  1079 

in  ncrve-cfIN,  851 

Auditory  centre.  (^28,  066 

nerve,  927.  io6») 

cochlear  division  of,  028 
vestibul.ir  l>r.inch  of.  gjS 
ossicles,  1000.  io(i<) 
path,  scheme  of.  927 
Auerbach's  plexus,  319,  330 
Augmentation   of   heart-beat,    157,    172, 
199 
nature  of.  167 
primary.  159 
secondary,  159 
Aupnientor  nerves,  effect  of,  on  quiescent 

iieart,  168 
.\ura.  973 
Auricular  canal,  81 
fibrillation.  151 
flutter.  151 
pressure  curve.  98 
Auriculo-ventricular    bundle,    81,     135, 
138. 147 
pulse-tracings  in  disease  of.  149 
junction,  stimulation  of.  198 
node,  81, 147 
valves.  89. 206 

moment  of  opening  of.  96 
Auscultation  of  breath-sounds,  231,  304 
of  heart-sounds,  207 
of  lungs,  304 
Auto-digestion  of  stomach,  389.  465 
Autogenetic  theory  of  nerve   regenera- 
tion. 801 
Autolysis,  578 

Automatic  actions  of  spinal  cord,  916 
Autonomic  nervous  system.  892,  1003 

functions  of,  1005 
Avalanche  theory.  7S5 
Aviator's  sickness.  299 
Axial  strand  fibrils.  801 
.\xis-cylinder  or  axon,  781.  852.  855 
bifurcation  of.  802 
fibrils  in.  851 

growth  of,  in  cultures.  803  857, 
Axon-reHexes,  400,  792,  913 

Babinski's  sign,  915 

Bacteria  and  digestion,  422,  423 

in  fa?ces.  424 

in  intestine.  343,  423.  618 

synthesis  of  amino-acids  by,  618 
Bactericidal  action  of  gastric  juice,  356 
Balloon  ascents,  deaths  in,  298 
Baryta,  absorption  of  carbon  dioxide  by, 

240 
Basal  ganglia.  932 

metabolism.  686 
Basilar  membrane.  1067,  1070 
Bat's  wing,  contractile  vessels  of,  81,  i8o 


Batteries,  197,  724 

Heals  (hearing).  III3 

Beaumont  on  digestion,  349 

Brchlcrew's  nucleus,  928 

lli-ckmann's  apparatus.  427.  529 

H(  Hows  recorder.  302 

Bell's  experiments  on  nerve-roots.  Hqi 

Belt  rfcordcr  for  respiration.  233 

Benedict  estimation  of  blood  sugar,  717 

Benzoic  acid,  481,  580 

Beri-beri  caused  by  polished  rice,  632 

thymus  in,  633 
Bert  on  double  conduction  in  nerves.  792 
on  effects  of  oxygen  at  high  pres- 
sure. 2^7 
Betz  cells.  848.875.959 
Bichromate  cell.  197 
Bidder's  ganglia.  141 
Bile.  363-370 

absorption  of.  384,  412 
acids,  365,  462 

circulation  of,  412 

formation  of,  384 

Hay's  test  for,  462 

Pettenkofer's  reaction,  366,  462 

adaptation  of,  to  food,  413 

and  absorption  of  fat.  369 

and     pancreatic     juice,     adjuvant 

action  of.  367 
and  surface  tension,  369, 462 
as  an  excretion,  424 
composition  of,  363 
curve  of  secretion  of.  413 
digestive  functions  of.  367 
formation  of.  384, 385 
freezing-point  of,  387 
gases  of,  267,  366 
in  emulsification  of  fats,  367 
influence  of  nerves  on  secretion  of, 

411 
inhibition  of  heart  by,  172 
mucin.  364 

pigments.  364.  385,  462 
circulation  of.  412 
Gmelin's  test  for.  365.  462 
production  of.  in  liver.  385 
relation  of.  to  spleen.  672 
precipitation  of   gastric  digest  by, 

370 
quantity  of.  367 
rate  of  secretion  of,  413,  419 
reactions  of,  462 
reinforcing  action  of,  368 
salts.  365 

action  of,  on  blood.  28,  70 
decomposition  of.  365 
in  urine.  Hay's  test.  528 
influence    of.    on    secretion    of 
bile.  413 
secretion  of.  influence  of  nerves  on, 
411 
influence  of  secretin  on,  408,  412 


INDEX 


Bile,  secretory  pressure  of,  414 

spectrum  of,  365 
Biliary  fistula.  369,  412 
Bilirubin,  364 
Bilivirdin.  364 
Bioplasm.     See  I*rotoplasm,  an<4  Living 

matter 
Bipolar  ganglion  cells.  856 
Bird's  blood,  coagulation  of.  36.  43 
Biuret  reaction.  8,  459 
Bladder.  310 

pressure  in.  in  lulotvirition.  310 
Blastoderm.  1125 
Blind  spot.  1044.  10(14.  1 107 
mapping  the.  1064 
Blood,  bird's.  36 

carbon  dio.xide  content  of.  26,  255 
chemical  composition  of,  47 
circulation  of.  80 
coagulation  of.  33,  62 
composition  of,  49 

-corpuscles,    coloured,    composition 
of,  50 
osmotic  resistance  of.  73 
crenation  of,  16 
destruction  of,  21 
dextrose  in.  50,  540. 717 
enumeration  of.  18,  67 
formation  of.  in  embryo.  20 
gaseous  metabolism  of,  252 
life-history  of,  20 
in  pernicious  anaemia,  21 
red, 15 

destruction  of.  2 1 
origin  of.  20 
rouleaux  formation  of,  i6 
shadows  or  ghosts  of.  70 
size  of,  15 
structure  of,  15 
white.     See  Leucocytes 
distribution  of.  36.  180 
»       electrical  conductivity  of.  26.  68 
flow,   calorimetric  method   of  mea- 
suring. 122 
in  different  organs.  127 
in  feet.  127 
in  hands,  126 

measurement  of.  219 
functions  of,  59 
gases  of.  245-266 

estimation  by  ferricyanide.  250 
quantity  of,  250 
tension  of.  258 
results,  261 
guaiacum  test  for.  76 
kinetic  and  potential  energy  of  cir- 
culating, 119 
lakingof.70 

measurement  of  velocity  of.  120-124 
morphology  of,  14 
opacity  of.  70 
pigment,  microscopic  test  for.  78 


Blood  pigmei\t,  preparation  of,  73 
plasma,  proteins  of,  47,  572 

relative  volume  of,  27,  68 
plates,  18 
platelets  and  coagulation,  39,  40 

anticoagulants    and    preserva- 
tion of,  40 

disintegration  of,  40 

functions  of,  62 
precipitin  test  for,  31 
quantity  of,  53 

in  lungs,  224 

which  may  be  lost,  191 
reaction  of,  24.  62 
regeneration  of,  22 
relative  volumes  of  corpuscles  and 

plasma,  27,  68 
serum,    electrical    conductivity    of, 
26,  27,  68,  386 

freezing-point  of,  386 
specific  gravity  of,  26,  62 
sugar  in,  47,  499,  302.  333,  540,  547 

349,  551.  552,636,637,717 
temperature  of,  680,  71 1 
testing  for  adrenalin  in,  656,  637,  662 
tests  for,  45-47 
titratable  alkalinity,  23 
vaso-constrictor  property  of  shed,  45 
velocity  of,  117-127 

in  arteries,  119,  123 

in  capillaries,  120,  130 

in  veins,  120,  134 

measurement  of,  120,  122,  219 
vessels,  sutiu-ing,  1144 
viscosity  of,  23,  302 
volume  of  corpuscles   and  plasma 

27,68 
why  it  does  not  clot  in  the  vessels, 

45 
Blood- pressure,  arterial,  measurement  of, 
107 
and  acapnia,  184 

curves  with  elastic  manometers,  93, 
III 
with     mercurial     manometers, 
no,  112,  210 
effect  of  changes  of  posture  on,  190, 
213 
of  extracts  of  bone-marrow  on, 

f'71,673 
of  freezing  the  cord  on,  184 
of  ha'niorrhage  and  transfusion 

on.  loi,  214 
of  kidney  on,  671 
of  muscular  exercise  on,  115, 213 
of  nervous  tissue  on,  673 
of  peptone  on,  173,  215 
of  pituitary  on,  668 
of  proteoses  on,  1 73.  215 
of  suprarenal  on,  171,216,635 
of  testicle  on,  642 
of  thvmus  on.  643 


INDllX 


Bloud- pressure,  estimation  of  the  arterial, 
2X0,  213 

factors  wliicli  niaiiitaiu,  116 

fall  of,  in  sleep,  <)«(> 

hydrostatic  and  hyilrodv  naniic  ele- 
ments, I()0 

in  capillaries,  i.?o,  i;,i 

influence  of  respiration  on,  289 

in  man,  influence  of  exercise  on,  115, 
measurement     of,     by    stetho- 
scope, 113,  213 

in  pulmonary  artery,  1 1(> 

in  right  and  left  ventricles,  116,  138 

mean  arterial,  loq,  1 1  j 

measureme'.it  of,  loi),  2H 

permanent  element  iu,  1 1 1 

systolic  and  diastolic,  113 

tracings,  165,  184, 186,  187,  188,  lyi, 
210,  213,  216,  237,  279,  280 
Blood-pump,  249 

Blood-serum,  freezing-point  of,  386 
Blood-supply,  regulation  of,  189 
Bloodvessels,  anastomosis  of,  1144 

rhythmically  contractile,  81,  175,  180 

structure  of,  82 

iowe  of,  1S4,  996 
Body,  composition  of,  6or 
Bohr,  on  blood-gases,  254,  261,  264 
Bolometer,  675,  783 

Bone-marrow  and  blood-formation,   20, 
22 

action  of  extracts  of,  671,  673 
Bones,  competition  of,  boi,  621 

influence  of  pituitary  on,  670 
of  testicles  on,  642 
■  Boot '  electrodes,  842 
Brain,  anaemia  of,  986 

chemistry  of,  991 

circulation  in,  9S9 

condition  of,  isolated,  975 
in  sleep,  913 

development  of,  849 

functions  of,  931 

heat-production  in,  689 

influence  of,  on  spinal  reflexes,  910, 
lOOI 

respiratory  changes  in   volume  of, 

295 
resuscitation  of,  990 
size  of,  at  different  ages,  988 

and  intelligence,  988 
temperature  of,  712 
volume,    respiratory    variations   in, 

295 
Bread,  720 

Breast-feeding,  superiority  of,  1140 
Breath,  holding,  234 
Broca's  area,  971,  974 

aphasia,  970 
Bronchi,  223 

movements  of,  in  respiration,  231 

nerves  of,  287 


Bronchial  breathing,  231 

nuiscles,  innervation  ai,  287 
Bronchoscope,  231 
Brownian  motion,  454 
Bro\vn-Se(|uard's  syndrome,  894 
Brunner's  glands,  380,  383 
'  BufTy  '  coat,  39 
Burdach's  tract,  866 

connections  of,  870 
Burdon-Sanderson  on  negative  variation, 

825,  82(. 
Burns,  superficial,  death  from,  299 
Buttermilk  diet,  422 
Butyric  acid,  562 

fermentation,  423 

Cachexia  strumipriva,  648 
Ca>cum,  nerves  of,  t,},2 
Caffeine,  481,  583,  594,  632 

as  diuretic,  3o<) 
Caisson  disease,  297 
Calcium  and  bone  formation,  621 

delicieficy  of,  621 

relation  of,  to  heart-beat,  152,  200 
Calorimeter,  air,  67<; 

differential  micro-,  680 

respiration,  240,  h-f),  678,  721 
At\vater"s,  ()76 

water  equivalent  of,  721 
Calorimetric   method   for   blood-flow   in 
hands,  219 
for  vaso-motor  reflexes,  188, 221 
Calorimetry,  675,721 
Campbell,  visuo-psychic  area  of,  966 
Cancer,  gastric  juice  in,  350 
Cane-sugar,  absorption  of,  435,  445,  464 

inversion  of,  10,  339 

by  gastric  juice,  356 

tests  for,  II 
Cannula,  three-way,  212 

gastric,  459 

to  put  into  an  artery,  63 
trachea,  202 
vein,  215 
Capillaries,  blood-pressure  in,  131 

changes  of  calibre  of,  173 

circulation  in,  120, 129, 193 

pulse  in,  131 

resistance  in,  120,  130 

total  cross-section  of,  130 

velocity  of  blood  in,  130 
Capillary  electrometer,  728,  729,  842 
Caproic  acid,  566 

Capsule,  internal.     See  Internal  capsule 
Carbo-hydrates,  absorption  of.  445 

amount  of,  in  standard  diet,  623,  625 

assimilation  limits,  540,  551,  637 

composition  of ,  i ,  3 

constitution  of,  3 

intermediary,  metabolism  of,  542 
in  diabetes,  553 

metabolism  of,  533 


INDEX 


Carbo-liydratcs.Mnlisch's  test  for,  II 
necessity  of,  in  luitritiim,  607 
passage  uf,  tiiioiigli  placenta,  1131 
protein-sparing  action  of,  606 
reactions  of,  10 
tests  for,  10 

tolerance  after  pancreatectomy,  637 
Carbon  balance-sheet,  618 
equilibrium,  618 
dioxide,    action    of,    on   respiratory 
centre,  2^ii 
and  blood- flow  in  heart,  178 
distribution  in  blood,  255 
estimation  of,  ::4o,  305 
excretion,    influence    of    forced 
respiration  on,  245 
mechanism  of,  264 
in  alveolar  air,  241 
in  blood,  condition  of,  257 
in  fu'tal  blood,  1129 
influence  on  ha;moglobin,  255 
in  serum,  255,  256 
in  \enous  blood,  tension  of,  261 
partial   pressure  of,  in   alveoli, 
261,  264 
in  blood,  259,  261 
in  tissues  and  liquids, 

272,273 
production,   Haldanc's  appara- 
tus for  measuring,  304, 305 
production     of,     in     different 
animals,  244 
in  muscular  work,  242 
in  relation  to  body-weight, 

244 
in  rigor,  270,  777 
tension  of,  in  tissues,  272 
washing  out  of,  245,  283 
monoxide  method   for   quantity  of 

blood,  56 
necessary  quantity  in  diet,  625 
Carbonic  acid  and  urea  formation,  589 

oxide  hamoglobin,  53,  74 
Cardiac  cycle,  85 
death,  171 
impulse,  90,  208 
nerves,  157,  it).',  196,  198,  203 
sound, 96 
sphincter,  320 
Cardio-augmentor  centre,  169 
Cardiogram,  91 ,  207 
inversion  of,  01 
Cardiograph,  90,  208 
Cardio-inhibitory  and  augmcntor  centres, 
169 
tone  of,  169 
Cardiometer,  139 
Cardiophonograin,  88 
Cardiopneumatic  movements,  128,  303 
Carnosii\  in  muscle,  767 
Casein.  354 

as  adequate  protein,  613 


Caseinogen,  354,719 
Castration,  effects  of,  640,  643 

on  thynms,  644 
Catalase,  76,  271 
Catalysers,  339 
Catheterism,7l6 
Catheter,  pulmonary,  259 
Cells,  structure  of,  4 
Cellulose,  digestion  of,  423 
Central  canal  of  cord,  849,  861 
gi-ey  axis,  861 

nervous  system,  action  currents  of, 
838 
arrangement  of  white  and 

grey  matter  in,  861 
development  of,  849 
functions  of,  887 
general     arrangement     of, 

«6i 
histological     elements     of, 

850-861 
localization  of  function  in, 

975 
methods  of  study  of,  848 
structure  of,  847 
Centre  for  smell,  967 
for  taste,  968 
of  gravity  of  body,  946 
thumb,  973 
Centres,  cardio-inhibitory  and  augmen- 
tor,  169 
heat,  701 

'  motor,'  of  cortex,  looi 
nmsical,  967 
of  cord  and  bulb,  919 
sensory,  of  cortex,  965-968 
vasomotor,  182-185 
Centrifuge,  64 
Centrosome,  5,  851 

in  the  ovum,  1122 
Cerebellar  ataxia,  935 
Cerebellum,  anat<imical  division  of,  942 
connections  of,  885,  935 
functions  of,  933 
inferior  pedimcle  of,  885 
Incalization  of  function  in,  942-944 
middle  peduncle  of,  886 
peduncles  of,  885 
structure  of,  934 
superior  peduncle  of,  886 
worm  of,  874,  885,  942 
Cerebral  anaemia,  190,  986,  989,  990 

stimulation  of  vagus  after,  187 
circulation,  f)89 
ct)rtex,  and  respiration,  276 

clinical  and  pathological  obser- 
vations on, 962 
development  of,  862 
functions  of,  947 
histological    differentiation    uf, 

..5« 
inhibition  from,  954 


IMDEX 


1223 


Cerebral  cortex,  Uyers  of,  <)3S 

lucali/atioii  <>f  l'uuctii)ii  in,  ()5i 
'  inotiir  '  areas  of,  1J51 
sensory  areas  of,  <>b5 
stability  of  reactions  of,  i)^t, 

hemispheres,  excision  of,  i)4  7-().ji) 
frog,  047,  1000 
piReon,  <)4H,  lOOI 

localization,  I'lechsig's  areas,  961 

peduncle,  H8^ 

vesicles,  841) 
Ccrebrins,  794,  <^<>i 
Ccrebro-spinal  fluid,  58,  466,  992 

displacement  of,  295 

secretion  of,  99^ 
ferebrum,  effects  of  removal  of,  947-()49 
Cervical  sympathetic.     Sec  Sympathetic 
Chalk-stones,  487,  590 
C  heese,  626,719 

Chemical  regulation  of  respiration,  281 
'  Chemical  tone,'  695 
Chemiotaxis,  61 

in  nerve  regeneration,  800 
Cheyne-Stokes  respiration,  287,  300 
Chiasma,  optic,  923 
Child,  food  requirement  of,  628 

basal  metabolism  of,  628,  686 

gaseous  exchange  in, 243 
Chloral,  anaesthesia  by,  190,  213 
Chlorides,  estimation  of,  515 
Chloroform  an;esthcsia,  inhibition  in,  170 

passage  of,  through  placenta,  1130 
Cholesterol  or  cholesterin,  4,  47,  570,  794, 
991 

circulation  of.  571 

in  bile,  36(1,  41^ 

reactions  of,  463 
Cholic  acid,  365,  3^6 
Cholin,  4,  421,  571 
Cholohsematin,  365 
Chorda  tympani,  179,  391-393,456 

stimulation,  of,  456 
Chordo-lingual  triangle,  391 
Chorion,  11 28 

Choroidal  epithelium,  1016,  1048 
Choroid  plexus,  992 
Chromaffin  cells,  665 
Chromatin,  5 

changes  in,  in  nerve-cells,  983,  984 

extranuclear,  984 
Chromogen,  482 
Chromophanes,  1049 
Chromosomes,  6,  1122 
Chrysotoxin,   action  of,   on    blood-pres- 
sure, 173 
Chyle,  14,58,443 

composition  of  fistula,  58 
Chyme,  326 

passage    of,   through    p>Iorus,   327, 
408 

to  obtain  normal,  459 
Cbymosin  (vide  Reunin),  353 


Cilia,  733 

movem'-nts  <jf,  811 
work  done  by,  734 
Ciliary  ganglion,  924 
muscle,  924,  1022 
nerves,  1033 
processes,  1014 

and   secretion    of   aijueous    hu- 
lunnr,  1016 
Cinematograph,  945,  1042 
Circulating  blood,  microscopic  examina- 
tion of,  193 
liquids,  14 
Circulation,  changes  in,  at  birth,  1138 
Comparative,  80 
cross,  through  brain,  284 
general  view  of,  81 
in  brain,  989 
in  capillaries,  129,  131 
in  the  embryo,  1138 
in  the  frog's  web,  15,  193 
in  the  lungs,  137,  223 
in  the  tadpole,  193 
influence  of  posture  on,  190,  213 
of  lymph,  192 
time,  135-138 

electrical  method,  135-137 
Hering's  method,  135 
methylene    blue    method,    137, 

217 
pulmonary,  137,  698 
Circus  movements,  943 
Citrates  and  coagulation,  37 
Clarke's  column,  864 

connections  of,  872 
Coagulated  proteins,  reactions  of,  9 
Coagulation  of  blood,  42,  62 

action  of  fluorides  on,  37 

of  citrates  on,  37 
birds,  36 
calcium  in,  36 
factors  in,  42 
hirudin  and,  37 
influence  of  platelets  in,  37 
of  proteoses  on,  37 
of  tissue  extracts  on,  36 
influences  restraining,  42 
intravascular,  42 
leech  extract  and,  38 
manganese  and,  37 
of  crayfish,  40 
of  Linuilus,  40 
peptones  and,  37 
relation  of  adrenals  to,  45 

liver  to,  44 
studied    with    ultramicroscope, 
39 
of  lymph,  57 

temperature,  to  determine,  9 
Coaguliiis,  41 
Coal-gas  poisoning,  53,  74 
Cobra-veuom  and  coagulation,  43 


1224 


INDEX 


Cocaine,  action  of,  on  ncrvts,  791 
on  pupil,  1026 
fever,  704 
Coclilea,  927,  1067,  1068,  1069 
Cochlear  root  of  eighth  nerve,  874,  928 
Cocoa,  594,  630,  631 

Co-enzymes  or  co-ferments,  343,  368,  548 
toffee,  5<)4,  631,  632 
Cola-nut,  632 

Cold  sensations,  1041,  1082,  1084,  1115 
after     section     of     cutaneous 

nerves,  1088, 1091 
paths  for,  896 
Collaterals,  781,  852 

of  posterior  root  fibres,  871 
Colon,  movements  of,  330,  333 

innervation  of,  332 
Colostrum,  11 39 
Colour,  body  and  surface,  1012 
blindness,  1059,  1 1 12 
temporary,  1061 
mixing,  1052,  IIII 
triangle,  1054 
vision,  1 05 1 

Hering's  theory  of,  1057 
V'oung-Helinholtz     theory     of, 
1053 
Ctiloured  shadows,  1056 
Colours,  complementary,  1052,1068,  IIII 

primary,  1033 
Coma,  congestion  of  brain  in,  985 

diabetic,  555 
Comma  tract,  867,  871 
Commissural  fibres,  863,  893 
Common  path,  principle  of  the,  899 
Conunutator,  Pohl's,  732 
Compensator,  727 

Compensatory  pulse  of  heart,  155,  156 
Complement,  28,  72 
Complemental  air,  233,  303 
Complementary  colours,  1032,  IIII 
Condensed  air,  effects  of  breathing,  295 
Conditioned  reflexes,  973 
Conduction,  double,  in  nerve,  791 
irreciprocal,  792 
isolated,  law  of,  793 
loss  of  heat  by,  681 
Conductivity,  molecular,  429 
of  nerve,  786,  790 

anaesthetics  and,  7(»o,  814 
effect  of  temperature  on,  791 
electrical  currents  on,  786, 
787,844 
specific,  of  electrolytes,  429 
Congo-red  as  test  for  acids,  351 
Conjugate  deviation,  <)(>3 
Conjugated  proteins,  2 
Conservation  of  energv,  law  of,  in  body, 

679, 683 
Consonants,  313 

Contraction,  formula  of,  788,  845 
for  nerves  in  situ,  789 


C.oiitrac  tioii,  law  of,  for  human  uerscs, 846 
paradoxical,  ^^2,  844 
seccjndary,  832,  842 
Contractions,  superpositimi  of,  756,  816 
Contrast  (vision),  1056 
Co-ordination  of  movements,  945,  981 

of  reflexes,  908 
Cure  models,  and  electrotonic  currents, 

831 
Cornea,  radius  of  curvature  of,  1017 
Corneal  reflex,  914 
Corona  radiata,  862,  875,  883 

path  from  cortex  in,  877 
Corpora  Araiitii,  87 

quadrigemina,  874,  881,  932 
and  respiration,  276 
anterior,  i)2i,  932 
posterior,  928,932 
striata,  850,  862,  870 

and  temperature  regulation,  701 
Corpuscles  and  plasma,  relative  volume, 

27,  68.     See  Blood 
Corpus  callosum,  863,  883 
dentatum,  863 
luteum,  643,  1120,  1121 

and  menstruation,  1121 

hsematoidin  in,  383 

internal  secretion  of,  643,  1078, 

1121 
origin  of,  1121 
striatum,  850,  862,  870 
Cortex  of  brain,  functions  of,  947 
'  motor '  areas  of,  951 
sensory  areas  of,  965 
Corti,  ganglion  of,  927 

organ  of,  927,  1067,  1069,  1074 
Cortical  epilepsy,  972 
grey  matter,  861 
Costal  breathing,  229 
Cotton  seed,  361 
Coughing,  288 

Cranial  conduction  of  sound,  1071,  III3 
nerves,  920 

bifurcation    of    afferent    fibres, 

924,  925,  926,  928 
homologies  of,  921 
nuclei  of,  920 
Crayfish  blood,  clotting  of,  40 
Cream.  718 
Creatiii,  481,  703 

Creatin  and  creatinin  in  protein  meta- 
bolism, 597 
in  muscle,  768 
Creatinin,  481,  523 

excretion  and  muscular  work,  611 
in  fever,  703 
source  of  urinary,  598 
Crenation,  16 
Crista  acustica,  936 
Cross  circulation  through  brain,  284 
Crossed  pyramidal  tract,  866,  875,  879 
connections  of,  875 


INDEX 


122i 


Crowbar  case,  American,  974 

Crura  cerebri,  870,  874 

Cnista,  870 

Cultivation  of  tissues  outside  the  body, 

ii4i 
Cuneate  funiculus,  86() 
nucleus,  86(» 

relation  of,  to  fillet,  874 
Cuneus  and  vision,  966 
Cuorin,  371 
Curara,  18:: 

action  of,  on  gaseous  exchange,  244, 

541 
on  heat  production,  694,  702 
on  nerve-endings,   182 
on  skeletal  nuiscle,  738,  811 
on  \oiiiitinj,',  v^O 
Curdling  of  milk  by  rennin,  353,  354,  459, 

7t9 
Current  intensity  and  stimulation,  741, 
784 
of  action.     See  Action  current 
of  rest.      See  Demarcation  current 
Cushny's  views  on  urine  secreticjn,  502 
Cutaneous  burns,  death  from,  299 
excretion,  511 
nerves,  section  of,  1085 
respiration,  299 
sensations,  1078 

Boring's  experiments,  1091 
cortical  centres  for,  969 
localization  of,  io()3 
Trotter  and  Davies'  experi- 
ments, 1085 
Cybulski's     arrangement     (velocity     of 

bkx^d),  123 
Cyclic  compounds,  615,  616,  618 
Cyclopoiesis,  615,  616,  618 
Cystein,  360,  365,  381,  582 
Cysteinic  acid,  366 
Cystinuria,  366,  488,  579 
Cytolysins,  31 
Cytoplasm,  5 
Cytosin,  593 

Dancing  mice,  labyrinth  in,  945 
Daniell  cell,  197,  7-24 

Daphnia,  Metchnikoff's  researches  on,  60 
Dark-adapted  eye,  1047,  1049,  1058 
Daturine,  action  of,  on  pupil.  1026 
'  Dead  space,'  respiratory,  236 
Deaf-mutes,    atrophy   of   temporal   con- 
volutions in,  967 

equilibration  in,  940 
Decerebrate     rigidity,    917,    942,     955, 
1000 

preparation,  998 
Dcccrebrator,  999 
Decidua,  1076,  1083 

absorption  of,  by  leucocytes,  60 

artificial  production  of.  1078 
Decinormal  solutions,  479,  522 


Decussation  of  afferent  impulses,  894 

of  efferent  impulses,  893 

..f  fillet,  870 

of  optic  nerve,  923,  966 

i>f  pyramids,  869,  875,  878 

of  sensory  paths,  894 
Defacation,  332 
Deficiency  diseases,  617,  632 

phenomena  after  nervous  lesions,  88  i 
Degeneration  of  nmscle,  804 

of  nerves,  795,  797 

chemistry  of,  798 

of  spinal  roots,  797 

reaction  of,  804 
Deglutition,  322 

centre,  325 

nerves  of,  325 

reflex,  looo 

sounds,  324 
Deiters'  nucleus,  884,  886,  893,  928 
Delirium  cordis,  151,  205 
Demarcation  current,  823,  842 

electromoti\T  force  of,  826 
theories  of,  828 
Dendrites,  852 

amoeboid  movements  of,  852 

and  sleep,  986 
Dentate  nucleus,  863,  869,  886 

of  olive,  869 
Depressor  nerves,  170,  173,  185,  186 
pressor  action  of,  188 

reflex,  reversal  of,  904 

in  cerebral  ana?mia,  188 
Descending  degeneration,  866,  875 
Deutero-proteose,  3,  10 
Development  of  embryo,  1124 

of  ovum,  1 122 
Dextrins,  3,  il,  347,  455,  715 

formed  in  salivary  digestion,  347,455 

tests  for,  11,715 
Dextrose,  3,  47,  338,  347,  455,  525,  5:.4 
537 

estimation  of,  in  urine,  525 

in  blood,  47,  50,  446,  499,  500,  540, 
552 
estimation  of,  717 

in  lymph,  446 

ratio  to  nitrogen  in  urine  iu  diabetes, 
551 

tests  for,  10,  488 

Trommer's  test  for,  10 
Diabetes,  546,  552 

dextrose-nitrogen  ratio  in,  551 

diet  in,  534,  556 

mellitus,  532 

oxygen  consumption  in,  242 

pancreatic,  346,  354,  636 

phlorhizin,  331,  717 

reaction  of  blood  in,  24 

respiratory  quotient  in,  242 

sugar-destroying  power  of  blood  iu, 
554 


1226 


INDEX 


Diabetic  coma,  555 
Diapcdcsis,  61,  194 
Diaphragm  in  iispiratioii,  226,  228,  275 

recording  movements  of,  2,^3 
Diastases,  87,  344,  370,  384,  534 
Diastase,  salivary,  344 
Diastole  of  heart,  87 
Dichromatic  vision,  1060,  III2 
Dicrotic  wave  of  pulse,  104,  1 1 1 
Dietaries,  standard,  623,  625,  627 
Dietetics,  622 
Diet  in  diabetes,  554,  556 
Diffusion,  426 

circles,  1021,  1062 

of  gases,  246 

through  lungs,  264 
Digestion  as  a  whole,  416 

and  absorption,   time   recjuired   fur, 
464 

bacteria  and,  422,  423 

changes  in  acidity  of  gastric  contents 
in,  418  ^ 

chemical  phenomena  of,  336-374 

comparative,  318 

gaseous  exchange  during,  243 

heat-production  in,  713 

in  intestines,  418 

in  stomach,  416 

mechanical  phenomena  of,  321 

of  carbo-hydrates,  356,  362.  416 

of  fats,  355,  363.  367,  461,  463,  464 

of  proteins,  351,  358,  417,  458,  460 

significance  of,  321 

time  required  for,  418,  464 
Digestive  glands,  microscopical  changes, 

374 
juices,  adaptation  of,  to  food,  369, 
398,  404,  410,  415 
process  of  formation  of,  383 
protection    of    mucous    mem- 
brane from,  389 
summary,  415,  416 
organs  in  different  animals,  318 
Digitalis,  diuretic  action  of,  509 
Dilator  of  pupil,  1025 
Diopter,  1021 
Diphasic  variations,  825 
Diphtheria  toxin,  action  of  enzymes  on, 

372 
Diplopia,  924,  1037 
Direct  cerebellar  tract,  866,  872,  892 
connections  of,  872 
pyramidal  tract,  866,  875,  878 
Disaccharides,  3,  371 

absorption  of,  445 
J^ischarge  of  ventricle,  period  of,  87,  1)7 
Dispersion  in  eye,  1028 
Dissociation  of  oxyhaemoglobiu,  253,  273 
Diuresis  by  salts,  509 
Diuretics,  509 

Double  conduction  in  nerve,  792 
Dromograph,  122 


Dulcitc,  3 

Duodciunn,  digestion  in,  417 

glycosuria  after  removal  of,  640 

reaction  of  contents  of,  419 
Dura  mater,  X(>i 
Dyspnoea,  283 

heat,  283,  302 

respiratory  quotient  in,  241 

ICar,  anatomy  of,  1065 

ossicles  of,  10O5,  1066 
functions  of,  1069 

resonance  tone  of,  89,  760 
Hchidnase,  53 
Kck's  fistula,  385,  585 
Ectoderm,  6,  11 24 
Ectoplasm,  4 
Edestin,  607 

tryptic  digestion  of,  361 
Ivffector  organs,  898 

Efferent   impulses,   decussation   of,   869, 
875,  878,  893 
paths  of,  893 
scheme  of,  890 
Egg-albmnin,  absorption  of,  447 

amino-acids  in,  i 

excretion  of,  448,  500,  716 

reactions  of,  9 
Eggs,  iron  in,  622 
lilu-lich's  triacid  stain,  i  7 
Eighth  nerve.     Sec  Auditory  nerve 
Elasticity  of  muscle,  735 
Electric  fishes,  840 

signal,  7:^2 
Electrical  conductivity  c)f  blood,  26,  68 
of  gastric  juice,  387 
of  milk,  1 139 
of  serum,  69,  386 

organ,  841 

response.     See  .\ction  current 
l-"Iectro-cardiogram.  human,  835-838 
Electrodes,  to   make,  808 

unpolarizable,  731,  842 
Electrolytes,  428 
Electrometer,  727 

capillary,  728,  729,  826,  842 
Electroinotive  force,  725,  827 
Electrons,  429 

Electrotonic    alterations    of    excitability 
and  conductivity,  786,  844 

currents,  830,  844 
Electrotonus,  785,  844 
Eleventh  nerve,  931 
Emboli,  artificial,  848 
Embryo    and    uterus,    coimections    be- 
tween, 1 126 

asphyxia  in,  1137 

circulation  in,  11 26,  1138 

development  of,  11 22,  11 26 

formation  of  the,  1124 

gases  of  blood  in,  11 29 

glycogen  in,  538,  1131.  ii33 


INDEX 


1227 


Embryo,  heat-production  in,  1135 

inverting  enzymes  in,  371 

liver  in,  11 32 

metabolism  of,  11 33 

physiology  of,  ii^K,  1129 
Emetics,  ;,v>,  459,  464 
limmetropic  evf,  loji) 
Emotions,  genesis  of,  1)74 
ICnuiIsitication,   iz,  367 
Emulsin,  338,  340 
Endocardiac  pressure,  o-,  'M 

amount  of,  in  ventricle,  92,  94 
curves  of,  ()3,  ()6,  «)7 
measurement  of,  93 
negative,  lot 
l-2ndocrine  glands,  635 
luidoderm,  6,  1125 
Endo-enzymes,  337 
Endogenous  fibres  of  cord,  .S()3,  867,  897 

metabolism  of  proteins,  573 
Endoplasjn,  4 

Endothermic  reactions,  689 
Enemata,  331,  451 

Energy  of  food,  influence  of  hydrolysis 
on,  683 

law  of  conservation  of,  in  body,  679, 
683 
Engrafting,  641,  1142 
Enterokinase,  372,  415 

nature  of,  373 
Enzjnnes.     See  Ferments 
Ependyma,  861 
lipiblast.     See  Ectoderm 
Epicritic  sensibility,  1091 
Epiglottis,  323 
Epilepsy,  cortical,  972 

Jacksonian,  972 

produced  by  absinthe,  964 
Epinephrin,  66,  173,  655.     See  Adrenalin 

function  of,  657 

indispensability  of,  657 

partition  of,  in  blood,  659,  II49 

secretion  of,  661 

testing  for,  656 
Equilibration    and    afferent    impressions 
from  muscles,  941 
from  skin,  <)4i 

and   orientation,    afferent    impulses 
concerned  in,  935,  936 

cerebellum  and,  934 

Deiters"  nucleus  and,  929 

in  dog,  937 

in  dogfish,  938 

in  pigeon,  937 

muscular  nerves  and,  941 

postural  reflexes  and,  938 

semicircular   canals   and,   928,   929, 
936-941 

skin  and,  941 
Erection  centre,  183 
Erepsin,  371 
Ergograph,  642,  750,  752,  813 


Ergot  and  blood-pressure,  173 
lilrucic  acid,  556,  558 
Erythroblasts,  21 

Ervthrocytes,  15.     S^c  Blood-corpuscles, 
red 

enuineration  of,  19,  67 

gases  of,  250-^57 

life-history  of,  20 
lirythrodextrin,  11,  347,  455,  715 
Esbach's  method  of  estimating  albumin, 

525 

Eserine,    action    f)f,   on    accommodation, 
lozz 
on  pupil,  1020 
Ether,  action  of,  on  blood-corpuscles,  28, 

29,70 
Ethyl  butyrate,  synthesis  of,  by  lipase, 

338, 444 
Eudiometer,  249 
Euglobulin,  48 
Eustachian  tube,  297,  1065 

\alve,  1 132 
Evaporation,  loss  of  heat  by,  682 
Excitability,  aproperty  of  living  matter,  7 

and    conductivity,    voltaic    current 
and,  787,  844 

direct,  of  muscle,  738,  81 1 

of  nerve,  effect  of  temperature  on, 
784,  790 
electrical  currents  on,  758, 
785,844 
Excitable  tissues,  the,  724 
Excretion,  475 

Exogenous  metabolism  of  proteins,  573 
Exothermic  reactions,  689 
Expectoration,  475 
Expiration,  226,  229 

duration  of,  234 

forced,  230 
Expired  air,  composition  of,  239-241,  305 
Extensibility  of  muscle,  736 
Extension  reflex,  crossed,  902,  997,  998 
Extensor  thrust  reflex,  the,  901 
Extero-ceptive  reflexes,  014 
Extra  contraction  of  heart,  155 

systoles,  in  man,  155,  156 
Exudation,  inflammatory,  6r 
Eye,  action  currents  of,  830 

artificial,  Kiihne's,  1 104 

chemistry  of  refractive  media,  1016 

compound  of  insects,  1013 

defects  of,  1027 

development  of,  850 

dissection  of,  IIOI 

extriiisic  muscles  of,  1063 

liquids,  1016 

secretion  of,  1016 

movements  of,  1062 

nerves  of,  1023,  1024 

optical  constants,  1017 

pupillo-constrictor  fibres,  1023,  liio 
dilator  fibres,  1023,  mo 


12  28 


INDEX 


live,  reduced,  1019 
refraction  in,  1017 
retinal  fatigue,  1055,  III2 
structure  of,  1014.  IIOI 
visual  acuity,  liil 

Facial  uerve,  926 

union  of,  with  accessory,  976 
palsy,  926 
I-acilitation  of  reflexes,  <)09 

in  motor  cortex.  934 
Faxes,  action  of  extracts  of,  424 
bacteria  in,  4J4 
composition  of,  423 
microscopical  examination  of,  463 
odour  of,  424 
I'asling  men,  metabolism  in,  604 

hunger  sensations  in,  1096 
Fat,  absorption  of,  441,  463 

influenced  by  bile,  ',69 
amount  of,  in  standard  diet,  623, 625, 

627 
chemistn,-  of,  556 
composition  of,  i 
excretion  of,  into  intestine.  443 
formation  of,  from  carbo-hydrates, 
560 
protein,  561 
intermediary  metabolism  of,  565 
melting-point  of,  12 
metabolism  of,  556 
liver  and,  567 
migration  of,  557,  563,  568 

in  phosphorus  poisoning,  563 
mobilization  of,  565 
non-nutritive  function  of,  568 
passage  out  of,  intestinal  epithelium, 

44- 
storing  of,  558 
synthesis  of,  in  intestinal   nmcosae, 

443. 444 
Fatigue,   changes    in   nerve    cells,    859, 

983 
influence  of,  on  muscular  contrac- 
tions, 749,  813 
on  nmscle-curve,  813 
muscular,  cause  of,  751 
of  muscle-nerve  preparation,  seat  of 

exhaustion  in,  752,  813 
seats  of,  in  voluntary  contraction, 

753 
Fats,  constitution  of,  3,  556 

tests  for,  II 
Fatty  acids,  absorption  of,  443 

and  glycogen  formation,  538 
decomposition  of,  in  body,  566 
formation    of,    from    carbo-hy- 
drate, 561 
synthesis  of,  to  fat,  444 
tests  for,  12 
Fechncr"s  law,  1100 
Fehliug's  solution,  526 


Fehling's  solution,  Benedict's  m<xlifica' 
tion  of,  527 

test  for  sugar,  525 
Ferment  action,  quantitative  estiiuatiou 
of,  34^.  453 

cellulose-dissolving,  423 

mode  of  action  of,  339,  341 

re\ersible  action  of,  339 
Fermentation,  butyric  acid,  423 

lactic  acid,  423 
Ferments,  336 

autolytic,  599 

in  the  liver,  600 

intracellular,  337 

list  of,  345 

specificity  of,  340 
Fever,  aseptic,  707 

caused  by  cocain,  704 
by  xanthin,  707 

changes  in  urine  in,  703 

derangement  of  heat  regulation  in, 
705 

metabolism  in,  706 

nervous,  708 

production  of  heat  in,  704 

'  puncture,'  701 

'  retention  theory,'   706 

significance  of,  708 

vaso-motors  in,  706 
Fibrillary  contraction,  151.  205 
Fibrin-ferment,  34.     Sec  Thrombin 

formation  of,  35 

preparation  of,  65 
Fibrinogen,  34 

production  of,  in  liver,  35 
Fibrino-globulin,  47 
Picks  theory  of  fusion  of  visual  stimuli, 

1050 
Fillet,  874,  88 1 
Flavour,  1078 
Flechsig's  developmental  cortical  zones, 

961 
Flexion  reflex,  U03.  997 
Flour,  719 

Flow  of  liquids,  with  intermittent  pres- 
sure, 85 
Fluoride  plasma,  clotting  of,  38 
Fluorides,    action    of,    on    coagulation, 

37.64 
laHal  heart,  11 35 
I'olin's  method  of  estimating  anunonia. 

crcatiiiiii.  524 

indican,  518 

uric  acid,  523 
Food  substances,  320 
Foods,  isiidynainic  relations  of,  773 
specilic  dynamic  action  of,  680 
Foramen  of  Monro,  850 
Forced  movements,  944 
Fore  brain,  850 
Formaldehyde  reaction  for  proteins,  8 


INDEX 


1:29 


Formatio  reticularis,  870 

I-'orinic  acid,  55() 

I'ornmla    of    contraction.     See    Law    of 

contraction,  845 
Freezing-point,  determination  of,  529 
!•" rev's  a>sthesioineter,  loHu 
Frog,  heart  of,  anatomy,  194 

to  pith  a,  193 

vagus,  dissection  of,  196 
stimulation  of,  198 

web  of,  circulation  in,  193 
Function,  localization  of,  in  cortex,  975 
l'"undus  of  stomach,  326 
Funiculus  cuneatus,  869 

gracilis,  861 » 

Gall-bladder,  411,  419 

reflex  contraction  of,  412 
Gall-stone,  pain  caused  by,  901 
Galvani's  experiment,  ^zz,  842 
Galvanometers,  726 
string,  727,  836 
Ganglia  habenula-,  933 

of  posterior  roots,  development  of, 
850 
Ganglion  cells,  sympathetic,  856 
spirale,  927 
vestibulare,  927 
Gaskell's  method  (heart),  195 
Gas-pump,  249 
Gaseous  exchange  in  lungs,  mechanism 

of,  263 
Gases,  absorption  coefficient  of,  247 
diffusion  of,  246 
of  blood,  243 

extraction  of,  249 
quantity  of,  250 
tension  of,  258 
of  muscle,  268,  269 
partial  pressure  of,  247 
tension  of,  248 

in  tissues,  267 
Gasserian  ganglion,  development  of,  854 
Gastric  digestion,  role  of  HCl  in,  353 
testing  for  products  of,  458 
glands,  influence  of  nerves  on,  401 
secretory  changes  in,  378-381 
juice,  349 

acidity  of,  350 

antiseptic  function  of,  356 

artificial,  458 

Beaumont's  work  on,  349 

chemistry  of,  350 

digestion  of  proteins  bv,   351, 

458 

electrical  conductivity  of,  387 
freezing-point  of,  387 
hydrochloric  acid  of,  350 
in  cancer,  350 

influence  of  substances  on  se- 
cretion of,  403,  405 
lactic  acid  in,  351 


Gastric   juice,  milk-curdling    action  of, 

353 
psychical  secretion  of,  404 
to  obtain  pure,  459 
secretion,  401 
Gelatin  as  a  forjd,  614 
from  nerves,  795 
tests  for,  9 
Geminal  fibres,  879 
Gemmules,  852 
Geniculate  bodies,  923 
Giant  pyramids  of  Betz,  959 
Gianuzzi,  crescents  of,  375 
Gibbs,  thermodynamic  law,  431 
Glands,  action  currents  of,  838 

iieat-production  in,  689 
Gliadin,  feeding  with,  617 
Globin,  54 

Globulins,  tests  for,  9 
Glomerulus,  function  of,  492,  493,  495, 

497-  305 
Glosso-pharyngeal  nerve,  929 

and  taste,  925 
Glottis,  in  voice  production,  308,  312 
Gluco-proteins,  2 
Glucose,  10.     See  Dextrose 
Glutamic  or  glutaminic  acid,  360,  575 
Glycerine,  i,  363,  366,  536,  556 

formation  of,  from  carbo-hydrates, 
561 
of  glycogen  from,  536 
tests  for,  12 
Glycerose,  537 

Glyceryl-phosphoric  acid,  366,  421,  571 
Glycin  or  glycocoll,  i,  360,  576,  580,  581 
Glycocholic  acid,  365 
Glycogen,  3,  523 

and  lactic  acid,  production  in  mus- 
cle, 771 
as  reserve  material,  539 
extra  hepatic,  538 

formation  of,  from  protein,  535,  538 
formers,  536 

function  and  fate  of,  539 
in  liver,  534 
in  liver  capillaries,  535 
in  muscle,  767,  768 
preparation  of,  715 
Glycogenase,  600 
i    Glycogenolytic  nerve  fibres,  549 
!    Glycolysis,  540 
i  pancreas  and,  545 

Glyconic  acid,  543 

Glycosuria,  after  injection  of  sugar  iato 
the  blood,  716 
adrenalin,  550 
alimentary,  540,  717 
caused  by  drugs,  552 
phlorhizin,  551,  717 
produced  by  asphyxia,  548 
puncture,  547 
relation  of  adrenals  to,  548 


IXDEX 


Glycurcmic  acid,  47,  .jHj,  526,  543 
Glvoxal  (inethxl-).  coiuersioii  into  lactic 

acid,  545 
Goitre,  cxophtliahiiic,  650 

i)f  brook  trout,  649 
Golgi's  method,  851 
Goll,  column  of,  863,  866 
connections  of,  870 
Gout,  487,  590 
Gowers,  tract  of,  866 
Graafian  follicles  in  ovarian  grafts,  641 
Gracile  funiculus,  86c) 
Gracilis  experiment  of  Klihiie,  913 
(irafting  tissues,  641,  1142 
Gramme-molecular  weight,  426 
'  Granule-cell,"  856 
Ground  bundles  of  cord,  867 
Growth,  foods  adequate  for,  614-618 
Guaiconic  acid  and  oxydases,  272 
Guaiacuni  test  for  blood,  76,  272 
Guanidin  and  parathyroid,  647 
Guanin,  592,  593 
Gudernatsch  on  influence  of  thyroid  on 

tadpoles,  653 
Giinzburg's  reagent  for  hydrochloric  acid, 

460 
Gyinnotus,  841 

Gyrus  postcentralis,  stimulation  of,  963 
precentralis,  963 

Ha^matachomcter,  121 

Hiematin,  54 
acid,  34,  75 
alkaline,  34,  75 

Haematocrite,  27,  68 

Haematoidin,  383 

Ha?matopoiesis,  20 

Haematoporphyrin,  35,  76 
in  urine,  483 

Haemin,  35,  79 

Haemochromogen,  54,  76 

HaMiioglobin,  composition  of,  50 
crystallization  of,  32 
crystals,  preparation  of,  73 
curves  of  dissociation,  233-233 
influence  of  carbon  dioxide  on,  233 
intracorpuscular    crystallization    of, 

52 
quantitative  estimation  of,  76 
spectroscope  examination  of,  74 
spectrum  of,  51,  53 

Hsemoglobinometer,  76 

Hainoglobinuria,  part)xysmal,  483 

Hii'molysis,  28,  71 

by  foreign  seruni,  -/l 
mechanism  of,  29 

H;rmometer,  77 

Ha'mophilia,  coagulation  in,  45 

Hitmorrhage  and  transfusion,   influence 
of,  on  blood-pressure,  191,214 
quantity  of  blood  which  may  be 
lost  in,  191 


Hair-cells  of  internal  ear,  937 
Haldane's  apparatus  for  CO,.  304 

for  H2O  and  CO^,  305 
Harmonics,  310 
Hay's  test  for  bile-salts,  528 
Head,  transplanting  of,  973 
Hearing,  1064 

analysis  of  complex  sounds,  1072 

l)eats,  1113 

cranial  conduction   of  sound,    1071, 

III3 
monochord,  III3 
perception  of  pitch,  1073 
range  of,  1075 

sympathetic  vibration,  313,  1113 
theories  of,  1074 
Heart,  action  current  of,  833,  844 
'  all  or  nothing  '  law  of,  134 
apex,  preparation  of,  194 
arrangement  of  libres  in,  78 
augmentor  nerves  of,  157,  162,  165, 

168, 198 
auricular  flutter,  151 
automatism  of,  142 
beat,  83,  194,  201 
cause  of,  141 

chemical  conditions  of,  152 
neurogenic  and  myogenic  hypo- 
thesis of,  142 
standstill,  action  of  augmentor 
nerves  in,  168 
conduction    and    co-ordination    in, 

146 
conductivity  of,  142 
excitability  of,  142 
extra  systoles  of,  133 
extrinsic  nerves  of,  156 
'  fractionate  '  contraction  of,  163 
ganglion  cells  of,  141,  163 
impulse  of,  90 
inhibitory  ner\-es  of,  137,  162,  164, 

198, 203, 212 
inhibition  of,  136,  167 
intrinsic  nerves  of,  141,  157 
nniscle,  action  of  inorganic  salts  on, 

198 
of  l.inuilus,  143 
output  of,  139 
pacemaker  of,  143 
pause  of,  97 
perfusion  of,  153,  205 
pressure  in,  variations  of,  97 
refractory  period  and  extra  contrac- 
tion of,  133 
resuscitation  of,  153 
rhythmicity  of,  142 
sounds  of,  88,  207,  837 
source  of  energy  of  contraction  of, 

77- 
suction  action  of,  loi 
temperature  in,  710 
tonicity  of,  142 


/.v/)/;a 


I-J3I 


Heart  tracings,  i(>.»,  iri.  194,  203,  H37 

siiuuUanr<)\is,  (loiu  auiiclf  and 
Nfiitriclo,    1611,    161,   196 
valves  t)(,  80,  204,  206 
wDik  done  by,  138 
Heat  centres,  701 

coagulation,  9,  819 
distribution  of,  7o<) 
equivalents     of     food     substances, 

684 
given   off   in    respiration,    measure- 
ment of,  08:1,721 
liberated  in  cleavage  of  food  sub- 
stances, 683 
loss,  681 

regulation  of,  involuntary,  690 
voluntary,  692 
production,  amount  of,  683 
and  work,  684 
effect  of  curara  on,  694 
in  brain,  689 
in  digestion,  686,  713 
in  fever,  704 
in  glands,  689 
in  heart,  688 
in  muscles,  687 
in  rigor,  778 
of  different  classes  of  workers, 

685,  687 
relation   of,  to  muscular  work, 

764, 765 
regulation  of,  involuntary,  693 

voluntary,  692 
seats  of,  686 

surface  and  blood-flow  relations, 
696 
rigor.     See  Rigor,  heat,  777,  820 
sources  of,  in  body,  683 
standstill  of  heart,  159,  194 
Heller's  test  for  albumin,  524 
Helmholtz's  theory  (vision),  1053 
(vowel  sounds),  314 
(pitch  perception),  1073 
Hemeralopia,  1060 
Hemianesthesia,  capsular,  881 
Hemianopia,  923,  965 
Heniibilirubin,  365 
Hemiplegia,  reflexes  in,  911 
Hering's  theory  of  colour  vision,  1657 
Herpes  zoster  and  trophic  nerves,  806 
Hexoses,  3,  537 

Hibernating  animals,  temperature  regu- 
lation in,  703 
respiratory  quotient  in,  241 
Hiccup,  288 
Hippuric  acid,  524,  380,  614 

formation,  580 
Hirudin  and  coagulation,  37 
Histidin,  54,  360 
Histones,  2 

Holmgren's  wools,  1 112 
Homogentisinic  acid,  483,  525 


Hoinoiotliernial   atiimals,    production   of 
carbon  dioxide  in,  244 
tliermotaxis  in,  690 
Homo-lateral  fibres,  879 
Homologous  stimuli,  1007 
Hormones,  404 

Humidity  of  air  and  heat  regulation,  691 
Himger  sensation,  930,  1096 
Hydr;L>mic  plethora,  462,  500 
Hydrocele  fluid,  39 

coagulation  of,  35 
Hydrochloric  acid  in  gastric  juice,  350 

formation  of,  379,  380 
Hvdrogen,   income  and  expenditure  of, 

619 
Hydrogen  ion    concentration  of    blood, 

24 

and  respiratory  centre,  282 

of  duodenal  contents,  419 

of  gastric  contents,  420 

of  milk,  1 1 39 
Hydrolysis,  2 
Hydrostomia,  401 

Hyoscyamine,  action  of,  on  pupil,  1026 
Hyperglycajmia,  300,  540 

adrenalin,  550 

alimentary,  540 

asphyxia,  548 

in  diabetes,  552 

pancreatic,  546,  636 

puncture,  547 

relation  of  adrenal  to  548 
Hyperis'otonic  solutions,  428 
Hypermetropia,  1030 
Hyperpna>a,  283 
Hypoglossal  nerve,  931 
Hypoisotonic  solutions,  428 
Hypophysin,  668 

Hypophysis.     See  Pituitary  body 
Hypoxanthin,  589,  592,  593 

Identical  points,  theory  of,  1037 
Idio-muscular  contraction,  759 
Ileo-ca'cal  valve,  331 

colic  sphincter,  331 
Illusions,  optical,  1041 
Imbibition,  426 
Indicau,  484, 517 

estimation  of,  518 
Indol,  formation  of,  in  intestine,  422 
Indophenyloxydase,  272 
Induction  machine,  arranged  for  tetanus, 
200 

arranged  for  single  shocks,  808 
Inductorium,  730 
Infundibulum,  infundibular  body,   666, 

933 
Inhibition  from  the  cortex,  954 

in  reflex  action,  903 

nature  of,  167 

of  heart,  156 
Inorganic  salts.     See  Salts 


12^2 


INDF.X 


Inosinic  acid,  767 
Inosit,  767 
Inspiration,  226 
forced,  230 
muscles  of,  226,  ^27 
Intellectual  processes,  seat  of,  973 
Intelligence,  size  of  brain  and,  088 
Intermedio-lateral  tract,  864,  865 
Internal  capsule,  881 

frontal  fibres  in,  882 
occipito-temporal  fibres  in,  882 
respiration,  265 
secretion  of  adrenal,  655 
of  kidney,  671 
of  ovaries,  641 
of  pancreas,  6;,6 
of  parathyroid,  646 
of  pituitary  body,  666 
of  pineal  gland,  671 
of  spleen,  672 
of  testicles,  640 
of  thymus,  643 
of  thyroid,  645,  6^7 
Intestinal    epithelium,    permeability   of, 
437 
juice,  adaptation  of,  to  food,  415 
collection  of,  370 
composition  of,  371 
influence  of  nerves  on,  414 
segments,  effect  of  blood-serum  on 
contractions  of,  453 
action  of  epinephrin  on,  453,  657 
658 
Intestine,  large,  absorption  in,  422,  451 

movements  of,  330 
Intestines,  absorption  of  water  in,  421 
contraction  of  isolated,  452,  330 
digestion  in,  418 
movements  of,  328 
nerves  of,  331,  332 
reaction  of  contents  of,  419,  420 
resection  of,  451 
Intraocular  tension,  1017 
Intrathoracic  pressure,  236,  237 
Invertase,  338,  339 

in  intestinal  juice,  371 
Inversion  of  carbo-hydrates,  356 
Iodine,  influence  of,  on  thyroid,  650-654 
loHS,  420 

Iris,  effect  of  stimulation  of  sympathetic 
on,  1023,  llio 
functions  of,  1026 
in  accommodation,  1023 
local  mechanism  of,  1025 
nerves  of,  1023 
Iron,  absorption  of,  447 
in  eggs,  622 
in  liver  cells,  463 
in  milk,  622 
Irradiation,  1061 
Island  of  Reil,  973 
Islets  of  Langerhans,  638 


Isodynamic  relation  of  food  substances 

773 
Is<jmaltose,  338 
Isotonic  and  isometric  contraction,  747 

solutions,  428 
Itching,  sensation  of,  1085 

Jacksonian  epilepsy,  972 

Japanese  dancing  mice,  labyrinth  of,  945 

Jaundice,  384,  414 

colour  of  stools  in,  369 

haematogenic,  385 
Jaw- jerk,  915 

Karyokinesis,  5 
Karyosome.     See  Nucleolus 
Katabolism.     See  Metabolism 
Kephalin,  42,  571,  794,  991 
Ketohexoses,  537 
Ketones,  537 

Kidnev,  bloodvessels    and   tubules    of, 
■489 

excretion  of  pigments  by,  495 

formation  of  hippuric  acid  in,  580 

gas  exchange  of,  266,  504 

internal  secretion  of,  671 

nerves  of,  504 

tubules  of,  490,  492 
Kinasthetic  area,  963 
Knee-jerk,  904,  915 

reinforcement  of,  911 
Kreatin  and  kreatinin.     5^^  Creatin  and 

Creatinin 
Kiihne's  artificial  eye,  II04 

Labyrinth,  927,  1067 

and  equilibration,  936,  938 
and  postural  reflexes,  918 
Laccase,  272,  337 
Lachrymal  glands.  475 
Lactalbumin,  719 
Lactase,  338,  340,  371,  410 
Lacteals,  463 

absorption  of  fat  by,  443 
Lactic     acid     and     heat-production    in 
muscle,  767 
as   stage   in    decomposition   of, 

dextrose,  543 
fermentation,  423 
formation  of,  in  muscle,  769 
Hopkins's  reaction  for,  821 
in  metabolism,  544, 345 
in  nervous  tissue,  705 
in  stomach,  350 
precursor  of,  in  muscle,  770 
Iffelmann's  test  for,  460 
Lakin;,  of  blood,  28.     See  Ha?moIysis 
Landergrens  hypothesis,  551 
Langerhans,  islets  of,  638 
Lanolin,  and  fat  absorption,  442 
Larynx,  action  of  muscles  of,  308 
and  voice  i)r(>ducti<>n,  307 


tSDE  V 


I2J3 


Latent  period  of  muscular  contraction, 

rts.815 
L.iler.il  uriinnd-bundlo,  Sh~ 

nucleus  of  bulb,  K;  5 
Law  of  contraction,  788,  845 
Lecithin,  i,  47,  .^66,  571,  7<>4,  «ic>i 

digestion  of,  421 
l.eclanciie  battery,  198 
Leech  extract  and  coaijulation,  38 
Left-handed  people,  aphasia  in,  971 
Legal's  test  for  acetone,  529 
Leucin,  .^60,461,  4>SS 
Lcuc<.)cytes,  chemistry  <A,  55 

cosinophile,  17 

number  of,  K) 

origin  of,  22 

polymorphonuclear,  17 

transitional,  17 

\  arieties  of,  17 
Leucocytosis,  ly 
Leuka-mia,  19 

Lcvatores  costarum,  action  of,  in  respira- 
tion, 227 
Levulose,  336,  538 

formation  of  glycogen  from,  537 
Liebcn's  test  for  acetone,  529 
Lieberkiihn'ii  crypts,  370,  374,  375 

functions  of,  431 
Lime  salts,  deficiency  of,  changes  caused 

by,  621 
Linmlus  heart,  143 
Linolic  acid,  336 
Lipase,  48,  338 

gastric,  335 

pancreatic,  363 

reversible  action  of,  338,  444 
Lipoids,  I,  3 
Lipoid-solubility  of  absorbed  substances, 

437 
Liquids,  fiow  of,  83 
Lissauer,  tract  of,  866 
Listing's  law,  1063 
Liver  and  aniino-acids,  584 

and  coagulation,  44 

and  deamidization,  388 

and  ghcogen  formation,  533,  535 

and  metabolism  of  fat,  567 

and  urea  formation,  384 

cells,  iron  in,  383,  463 

temperature,  689,  71.: 
Li\ing    matter,    chemical    composition 
of,  I 
functions  of,  6 
structure  of,  4 
Living  test-tube  experiment,  34 
Localization  in  different  animals,  980 

of  functiori  in  cortex,  973 
Locomotion,  946 
Locomotor     ataxia,     disappearance     of 

knee-jerk  in,  915 
Lungs,  area  of,  224 

auscultation  of,  231,  304 


Lung.,  blood-supply  of,  223 

circulation  time  of,  224 

mechanism  of  gas  exchange  in,  263 

i|uaiitit-\-  of  blood  in,  224 
Lynipli,  Composition  of,  57 

different  kinds  o{,  466 

flow,  factors  in,  192 

formation,  and  activity  of  organs, 
47^ 
factors  concerned  in,  467 
influence  of  nerves  on,  473 

freezing-point  of,  473 

hearts,  192,  193 

post-mortem  flow  of,  474 

pressure  of,  192 

r.ite  of  flow  of,  192 
Lyniphagogues,  468 
Lymphatic  circulation,  192 

glands,  192 
Lymphatics,  valves  of,  192 
Lymphoblasts,  22 
Lymphocytes,  17 
Lysin,  360 

synthesis  of,  in  body,  614 

Macula  lutea,  973,  I107 
Magendie-Bell  law,  891 
Make  and  break  sliocks,  807 
Malapterurus  electricus,  840 

nerve  of  electrical  organ,  850 
Maltase,  340,  345 

in  intestinal  juice,  371 
Maltose,  absorption  of,  443 
Mammary  glands,  fat  formation  in,  565, 
I  1141 

j  line,  90 

j    Manganese  salts  and  coagulation,  37 
Mannite,  3 
Manometer,  92 

differential,  96 

Hiirthle's  elastic,  n.) 

maximum  and  mininmm,  92 

optical,  93 

with  side-tube,  212 
Marchi  staining  reaction,  797 
Marginal  veil,  830,  858 
Marie,  tract  of,  867 
Mariotte's  experiment,  1044,  I107 
Mast  cells,  18 
Mastication,  321 
Mate,  632 

Maxwell's  spot  fxisioii),  1107 
Meconium,  424 
Mediastinum,  223 

Medulla  oblongata,  structure  of,  869 
'  Medullary'  groove,  849 

sheath,  development  of,  959 
Megakaryocytes,  18 
Megaloblasts,  21 
Meissner's  plexus,  320 
Meniere's  disease,  940 
Menstruation,  1120 

78 


1234 


INDEX 


Mcrcapturic  acid,  581 
Mrscncrphal'iii,  850 
Motatxjiisin,  6 
basal,  Mit 

in  fcvrr,  706 

in  starvation,  60; 

intermediary,  of  carbo-hydrates,  542 
of  fat,  565 

of  aniinoacids,  58J 

of  nucleic  acids  and  purin  basts,  592 

of  phosphatides,  571 

of  proteins,  57- 

and  muscular  work.  610 
in  star\ation,  603 

of  sterins,  570 

relation  of,  to  surface,  695,  696 
Meta-proteins,  3 
Metcnccphalon,  850 
Metharnioglobin,  53,  75 
Methylene  blue,  behaviour  of,  in  tissues, 

137,218,956 
Mcthylglyoxal,  545 
Methyl  orange  as  indicator,  523 
Metronome,  195 
Metts  tubes,  34^,  454 
Microblasts,  21 
Microtonometer,  259 
Micturition,  510 

centre,  511,  915,  920 
Milk,  1 1 39 

as  a  food,  62 1 

chemistr>-  of,  629.  718,  1139 

clotting  of,  353.719 

digestion  of,  353,  417 

hydrogen  ion  concentration  of,  11 39 

secretion  of,  11 40 
Millon's  reagent,  8 
Mitosis,  5 

Mitral  valve,  86,  96 
Moist  chamber,  809,  843 
Molecular  concentration,  420 
Molisch's  test  for  carbo-hydrates,  11 
Monakow's  tract,  S67 
Monochord,  III3 
Monosaccharides,  absorption  of,  445 

fonnation  of  glycogen  from,  537 
Monro,  foramen  of,  850 
Morphine,  quantity  of,  for  dogs,  63 
Morphology  of  the  blood,  14 
Motor  aphasia,  970 
■  Motor  '  areas,  951 
Mountain  sickness,  298 
Movements,  forced,  044 
Mucin  in  bile,  3O4.462 

in  >aliva,  344,  454 
Mucous  glands,  secretory  changes  in,  381 
Miillers  experiment,  296 
Muscarine,  action  of,  on  heart,  164,  199 
Muscle,  action  of  curara  on,  738, 811 

action  of  nicotine  on.  730 

anaerobic  contraction  of,  269,  306, 
770 


Muscle,  arrangement  for  tracings,  8l3 
chemistry  of,  767,  819 
composition  of,  767 
contraction  of,  743 
theories  of,  744 
influence  of  load  on,  747.  813 
of  temperature  on,  749,  813 
degeneration  of,  804 
diffraction  spectrum,  745 
direct  excitability  of,  738,  81I 
direct  stimulation  of,  740 
efficiency  of,  765 
elasticity  of,  736 
extensibility  of,  736 
fatigue  of,  749.  813 
cause  of,  751 
seats  of,  75^.  753-  813 
formation  of  lactic  acid  in,  751,  769 

820 
gases  of,  270 

general  physiology  of,  723 
heat- production  in,  686,  762,  764 
'  idio-muscular '      contraction      of, 

759 
nerve  preparation,  808 

fatigue  of,  752,  813 
of  eyes,  extrinsic,  1063 
oxygen  consumption  of,  269 
permeability  of,  773 
physical  properties  of,  735 
reaction  of,  769,  820       / 
receptive  substances  of,  739 
respiration  of,  269 
smooth,  contraction  of,  745,  747, 817 

wave  of  contraction  in,  759 
spindles,  804 
stimulation,  737 
structure  of,  742 
trough,  809 
Muscular  contraction  and  lactic  acid,  767, 
770 
changes  during,  744 
chemical  phenomena  of,  767 
CCj  production  in,  270,  768 
duration  of,  745 
graphic  record  of,  811 
heat-production  in,  762,  763 
in  absence  of  oxygen,  269.  306, 

770 
influence  of  fatigue,  749.  812 
of  load  on,  747,  813 
of  mental  fatigue  on,  754 
of  previous  stimulation  >  n, 

749,813 
of    temperature    on,    749, 

813 
of  veratrine,  on  754,  814 
isotonic  and  isometric,  747 
latent  period  of,  745,  815 
mechanical  phenomena  of,    745 
optical  phenomena  of,  742 
oxygen  cunsuniption  in,  768 


INDEX 


1335 


Muscular  ctmtraction,  physico-chemical 
cuiiditioiis  of,  773 
rate  of  wave  of,  751) 
relation     between     nieclianical 
energy  and  beat-production, 
765 
relation  of  glycogen  to,  771 
substances  metabolized  in,  771 
superposition  of,  736,  816 
theories  of,  744 
time  relations  of,  747 
voluntary,  760 
work  done  in,  747 
sensations,  101)4 
tissue,  action  of  extracts  of,  673 
tone,  917,  938,  1000 
work  and  nitrogenous  metabolism, 
610 
source  of  energy  of,  611,  767, 
771 
Musical  centres,  967 
Myelencephalon,  830 
Myelin  sheath,  fragmentation  of,  796 
Myelination  of  tracts  at  different  times, 

<)0I 

Myeloblasts,  22 
Myocardiograph,  162.  203 
Myograph,  195,  743,  812 

spring,  74t),  815 
Myohamatin,  767 
Myosin,  820 
Myosinogen,  820 
Myxcedema,  648 

Negative  variation.     See  Action  current 
Nerve,    carbon  dioxide    production    in, 
782 
chemical  changes  in,  782 
chemistry  of,  794 
conductivity  of,  790 

anaesthetics  and,  814 
degeneration  of,  795 

phosphorus  in,  797 
endings,  action  of  drugs  on,  182 
excitability  of,  784 

and  conductivity  of,  786 
fibres,  inedullated,  781,  860 

structure  of,  781,  851 
heat-production  in,  782 
impulse,  nature  of,  781 

velocity  of,  793,  818 

temperature  coefi&cieat  of, 
782 
muscle  preparation,  808 
pattern  of,  799 
polarization  of,  829 
propagated  disturbance  of,  781 
regeneration  of,  798 

autogenetic,  802 

chemiotaxis  in,  800 
stimulation  of,  783 
trunks,  cooling  of,  979 


Nerves,  anastomosis  of,  798,  976 
classification  of,  807 
posterior  roots,  section  of,  797,  964 
preganglionic,  185,  865 
specilic  energy  of,  979 
trophic,  805 
Nerve-cells,  growth  in  vitro,  802,  803,  856, 
857 
effect  of  anaemia  on,  859 
anaesthetics  on,  859 
division  of  axons  on,  795,  859 
fatigue  on,  859,  983,  984 
of  Golgi's  second  type,  856 
Nervi  erigentes,  r8o,  332,  334 
Nervous  activity,  chemistry  of,  782,  795, 

991 
Nervous  system,  autonomic,  1003 

development    of,    in    different 
animals,  898 
tissue,  action  of  extracts  of,  673 
Neural  canal,  849 

groove,  849 
Neuroblasts,  849,  858 
Neuroglia,  861 
Neurokeratin,  795 
Neurons,  851 

growth  of,  857 
nutrition  of,  858 
scheme  of  lower  motor,  855 
varieties  of,  835,  856 
Nicotine,  action  of,  on  ganglion  cells  of 
heart,  166 
on  skeletal  muscle,  740 
on  sympathetic,  182,  1005 
effect  of,  on  nerve-cells,  182,  913 
Night-blindness,  1060 
Nissl  substance,  851,  984 
Nitrogen  balance-sheet,  602 

necessary  quantit}-  of,  in  diet,  623, 

624,  625 
total,  estimation  of,  521 

variation    of,    with   protein    in 
food,  720 
Nitrogenous  equilibrium,  O02 

protein  necessary  for,  605 
metabolism    and     muscular    work, 
610 
Norleucin,  360 
Normal  solution,  479 
Normoblasts,  21 
Nuclease,  594 
Nucleic  acids,  chemistry  of,  593 

metabolism  of,  592 
Nuclco-proteins,  i,  2,  47 
digestion  of,  417,  592 
Nucleosides,  synthesis  of,  597 
Nucleotidase,  594 
Nucleotids,  593 
Nucleus,  5 

globosus,  885 
importance  of,  for  cell,  795 
tecti,  885,  928 


1236 


INDEX 


Oatmeal  as  a  food,  626 

in  dialx'tos,  555 
Obesity,  568 

Banting  cure  for,  606 

trcatiiH'iit  of,  570 
Occipital  lesions,  0^)6 
Oculo-niotor  nerve,  t)Z\,  ijSj,  1023 
Odours,  classification  of,  107b 
Uisophagus,  contractions  of,  323,  817 

pulse,  90 
Ohm's  law,  725 
Oleic  acid,  556 
Olein,  4 

Olfactometer,  1076 
Olfactory  bulb,  922 

nerve,  921 
Olivospinal  tract,  867,  885 
Oncometer,  507 
Oophorin,  642 

Oplitliahnometer,  1021,  I105 
Ophthalmoscope,  1031,  II08 

(ieneva,  1 1 10 
Opsonins,  61 
Optical  illusions,  1041 
Optic  lobes,  932 

and  inhibition  of  reflexes,  910, 
996 

nerve,  922 

radiation,  883,  923 
thalaums,  883,  932 
Orcin  reaction  for  pentoses,  528 
Orientation,  mechanism  of,  936 
Ornithin,  587,  613 
Osmosis,  426 

and  diffusion,  in  lymph  formation, 

471 
Osmotic  pressure,  426 

resistance  of  coloured  corpuscles,  73 
Ossicles,  auditory,  1066,  1069 
Otoliths,  937 
Output  of  heart,  139 
Ovaries,  internal  secretion  of,  641 
Ovary,  influence  on  metabolism,  642 
Overtones,  310,  313 
Ovum,  development  of  the,  1 122 
Oxalates,  action  of,  on  coagulation,  37, 64 

in  urinary  sediments,  478,  532 
Oxalic  acid,  481 
Oxidation,  seats  of,  265 
Oxidative  process,  nature  of,  271 
Oxidizing  ferments  or  oxydases,  271,  272, 

306 
Oxybutyric  acid,  555.  5('-.  567 
Oxydases,  48,  76,  271,  3°^ 
Oxygen  absorption,  mechanism  of,  263 

capacity  of  bhjod,  251 

coefficient  of  utilization  of,  697 

consumption  of,  242,  243 

in  different  animals,  245 
of  different  tissues,  268,  271 

deficit,  620 

diitiibutiou  of,  in  blood,  252 


Oxygen,  income  and  expenditure  of,  619 
partial  pressure    of,  in  aheoli,  241 

261,  263 
passage  from  blood  into  tissues,  266 
tension  in  blood,  258,  261,  262 

Oxyntic  cells,  375,  378,  380 

Oxyprolin,  360 

Pain,  in  internal  organs,  901,  1093 
referred,  891 

sensations,  1085,  1089,  II16 
paths  for,  896 
Pancreas  and  glycolysis,  546 

and  spleen,  nnitua!  relations  of,  41 1 
influence  of  nerves  on,  405,  407 
internal  secretion,  636 
islet  tissue  of,  638 
removal  of,  in  pregnancy,  638 
secretory  changes  in,  376 
Pancreatic  diabetes,  546,  636 

juice,  adaptation   of,  to  lactose,  410 
and   bile,   adjuvant   action  of, 

367,  368 
artificial,  460 
composition  of,  358 
ferments  of,  35S-363,  460 
freezing-point  of,  386 
rate  of  secretion  of,  410 
secretion,     influence    of    food    on, 
409 
Panniculus  adiposus,  568 
Parabiosis,  638,  1146 
Paradoxical  contraction,  832,  844 
Paraglobulin,  48 

'  I^aralytic '  secretion  of  intestinal  juice, 
414 
of  saliva,  397 
Paraphasia,  972 
Parasternal  line,  90 
Parathyroid,  effects  of  removal  of,  646 

location  of,  645 
Parenteral  absorption  of  proteins,  33 
Parotid,  secretory  ciiaiiges  in,  375,  376 
Paroxysmal  tachycardia,  electro-cardio- 
gram, 836 
Parthenogenesis,   1123 
Partial  pressure  of  gases,  248 
Parturition,  1137 

I'edunck\  inferior,  of  cerebellum,  885 
i'ellagra  and  vitamines,  632 
Pelvic  nerves,  179,  },},i 
Pendulum  movements  of  intestines,  328 
Pengavar  Djambi  as  styptic,  looi 
Pentoses,  528,  593 
Pentosuria,  487 
Peptases,  361 
Peptides,  2 
Peptones  and  coagulation,  37 

tests  for,  10 
Percussion,  232 
Perfusion  of  heart,  205 
Perikaryon,  850 


TNDEX 


1237 


Perimetry,  1048 

Periodic  brfathinp,   production  of,  287, 

300 
Peripheral  reflex  centres,  912 
Peristalsis,  324,  ,326,  .121),  3;,o 
Peritoneal  cavity,  absorption   from,  439 
Peroxydase,  76 

Persistence  theory  (vision)  1050 
Perspiration,  visible  and  invisible,  512 
Pettenkofer's  test  for  bile  acids,  366,462 
Phagocytosis,  59 

Phakoscope,  Helmholtz's,  102 1,  1 103 
Phenol,  excretion  in  starvation,  604 
Phenyl-alanin,  2,  352,  360 
Phenyl-hydrazine  test  for  sugar,  525 
I'hlebogram,  loi 
Phlorhizin  glycosuria,  551,717 
Phloroglucin  reaction  for  pentoses,  528 
Phosphocaniic  acid,  767 
Phosphates,  estimation  of,  516 
Phosphate  triple,  sediments,  479,  531 
Phosphatides,  571,  794 
digestion  of,  421 
metabolism  of,  571 
synthesis  of,  597,  607 
Phospho-proteins,  2 

Phosphorus  in  degenerated  nerve,  797, 
798 
in  milk,  621 

poisoning  and  fat  migration,  563 
Photo-electric  reaction  of  eye,  839 
Phrenic  nerves  and  respiration,  275 
afferent  fibres  in,  284 
anastomosis  of,    with    sympa- 
thetic, 801 
Phytosterins,  366,  570 
Pia  mater,  861 

Pilocarpine,  action  of,  on  nerve-endings, 
182 
effect  of,  on  heart,  166,  199 
on  salivary  secretion,  457 
on  pupil,  1026 
PUo-motor  nerves,  180,  913,  1004 
Pineal  gland,  671,  933 
Piotrowski's  test,  8 
Piston  recorder,  233 
Pitch,  310 
Pithing  a  frog,  193 
Pilot's  tubes,  121 
Pituitary  body,  666,  933 

action  of  extracts  of,  668 
functions  of,  670 
removal  of,  667 
Pituitrin,  testing  for,  670 
Placenta,  exchange  of  materials  in,  1129 
IMantar  reflex,  915 
Plasma,  proteins  of,  49 
Plasmine  of  Denis,  34 
I'lasmolysis,  428 
}'latelets  and  coagulation,  37 
I'lethysmograph,  128 
Plethysmographic  tracings,  129,  210 


Pleural  cannula,  234 

Poikiloi hernial    animals,    production    of 
carbon  dioxide  in,  244 
heat  in,  693 
Poiseuille's  lasvs  of  flow,  85 

space,  15,  193 
Polar  stimulation,  law  of,  741 
I'olariincter,  528 

Polarization  of  muscle  and  nerve,  829 
Polygraph,  103 

tracings,  209 
Polymorphonuclear  leucocytes,  17 
Polypeptides,  2,  352,  361,  578 
Polysaccharides,  3,  347,  348,  535,  537 
Pons,  932 

connections  of,  883 
grey  matter  of,  883 
Post-central  gyrus,  963 
Posterior  longitudinal  bundle,  885 
Posterior  root  ganglia,  development  of, 

850 
Post-sphygmic  interval  of  heart,  97 
Postural  reflexes,  917,  looo 
Potassium  in  muscle,  767 

salts,  influence  of,  on  heart-beat,  153, 
200 
Potential,  electrical,  725 
Precentral  gyrus,  963 
Precipitins,  31 
Prepyramidal  tract,  867 
Presphygmic  interval  of  heart,  97 
Pressor  nerves,  173 

bases,  672 
Pressure  sensations,  1041,  1081,  1114 
blood-,  measurement  of  arterial,  109- 
112,  210 
in  man,  1 13-1 16,  213 
influence  of  exercise,  115 
Primary  colours,  1053 
Prisms,  loio 

Proferment,  343,  351,  358,  376,  382 
Prolamins,  615 
Pi-olin,  352,  360 
Propionic  acid,  556 

transformation    into    dextrose 
538 
Proprio-ceptive  fields,  914 

spinal  fibres,  868 
Prosecretin,  408 
Protamins,  2 

and  coagulation,  44 
Proteins,  i 

absorption  of,  447 

'  building  stones  '  of,  576 

cleavage  of,  and  absorption,  448 

products  of,  360 
colour  reactions  of,  8 
complete  and  incomplete,  613 
consumption  determined  by  supply, 

607 
digestion  of,  351,  359,  361,  370,  417 
formaldehyde  reaction,  8 


123* 


INDEX 


Proteins,  formation  of  glycogen  from,  536 
of  sugar  from,  538 

general  reactions  of,  7 

Heller's  test  fur,  524 

in  nutrition,  relative  value  of  dif- 
ferent, 612 

living  and  dead,  576 

metabolism  of,  572 

necessary  amount  of,  623,  624 

of  tissues,  specificity  of,  321,  575 

parenteral  absorption  of,  33 

precipitation  reactions  of,  8 

specific  dynamic  action  of,  686 

synthesis  of,  573,  612 

temperature  of  coagulation,  9 
Protein-sparing  action  of  fat,  606 

of  carbo-hydrates,  606 
Proteoses,  3 

action  of,  on  coagulation,  37, 63 
on  clotting,  44 

(and  peptones),  influence  on  blood- 
pressure,  173,  215 

formed  in  gastric  digestion,  352,  458 
action  of  erepsiii  on,  371 
of  trypsin  on,  362 

in  blood  and  tissues,  574 

in  urine,  489,  525 

secondary,  13 

tests  for,  10 
Prothrombin,  36 
Protoplasm,  structure  of,  4 
Prozymogen,  343,  351,  358,  382 

granules,  376 
Pseudo-globulin,  49 

-podia,  17 

reflexes,  904 
Psychical  secretion,  309,  404,  1099 
Ptyalin,  346,  416,  455 
'  Puberty  gland,'  642 
P\ilm()nary  catheter,  259 

circulation,  223 

ventilation,  235 

regulation  of,  281 
Pulse,  anacrotic,  106 

arterial,  loi 

curve,  variation  in  form  of,  106 

effect  of  amyl-nitrite,  208 
exercise  on,  208 

frequency  of,  107,  210 

tracings,  103,  209 

venous,  09,  100,  loi,  131,  209 

wave,  rate  of  propagation  of,  108 
Pulsus  alternans,  155 

bigeminus,  155 
Pulvhiar,  i)2i,  933 
'  Puncture '  fever,  70X 

glycosuria,  547 
Pupilln-dilatitr  fibres,  1023,  1025,  1 1 10 
Purin  bases  in  urine,  481 

metabolism  of,   592 

bodies,  chemistry  of,  593 

excretioQ  of,  594 


Purkinje  fibres  of  heart,  147 
Purkinje's  figures,  1042,  III3 
Putrefaction  in  intestine,  422,  588 

of  proteins,  action    i>f   products  of, 
072 
Pyloric  sphincter,  relaxation  of,  327,  418 
Pyramidal  cells,  853,  875,  958,  959 

development  of,  854 

path  in  internal  capsule,  878,  882 

tracts,  866 

connections  of,  875 
in  different  animals,  877 
Pyramids,  decussation  of,  869,  875,  R78 
Pyrimidin  bases,  593,  595,  597 
Pyruvic  acid,  544.  545,  546 

Quadratus    lumborum,     action    of,     in 
respiration,  227 

Radiation  from  the  skin,  681,  683 
Radiometer,  681 
Raftinose,  340 

Rarefied  air,  effects  of  breathing,  295,  298 
Rations,  soldiers',  623,  627 
Reaction  of  blood,  24 
of  degeneration,  804 
of  gastric  juice,  420 
of  intestinal  contents,  419 
of  milk,  1 139 
of  urine,  479 
■  Receptive '  substances,  182,  739 
Receptor  in  reflex  action,  role  of,  900 
Receptors,  898 

Reciprocal  relation  of  vasomotors,  186 
Recurrent  sensibility,  892 
Refened  pain,  891 

Reflex  action,  anatomical  basis  of,  8y8 
extensor  thrust,  904 
flexion,  i(03,  904,  997 
inhibition  in,  903 
irradiation  of,  905 
of  spinal  cord,  897 
scratch,  901,  902,  997 
arc,  fatigue  of,  902 

isolated  conduction  of  impulses 

in,  890 
peculiarities  of  conduction  in, 

902 
properties  of,  902 
refractory  state  in,  903 
cardiac  death,  171 
centres  in  cord,  915 
peripheral,  912 
inhibition  of  heart,  170,  210 
time,  014 
Reflexes,  axon,  803,  913 
common  path  of,  899 
co-ordination  of,  908 
effect  of  strychnine  on,  899 
tetanus  toxin  on,  899 
facilitation  of,  909 
in  disease,  914 


INDEX. 


1239 


Reflexes,  influence  of  brain  on  spinal,  910, 
996 
in  heniiplcRia,  ')i  i 
inhibition  nf  antagonistic,  910 
lurp  spinal,  007 
p<istnral,  «)i/,  lOOO 
reiiiforcemeiii  of,  .ni,  998 
reversal  of,  iHH,  00^,  <)04 
role  of  the  receptor  in,  900 
short  spinal,  ')o6 

simultaneous,  combination  of,  908 
successive  combinations  of,  008,  909 
superficial,  914 
vasomotor,  185,  212 
Refractory  period  of  heart,  155 
Rffjeneralion,  of  nerves,  798 

autogenetic  theory,  801 
bifurcation  of  axons  in,  802 
of  tissues,  1117 
Reil,  islaticl  of,  973 
Renal  calculus,  pain  caused  by,  901 
Rennin,  33.^,  459,  719 

functi<-)n  of,  354 
Reproduction,  11 17 

in  higher  animals,  1118 
Reserve  air,  236,  303 
Resistance,  electrical,  724 
measurement  of,  725 
of  blood,  26,68 
Resonance,  232,  310,  314 
Respiration,  accessoi^-  phenomena  of,  231 
afferent  nerves  of,  276,  300 
and  blood-pressure,  iii,  289 
and  nervous  system,  274 
artificial,  202,  230 

by  insufflation  of  oxygen,  204, 

236 
influence  of,  on  blood-pressure, 
292 
breaking-point  in,  234 
calorimeter,  240,  676 
chemical  regulation  of,  281 
chemistry  of,  239 
comparative,  222 
cutaneous,  299 
efferent  nerves  of,  274 
external,  225 

forced,  influence  on  carbon  dioxide 
excretion,  234,  245,  282,  283,  300 
frequency  of,  234 

heat  given  off  in,  681,  682,  683,  721 
in  condensed  and  rarefied  air,  295 
influence  of  cutaneous  nerves  on,  280 
of  muscular  exercise  on,  280 
of  superior  laryngeal  nerve  on, 

278,301 
of  vagi  on,  276,  300 
internal,  222,  265 
mechanical  phenomena  of,  225 
methods  in  chemistry  of,  239,  305, 

306 
of  muscle,  269 


Respiration,  regulation  of,  276,  281 

types  of,  229 
Respiratory      apparatus,      physiological 
anatomy  fif,  22 '» 
capacity,  2i<t,  303 
centre,  274 

action  of  carix  m  dioxide  on,  281, 
282 
of  deficiency  of  oxygen 
on, 281 
automaticity  of,  284 
spinal,  285 
'  dead  space,'  236 
exchange,  239,  242,  243,  305 

gravimetric  method,  240,  306 
Zuntz's  method,  239 
movements,    tracings   of,    233,    278, 
279,  280,  289,  301,  302 
in  man,  233,  289.  301 
recording  of,  233,  301 
pressure,  238,  304 
quotient,  241 
sounds,  231 

tracings,  233,  278,  279,  280,  289,  301, 
302 
Restiforni  body,  885,  892 
Resuscitation  of  heart,  153 

of  central  nervous  system,  990 
scratch  reflex  in,  908 
Reticular  formation,  865,  870 
Retina,  development  of,  850 

epithelium,  pigmented,  1048 
fatigue  of,  1049,  1055,  1056,  Ilii 
formation  of  image  on,  1017,  1102 
intermittent   stimulation   of,    1050, 

II13 
sensibility  of  different  parts,  1058 
time  needed  for  excitation,  1049 
Retinoscope,  Geneva,  ilio 
Retinoscopy,  1034,  1 109 
Rexerser,  current,  732 
Rheocord,  727,  810 
Rhinencephalon,  922,  968 
Rhcxlopsin,  1046 
Ribose,  593 

Right-handed  people,  aphasia  in,  971 
Rigor,     heat-,     production     of     carbon 
dioxide  in,  270,  777 
mortis,  774 

and  muscular  contraction,  776 
production   of   carbon   dioxide 
in,  270,  777 
of    lactic     acid     in,     776, 
208 
removability  of,  779 
time  of  onset  of,  776,  778 
production  of  heat  in,  778 
Ringer's  solution,  66 
Ritters  tetanus,  S31,  846 
Ritter-\'alli  law,  785 

Riva-Rocci  apparatus  for  blood-pressure, 
"3.213 


I -MO 


IXDEX 


Rulandic  aroa  of  cortpx,  051 

spiisoiy  fiinctiun  of,  963 
fissure,  875 

Thane's    rule,   for    position    of, 
956,  963 
Rontgen  rays  for  study  of  gastro-intes- 

tiiial  movements,  327,  328 
Rouleaux  formation,  ib 
Rubro-spinal  tract,  867 

connections  of,  884 

Saliva,  action  of,  in  stomach,  348,  417 
amylolytic  action  of,  346,  454 
antilytic  secretion  of,  398 
chemistry  of,  344,  454 
effect  of  drugs  on  secretion  of,  392, 

394,457 
freezing-point  of,  387 
functions  of,  346 
paralytic  secretion  of,  397 
psychical  secretion  of,  399 
reflex  secretion  of,  398 
Salivary  centre,  400 

glands,  cranial  nerves  of,  391,  394, 

396,456 
extirpation  of,  673 
oxvgen    consumption    in,    266, 

268 
secretory  changes  in,  375,  3S2 
secretory  pressure  in,  393 
sympathetic  nerves  of,  391,  394, 

397,  457 
trophic-secretory  fibres  of,  395 
Salt  hunger.  381,  621 

solution,  physiological,  194 
Salts,  absorption  of,  446 

in  diet,  620,  625,  629 

in  fixxl,  r61e  of,  in  nutrition,  625 
Saponification,  II,  367,  421 
Saponin,  laking  of  blood  by,  70 
Sarkin,  589 

Scalene  muscles  in  respiration,  227 
Scheiner's experiment  (vision),  1031,  II03 
Schiitz's  law  of  ferment  action,  342 
Sclero-proteins,  2 
Scratch  reflex,  901 

in  resuscitation,  908 
Scurvy  and  deficiency  in  diet,  632 
Sealing  of  wounded  vessels,  46 
Sebaceous  glands,  fat  formation  in,  365 
Sebum,  312 

Secondary  contraction,  203,  833,  842 
Secretin,  407 
Secretion,  internal,  633 
Segmentation  of  f(X)d  in  intestine,  329 
Semicircular    canals    and    equilibration, 

936 
Semilunar  valves,  8g 

and  dicrotic  wave,  105 
moment  of  closure  of,  96 
Semisection  of  cord,  effects  of,  894 
Sensation,  relation  of  stimulus  to,  iioo 


Sensations,   cold,   1082 

cutaneous,  1078 

heat,  1 08 1 

hunger,  1096 

muscular,  1094 

ordinary,  cerebral  localization  of,  968 

pain,  1083 

tactile,  cerebral  localization  of,  968, 
969 

thirst,  1096 

touch,  1078,  1080 
Sensibility,  recurrent,  797,  892 
Sensori-motor  area,  963 
Sensory  aphasia,  972 

areas,  visual  centres,  923,  965 

functions  of  Rolandic  area,  963 

paths,  decussation  of,  894 
in  internal  capsule,  881 
scheme  of,  880 
Septo-marginal  bundle,  868 
Serin,  360 

Serratus   posticus,  action  of,  in  respira- 
tion, 227 
Serum,  action  of,  on  artery  rings,  46,  66 

albumin,  47,  65,  3"3,  819 

coagulation  of,  47 

composition  of,  47,  65 

globulin,  34,  47,  65,  575 

immvme,  31 

inorganic  salts  of,  49 

proteins,  49,  65,  37-2 
Sexual  organs,  internal  secretion  of,  640 
Sham  feeding,  402 
Shock,  anaphylactic  or  protein  32 

spinal,  888,  912 

surgical  or  vascular,  i<)2 
Sighing,  2S8 
Sino-auricular  node,  81 
Sinus  venosus,  80,  81,  141,  194 

stimulation  of,  198 
Skate,  electrical  organ,  841 
Skatol,  424 

formation  of,  in  intestine,  422 
Skatoxyl  in  urine,  484,  518 
Skiascopy,  1034,  II09 
Skin,  action  currents  of,  838 

effects  of  varnishing,  21)9,  699 

excretion  by,  311 

respiration  by,  299 

sensations,  1078 
Smell,  1073,  III4 

centre  for,  022,  967 
Smi.Dth  nniscle,  composition  of,  768 
Snake-venotn,  effect  of,  on  coagulation 

43 
Sneezing,  288 

Solutions,  scheme  for  testing,  13 
Sorbite,  3 
Sp<'citic  energy  of  nerves,  979 

dynamic  action  of  f(X)ds,  686 
Speech,  312 

nervous  mechanisra  of,  315 


INDEX 


1241 


Sprnnin,  642 
SphiiictiT  aui,  320,  33:1 

caidiar,  320,  324,  331.  335,  336 

ileocolic,  331,  335,  421 

pylori,     320,    326,    327.     331.    335. 

418 
vesicae,  510 
Sphygmograph,  Marey's,  103 

Dudgeon's,  208 
Sphygmographic  tracings,  103,  104,  209 
Sphyginoniauomcter  of  Erhmger,   114 

of  Hill  and  Barnard,  113 
Spinal  accessory  nerve,  ()3i 

united  with  fa:ial,  976 
cord  and  bulb,  centres  of,  919 
automatism  of,  916 
conduction     of     nervous     im- 
pulses by,  890 
consciousness  in,  889 
effects  of  transection  of,  888 
grey  matter  of,  863 
reflex  action  of,  897 
scheme  of  cross-section  of,  867 
section  of,  to  show  tracts,  865 
semisection  of,  effects  of,  894 
ganglia  and  reflexes,  912 
cells  of,  854 
development  of,  850 
fatigue  of,  913 
roots,  degeneration  of,  797 

function  of,  891 
shock,  888,  912 
Spinotectal  fibres,  874 
Spino-thalaniic  fibres,  874 
Spirograph  of  Fitz,  233,  300 
Spirometer,  233,  303 
Splanchnic  nerves  and  adrenals,  661 
and  hyperglycemia,  547,  55° 
and  intestines,  332 
and  kidneys,  506 
vasomotors  in,  177 
Spleen  and  hannatopoiesis,  21 

and  pancreas,  mutual  relations  of, 

411 
functions  of,  672 
grafting  of,  672 
proteolytic  enzyme  of,  411 
Spongioblasts,  849 
Staircase  phenomenon,  156,  749 
Standing,  943 

Stannius'  experiment,  144.  194.  ^99 
Starch,  tests  for,  II 
Starvation,  excretion  of  urea  in,  604 
loss  of  weight  of  organs  in,  603 
metabolism  in,  604 
protein  metabolism  in,  602 
Stasis,  61,  103 
Steapsin,  358,  363.  4^1 
Stearic  acid,  536,  55^ 
Stercobiliii,  424 
Stereognosis,  963 
Stereoscopic  vision,  1039 


Sterins,  or  sterols,  366 
(ligesiion  of,  421 
metabolism  of,  570 
Stilling,  cervical  and  sacral  nuclei  of,  864 
Stiinulaiils  in  diet,  630 
Stimulation  hv  voltaic  current,  741,  784. 
810,  845 
chemical,  737,  783 
law  of  polar,  741,  810,  845 
recording  beginning  and  end  of,  201 
Stimuli,  adequate,  901,  979,  1007 
different  kinds  of,  7^7 
summation  of,  736,  816 
Stimulus,  relation  of,  to  sensation,  iioo 

Weber's  law,  iioo 
Stokes- Adams  disease,  150 
Stomach,  absorption  of  proteins  by,  418 
auto-digestion  of,  388,  465 
digestion  of  fat  in,  355,  421 
excision  of,  357 
movements  of,  326 
nerves  of,  331,  401 
pouch,  403 

protection  from  gastric  juice,  388 
Stria;  acustica-,  928 
Striped  muscle,  structure  of,  742 
Stromuhr,  120 

Strychnine  and  reversal  of  reflexes,  904 
effect  of,  on  reflexes,  899 
in   localization   of   sensory    cortical 
zones,  968 
Substantia  nigra,  870 
Substrate,  338 
Succus   entericus,    370.     See    Intestinal 

juice 
Suckling,  food  requirement  of,  628 
Sugar  and  muscular  work,  541,  772 
constitution  of,  337 
consumption  of,  in  diabetes,  554 
destruction  of,  541 
formation  of,  from  amino-acids,  538, 
545,  590 
from  fatty  acids,  538,  545,  566 
in  blood,  47,  50,  446,  499,  500,  540, 

552,  717 
intermediary  metabolism  of,  542 
ill  urine,  tests  for,  488,  525 
regulating  centre,  548 

mechanism,  547 
tolerance,  340,  351,  637 
Sulphates  in  urine,  484 

estimation  of,  517 
Sulphocyanide  in  saliva,  346,  454 
Summation  of  stimuli,  736,  816 
Superposition  of  contractions,  756,  816 
Supplemental  air,  236,  303 
Suprarenal  capsules  and  coagulation,  45 
extract,  effect  of,  on  blood-pressure, 
173,  177,  216,  655 
Suprarenals,  655.     See  Adrenals 
Suprarenin.       See   Adrenalin  and  Epi- 
nephrin 


124: 


INDEX 


Surface  and  mass  of  body,  relation  be- 
tween, 693 
lieat-pioduction  and  blrx^id-flow,  re- 
lations of,  696 
phenomena  and  absorption,  431 
tension,  429 

and  muscular  contraction,  744 
Surgical  shock,  192 
Suturing  bloodvessels,  1145 
Sweat-centre,  513 

composition  of,  511 
function  of,  514 
quantity  of,  512 

secretion  of,  influence  of  nerves  on, 
513 
Swim-bladder,  secretion  of  gases  in,  265 
Sympathetic  cardiac  tibres  of,  in   frog, 

137,  196,  199 
cervical,  vaso-motor  fibres   in,   175 
ganglion  cells,  action  of  nicotine  on, 

182 
nervous  system,  1003 
vibration,  314,  760,  1073,  II13 
Synapse,  852 

resistance  of,  899 
Syntheses  in  the  body,  542,  570,  571,  573, 

578,  579.  580,  591,  597 
Systoles,  extra,  155 

Tachycardia,  930 
Tactile  sensations,  1079 

cortical  centres  for,  968 

paths  for,  896 
Tadpole  test  for  thyroid  active  substance, 

633 
Talbofs  law,  1040,  1113 
Tambour,  91 

for  respiratory  movements,  233 

Marey's,  208 
Taste,  1077,  I113 

centre  for,  968 

ners'es  of,  925 
Taurin,  365,  579 
Taurocholic  acid,  365,  462 
Tea,  594,  630 
Tears,  475 
Teeth,  320 

Tegmentum,  870,  874 
Telencephalon,  850 
Telodendrion,  852 
Temperature,  674 

daily  curve  of,  712 

discrimination,  1116 

in  cavities  of  heart,  710 

in  mouth,  712 

in  rectum,  712 

normal  variations  in,  71a 

of  blood,  711 

of  body,  680 

measurement  of,  675 

of  brain,  689,  712 

of  coagulation,  9 


Temperature  of  different  parts,  711,  712 
of  skin,  676,  712 
post-mortem  rise  of ,  714 
regulation,  690 

influence  of  curara  on,  693 
in  iiibernating  animals,  703 
sensations,  1082,  1088,  1092,  HIS 

paths  for,  896 
topography,  709 
Tension  of  carbon  dioxide  in  blood,  261, 
264 
of  gases,  247 

in  alveoli,  241,  263 
of  oxygen  in  blood,  253,  261 

measurement  of,  238 
surface.     See  Surface  tension 
Testes,  interstitial  cells  of,  641 
Testicle,  action  of  extracts  of,  642 
Testicles,  internal  secretion  of,  640 
Tetanizing    current,    arrangement     for, 

200 
Tetanus  (electrical),  composition  of,  756, 
816 
Ritter's,  831,846 
secondary,  203,  833,  842 
toxin  effect  of,  on  reflexes,  899 
Tetany,  after  parathyroidectomy,  646 
Tethelin,  670 

Thalamico-spinal  tract,  867,  883 
Thane's  method  for  position  of  fissure  of 

Rolando,  956,  963 
Theine.  481,  383,  394,  632 
Theobromine,  481,  583,  594,  631 
Theophyllin,  481,  594 
Theory,  Hering's,  of  colour  vision,  1057 
of  identical  points,  1037 
Young-Helmholtz,  1053 
Thermo-electric  junction,  675,  680,  763 
Thermogenic  nerves,  780 
Thermometer,  electrical  resistance,  676, 
677,  783 
maximum,  675 
Thermometry,  674 
Thermopile,  763 
Thennotaxis,  690 
Thirst,  sensation  of,  930,  1099- 
Thiry  s  fistula,  370 
Thrombin,  35 

formation  of,  36 

nature  of  action  on  fibrinogen,  41 
preparation  of,  41 
specificity  of,  40 
Thrombocytes.     See  Bl(x»d  plates 
Thrombogen,  36 
sources  of,  38 
specificity  of,  40 
Thronibokinase,  36 
preparation  of,  65 
sources  of,  38,  40 
specificity  of,  40 
Thromboplastic  substances,  41 
Thrombo-regulative  mechanism,  43 


ISDEX 


1243 


Thrombrisis,  45 
Thro'ubotaxis,  42 
Tluinib  ceiitrt',  073 
Tliyinin,  s>},\ 

Thymus,  iiivolutidn  of,  644 
grafting  oi,  645 
lymphocytes  of,  643 
Illation  of,  to  sexual  glands,  644 
removal  ot,  645 
Thyroid  and  heat-production,  650,  699 
changes  with  meat  diet,  650 
grafting  of,  648 
hyperplasia  of,  640 
influence  of  iodine  on,  650 

of  nutritive  conditions  on,  C40 
iodine  in,  632 

influence  on  tadpoles,  653 
nerves  of,  653 
Thyroidin,  649 
Thyroids,    effects   of    excision    of,    647, 

648 
Tickling,  sensation  of,  1078,  1080 
Tidal  air,  235 

measurement  of,  303 
Timbre  of  sounds,  310 

of  vowels,  313 
Time-markers,  195,  732 
Tissue  extracts  and  coagulation,  36 

respiration,  265,  269 
Tissues,  cultivation  of,  outside  the  body, 
1142 
gas  tensions  in,  267 
transplantation  of,  641,  1142      * 
Tone  of  muscles,  917 
vaso-motor,  184 
Tonsils,  320 
Topognosis,  963 
Torpedo,  840 
Torricelli's  theorem,  83 
Touch,  1079,  1080,  1114 

spots,  1080 
Trachea,  to  put  a  cannula  in,  202 
Tracheal  cannula,  201 
Tracts  in  spinal  cord,  865 

myelination  of,  961 
Transfusion,  influence  on  blood-pressure, 

191,214 
Transplantation  of  tissues,  641,  1142 
Traube-Hering  curves,  294 
Tricuspid  valve,  86,  96 
Trigeminus  nerve,  924 
Tripalmitin,  556 
Tristearin,  i,  556 
Trochlear  nerve,  924 
Trommer's  test,  for  sugar,  10,  525 
Trophic  nerves,  805 

tone,  919 
Trypsin,  345.   358,    359,  411,  418,  420, 

460 
Trypsinogen,  358,  372,  377,  389,  39i 
Tryptophane,  2,  360,  487,  615 
'Twitch,'  745,811 


Tympammi,  1065 

Tyrosin,  2,  360,462,  4«S.  575.  576 

Morner's  test  for,  462 
Tyrosinase,  272 

Uffelmann's  test  for  lactic  acid,  460 
Ultra- microscope,     coagulation     studied 

I'V.  39 
Uncinate  gyrus,  968 
Uracil,  593 
Urea,  in  blood,  47,  400 

estimation  of,  518,  520 

excretion  of,  by  kidney,  402, 496, 497, 
498, 502 
in  fever,  706,  707 
in  starvation,  604 
premortal    rise    in    starvation, 
603 

formation  of,  583 

processes  of  formation  of,  588 
Urease,  478 

method  of  estimating  urea,  518 
Uric  acid,  481,  523 

destruction  of,  595 

exogenous  and  endogenous,  595 

formation  of,  585,  590 

in  gout,  487,  590 

sources  of,  591 
Uricolysis,  595,  596 
Uricoxydase,  596 
Urine,  acidity  of,  478,  479,  515 

albumose  in,  509,  525,  572 

alkapton  in,  483,  581 

amino- acids  in,  481,  488,  579 

ammonia  in,  480,  519,  521 

bile-pigments  in,  483,  531 

bile-salts  in,  489,  528,  531 

carbo-hydrates  in,  482 

chlorides  in,  477,  483,  515 

composition  of,  476 

creatinin  in,  481,  523 

cystin  in,  488,  532,  579 

ethereal  sulphates  in,  484,  517 

expulsion  of  510 

ferments  in,  483 

freezing-point  of,  485,  529 

ha-matoporphyrin  in,  483 

hippuric  acid  in,  481,  524 

in  disease,  485,  524 

in  fever,  703 

incontinence  of,  511 

indican,  indoxyl  in,  484,  487,  517 

oxalic  acid  in,  478,  481,  532 

phenol  in,  484,  604 

phosphates  in,  483,  516 

phvsico-chemical   analysis   of,   4S5, 

529 

pigments  of,  482 
proteins  in,  482,  488,  524 
purin  bases  in,  481 
reabsorption    of,  from  the  tubules, 
494.  502 


1244 


INDEX 


Urine,  secretion  of,  489 

Heidenhain's   experiments    on, 

495 
influence  of  circulation  on,  506 

of  nerves  on,  308 
Nussbaum's    experiments    on, 

498 
pigments,  by  the  kidney,  495 
theories  of,  491,  502 
work  done  by  kidney  in,  504 
secretory  pressure  of,  y>(^ 
sediments  of,  478,  479,  488,  531 
skatoxyl  in,  484,  518 
specific  gravity  of,  4  7(>,  515 
sugar  in,  487,  488,  526 
sulphates  in,  484,  517 
systematic  examination  of,  531 
temperature  of,  712 
total  nitrogen  in,  477,  521 
urea  in,  480,  487,  518 
uric  acid  in,  480,  4S7,  523,  531 
Urobilin,  365,  424,  482 
Urobilinogen,  365 
Urochrome,  482 
Uroerythrin,  482 
'  Urohypertensine,'  672 
Urorosein,  482 

Uterus  rings  and  segments,  isolated,  II47 
Utricle,  936,  1067 

Vago-sympathetic   nerve,   in   frog,    141, 

196,  198,  199 
Vagotomy,  death  after  double,  286 
Vagus,  stimulation  during  resuscitation 
after  cerebral  ana-mia,  187 
in  mammals,  162,  164,  203,  212 
inspiratory  and  expiratory  fibres  in, 

276-279 
negative  variation  of,  277, 828 
nerve,  functions  of,  929 
of  frog,  dissection  of,  196 
relation  of,  to  respiration,  276 
stimulation  of,  in  dog,  203,  212 
in  frog,  198 
Valin,  360 

Valsalva's  experiment,  296 
Valves  of  veins,  82 

semilunar,  moment  of  closure,  96 
Varnishing  the  skin,  299,  SM.  690 
Vaso-constrictor  and  vaso-dil  ator  nerves, 
173 
differences  in  excitability  of,  175 
property  of  shed  blood,  45 
Vaso-dilator  fibres,  179 

in  cervical  sympathetic,  176 
Vaso-dilators  of   chorda   tympani,    179, 
392 
of  nervi  erigentes,  179,  180 
Vaso-motor  centres,  182 

anatomical  relations  of,  185 
nature  of  tone  of,  184 
spinal,  183 


Vaso-motor  nerves,  173,  175,  176 

course  of,  181 

in  cervical  sympathetic,  175 

in  splanclinir,  1 77 

ill  trigeminus,  176 

of  brain,   i  7() 

of  extremities,  177 

of  heart,  178 

of  lungs,  179 

of  muscle,  178 

of  veins,  180 

reciprocal  relations  of,  186 
reflexes,  183,  212 

studied  by  calorimetric  method, 
188,  221 
tone,  184 
Vaso-niotors,  methods  of  investigating, 

174 
Veins,  action  of  adrenalin  on,  181 
circulation  in,  132 
factors  concerned  in  flow  in,  133 
pressure  in,  132 
measurement  of,  in  man,  133 
pulse  in,  100,  131 
vaso-motor  nerves  of,  180 
velocity  of  blood  in,  134 
Vella's  fistula,  370 
Velcjcity  of  blood,  117,  127 
in  capillaries,  130 
in  veins,  134 
measurement  of,  120 
Vena  porta?,  vaso-motor  nerves  of,  180 
Veuous  blood,  tension  of  carbon  idoxide 
in,  261 
pressure-curve,  98,  100 
pulse,  99,  100,  131,  134 
tracing,  100,  209 
Ventilation,  242 

pulmonary,  235,  281 
Ventricle,  suction  action  of,  loi 
Ventricular  pressure-curve,  94 
Wratrine,  action  of,  on  muscle,  754,  814 
Vesicular  murmur,  231 
Vestibule,  paths  from,  928 
Vestibulo-spinal  tract,  867 

connections  of,  884 
Visceral  pain,  891,  901 
Visuo-psychic  area  of  Campbell,  966 
Vision,  ;ifter-images,  1053 

apparent  size  of  objects,  1042 
astigmatism,  1031,  1105 
blind  spot,  1044,  1 107 
colour,  1 05 1 

Hering's  theory,  1057 
mixing,  1033,  IIII 
triangle,  1034 

\'oiing-Helnili(jlt7.  theory,  1053 
Cf)lour-blindness,  io5(),  11 12 
ct)mparative  anatomy,  1013 
contrast,  1036 
duration  of  stimuli,  1049 
I'icks  persistence  theory,  1050 


IXDHX 


1245 


Vision,  Holnigron's  wools,  11 12 

irradiation,  1061 

Listing's  law,  1063 

Maxwell's  spot,  1107 

nu-asurcment  of  field  of,  1038,  II06 

oplithalnionictcr,  loji,  II05 

ophthalmoscope,  m;!,  II08 

pfriinetr\',  los^s,  1106 

Purkinje's  linuri's,  104J.  III3 

relation  of  rods  and  cones  to,  1045 

skiascopy,  1034,  1109 

stereoscopic,  1039 

Talbot's  law,  1050,  III3 

thet)ry  of  identical  points,  1037 
Visual  acuity,  IIII 

centres,  965 

path,  883,  923,  966 

purple,  840,  1047 
Vital  capacity,  236,  303 
Vitaniines,  617,  632 
Vitreous  humour,  466.  1016 
Vivi-diffusion  apparatus,  48 
V^ocal  cords,  307 

in  voice  production,  308 
movements  of,   in  respiration, 

311 
paralysis  of,  316 
Voice,  307 

air-pressure  necessary  for,  309 
falsetto,  312 
in  children,  310 
nervous  mechanism  of,  315 
\oltaic   current,    alterations    in    excita- 
bilitv    and   conductivity   by, 
785-788,  844-846 
stimulation  by,  741,  784,  810 
Volume  pulse,  127 
Voluntary  contraction,  760 

electrical  changes  in,  762 
fatigue  in,  753 
movements,  acquisition  of,  981 
Vomiting,  335 
centre,  336 


VoniitJMf;,  induced  by  apomorphine,  336, 

459.  464 
Vowel  cavities,  314 

formation,  theories  of,  314 
V(jwels,  timbre  of,  313 

Warmth,  sensations  of,  1081 
Water,  absorption  of,  446 

in  diet,  029 

production  of,  in  the  body,  620 
Weber's  law  (stinmli),  iioo 
Wernicke,  aphasia  ot,  971 

zone  of,  971 
Wharton's  duct,  391 

insertion  of  cammla  in,  456 
Wheatstone's  bridge,  726 
Whey  protein,  354,  719 
Word- blindness,  972 

-deafness,  967,  972 
Wounded  vessels,  sealing  of,  46 

Xanthin,  481,  589,  592,  593 

fever,  707 
Xanthoproteic  reaction,  8 
Xerostomia,  400 

Yawning,  288 

Yeast  and  vitamines,  633 

test  for  sugar,  4S8,  526 
Yellow  atrophy,  acute,  and  excretion  of 
amino-acids,  586 
spot,  975,  1 107 
Yohimbine,  action  on  refractor>-  period 
in  nerve,  783 
vaso-dilator  action  on  submaxillary, 

Youug-Helmholtz  theory  of  colour  vision, 
1053 

Zein,  as  a  food,  615 
Zoosterins,  366,  570 
Zymase,  337 

Zymogen,  351,  356,  382,  383,  389 
granules,  376 


BAILLlfeRE,   TINDALL   AND   COX,    8   HENRIETTA   STREET,   COVENT  GARDEN,    LONDOH 


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